·No text on this page.

·Epidemiology
of
Cardiovascular Diseases
Methodology
hypertension and arteriosclerosis
Guest Editors Herbert Pollack MD
and Dean E Krueger

·!
ingericht is the Amer an 1
11 alth A wat al., 190 ir atnay Sex Sark NY

·EPIDEMIOLOGY OF CARDIOVASCULAR DISEASES CONTENTS PAGE Preface 1 Participants 3 Chairman Address 6 Frame of Reference of Conference Committee Reports 9 Conference Committee heports on Design and Analysis 10 20 Criteria for Diagnosis of D ea e and Clinical Evaluation Clinical Evaluation Blood Pre sure Measurement and Electrocar diography Morphology 20 28 39 39 Diet Physical Activity and Biochemical Measurements Methodology for Diet Appraisal Physical Activity and Body Form Biochemical Measurement 52 67 71 71 72 80 Cultural Societal Tamilial Pychological and Genetic Influences Introduction Stres and Adaptation Environment Culture Environment Society Environment Family The Individual His Per onality and Pychological Reactions Genetics 85 87 89 91 Lpidemiologic Method in Current Cardiova rular Di ea e Re earch 105 Co Chairmans Addres 121

·No text on this page.

·PREFACE HE Conference on Methodology in vascular Disea, es was devoted to prob lems of measurement in selected a pects of these studies Held at the Princeton Inn Princeton N J April 24 26 1959 It was co ponsored by the American Heart Association and the National Heart Institute United States Public Health Service Subjects considered include criteria for the diagnosis and clinical evaluation of arteriosclerotic heart dlease and hypertension dietary phyical activity and biochemical measurements asse s ment of cultural societal familial psy chological and genetic influences and general problems of design of tudies and analysis of data This is the report on the third confer ence co ponsored by the two organıza tions and directed to research on cardio Vascular diseases The First National Conference on Cardiova cular Disea es held January 18 20 1950 in Ta hing ton was concerned with the entire range of technical knowledge and re earch community ervices and facılıties pro fes ional education and with all cardio vascular disea es 1 The Conference on Epidemiology of Atherosclero is and Hypertension at Arden Hou e Harri man NY January 29 February 2 1956 reviewed current etrological con cepts in those diseases and tool avail able for studies of population groups to te t tho e concepts and provide new lead for further investigation By 1957 everal groups had either begun or ere planning long term studies of cardiovascular di ea es in population grou (Representatives of thene groupa met at the Hotel Beaconsfield Brookline Vas June 17 18 1957 at the invitation of the Framingham Heart Di ea e Epidemiology Study National Heart Institute to exchange information and consider problems of diagno fic criteria and chnical and laboratory pro cedures ) With this background of interest and experience in epidemiological research in cardiovascular di ea es the cospon oring organization, felt that the time had come to devote pecific attention to problems of mea urement faced by indı dual investigations and to the potential value of being able to combine or at least compare results of several investi gators u ing tandard measurements The conference worked toward this goal not with the idea of selecting the best method for measuring any factor which might be important in epidemiological studies of cardiovascular diseases but by con dering all available methods giving their judgment about minimum base line measurements which should be included in every epidemiological study of cardiovascular diseases and about optimum mea urements which should be made in some studies when the circum tances enable use of these more precise methods Prior to the conference nine working groups met to con ider problems in the subject areas noted at ove and prepared preliminary report for presentation to the conference Members of the Com mittee on Design and Analy is of Studies participated in meetings of each of the This was a highly pro ductie preconference acuity I wish to expre my appreciation to each of the 60 people who contributed to the preconference work a members of com mittee and especially to the chairmen of the e groups to Dr Herbert Pollack chairman of the conference and to Mir Dean E Krueger executie ecretary All of these a well as other persons who attended the conference are li ted following this preface The report of each of the nine groups which met prior to the conference was pre ented and di cu ed at length in other group ·to and during the conference and typed the manu cnpt of the report JOHN FERREE VD. Aociale Medical Director American Heart Asociation REFERENCES general e son Each group au,menled In other conference participants who were particularly interated in the sul ject ana al o met eparately to con der the preliminary report and the dr cision in general ser con her ed reports were presented at the clo ing general mas con The publication alo reflects sork bs committee chairmen and in some in lance committee members after the conference a well as the continuing attention of the editors and technical a i tance from the leart Informa tion Center National Heart in titute Mr Mary llones National Heart In htule prosaded ecretanal ersice prior Dire o A PAR I no 8 H dent R Epal If yp Re $956 (dpl 1 * (Ed) Logic 1 A !! RI 9 () d) C Ine # 18) 115 dp is of September 1999 executie dsrector National Society for the Pse ention of Blad YOL 50 NO 10 APH ·Participants in CONFERENCE ON METHODOLOGY IN EPIDEMIOLOGICAL STUDIES OF CARDIOVASCULAR DISEASES CH ARXIA Hert ert Pollack VD Comm ttee on Nutrition Amer can Heart Association New York NY Co CHAIRMAN Herman E Hilleboe VD State of New York Department of Health Albany EVECLTIVE SECRETARY D an Ekru. Nat onal H art In Istut Bethesda Md COMMITTEES DESIGN AND ANALYSIS OF STUDIES CHAIRMAN Fel E Moore Univers ty of Mich gan School of Tutle Health Ann Arbor Mich Marjor e T Bellows Am r an Heart As sociation New York NY Antonio Ciocco Sc D Uni ersity of Pitts burgh Graduat School of Public Health Pitt burgh Pa. Leonard Cook American Heat Assoriat on New York NY arold Dorn PhD Nat onal Io titutes of Health Beth sda VIJ Jack El a on PhD Columb a Univer ty School of Public Health and Administratie Medicine Mew York NY Ph lıp Enterlin lleart D sease Control Branch USPILS Vaslun ton DC Z Fejla VD Worll Ilealth Organization Gena Switzerld E Cuyl, llammoni Sc D Am can Can er Society New York VY Herman E H lleboe VID State of New Yok Department of Health Altany NY Dan E Kruerer at onal He rt In titute Berbes la Md. Donalt Mainla d MD Ney York Um ersity College of Medicine New York NY Ralph S Pafíenbarger MD National Heart Institute Bethesda Md George St. J Perrott B te da Md Pobert Reed PhD Har a d Univer ty School of Publc Health Boston Mass Dand D Rutstein VID Hara d Med al School Bo ton Vla O San Ph D Nional Health Survey Proqram USPHS skin ton DC Donovan Thomp on PhD Uni ersity of Pittsburgh Gradu te School of Publc Health Pitsburgh Pa hnut v tlund VD Life In u an e Com panie Inst tute for Vedi al Statit ܘܐ 0 Nowy Ja ob le u balmy PhD Univers ty of Cal fomnia School of Publ II alth Berkely Calf CRITERIA FOR DIAGNOSIS OF DISEASE AND CLINICAL EYALUATON CHATRYAY Joseph Doyl VID Albany Medical Colleg llbany NY Blood Press re Measurement nneth I l Istadt VD In la School of Med in Ind anapol Int. George Veneely MD Van derb lt Un verity School of Vedin Nah slle Ten EcOg den VD Oh a State Unner ity Col lege of Vedon Columbus Oh Rolan! Schneck! th VD Cleseland Cl nic CI eland Olo Un er ity Al o part cipated preconf ne work ·Chocal Evaluation Thom3R Pawber 13) rambam Heart Diseg e Study bramın ham Vass Ole by Paul HD Unserney of Blinors Cole e of Me licine Chica o II ECG Interpretation Freleri Erten VD Liversity of Wich fan School of Medicine inn Arbor 1lich Robert Prant ID National Heart Insti tute Bethes Charle Armand VD) Jork ser of Vedeme Teu lorhi F1 Simonsan YD Lalorats of Ph sio logical th gene ther its of Minn vs Vs anos nn y (ottt Morphology LIAI! 14% OF SLDCOX 117TEE Da ad Spain VD Bell El llo al New York NY Jo epi Blum er AD Armed Forces In ful of arholomy Washington DC P Stron, TD Lous85804 State Uni er School of Ntedicine New Orlean La DIET PHYSICAL ACTIVITY AND BIOCHEMICAL MEASUREMENTS CHIHUAN James Blund - 1) tonal C: \ 45 > 131E Warila frut ann erszty of Pulls Health into Kuth LR ttute ! nom turulu Reyr re Aubrey havan AD London Hospital Re earch Laboratories London England Ancel hey PD Laboratory of Physiolo! ra! Hygiene University of Minnesota Min asrapol Vinn It Morris. PD Purdue Unsversity De partment of Agricultural Economics Lalan ette land Henry Taylor PhD Laboratory of Phy 10 lo al llygrene tinnersity of inte oke Ynneapolis Minn Will am Zukel VD Ofice of the Surgeos General USPEIS Washington DC Ilerle it Am 11 en 11 nun fase 31 D Den Marjor { at in rographic Ilu atis !! Nalusal fun Blachemical Measurements LKAR IAN of blacOSIITTEE Forse hen PM) Columbs Unsernity Divison Coldwater Vemorial Hospital New York Tho(aduate School of uni Pwysical Activity M>117T2+ llaruant Beld 1 tl) of It hurgts raduat Plest alth res 1 osh P'A An 3337 13 Harvard Bas erst School of Iutt 11 a!th Beton 124 Amaia R torte ter Rosene Vehi al College land Ohso Lime 1 THD Columbia Uni erity Dar Non Coldwater Memorial Ilo putal new York NY Jourph Bragim MD National in titures of }} 215 Besh ta ya erald Looper VD Communicable 1 *4 (enter U5IS Chamlilee Ga Georg Vann MD Vand built Unisesity Shool of Heine Na hull Tenn John Feirs HD Imerican Ileart Aca I on e» York NY w Alu) para ipales The following persons are part in picronlerence work but I not attend the ran! : roer ss de Alon In itute of li me Ermin wit aral Hearch restre 2011 Valurgton Norm 48sway new york # Dept of it alch All any urgin Bral Chat Ruch Coun in Na ty of inloras vool Helt is {}ster All Brousky V **** ty of Michi10 School of Tut! lealth Ann Autor na Brew Sh A 5121 I RITMIT Deparment tool and rear an Amat Vaty Cantoni Il art Draw Control Pran istis H. hinta c) torbi ih Viem! *met hul Tretrait an! Bumice Watt, MD Intel of Flora Frosinopf Agricultural Pearl Ynier is) Washingtot DC YOL 50 NO 10 IH ·CARDIOVASCULAR DISEASES CULTURAL SOCIETY FAMILIAL PSYCHOLOGICAL AND GENETIC INFLUENCES Charles Wilkinson MD New York Um verity Po tgraduate Medical School New York NY CHAIRMAN Harry hru e MID New York Academy of Medicine les Jork NY Mathan Ackerman * MD Columbia Uni Yer ity Colle e of Physi ians and Surgeons New York NY Walter Block PhD Unserity of Mich; an Ved cal School Ann Arbor Mich Lawrence Hinkle MD Cornell Univer ity M dical College Ne Yok N Lis y Jarvik * VD Columbia University De partment of Medical Genetics New York, NY Herman Kalckar MD Johns Hopkins Un Ver ty School of Bology Baltimore Nid. Carney Lan los PhD Columbia Unner ity Department of Psychology New Yok NY Alhet Pollack VD Mutual of New York New York NY Armand Quick VD Marquette University S hool of Med cine Milwaukee W. Hang Selye VD Institute of Exp rimental Medicine and Surge y Univerity of Mon treal Intreal Canada Ha ry Shapiro PhD American Mus um of Vatural History New York, NY Leo Simmons PhD Yale University De partment of Soci l sy Nw Haven Conn Jeremiah Stamler MD Chica o Board of Health Chica_o III General R. C Arnold MD Heart Disease Control Branch USPHS Washin ton DC Corcoran NID Cleveland Cl nic C} reland Ohio Jol n + Ferre MD American Heart Asociation New York NY W Stanley Hartroft MD Washington Um ser uty School of Med cine S: Louis Mo Archie A Hoffman VD Andrews Air Force Ba e Wahn ton DC Abraham ha an MD Heart Disease Epi denuolory Study Framingham Mass Lawrence E Lamb MD Department of In ternal Med cine Randolph Air Force Base Tec Fred rch Lewy HD American Heart As so lation Nev York NY Luth L lerry MD National Heat Init tute Beth da Md Geore E Wakerlin WD American Heart Aoc on New York NY Al ce M Waterhouse MD National Health Survey Pro m USPHS Wa beton DC Also parti pated in reconf rence 1 ork OCTOBER 1960 ·CHAIRMANS ADDRESS Herbert Pollach VDF 1.PILA wa MAVT to i clcome you to this (nier ence on Methodology in Epidemiologi cal Studio of Cardiova cular Diae One might al How did thi nſer ener get tarted and who parked it into being The point of origm would ar peir to be a letter from Dr A Cor coran to Dr James Watt written by Dr Corcorin horts after it furning from a the hool of Iublic Health at the meats of Vich an in Jul 1957 Dr (ort ran wrote that Tule there he luids cu pull the urgent need for tindardization of proedures in curiosa (ulir uri v This Petter ct in molwon the inachinery which resulted in the meeting Illaough the purpos of this conler ence have lern prplained to you 5 Hould like to reinte them briefly Oni lo «t up minimum acceptable se line tnea re in pecific irea tu prosiding comparability in em demiol exal ureje flimum procedure Three to define gap in methodology and to rischirm to fill there cap Dumne the stellerntions of this conference he hull continuouls lear in mind these major oljelies which will her the funt report The chairman kilp to espres 1 fint hi deep api reriation for the liari mark of ile many song spot 1 I le for the admin trative and ox ra funal chores insolved in a meeting of tine tv The conference 1 1x the American Heart Ortation and alional Inter of lealth throu h the \tional liart in titute Vir Dean Anret escrit e erretats i la calls Treponatle for me t of what has taken place Dr Valham Zulel Dr John Ferree and many others have devoted a tremendous amount of time to the organization of the mecting--the happy culmination of which we see here In Biblical time the concept of the relation hip of the environment to the individual and the indus dual to the en vironment was ted omewhat differ Intly than it is today Formerly the phra e The world the fle and the deu? und Today we di cu the environment the host and the cau e of the di ea es The liealth of the com munity as well a the di ea es of the community are expresions of the rela tion hip Ietween the three factors enu merated Fucn in Biblical times therr wa a concept of the epidemiological or the ecological appro'ich to da es Io fully under land the variations of the incidence of ma di ea c one mut draw upon world evenience rather than the mall segment represented by a given community Di ea and dita e tales how many variation depending on en vironmental conditions under wuch thm are o prsed The rydemiological arproncima rd upon the ecolo, of the individual-mahes e of the e tyx of data itues the methods of all the stientific al aplines repre ented here today clinical medicine tats tie* social cience Jathology Iwochemitry PYETI mental hy inlogy and many other Those attending thus conference recornize that in the lu tory of medicine no di ea e le eserleen ronquerell an altempt in treat esers allected ind, sidual It 14 only I tudying the etiol throurh the epidemioloaical ap proarhi that man has been alle to tamp Tuo to get uso! 2t pon ored VOL. 50 NO 10 AJPM ·CARDIOVASCULAR DISEASES out ma di ea e It hoped that this approach can be applied to the problem of cardiovascular disease One purpo e of this conference is to point out to tho e Interested in this ares of ini estigation the que hons that remain to be answered Certain criteria will be set up which can be made ap plıcal le to large areas as tandard for the collection of data If we are to rompare data from one area of the country with that from another or data from one part of the world with that from another obvou ly the e mut be collected with such compari ons in mind Standard ued in all tudies when re porting deviations from the normal hould be mutually acceptable and under tandable that end results can le meaningful in all countries to ue different tandards in various parts of the world is like conversing in different languages without a tran lator As chairman I am enthusia tic at the opportunity of working side by side with pecialists from the many disciplines repre ented here It is a challenge and al o a real problem in coordination l'ut then the esence of good epidemi ological re earch is the coordination of many special is toward a common goal One mut not minimize the value of per onal views the concept that permits any person to report but only certain ones to advie is unaccept ible for this meeting If it were acceptable it would re-ult in too creat a relance on so called tudy groups of all types While this is a new panel it can al o he viewed as a hi torical exten ion of the Brooklin Conference Let us not therefore fall into the error of many new panel that act as if nothing had ever l een done before-perhap hecau e the continued exı tence of the problem lefore the panel i taken by ome a an indication of the inadequacy of previou conferences The effective results of a conference of the type depend not only on the con tributions of each participant but on omething even more important namely the working relationship of each indi vidual to his fellow member, and to the group The value of the final report could be negated if the individual prob lems of peciali ts became i olated from the group and each problem were di posed of in its own way--by expert to be sure but by experts who e only in tere ti the pecial difficulties involved in their own particular area Conferences of this type can be ex traordinarily u eful not only can they provide us with fre h points of view but they can al o provide with an excel lent way of locating talent that would otherwi e be unavailable The number of out tanding individuals with experi ence in any one field is limited As a result the ame group is called upon time and time again to review the p and related ta ks The type of panel pre ent today 13 omewhat different from the u ual one Usually in panel delibera tions the question tands or fall on the kill with which it is pre ented Hence there is a premium for quickness of com prehension by the ucces ful committee Here we hope that the more important quality of reflectiveness rather than fluency in peaking wall pre dominate There will be a further difference from previous panels Usually panel are expected to adjust differences that exist between participant therefore it is not urpri ing to find them endmg up with a re olution which is denominator rather than a well rounded creatice pomt of view I hope he wa) not return to the common denominator type of resolution If we do not thi conference will contribute an important concept to the technic of solving prol lem The development of hort term expedi enci i not the purpo e of this confer nor are we attemptin, to fin! Utopia where all questions will le nian common ence OCTOBER 1960 ·OHT answered and all problem olied Te are not looking for the registration of di pnting points of view We do seek from you a significant contribution to the field which will gue a sense of direction to the development of em demiological method for study of the cardiovascular di ca es In bringing together the variou dis ciplines for thus conference we hope that each of you will have the ori ortunity to pre ent your mo l inportant con iderations and to under tand the point of view of other of ipline it will be necesars to place a premium on those phases of other di ciplines wluch can not be most ea ily duplicated by your Personally I would recommend that you listen particularly to places of ancillary di ciplines which are unrelated to your own these are the ones that require integration into your own field of expertnes The rculation which we eek can exit only when the facts are not known with the desclopment of these fact the area of prculation are gradually narrowed and then di appear 6 VOL. 50 NO 10 AJPH ·FRAME OF REFERENCE OF CONFERENCE COMMITTEE REPORTS There HE committees took advantage of re ports on prior conferences on cardio Vascular di ease re earch in the United States cited in the Preface as well as those by Expert Committees of the World Health Organization to which some of the committee reports refer The scien tific knowledge of members of the com mittees however provide the major basis for this report The committee reports reflect the in formation most acceptable to partici pants in the conference and in general their consensus regarding the adequacy and limitations of presently available methods and their ideas about research needed to improve or des elop new methods Credit and re ponsibility for the con tent of these committee reports rets primarily with the chairmen and econdanly with committee member and other participants in the confer ence A special note is in order about the report of the Committee on Cultural Societal Familial Psychological and Genetic Influences on Cardiovascular Diseases Diverse scientific di ciplines —in many instances represented by one person—were included in this group The report is presented as the chair mans interpretation of information pro vided by members of his committee coupled with his own broad knowledge of the subjert It did not seem fea 1 ble in the limited time available to attempt to arrive at a synthesis of ideas on methodology in an area of study in which there are o many unknowns OCTOBER 1960 ·COMMITTEE ON DESIGN AND ANALYSIS OF STUDIES Felix E Moure i PII 4 Chairman IT and he anat; 13 O is clear that the prol lem of 1 ign in epidemiol gical studies of long term di ea e varied and comply that nothing hort of a lengthy treatise could provd ade quate coverage such a trati < ht not yet heen writta and its formulatın is clearly out ide the rapibslitics an ad lioc committte meeting for a limited period Thermitir has concerned ilelf therefort with a mall numl r of rather general roblem wuch appear to be recurrin Ten in this type of in vestigation 11 e are dealt with under tuo main heaong 1 Cuneral Proller of Definition ind De ign and II Mea urement Proll m The committee ha al o conder if necesary to con altenlun to those ludies which are la ed on the clinical or pathological examination of individual thus omilting from con neration the types of tudies ba ed primarily on information <curel hy lay interviewers from household in formants (morbidity curseys) and the types of tuches ba ed primarily on in formation from death certificates (mor tality tudres) of re uilt which differentiate them from other apptorche to the tudy of dica e The committee lipliesens that it will be more proſital le to outline thene common clements and problem than to attempt to formulate 2 narrow definition Epidennological tudies have been re ferred to larou ly a de cripture tudie population survey tudies of a cociation rather than cau ation anillarecen contra ted with clinical or laboratory tudies or controlled typerimente Lach of these term has connotation wsłuch undoubtedly will vary from one inietigitor to another By way of clarification of the concept the committee Ilgp ty that the follow ing elements are characterı tic of epı d miolorical tudies In an epidemiological tuch the uljeris tudied include not only pry on knoi n to have the di cae under con aderation lul alo person who are free (or apparently free) of the dep as well This mahes posible the search for factors which differentiate the two rou) or alternatively the earch for factors differentiating the among tho e free of di case who ube quently develop recogniral te di ea e from the subgroup of thio e who do not A frequent implication of the term fine it ul group 1 General Problems of Definition and Design A Some General Chorocteristics of Epidemiological Studies Vany types of tydse which have contributed to ads ances in our knowl edge of cardiova cular di ea es have been termed epidemiological' There appear to be common elements of design which characterize these tudies and common problem in the interpretation • In order to free the text of th:4 repost from the recurrin, circumlocuti n apparently free ol dysea the terms free of di ease or "pot d eased will be u ed as lal els for th se pet ons in whom Igns of cardiova cular d sea (arteriosclerot c or hypertene appropriate cannot be oberel) tandard cinical or laboratory methods of a wement It is terogn z d that the leg an important que tron which i dL cus ed in ection 14 of this report a 10 YOL 50 NO 10 APH ·CARDIOVASCULAR DISEASES a previous studies clinical tudy is that it is roncerned only with the group which seeks medi cal attention for disea e jet in many rlinical tudies di eace group_15 compared with a control group The difference if any lies in the method by which the tudy groups are selected and the breadth of generalization which that plection permit ince epidemiologi al studies frequently require exhau tive clinical method of evaluation (See ections IA2 and IID for further elabora tion of this point) 2 The deal epidemiological tudy Kould be based on probability amples from a very large population in order to per generalization from the tudy group to the larger population with pecifiable limits of precision It is rare however that the ideal approach as po sable the circumstances under which epidemiological tudies can be conducted often do not permit the draw ing of random amples from the very large population to which it would be desirable to generalıze It 19 important to recognize therefore that generalıza Lilit 1% a relative matter rarely in practice will generalızations apply to broader populations without strictions Knowled,e of the parent population and the way in which the ample subject were drawn are e sen tial in evaluating limitation on gen eralizability in any epidemiological study This information hould be pro vided in the publi hed report of tudies The extent to which generalızability 15 required is dependent on the tale of knowledge at the time at an early tage of knowledge a mall tudy on a limited population may proude clues which can le explored in sample from broader population to permit e ten ion of the generalization 3 The fir t aim of epidemiological tudy is to identify character tic of in dividuals and of their environment (broadly defined ennronment includes all agents impinging on the induudual) which are asociated with the existence Or occurrence of di ea e These asocia tions can be tested for stato trcalig nificance by tandard technics and it is nou generally under tood that the ac ceptance of the finding of significant a ociation does not imply the establish ment of a cause and effect relationship Der erthele the search for as ociations is a search for factors which may be etiologic in the di ease the degree of confidence in which the asociations are held taking into account information from other sources such as hypotheses about mechanisms involved should point the way toward conclu ve tudies of etiology 4 In tudies of human populations it is rarel appropriate to tudy a single factor u ually multiple factor and as sociations are studied A number of probable factors in the etiology of cardio 19-cular di ea es have been identified in In the search for new factor those already implicated hould wherever po ble be ob ersed and taken into arcount in the analysis of the new study Alternatively certain variables may be controlled by Jimit ing the study to group of per ons which are relatively homogeneous with respect to these variable el persons with specific age sex race occupational or other characteri ties 5 The ob ervational epidemiology al study lacks the important elements of the clinical or laboratory experiment First no attempt is made to alter tu characteri tics of the group under tul) rather there is dependence on the called experiment of oportunity which concomitants of vanalin mo eu ting envitonment (external or temal) of the indesidual are analsex the ame fa hion as the beati pri perimentally Introduced chung controlled laboratory unti, becau e no attempt is De Parent pecific variał les the promo of randomization of an iyi fits pour protesto ome re 7 OCTOBER 1960 ·+ mortal ty experienced appear to be applicable viduals to treatment and control mut be balanced in the individual in groups is mi ing from this type of epi stanice demiological sud, For example in The pro pective and relo-pecinte a a study of the asociation of smoking proaches will be con id red first with with rk of coronary artery dita e by the di cu ion of the CION actional analogy with the clinical trial mok tudy se ensed for a later ection (IC) ers may be regarded a the treated In the typical prompective audy group and non mokers as the control (which is frequently referred to as a group Failure to randomize places longitudinal tudy or studs of colort) re triction on) certain 1711 tical een a population is elected for studs with eralizations and requires that th , te out prior knonledge of the diea e status con dered approximations to the ex of the indiduais making up the popula perimental siluation where true random tion Each individual is examined at azalıon a pled On the other hand the outet of the tuds and classified as the attempt to control all relevant di cred or free of disca e At the are factor in the paperimental 11ation time data on other individual charac may well re uit in the lo s of informa feri tics which might po ibly Le related Hon on ymportant interrelation le au c to III of di ea e are ecured and the rane of environmental factors 13 recorded Tho e Irre of disease are re Truficalls tuotted The may con titute garded as the population at rk and evere limitation to generalizalion + are ol er et over ome time period Ittle end of the period the population B The Time Reference of Studies at rih can be clasified into two group Retrospective and Prospective thor who have dle seloped manife! di ca e and thio e who remain free of The patholo ic changes involved in disease It is al o po ible to cla sıfy arterio clerotic heart disea e and hyper tension develop over 1 period of years the population at rik into groupings on other factors (eg lipid lesels lody and appear to be influenced is host or fitnes environmental factors which evert their dırlary patterns) which char acterized ench individual at the time of force over much of the lifetime of an individual prior to the time the di cases entry into the tudy if differences in inculence of disease are found in the be ome chimically rerognizable Data pertaining to a cub tantal portion of Various groupin, on some clasification ihr hfe pan of the individual prior to There is not full agreement on appropriate Identification of fus di ea e are much terminology for descriting arous type more likely therefore to yield inform tron ol value than contemporary lon itud nal are use 1 synonymou 1 for data tudies in which groupe are followed from th alone for this rea on that time of definition fornard in time The term time span tudies either retrospective cohorts tudy has been propo ed to dear be the prospective study in which specific in 1 or prospective are often regarded as viduals are followet in contrast to an allerne superior to cros sectional studes In the type of lon tudinal study in which suc fact each of the three methods has bath fes i samples of an orionally defined group are studed talbr than identical individual advantages and disadvantages which (The latter type of design has I een discusci in reference 3 and is not further d cu sed in * It 13 recognized that there is an area of this report.) Si ce the terma cohort" in le pxperimental epid malogy which ha maoy table analyse implies a group of persons of the a pects of the chin cal tr al includ no bom in the ame rear whoe subsequ nt randomization This special type of study will 19 described the teren not be escu ed in th report cohorts study" For mor etlended di cusions of the to the type of lorg tud n 1 studs where indı points ra: ed in this section and references to Hiduals of vaning ages at entry to the study the literature see referenc s 1 and 2 are followed on time N VOL. 50 NO 10 AJIH ·CARDIOVASCULAR DISEASES the a ociation uggents the pre ence of an etrological factor In the typical retro pectise study one group of individual is brought into the tudy because they have exhibited manı fest igns of drea e A econd group of indiuidual are elected for tudy who are free of di ea e Often the latter group are matched with the former with respect to aoe er or other factors Data are then ecured on other inday dual characteri tics of the persons in the two groups in re pert to life er perience prior to development of di ease or in the case of those free of di eae prior to entry to the study As in the care of the prospective tuds the characten tics of the two groups are examined for differences which will iggest etiological factors f There are many posible variations within these two types of tudie but the important difference between the two is that in the prospectue study data on the di ea-ed are recorded before the criterion event (or diagnosi ) and in the retro pectre tudy after the cri terion event (though with re pect to a time period before the event) In prac tire nearly every pro pective tudy make u e of some retro pective data a lifetime hi tory of smoking ob tained at entry to the tudy but the important difference is that it i ecured before the occurence of the criterion event The retro pective approach contams certain problems of sampling de ign which mu be very diffirult though not necessarily impo utle to overcome any ylven point in time it may be ex tremely difficult to ecure a representa tive coronar) population The us vivor who are the only ones available for tudy may he quite different for example from those who died in their firt attack If usual inedical sources are u ed for the election of the cor onary population ome important groups of the population may be omit ted It i al o difficult to pecily the method of sampling for the election of the appropriate compari on group I Another problem in the retro pective tudy that the occurrence of the cri terion event may cau e the affected in dividual for his phy ician or a family informant) to resre the information that would have been pre ented in ad vance of the criterion event It is for this rea on that the burden of proof lies on the inte tigator in the retro pec tise tudy to demon trate perhap by ancillary tudies that the occurrence of the criterion event does not affect reporting of prior events The kind of data available for retro spective studies are frequently not de termined by the investigator recorded with his purpo e in mind nor a ea ily subject to validation proced ures as are data recorded in a pro pec tive tudy Thus the study dependent on pa t ho prtal record may encounter frequent gaps and hifts in recording method The pro pective tudy encounters other and different ampling problems One of the chief of these the prob lem of nonrespon e either in terms of refusal to participate in the initial ex amination or refu al to participate in the follow up examinition pen e of the pro pectuse study almost invanably limits the repre enfativeness of the group which can be studied There are certain ni hs of inay in the pro pective tudy in that the process of ob ersation may itself influence the rate of development of di ea e in the popula tion There is also the po ibility that early findings in the tuds will caue observation nor The er In I jases in ul equent Descript on of the pr pect se tud the dio a cular field will like I und in elerence 4 + See eferenc 5 for descnpt on of a retro pe lise 11 dy ! th s gen al type # Fo ended drus on tamping spe ref te e-68d mܐ OCTOBER 1960 ·Sulic ek ned to at art muslesi t 051 studs Itse rot of maintainm, a pro-pertise studs in operation for a quriod of time long, i nows to provide u eful data and the prolilem of maintaining confinitis of ironcları untoul trells hankaja to at urer Cisl prosecution Both the proprie and the retro spectise fuely rent trialjonal tubes and mithier ein demon trale (au atson 18 the same (11 as an experimental tudy The projecte study : theo retically uperior to the retro pertise study s ami le de ign and in proter von again ! the tik of bsan for leriori of nation and recording of data and for these reasons us has been preferred 11 latı tician ( 1 othet hand killed melgators have de velope I methods for protecting again : many of the dangers of the retro pectne If thene nk can he mins mized by appropriate afeguard retro precine tudy will le attractite le caul of sizable avings in both the length of time sequel to prockne ig nificant finding and in cot Pro pipere fuckle can m me in stance achieve one of the Cononi trually writted to rrito poetse studies 1, de lasing procting of data unulit pertinence has liene talltsed For example a propertise tudy of total verum hole terol and coronari hear it ea e era for the entire tudy population could be tored and cholen terol lese! le ted only for ubject 1 whom the di cave occurs plus a rila trvels small ample of the vat majority of uł jects in hom i doe Bot soeur In Kalance at an early kno, ledge the retro per tute turly 1 a relately quick and respen ne fut in secure method for garung in suht shto the etiology of ra e If the finding of such a tudy are challenged on the Pelerere 5 pro de examples (tal methou for te iss alid ty of retro et se data Found outlined above the challenge can only fit an hered in conducting a pin pectric til But as in the coe of the more and lung cancer con tro) it is clear that even the pro piecere tudy is not immune to challenge hen offered as proof for au al re lation C Cross Sectional Studies In the cro actional tuds trat 10 le 2114 pan analy 19 fa ed on compari on of oft ination on groups of indexual at a anun point in tim Iti ucful to com der to ispr of iron et trorat tudi In the fir t tyre a group of perman Sith known as eas are availall for tudy and a group of persons free of stie sera are elected for comparson kach indıraduals thus characterized as 10 premenile or absence of dea ( and in addition is contemporary obrations on otser factor felseved to be relevant to the disea e proces The interpreta tion of the results mut nece anıly le ha ed on the a umption that the differ Threm ab eozesł besneen the tio group 3re similar to tho e which would have biexen found if it had been rom ible to oli erre the groups i efore the criterion fient The time of iud; differs from the retro pective tud, preniouly de cribed onts in the fact that data are pured by contemporary ol ersation and not by recall it huile the crosection tudy 15 thu protected against the posshly effects of the criterion event on recall the protection is ernred at the expene of omitting data on the period prior to the criterion esent fctional study i subject to the pond fility of bias of the di ea e group ha lecay e of the orcurrence of the di ea e shifted it po 3tion with respect to pre di esse characteristics hifts in chat arteri ties may he play lological equelae of the attack it elf or a result of sub aquest treatment The certain lipid tage of The CTO VOL 50 NO 10 AJPH ·CARDIOVASCULAR DISEASES location (with accompanying racial cultural or other difference) It is clearly profitable to eeh groups differ ing widely in di ca e prevalence and to explore other factors characterizing the e groups with the hope that factors which dfferentiate the group may pro vide leads for further investigation Fre quently a direct interpretation will be difficult becau e of the confounding of mans fariors or level or blood pres ure or weight for example might differ from tho e which eu ted before overt dı ea e occurred The cro y actional study is subject to the ame problem of sampling as the retrospective tudy in that tho e in the dispa e group repre ent only the sur wors of some larger group which had experienced di ease The relatively large group of coronary (a e which die sud denly 11 the first attack for example are rarely included in hospital series If it should be hown that the sudden de uth group differed ignificantly from other coronary ca es then a tudy based on Urvisors only would yield a bia ed finding Alo as with the retrospective tudy it is difficult in specify what non coronary group is appropriate for com parison because of unrertainty concern ing the original disea e free population from which the coronary grip arose In a second type of cros sectional tudy group are characterized as to di case prevalence (or incidence) rates and imultaneously characterized in terms of group averages with re pect to other factors eg proportion of caloric intake in the form of fats of various types If differences on prevalenre rates are found to be a dated with group differences in other factors it may be inferred that the factors have etiological significance Groups may be cho en on many different grounds For example when it is found that groups selected for tudy on the lai of age and sex how different prevalence rates of the inference is made that the e factors are significant in a e ing nk of di ea e It is clerr from thi trval example that analy is at this level will not throw much light on differ enfial, inrik within age er groups unles individual can le further ub cla sified both with re pect to di ea e tatu and other character, tics More frequently the approach i u ed in comparing dra e prevalence in groups differing in occupation or in gengraphic D Problems of Sampling Selection of Comparison Groups In previous ection a number of problems of ampling have been touched upon It has been pointed out that no population 1 general whole in the sen e of not having its own peculiar characteristics reflecting factors whuch may be of amportance to the study of di ease such as its prlor mortality er perien e ethnic origin age and sex composition and a wide variety of en vironmental circum tances Thu the most defensible ampling method insure only that the ample statistics will provide e timate of the parameters of the population ampled within recifi able probability limit It eems prob able that studies of cardiova cular dira e of the depth required by the present state of knowledge will continue to be limited as to cope in both time and area coverage } ecou e of cot and limited nailatulty of trained per onnel Under the e ciruum lance the rejeli tion of tudies under comparable con dition with ell designed ample and in different places will provide ruin forcement of imilar finding eien though there may be no łatı tical method for making a probal ility state ment al out the combined results In a number of international cros di ease Th approach som tom s termed get graphs al pathol my or hum nec logy ha been d scu sed in som det i Jub! cat n which be ame a a lable ul rue to th con fe ce see rel ren e 8 OCTOBER 1960 15 ·Whe gurn Incalt pelas cetronal flies now lzeing cursed out the group clocked for tuds are liern cho en by a method sluch luas Iren re ferred to clima ampling chunk may he a cireum enhed occurra tional group (such as bremth in 1 or the ridents of a small vallan hun the clunk an afttmpt is made f. ecure 100 per cent rostrage sn order to avoid the boas o antsssdual milertion Lomparisons are thun made Letween imlar group culte rent countri ??? order to dras in lerer et aliout poible cau al factors when differences s dva e presalence are found This approasts ha min advantage and permits the carrying ont of Oudks in areas where mari ten ne sampling would not le len the It mut he nemzed houeter that there are extre factors in affiliation of indossdual sths occupational group and that the + mas vars from Bres to area The ushts of the church 3m pling approach will le increa edi a4 more comparatne information made a1 211 able not only concerning variations between chunks in different countries but slo between individual thanks within a country and the romandes of the population of that country Reselts from tudies of the type mu: le in terpreted in terms of pre ent Imutations on knowledne of the representativert pre epils availabile tat: fical tory of propriale for analy as In the long Itxial fly the treatment 11 C 1 igner at random ware other ind Bubual nonrudom element come in il the placement of individual 3210 17€ 31ment groupe on facto for prample for fatnes llowmer in the longitudinal terly thu population out of which the chea ce Lroup> orgmated pecified at the fint of the tudy and can be cła ifier on a 191git character tre uch a degree of lod fatnes from the beginning oi is olursation I nder then, 1TI UM tancat appropriate in true the a ovation leturen lods faine and as of its easy fotos, tether the new la es of es eu e are a tributed among the various lody fatns kroupas na nannur vompatible with the as um tron that think onls rondom Yaration from a uniform average small grouksets upport the dension of nod oration Uternatively of the distribution of Bew ca es among the arou 1 ody group. 15 wh that it nould have been very unlikely 10 Oct ur of than were only random sana tion from unsforon asorage rikthen the test son of amficant a octation is upported #It has already been re marked that a curation do not neces ar's upport the inlenme of cau al connection In the type of study where a comparı on group of free of du ca e per ons are elected for contra t with the di cac group there 18 neither the elerssent of randomization in a signment of treat ment found 1 the ideal experiment nor i shere the certain knonledge that the per ons free of ds eae at conclu ron of follow up are the remainder of the original population from wuch the new drea e caces came the situation which mahen permissble the type of atat tical te cle cathed above in the typical Jongludinal study in fact na logically de of the group In the di cui son a tie 13 peal setto spective and cro ectional tudies it was pointed out that there are enous problem of amling in the election of the appropriate free of di ea e group for com333-08 with the di ca e group Thene problem are of ufficiens uz portance to warrant further elaboration here in the traditional design of the experimental tudy patients are signed to treatment and control groups at random before the experiment and it to tht random a ignment which makes For a dion of this approa h and gen eral problems 11 ur ey kee reference 9 There are VOL SO NO 10 AJPH ·CARDIOYASCULAR DISEASES fen ble rules which can be pecified for the election of a compari on group in the type of retro pective or crosec tional tudy where independent election of di ea ed and free of di ea e groups 1 necessary What can be pecified is that the two groups should be as much althe as possible with respect to factors which are known in advance to differ entiate the two groups The difficulty is to in ure that the election process does not permit the introduction of other factors which would differentiate the two groups and yet be unrelated to the di ea e proces it elf Thu when turlie of this type are undertaken a large part of the protection again t mis leading interpretations mu t rest on that part of the hill of the experienced in Sestigator-medical OT stata tical which i art rather than cience The conipletenes of examinations in terms of procedures to which the sub ject is a ked to ubmit and the time required to carry them out appears to de courage participation The desira bility of completeness of information must therefore be balanced in any tudy again t the de irability of a high rate of respone In longitudinal tudies where the major conipan ons are among groups of persons who actually participate initial nonre pon e ss leay eriou than in cros ectional tudie provided that virtually complete follow up of the initially respondent group can be cured A high drop out rate ub-equent to initial respon e could however be related to health tatu and thus intro duce eriott bra Fortunately it has been demon frated in everal longi tudınal studies that while it was im po zble to secure complete re ponse from the original sample it ha been much less difficult to secure reexamina tion on the original re pondent four types of information are u eful in evaluating the effect of nonre pon e in both longitudinal and cro sectional e tudies E The Problem of Nonresponse General population studies in which clinical methods have been u ed for diagno 15 of disea e have rarely ecured participation in American populations from more than three fourths of the de ignated ample Pre ently available technic including u e of mot ile er amining units conveniently located ap partntly are not adequate to rai e the re pon e rate above this level † Incom plete re pon e introduces the trong po tbility of bias in re-ult but the nature of thibias has not been ade quately studied becau e suitable means for doing so have not been found There i urgent need for further methodology cal tudy in this area It al o im portant that data on re pon e rate be pull: lied in detail with the report of each study Sm metło for tatist al hndig i d ta wh e matche control are vei in tudi of the trpe a e described in ter enc 10 + P el m nary report from the tonal 11 alth Su ey ha é ind cated that it may b pex of le to peure h he e ponce rat s in Cmtinue methodo! al gati nb Ende taken 1 I format on about th didual h alth status a reported b h min hom Interview by a lay inter sener-obtai ed prior to the inv tation t pat pate in med cal etamination procedure Mort ! ty data and data 1 m bo pitals nt phyiciun on no pa to ipants for com parison with imilar data for participant 3 th the prt Pt6 soup analy is of h alth tatus amon, resp ndent s! fed a odn to th am unt and type of effort rezu ed to e pat pal on 4 Special sample studies of nonrespond nt gcom mi mal cl ni al o rrato in the h me. an e 11 1 Measurement Problems A Definition of the Disease Being Studied Our concept of diea e changes when method availat le for от ае re to diurno in OCTOBER 1960 ·tha 101 adlayalile to the next of large scale tudies teed to be desclupeal In any esent the methods employed in ciirrett Cutie hould be explacitly d sented and knowledge of their lima lation should be taken into Arcount in Interpreting result the ami Or IS dewas change The ser sos to make an epidemiological tudly urdinals ist pilies that there are alailable ufficients prece methoil of dhanus to permit thic Klentfication of can of all ar unter tuuly In this magneet the louds of hyperten ise in allicro cleroti ridiosa cular de 3 lpst Hits s nors grolle ins for Juk of oligertise criterst for identification Thie es alusa tion of Blood pre ure level is difficult enough fut cien granting a reliaf le preu ure esaluation there appears to be Inute 19animity 34 to the other med ur able chararteri lice #luch hould te 44 ed in order to cla tify 3 Fran ini) thic grouping lup the name dac not hyperten ne dreae Similarly with stupect to coronary artery di eace Buile the os aluation of the frank coronary wilach can Un doulsteally be made with relatise pre Cr son there apper to be no adequjte methout for antimating the retent of advancement of the underluan, ather o clerotic proces In longitudinal tudies a well as in elmcal experienre a significant proportion of found to rxperience frank coronar event haie icen cla ined a appar ently {ret of di ease at ttamination not long before the event Cron ectional studies much ca en entirely The exi lence of the prolilım has ledt to what might le called the Sub mitu ton Game in which level ul tuted for hyperten ne di ca e or prim cholesterol Hvel for coronary artery di ea e It would apnear that the pub tstute can at lient be only crude indetes of the di ese which is deured to tudy and theis uncritical we may ob cute important relation tipe * It eems clear that better method of It is not intended so imply that the descriptive epsdem 3 ay of blood pres ure si cholesterol le c*le uaprofitable At the present stage of knowledve such tudies may make Faluable contr hutans the under standing af d sease uljilt 8 Yalidity of Measurements Ante a un munt procedur 1 salutar umra up« «liat it purport to mea utk a procedure is relaut fe the ame re-ul nhen un repeatedly in tuation (10 When attre poulet 4 mua utement proxelure m) It alul ven though at nilalaman } low a highly relialle for renrulues ki procedure may le of lon validity The salidity of me a useme 33 whether of the exi femre of divesc or of one character, tre of an indsidual #phy tologseal biochemical unson mental and so forth) : relatise validaty ften judget quahtaftvely should be quintified whenuser prom ble For example a esen ponderal index ta ed on some to letuen seght and kerghi mas ise con xered a good mder of fatne ut can be checked acaint the more nearly cract mure of under water en lang Tholage ampling weful in elecking the validity of a comienient relatively inexact test asr plied to an entire tudy group bus st cquently applying a finer but le s ton Sepient mea. ure to a subsample C Reliability (Reproducibility) of Megsurements There are two factor hach affect reproducibility of Lological mes une mentarability in the mea urement process Lell and indos adual biolo, ical varialality The former can ofters lic controlled to some extent provided that the investigator is farewamed of its exi tence ky routine reproducibilsty An nestigator can rarels control indusdual biological sanability 2 lood pressure 13 18 Yot. 50 NO 10 AJPH ·CARDIOVASCULAR DISEASES he can only reckon with it in lus analy is but again only if he has ade quately evaluated it Every tudy hould make some pro v son for texts of reproducibility of at lea t selected types of mea urements on amples of suhject throughout the coure of the tudy The essential factor in such tent is the independent applica tion by two or more person of the ame procedure to the same object of study whether the object of tudy be a pecimen of erum an x ray film or a utjects de cription of his symptoms With advance planning incorporation of such tents 15 fea ible though it is recognized that tests of particular kınds of measurements are time con uming co tly and not without technical prob lems in execution An attitude of un questioning confidence in procedures cu tomarily u ed may be major obstacle It would be desirable to estab Ii h agreed upon tolerance levels of measurement error for tho e measures common to epidemiological studies in the cardiovascular field Individual biological variability is much more difficult to evaluate than imple lat oratory reproducibility yet it may be much more important in intra indiuidual compari ons in longitudinal studies There 19 need for more com plete documentation of individual vari ability for many widely u ed mea ures and in some in tance, this will require the etting up of pecial tudies The committee notes that other committees of the conference have considered this Temn they pyt D Minimum Base Line Measures and Standard Methods of Presentation The ronimittee believes that the epi demiological tudy of cardiova cular du ca e will le more productne if step are taken to ecure a greater degree of comparal»hty letneen the studies such are leing carried out ly inietigator in different population group One re qurement for comparability is agree ment among inte tigators to include in each study a pecified minimum set of Tea urements to be carried out under tandard pecifications Aecond requirement is that publi hed reports of studies pre ent the e minimum data in ome standard format (Alternatively it could be agreed that standard tabular material be deposited with the Ameri can Documentation In titute with the depo it noted in the published report) The committee believes that the progress made by the other committee of the conference toward agreement on stand ard patterns in several areas of inve tu gation is evdence that these aims are achievable and that they can be achieved without putting any undue burden on the individual study or re triching the freedom of the individual inse tigator The committee recom mends that the sponsoring organizations con der setting up a continuing group to make recommendations in these areas and to suhject the e recommendations to periodic review and revi ion as required by changing development in the field a REFERENCES OCTOBER 1960 ·COMMITTEE ON CRITERIA FOR DIAGNOSIS OF DISEASE AND CLINICAL EVALUATION Josepi T Onde Charman SUBCOMMITTEES ON CLINICAL EVALUATION BLOOD PRESSURE MEASUREMENT AND ECG INTERPRETATION Ischemic Heart Disease Definition-Constent with the rec ommendation of the World Health Or tanization audy Group on Athero sclerosis and I cleruic lleart Di ra the tum i chemic heart disea e all know The definition is as follows i hemic heart disease 19 defnet, 11 card a d ability acute ani ct me ari ng from reduction or arrest of blood suppl ta th my cardum an ocalion with lyran proceres in the coronary art nat teny The two main pathologs al process intohet pre 1a) atherosclero s of anthromios in the e anels. The ame proces e may be re son able for atherocterolic and a chema cerelial and jer pheral va cular d ca e This H11S report ummarizes the deliber1 trony of three subcommitires which conderact the definition and the clini cal evaluation of 1 chu mir heart di ea and of hyperten ne dhe the us of rlectrocarshopraply in epidemiologic tudies and the mira urement of arterial blood prenatre An attempt is much to offer reali prera mmendations concern ing dagno tic methods The numerous lacunae in our knowledge of degenera Inc heart dhe e are urment indications for further re-earch The committee feels that epidemiologic uneys offer an unusually good opportunity for smearch in many lesel and strongly recommend that uch opportunities le exploited Ememologir studies are ennrerned with the incidence and presalence of diseases in population groups rather than in individuals The occurrence of diaea e re then correlated with other charcftri tirs of the population What 25 needed as a relable under of disease which will identify the same proportion of ca es of disease in various popula trons rather than a method of locating every single ca e of disea e An objet tre method such as electrocardiography which is relatnıely free from {z} {{zin, factors can give a better index of di ea e rates than the subjerine menu fe tations of the ingrnal syndrome which may mentify larger numbers of cases but are affected by andnudual differences unrelated to the drepa e The dla fication recommended by the WHO Fxpert Committee on Cardo 11. lutar Bi ea ex and Ilyperten son 15 endored with a number of modifica tion which are contained in the follow ins eitratt The principal manifesta tions and clinical syndromes of chemic heart stt ca e are as follows 1 Myocardial Infarction (al Definite Myocardial infarction - di ea e due to obstruction of the coronar circulation ani cantino le crosis of a macroscopic curcum cried area of myocardium Surh in zrez wł? if death does not en te undergo fibr) The well known signs and symptoms of acute myocardial infarction will rarels be encountered in field tudie Thie diagnosis of previous acufe myocardial being „tudied 20 VOL. $0 NO 10 AJPH ·CARDIOVASCULAR DISEASES 1$ ba ed on infarction features these two OT may radiate to the left arm or both arms the shoulders the neck or jaw It is pontaneolly described as press ing tight heavy constrcting or crushing or as numbing burning It is usually relieved within a few minutes after cessation of effort or of taking sublingual nitroglycerine Cases of angina at rest will rarely be encountered in field studies (b) Possible Anginal Syndrome (1) Da comfort or pain as in d finite an na! syndrome but berion ng in any of the site of radiat on mentioned. (11) Discomfort or pain definite anginal syndrome but commencin in the left or nicht anterior chest or in thepi gastrium (111) Discomfort or pain detinite an inal syndrome whi h may sub ide d pite continued effort a e as in as in (1) II tory--4 lear history g1 en by the patient of the sudden les often of the g adual onset of severe chest pain or discom fort usually at rest and located a in an inal syndrome ('a below) frequently associate with va omotor collapse and often requirin. prolonged bedrest If the paz ent was hos pitalized the information obta ed f om hos pital records should be separately entered so not to bias comparisons with result f om a eas where such informatın cannot be ohta ned (2) Electrocard ogram - Serial electrocardiograms taken durin, the acute phase of myocardial infarction are usually conclu eviden e of the lesion The electrocardiootam often reveals stigmata stron ly su, estive of or diagnostic of old myoca djal infarction An example of some tentat e cnteria for the recogn tion of old myocard al infarction 19 iven in Appendix A Techni al a pe ts of electrocard o raphy are di cu. ed in a sub sequent sect on of this report (b) Possible Myocardial Infarction -The history za not as clear cut as in definite myocardial infarction but in cludes pain or discomfort similar in Jocation but more inten e and/or of longer duration than in anginal syn drome (see 2 below) The electrocardio gramı not normal but is not typical of definite myocardial infarction 2 Anginal Syndrome-It has been argued against the use of this syndrome that it is entirely subjective and de pends on the ob crved and the ob erver It is felt however that the manner in which the patient describes anginal pain 13 o characteristic that it cannot he con sidered only subjective and warrants the diagnosis of anginal syndrome as a ubcla ification of ischemic heart Due care must be taken to recognize the exclusion categories (see 2c below) (a) Definite Anginal Syndrome-A di comfort or pain occurring across both sides of the anterior chest wall or located centrally in the ternal region brought on by effort eg erercise emotion exposure to cold and wind It л N (c) Exclu ion Categories--- (1) Discomfort or pain as described above occurring aftr es ation of effort as con trasted with discomfo t occurrin during effort eg in anxiety states (11) Discomfort or pain a described above o curring only elation to meals and posture eg hiatus hernia (11) Du comfort op 11 s deserb d abo e but related only to pecual mo ements and positions of the body eg arthritis fibrosits (nv) Stabbing or lancinating p n the region of the left tre steg in anxiety tates O Localized or general cht nd/or arm di omfort or fan de to thoracic outlet or hype abduct on syndrome 3 Sudden DeathAt the present time there is insulficient quantitatre evidence to ju tify the use of udden death as an index of the frequenry of i chemic heart do ea e Except for pecial tudies this term hould be used en e of instantaneous death Sudden death hould become a u eful inder of quantitatise e timates can be obtained in un elected population of the relative numbers of deaths due to s chemic heart di ease and to other vascular cata trophes This problemi con idered in detail in the Report of the Subcommittee on Worphology di ea e in the OCTOBER, 1960 ·Yefulم syndromt cxhrlnt normal seifing elec trocardiograma" An unknown number of inendual Nom from acute myo latdhal inlaridjon with no residual electrocardiograplu alınormalities or with intrare nincular conduction de lect4 not 11 ually o cilied to myocardial in fartfon There! Interet ing Indration that an abnormal clectrocardhographne te spate to fres i talusi le credence of 1 chic mc kart de ce 11 time and Judget purmut and of adequate musical uji nison available it that an elettrocardovrapluir stre It inrorporates in some epuck monological tudies It mut he recognized that uch 1r carry 4 mall but definer The diagro uc cnteria of an almormal electrocardiographic opon p 10 esercs c pirogu ed In Robbs and Vatinels are endoned tipoge last | Conge le lleart Failure com pler syndrome manſetid li dyp nea dımını Erd tolerance pulmonary congemlion water and allt retention hypy plemia vt nou lager ten ton plancine rongestion and per pleral de pennt eitem1 Ist the al, ence of other ensologie factor 1 often a umed that congi lile heart fylure 14 clue to diffuc myocardial damage caused luy coronary artery occlusion Thi a tmption 1 imfomadest Chirotic heart failure cannol therefore le cont Idared a reliable index of chemie heart i ease The following comment were made by the committee on diagna lic nxthod 1 }} tory--in the al ency of any ober information amu ) med that a hys lors of anginal y pudrome or pat myocardial infarction can be re Tably obtained only ly a polis kian There a no information concerning the reproducibility or the rehability of such łu tortes taken by physcians of varying levels al training and experi ence It mul albe conreded that the accuracy of a h tory of , chenye heart di ea e olanded by a pecially trained lay interviener has never leen evalu ated This posibility deserves unten ne ne tigation for use in epidemiological tudies There is ufficient experience with elf admini fered questionnaire to condemn their ue in field tudies 3 2 Phyical Framination. There are NO readils discernible abnormalttes characteristic of chemic heart di ea e however po ble to detect eu clence of athero clerotic obliteration of Other va cular tentories uch 25 the brain retinal ve el and the lower extremitie- This information may be epittemsologically jut a important as esidence of i cheme heart di ease 3 Electrocardiogram-t is a trunsm that the clectrocardiogram does not identify atherosclerosis at only ifs myocardial , chemic complication majority of induzduals with the anginał Hypertensive Disease The following appears to be a satı {reton definition of the hyperten Ne process The term perter e des e nonymous th peent al hyperten ion and hould properly be testricted to det nare the & yet unidentified physiologyral d turbance (or dis. turbances) claracters tic of this date and #hch lead ultimately to elevation of diastolc and sy tolic blood pressurts anatomical changes the evalar inte and funct onal impairment of the in olied due Flyrer ter ion the cathe : clssically re olmalle d turbance and results from con archion of te peripheral arteri lest 114 con trsct on lead se is an increase in the total effectate geripi eral resc tance and hence in elevation of da lolic and talc blood pre army Thypertensi e does e 19 ansidered to tea clinical entity On "hich an unknown presso mechani min18ses arteriolar va con trenon ele aled blood pre use and vascular sequelae Ilyperted on a uch Ike arteriolar changes 18 con ested to be a equela appetrin during the progrt sie dselopment of the dea 1 Blood Pre ure Criteria-ti adio cated that cumulative frequency di iri frutions and conesley ed to report the 22 YOL 50 NO 10 AIPK ·CARDIOYASCULAR DISEASES seem but not a level of arterial blood pressure found in any defined population these pro vide the best way of comparing popula tions It is recognized that clinical usage demand arbitrary criteria of normal and of abnormal arterial blood pressure The following criteria are therefore sugge ted as a supplement to a substitute for cumulative frequency curies The propo ed numeri cal values can obviously he adjusted to ut the needs of any particular investi gator (a) Mormoten ion-Sy tolic blood preure below 110 mm Hg and diastolic blood pres ure below 90 mm Hg ie both belou () Hyperten ion-Systolic blood pre ure 160 mm Hg or over or diastolic hlood pres ure 95 mm Hg or over 1e either one or both at or above the peci fied level (1) Sy tol c Hypertension-Sy tolic blood pe ure 160 mm H or o er and dia tolc bl od pressure under 90 mm Hg (11) Diastolic Hypertension-Sy tolic blood pres ure u de 110 mm H and diastolc I lood pressure 95 mm Hg or more (c) Borderline Hypertension—This is the residual category le the systole I lood pressure is below 160 mm Hg and the dia tolic blood pres ure is below 95 mm Hg but they are not simultaneously below both 110 mm Hg sy tolic and 90 mm Hg dia tolic Note that the diag nosis of hypertension is based either or criteria while normoten ion requires that both the tolic and the dia tolic reading he below the cutting points When multiple determinations are made the asignment should be ba ed on the fir! determination or on the elevated artenal blood pressure is the only dentation from normal No symp toms characterize this phase Complete clinical es aluation requires the exclu son of " ceral invokement and of causes of secondary hypertension Since secondary hyperten ion is rare it would unnecesary in epidemiological tudies to make special efforts to identify such cases 2 Hypertensive Disease Complicated ---This term implies visceral involve ment which depending on the degree of organ compensation may or may not be characterized by symptoms The vascular territories most commonly affected by the hypertensive process are in the heart the brain and the kidneys Marked elevations of the dra tolic blood pre sure accelerate and aggravate atherosclerosis. The definition of hyper tensive heart disease is inevitably cir cular since it is dependent on the demonstration of what is considered to be an abnormally elevated blood pres ure associated with igns and ulti mately symptoms of an increased left ventricular work load In many in tances the visceral complications of hypertensie de ease may be due to ischemia con equent to athero clerotic thrombotic vascular occlu ion The fol lowing clinical and laboratory pro cedures are sucgested for field u e (a) Heart-Hi tory and physical sims of (paroxysmal) left ventncular failu Rad o 1 c evid nce of early left ventricular en larg ment $ notoriou ly unreli ble Electrocardiographic e iden e of early left e tricular enl rgement 13 lihen se unreliabl Large QRS oltaes in youth and early adult I fe cannot be accepted as testimony of left ent cular enlarg ment. There is poor correlation be (keen th raya d the electrocard ogram in early left Senin ular enlargement (b) B n-II story of or neurolomc 1 resi dua of a preous cerel ro sculara Jent. itory of hypertensive en ephalopathy Ret opathy fundoscopy is et ely fe bi in the fild and should at landstingu sh normal o moldly al mmal eyeg nd frm gros ly al normal emplos ng th heith Wagener clax fication 10 U dr om on mern in The following general tatements can le made concerning clinical et aluation of participants epidemiological tudies i Hypertensile Drease Uncomplı cated the term imple con i tently CITU OCTOBER, 1960 ·steners !! may le poi le totale funda] pli graph an objective recot (c) hi Ine S-There are na całı faci ry tell metal for chmatine renal function 31 orth fale proteinunale erclud i protesnunia relatte » er of renal functional trapart ment Verneops cxamination of the tail?? furl urmary soment is fesyal le Cylin Irure may be taken a eid nce of renal tular dums yuris in the male prima fa te e dae of kenit urinary mlection 3 The Prelyperten tit. State--The ext tence of this phase 1 thron tical This no cidence thal lalale artenal blood pure ure neces znih pre Hae later hypertensie is eas 11 Te! for a cular hyperreariat) such a the cold pre or test art of no partu ular diagnostic value ani ar of unknoi ni pragno le gnificance due to lack of prolanged follow up data? metric Thailing » recognized surge led nonetheles that the oli erser read the rale to the meine I evet number Oljecnie automade metlod of mea uring and recordin, the arterial flood gore are should be sell within current technical spatulats and are fughly e rrahlt to avou the problem ol olener bota De pilt the official Inommendabon that the art nal dia tolue presure be lalon a the point of di appearance of the Loroshus sound the st 15 1 tanta exsdence that the point at which the horotko round Iecome mufik d may correspond more acestriks uith the tre dia tol. A ure !+ 16 !! Therefore recommended that loch points le routich recorded For the pre ent the point of di appear aixe of Dorothox Oundy shonid le ucd the tha lola pre ure for tat scal a Notes on Technical Method's ה אזנון 1 Measurement of the Arterial Blood Pressure in trumentation The Recommenda Nons for Human Blood } re ure De termination 3,4 phygmomnom ter ponsored the American Ileart As ocation are trongly endor cd 15 ssth the exceptions noted below It is felt that the following item merit emphast recommended that a cuff 12 Item 111 widtl he u ed the ruff should it dt igned that clo ure and inflation it exert umom tension over the whole width of the cull Where large numbers of mes trements are to be made in a hort time con il eration hould be gren to the ul of a pre ute Yelloir to mflate the cult The mercury manometer is the standard of calbration The zero should be clearly 1 able the upper end of the hould be freely rented Aneroid manometers are acceptable il cheched frequently (every few days) again I a mercury column The ten dency of ob ervers to round off mano 1 he (criert cifesident that of the au cultatory method of plasmo manometry Ex wed the ol encr mut have adequate herring Urheid that in epidemiological tudies the ob sner lould pre erst a normal complete audiogram as a preliminary qualifica ton An acou locally acceptable lerho core kould be u ed it would be lughly de irall for the elaminer in all propu lanon tudies to pracine together on the ametlject until a atı lactory un formats of blood gore ure mea tirement tsad I een acluered 3t would likene le nulih desırai le for similar inter stuch corapari on to le made to both the e end it i loped that audiov ual training devices may con le fal rented The clinically truduono) ve of custoff points to criminate between norm? and at normal lese of blood pre ure inevitahis creates ob ener Ita 1441 denred by anomalie in fe in urance staf: in and the meral tendency of numerical value for the dia tolic Mood fire tire in particular to cha ter at certain points" The prol lems acute that thous con ueration mht pla a tube 0 YOL 50 NO 10 AJPH ·CARDIOVASCULAR DISEASES be guien to the use of off et manometer cales to give a purious reading later decoded by the statistician Provision should be incorporated in all tudies to code the ob erver o that the source of po ble sy tematic deviations may be identified Since however the level of the arterial blood pre sure may not mally fluctuate widely 19 ince almot all proposed criteria di tingui h between dia tolic normotension and diastolic hyperten ion on differences of only a few mm Hg ince as previously noted the indirect measurement of dia tolic blood pre ure is uncertain unrelable and subjective and ince there is no predictable as ociation between the level of the arterial blood pressure and the pre ence of vascular damage the aban donment of arbitrary and rigid cutoff points to di criminate between normal and abnormal levels of arterial blood pres ure 19 advocated It is felt that proper training and sound motivation are more important than the profes sional background of the individual who measures arterial blood pressure in population surveys The Observed-It is probable that the casual blood pres ure is most often meas ured with the ubject in the eated posi tion The arm must be at the ame level as the heart There may be ome advantage to measuring the blood pressure when the uhject 1 upine since the arm 15 then at heart level and ortho tatic hypo tensive influences often exaggerated by antipre or and other drug ished The dia tolic pressure 15 less affected by changes in posture The sy tolic pressure may however be con siderably affected by change in posture so that five minutes hould elap e before it is mea ured 19 More comparative mea urements of the arterial blood pres ure in the supine itting and even tanding positions are required The minimum clinical data that hould le recorded include the sex age height and weight and pule rate of the ub ject Vot hypertensies under treat ment seem to be ignorant of the exact nature of their medication It seems nonetheless desirable to inquire of all uhjects whether medication is being taken and to record whatever informa ton is elicited The extent to which obe ity of the upper arm may invaldate the indirect measurement of the arterial blood pres ure is not completely known For thi reason it would be worth while when fea able to make a comparatrie measurement of blood pre sure in the forearmi ho definitive statement is posible on the optimal number of blood pressure mea urements to be taken There is ome evidence that when taken in rapid (30 econd) sequence there is ucces ive decline of the second and third reading and that the third read ing s fairly representative of tho e made sub equently When multiple mea urement of the arterial blood pren sure how rea onable con istency the use of average values for tatı tical pur poses is probably valid a are abol ll Electrocardiography The Electrocardiogram-The electro cardiogram is an objective record of bioelectrical phenomena Strictly peak ing anatomic inferences should not be based on this record Practically the diagno tic interpretation hould be made only after collation of all clinical data The ECG plays a small and uncertain role in epidemiologic tudies of cardio vascular di ease For example in atherosclerosi it wall confidently identify only that small per cent of ca.es of coronary artery athero clero is where frank myocardial infarction has taken place Criteria for identifying normal from abnormal QP'S items are reason ably reliable in many in tances with the notable exception of QRS cnteria for left sentricular hypertrophy ST and T criteria for normal and abnormal are much les reliably known The OCTOBER 1960 ·ser ti rofܕܐ?ar ܙܐܢ committer is of the opinion that while large LCG ursesa mas usefull lend them clues to identifying the normal a normal (CG they do not tend them efses reliably to identifying specific <h ease Puriht mort huile criteria for the normal FCG ar reason ally rehable in the age sange 1060 Tean other age group lave not yet borin adequately tudied in tht rt gatal Direct woon, clectrocarthographis are table for population upay but hould be frequentis checked to in ure the accurary of raper peed and of (als Britton soltage Iylu thering and ercurion raculin tuve talnity and o forth Standard elec trode jelly pa te 109 x u ell as the electrolitx contact agent although pła tie glectrode jells i acceptahle Lead Selection---Informal polls indi cate that electrocardiographers con des the 12 kad three l polar and thre unsolar limbs leads and it or esen precordial V lad electrocardiogram the diagna tic tandard There hos eser no evidence that the 12 lead cler trocardiogram pential to adequate diagno No more information is con tained in unipolar than in Inpolar limb lead Comentional pre cordial lead placement is arktrart and presente no intrinsic merit eive that of pentral v age Indeed the placement of precordial leads at the three four and fise po ition is ubject to anatom cal variation and particularly to tech nician The polental gain perd and money commend the tudy of the value of limited numbers of Hectrocardiographic lead The Electrocardiographer-Consen tional traming in electrocardiographic interpretation requires an apprentice hip of a year while competence can be maintained only by continuing experi ence Relahvely hulle is known on either an indivdual or a group ba is of the accuracy reproducibility and re lability of electrocardiographie inter prelation If large population fuckies are to be conducted these que tionis mut }l an cred In addition many my le dened to cope with the enormou numlan of electrocardiograms taken 12t l; !!1sd24 Inque-tomally competent electrocarlo,rapler could rapually and accurately ort electro cardiogram into normal orderline ane al normal groups up to the limit impo ed lys fali, It felt that in tenir iniestation hould le made of the problem of developing generally arreptalle crite na al (lectrocardio grapłuc mterfere tation imple enou imut et viennits accurate to be ned effectively by a phat kian or try a tech rlic tan tot pecials trained in clectro cardiography The use of implified improved lead rolem particularly germane to the problem If a com Ishely mlectronist computers come to le uud more commonly in biological in Hemligation the development of malle electrocardiograpluc «agna lic calenia st!! Luer ential to intelligent program mning of urban trument The Lahora lory of Philological Hygiene of the lmperity of Alinne ota with these purpos tiew ka desi ed act of eriti na for the electrocardiographic diamo of myorardial infarction (Ap or ce sera pend A) REFERENCES ܐܐ etror in ea e 1 P A la Buch ST KR 7 12 175 1 styp 3 SC Ty II 6 dc 11 Epimu крп Com et D un HO TRPS 168 9959 1 ICS ABY NYIM) a buery # Dy? I THAS 311 he F PF JX # FA Pro 547 IDE C1 Alby R Y FPE N >> PHUT 2-3 (ar 12 5 G RP LHAD Mad c D 7 43-443 (F) 1958 6 M i RGP fh Doubi Two-S DE TI То б Ftw Up Sty fi 004 M II ry P 1 A at a តា fi Rd } 1 PS 26 YOL 50 NO 10 AJPH ·an lead V on APPENDIX A Excerpt from Classif cation of ile Electrocardiogram for Epidemiological Stud es This excerpt is presented as an ex 1 Q/R ratio of 1 or more in any of ample of the kind of criteria for old lead I II V2 V3 V4 vs V. or if the tra itn zone is to the 1ſt of myocardial infarction which can be constructed based electrocardio 2 Q wae duration of 001 second or graphic surveys of large groups of per lon er in any of lead I ITV V2 V3 ons The examples pertain to resting V and if R is plu 3 mm or electrocardiograms taken in the upine more in all po ition on adults under the age of 3 Q wa e duration of 005 second or 1) DE o lead III o IR plu 3 mm seventy Further information about the or more alf Some Q mu t be pres complete clasification can le obtained ent n F from the author 4 QS ptten bent Rwae) nay of lead throu h Ve when an Rwae A QRS Cnter a Type I (Myocard al Infarc pesent in the adjacent precord al tion) lead to the r ght (Q mu t belmo o me to te des gn ted a such) B ORS Crite Type II I'r pared by Henry Blackbun Ernt TQ mub 1 mm rmo e to le dempat S monson 4 cel Keys, et al Lab try of och ) I hy local Hygene Um ersity of Minn sota Th omplete criter a include mot 1 /R ratio of to's in any of leads electrocard orraph c al normal tes {mpot III. or I right sentr cular ance for er d m ol g cal tudes hypertrophy is not p esent in lead 1 A OCTOBER 1960 ·nare duration of 003 to ODS second (10 41 y of lead I 11 il. und K 14 pilux 3 mm or more in all > 3 Owale duration 001 to 00, fecond in Ica s 111 or alt (Satre mut be gir ent in all! amplitude of 5 mm or greater in Tradi lor alt when an R wave 15 Jersent 5 OS pallera in bil, in the afwence of let une franch loch an I left sen rular hypertrophy SUBCOMMITTEE ON MORPHOLOGY Daily Star WD Chairman that agreed upon by the WHO Study Croup in 1938 T1114 demtion as as follows Aih ro ciero Sa Arable comtination of lan of 16 ma of arterie on 1 fins of focal accumulations of pud compler car tohydrates for 1 and blood products fibrous 1 ve an calamum depot and a ociated » ih meus al hange" In Introduction *1725 report presents the comlined effort of the committee and the con clar ions represent complete agreement among the members of the committee It is particularly worthy of mention that a to agreement as rapidly reached in all major a pects of this re fort Compari on with the conclusons reached by the WIIO Study Group on Athero clera » also reveal majos sutra larities with this committee conciu sian The recognized difficulty epidemiologic studie coronary athero clero is in love population groups thic inability to obtain prec) € measurements of the degree of ather o clero is that may be present in any of the individuals tudied In autopsy studies this difficulty is to a great ex tent eliminated lut studies on autop) populations offer from lack of ability to properly generalize the findings to the population as a whole Melerthe le it is belesed of comparable pot mortem methods are used in different areas of the world a valuable contribu tion may be made to further the under standing of the pathogenesis of tuis disease 1$ The lesion to be con dered within this cia fication may kue ubdivided or cla afied an everal different way The manner of subcla ification as les important than the preci ene and clarity of the definitions Some wall clasifs the various lessons into fatty or loped reals fibrous plaques atheroma and complicated lesions The complica trons include hemorrhage into the lexion uperimpo ed thrombi ulceration and calcification Othere suggest that the le ions se divided into lipid strcal Sihtowe plaques complicated lesione and calcifications definitions of the ecla is of lessons are gsen in Appendix A Ls ting of the e lesions in the abose order does not necen anty imply any exact brological sequential relation hip It is alo under lood that the term fibrous plaque does not preclude the presence of lipid complexes within its depths The importance of defining and Cla sification of Athero clerotic Les ons (Report of a Study Croup) WHO Tech Pep Ser No 143 1938 Definitions The definition of the athero clerotic le ions to be mea ured was similar to 28 yot 50 NO to AJPH ·CARDIOVASCULAR DISEASES ubclassifying the e le ions resides in the fact that in any measurement or grading sy tem the limd treaks hould at least be clearly delineated from the others * In measuring the surface area of involvement in the aorta or coronary artery 40 per cent involvement with only lipid treaks may have an entirely different ignificance than a similar de gree of urface involvement with any combination of the other cla es of lesions Any such study on cerebral athero clerosis however must take into ac count the fact that cerebral schemia may develop as a result of athero clero is in carotid artery branches entirely er ternal to the kull while the intracere hral vessels may show comparatively little change The examination of other ves els in a piece meal fashion such as mesenteric arteries or renal arterie would not contribute any significant information to the over all picture At pre ent legal religiou and embalming ob tacles preclude the posibility of routine en amination on all the major vessel of the lody Vessels to Be Studied Preservation and Records a erie The coronary arteries and aorta hould be examined in every instance It is not fea ıhle to consecutively tudy the cerebral vessels becau e in this country at least po t mortem permi sion for such examination is often not ob tained There are al o greater techni cal difficulties for making measurements of the degree of athero clerosis that would interfere with a reasonable ability to compare one tudy with another It is not ufficient to either examine the coronary arteries or the aorta alone The findings of the degree of athero sclerosis in of aortas do not necessarily parallel thome in the coro nary arterie Sex race age and geo graphic differences also affect compara bility of the degree of athero clerosis in the aorta with the amount of athero clero is in the coronary arteries (ee Table 1) Therefore as a minimal oh jective in order to obtain a more mean ingful over all picture at lea t oth Vessel should be tudied Where routine and consecutive brain examination can le made and where uffirient attention can le grven to the proper examination and grading of cerebral athero clero is it is of roure highly de irable to do so The conditions under which examina tion and grading of the vesel are con ducted will determine to a great extent the oljectivity accuracy and compara bility of the finding Whether or not the specimens should be examined in a fre h or fired state will depend upon the particular circumstances under which the tudy is being conducted Which ever the method It should be con i tently employed throughout the study because there is evidence to indicate that variations in grading particularly as regard coronary arterial Juminal exit between the fixed and un fixed tate in the same peuimen Pro vi son hould be made for preservation and emipermanent torage of the ves el A practical method utilized by one member of this committee is excellent for this purpo e f Permanent torace of the ve el not alway fea ible te cau e of expen e per onnel and time con uming effort involved in any esent the finding hould always be reduced Size Tjada Stron JP VICC III CJE Cand II Iman PL Th At al ll tory of Ath olo mparis n of th Early Art leo nw Orl an cu temala and Co ta R: Am J Path 31 31-111 (July Aug ) 19 t Holm RL VIG! CJ Stron JP and beer JC Technis for Stud ing Athe sclerotic Les ons Lab In er 7 19-1 (Jan I b) 1978 OCTOBER 1960 29 ·Table felitur Degre of thereuclera in urria and Cronary Arterres oft Conureutae tittop les of Sadlen Death (VF Carrs) from Natural or Iccidental Deatles Total Caves SC Age group 30-50 years Females Males 32 (12) 16 (100 c) 147 (1000) 29 437) 47 (316) 16 (217) 87 (57) Age group 51 70 years Females Males 72 (1004) 16, (![X000) 6 136 ) 35 (21) 29 (39 ál (37) 18 (who? 69 (40%) 1> lorlalas & relarnely greater degree of ath rosclerosis than coronary arteries ** Aorta has an equivalent degree of stt noeclero ss to that of Coror an art na << (orta has a relarnely lesser degree of atheroulerosis than the coronary arterye brain D and Bradessv Unpul libed data froin Weicher ler Ves al Framı r Coronary Wendy ta ome form of che matı diz rim sted can be pertinently hept Тbe clal oratone > and drial ni such a sha uratr will sars with thic nie ds and the 4191 of the particular study Exam; it of imple and morr detailed (12,ram are li tol an Sppendnes bi B 2 and ) If the eto Examination of the Vessels termined in conigetel coled material The method of railing lesions de pend 10 m. xtend on the technic emploved in de tune the spa The standard melod of examining coro har arctic-dros sectional cuts or longitudinal denartson- ire acceptai le echoning method is used theve hould be performed at inter als no further than 3 mm apart recognized that the WF10 report kug gets a 5 mm difference as being uuent but it requires very hulle extra cffort to reduce thi intertal and in the experience of some an interval as wide as 73m can mis nificant, large numer of thrombt or occlu ne arhero clerotic plaques the longitudmal method the recel is opened as far as po ble tham+]} coronary di secting ryssors tity and quality of the urlace area in olied then recorded The Diree major coronary le et mut be ex amited The aorta shoulil br examined by a len_thwe opening and thert preadi flat The entire aorta hould be de nied but for grading purpo cs the surlace area between the upper markin of the first interco tal artery onfire and the furcation mio the liars lould le The exarumations interpretation gra? na nd mea vrensent of the lessons in the se el hould be performed by competent patholoo ts well tersed in the various le con of athero clero ? I'referably one praminer should rarti put the entire tudo When this can not be done a team af emines should le trained in adı ance o that their measurementy cro chech nith each ctherm order for the finding to le Tea onally content and reprodyalle Unhased grading is difficult in the al ence of a coding si tein Sometime the atuation demand that a pecimen lie esaminert immediately at the site of autop) In uch situations it 13 ome times impo sylie to conceal a e EY ruce and so forth But when pas able the project hould be o de igned that thie griding und Primination can {p dle The quan Yol 59 NO 1 APH ·CARDIOVASCULAR DISEASES IS considered Some have recommended that the circumference of the aorta hould be measured at various levels This information would not appear to contribute to the olution of any of the desired objectives and would only add unnecessary detail to the examining procedure occurs usually in young individual uncommon and is often found in associa tion with an anomalous coronary arterial circulation or underlying inflam matory lesions of the ve sel wall The e occasional cases cannot materially in fluence the findings in any large scale autopsy studie Grading may be in terms of moderate or severe in terms of pluses or in percentage but these must always refer back to clearly defined limits or categories In the recording sy tem the di trabu tion and extent of the different types of hould be indicated wherever As for the aorta the degree of urface area involvement should always be recorded with attention given to the distribution and relative propor tion of the variou types of lesions le-ions po it le Grading It matters little as to what termin ology is used in the grading method provided the terms are clearly defined within an accurate and clear frame of reference If this procedure is followed regardless of the terminology employed the result of one study may then be reasonably compared with those of another The grading in the coronary arteries may take into consideration egments of steno: mean or maximum diminution in lumen size the extent of surfare involvement and the types of lesions present If one excludes Hat lapid streak there is considerable en dence which indicates that the mean lumunal diameter relates closely to the extent of urface area involvement In a study at the Albany Ho pital under the au pices of the Albany Medical School and the New York State Depart ment of Health it has been found that the curies for muan wall thicknes and mall lumen size parallel each other very clo ely Alo each measurement Fore a imilar relationship to the inci dence of myocardial infarcts in both exes It i generally agreed that if either the degree of urlace area of involvement of the oronary arteries or the maximum area of lumen reduction is u ed a a method of grading the end results hould be imilar There has leen need! s concern over the number of individual who may have i olaled egmentul orcluste plaques in the coronary artery tree in the al ence of any ignificant degree of more wide pread allot so clerotic involvement This Thrombi and Intimal Hemorrhages There is a problem at times of differ entsating organized thrombi in the coronary arterie from athero clerotic plaque For recent thrombı this, relatively simple For remote and or ganized thrombı thrs diffcult and in many in tances not po ible Canalıza tion of the lesion was considered as po ible evidence in favor of an old organized thrombus as oppo ed to an athero clerotic plaque but this is by no means conclu ne However such errors that would an e in the grading an 1 cla sification of le ions relative to the difficulty should not ignificantly influ ence the validity of the finding evek nce indicates that the more e treme and older coronary athero clerotic le anns are asociated more frequently 1ith uperimpo ed thrombi ( ee Table 2) The gross recognition and recording of intimal or intramural hemorrhage a a routine in any large scale autor > tudy can erre no meaningful purpo e and may lead to erroneous concluson Proper tudy of intimal hemorrhases re Vot OCTOBER 1960 31 ·Table 2-rameney at Various ige levels of Iterett Tline milan hudlen Death in uit Maley with u anere Cotanar teravelcra is (377 tutop in CAM) Age in Tears 302 50-57 Under 39 60-69 Mamler nf cams with ad ancel roronary athero clem is (rotat) Number of cases with recent superimposed thromt 46 116 5 (1) 35 (27 31 (1) 25 (29) train D V and Brade 594) 1 Ln old hed data from He i Irsler Hedi al Fantner Loronary qures metrulous attention to detail erral microscope ichioning claring terhin and forth These procedere can generally not be per formed with the mumal metholdloss availalite for inrge scale fuilse Thu 10 way meant lo under estimate the desirability and potential firmne of tudying the problem of erstmal kc morchage. This mighe very well lie pre tlormed as a pecial investiga tion within a limited egment of an over all Inrger sudy 1 ከ group that u li ani sade tem which arlutarıls dign value to certain a poet of the lt ions inologically un ound and mas kail to ersors The tale of our present knowledge of athero clero 19 do not as yet permit ische quantitation Injertion technics involving the in trodurtion of radio o aque matenal into thıc coronary arteries or the utiliza tion of pla tic technins are of con deral le importance for tudies de igned to snse-tigate the development of collateral circulation in the coronary arterial tter These technics Slowever are necessars and too detailed to be performed routinely in rudies undir con idcration The utilization of uch technic in order to gain informa tion on the relation lup Ictueen phyar cal actuut) coronary atherosclero age and collateral circulation i IM portant and kould lic encouraged Other Technics the The Heart croscopic studies do not contribute enough auditional information to ig nificantly improve the exactnes of the grading proceng to be required as a routine procedure Such technics that determine elasticity 11 cosity of the le sel wall as well as detailed cliemical contents of the le 1001 do not appear to enliance the accuracy of the grading procedure The value of an index system of grail ing which arlstranly prea sans cestasn salue to the quality of the lesions to the extent of the incollement etc open to que fion Such index systems have been developed in comparing the degree of athero clerosis in one popula tron group of autop les with that of another It was the convent of this 2 In order to properly evaluate the sig nificance of the atherosclerotic le ton in the forta an coronary arterice it is pentsał that certain minimal findings 3 tbe heart be determined The condi tion of the values and percardum should be routinely recorded proper evaluations may be given to the factors that contribute to any increa e VOL 50 NO 10 A.PH 32 ·CARDIOVASCULAR DISEASES in the weight of the heart The heart hould be weighed with at the mot only the ascending portion of the arch of the aorta attached It is not neces ary to determine or record right and left ventricular wall thickness ince uch errors as the inclusion of epicardial fat or papillary mu cle in the measure ment and the posibility of measuring tangential cuts a well as variations in wall thickne s at different levels would render compari on of re ults almo t meaningles The heart may be opened and ex amined in the u ually accepted manner whereby the cour e of the blood as fol lowed and the eptum is plit up from the apex to the hace Pre eration and proper examination of the coronary artery presents a cros sectional slicing technic of the myocardium from being utilized The pre ence of all recent infarcts should be recorded and hould include a tatement a to their ize location and age The clasically recognized text book description of myocardial infarc tron furni he the criteria for recent infarct Any gro ly v ble scar should be recorded in the ab ence of any other obvious cause for such a car and in the presence of advanced coronary athero clero i this may be regarded a a healed infarct Miero scopic confirmation of recent and old infarct? de irable but not always e ential The condition of the coro nary o tia hould be noted be determined and wherever fea able the weight should be actually mea ured and not e timated If the weight is esti mated it should be so stated Panniculus thickness should be measured in the midline midway between the viphoid and the umbilicus Another method for increa ing the accuracy and completeness of ho pital records for the purpose of correlating certain finding with tho e at the autopsy is to send trained personnel into the home of the decea ed within everal weeks after the death and ol tain information from close relaties atout moking exerci e diet and other living habit In the Albany tudy this has yielded significant information and has given more meaning to the pathological findings no Hypertension and Diabetes Mellitus Autopsy verification of the previous existence of hypertension and/or dia betes mellıtus would be highly de irable Infortunately there are certain morphologie findings for both condı tions po ite or negative to prove that the e did not exit The pre ence of definite myocardial hypertrophy predominantly of the left ventricle) the ab ence of any other cau e for the hypertrophy in combination with arteri olar change particularly of the kidney trongly suggestive evidence that hyperten ion was present at during life The presence of intercapil lars glomerulo clero is strong evi dence that diabetes mellitu. was present Is ome time the age Information on Autopsy Record All autopsy record hould include ex race and if posible to authenticate the country of birth country of residence duration of the residence ethnic origin tional hi tory The immediate caues of death as well a the ba iç or underlying di ese proce or cause of death hould le recorded eight and weight hould and occupa Standardized Post Mortem Examination as an Integral part of Longitudinal Epidemiologic Studies* A review of the variou project de igns of the epidemiologic studies a Dauber TR (Ed.) R port of the Co ference on Longlud: 1 Card ovascular Studies at th Hotel Beacon feld Boohi ne Vas (June 1, 18) 1957 OCTOBER 1960 33 ·di rae are die cribed in the conference at Brook June 1957 seierled that none ol these studies had included anı meclian m (or the paturing of tandardized autors material This appears to be a erious deficiency Any procedures wlierel tandardized post mortem data collected on both sudden and ho pital death of individual on hom informa tion has been obtained over many years in uch studies can enhance the value of ich inre tipufion It would tem to br taller simple to arrange for the pathologits in the involved community to et up minimal tandards to obtain the nece an informalion relative to cardiola cular disa e ration a con iderable proportion of the case of unexpected in tantaneous death where eye witnesses were avail able may be ascribed to cardiovascular Before utilizing tl114 category at esulence for i chemu myocardial di-case in epurmiological tudies more tract information should be obtained Alaphils de sable project would be to set up a cooperati tudy among medu cal examiners offices for the purpo e of determining the proportion of explained instantaneous death that are due to coronary athero clero 19 ani! i chemir myocardial disea e Such a tudy should be relatively imple to arrange CITT or no ענת Unexpected Unexplained Sudden Instantaneous Death In the ab ence of adequate clinical laboratory or po t mortem finding the uc of unexplained udden death as eve dence of coronary athero Hero is with schemic myocardial di ea c is at present generally not acceptable The criteria for the classification of as a thio e of sudden death varies consideralls in different areas Refinement of the definition of sudden deaths to include onls tho e cases un rom there las been an eve witness account and in whom the unexplained or unexpected udden deaths have occurred within a matter of minutes 13 de irable This group of ca es hould be clearly eparated from ilor m whom the fatal esent took a longer time and from tho e where the individuals were found dad with no witnesse 21ailable as to the exact circum tances and their duration In various parts of the world depend ing upon the general health and di ea e panorama of that area the proportion of ca es of sudden death that may be at tributed to i chemic myocardial disea e may vary In thi country it is highly possible that when the proper age sex and race factors are taken into consid Biostatistical Evaluation It is recognized that the value of any morphologir tudy matter how meticulous the method of grading de pends for the tated purposes upon the ability to relate the autopy findings to the population group from which the autopsies are obtained Information also be available concerning the characteristics of those individuals from this same population group who are not represented in the autopy pries Careful brostatı lical chaluation and de sign i therefore pysential and hould be part of every such tudy The fact that previous statistical studies have pointed to dancers in drawing conclusions from ho pital autops studies xloes not pre clude the proper utilization of such material for the advancement of knowl edge in this field It is the belief of this committee that with these minimal methods of studying autopsy populations a si mnificant con tribution toward a solution of the prob lems concerning the pathogenesis of athero clerosis could be made There 1 still no substitute in the under tand ing and olution of human di ear for primary accurate observation in the human laboratory it elf VOL. 50 NO 10 AJPH

·CARDIOYASCULAR DISEASES
APPENDIX A
Definit on of Terms
(Frm P Stron, from Proto ol of Latia American Project)
Fatty Streak Any intimal lesion that is tion or calicificat it will be cla ihed
stained distinctly by Sudan Rand that under tho e cate ories and not as a fibrous
does not how any oth r type of chane plagu
underlying
mp catei Le von Tho e areas in wh h
Fibrou Plaque Any firm elevated intimal
there )
hemartha e ulceration
песто
le on wh ch in th fr h state s pal grey or overlyin, thrombosis
gli tening and tran luc t After stain g Calcifi ation Areas in whi h there is calc um
it may b partially or complet ly cover dły depo ition detectable ethr y ually or by
sudanoph I c d po its If a lesion con palpation without overlyınhemo rha,
tain
a y h morrha
thromb 19
ul ra ul rat on or thrombosi
OCTOBER, 1960

·IF DIXI Ireliminar I rotocol of Latin inicrie in Iroject vel ull if (. and Strong J P et al Necropsy Accee on no 0 8 0 OOOO OOOOOO AORTA Total Area Involved Per cent of Involvel Surface Composed of Fibroirs Hemorrhage Fatty Streaks Plaques Thrombosis Calcifcation Ulceration Descendin, Thoracic Abdominal Total Circumfler CORONARY ARTERIES Anterior Descending R: ht Total Area Involved Ter cent of Inxolsed Surface Composed of Fibrous Hemorrhage Fatty Str aks Plaques Thrombos Calcification Ulceration Right Leit Circumflex Left Anterior Descending Total 36 YOL 50 NO 10 AJPH ·CARDIOVASCULAR DISEASES APPENDIB 2 Comparative Ail eroselero Stud Laboratory Accesion No Hospital Necropsy No Name Age. Lits Sex Race O cupat on Country of birth Cntry of re ni nce at t me of death -yrs YTS Princ pal Fın 1 Diagnoses Primary disea e Immediate care of death Other dia noses Code for principal di po is..- ks We ght Llbs Length .cms Th ckness of subcutaneous fat D seases presumably due to atherosclero is State of Nutrit on (unknown () severely obese () moderately ot se () average o normal () thì ( malnourished ? cms (in ph ld mbi 1 (() () angina pectoris 2 () () () coronary occlus on 3 () () () myocardial infarction 4 (0) () cerebral thrombosis 5 ( ( ( cerebral hemorrbare 6 ( ( ( disabling peripheral ath roscleross () () () mesenteric o clu on 8 0 () () aort o clu on 9 () () () aortic a urysm 10 () () () art rial neph osrleroi 11 (0 (other un la sified Dra es po bly nfluenc ng athe osclerosis ? Heart We ht TILS 100 hypertension established - ( ( ( hypertens on presumptive 3 0 0 0 arterolar nephrosclero 13 bnn 4 () () () arterolar neph oscleroi mal na! 5 () () () pyelonephr tis acute 6 () () () Pyelonephritis chronic 7 O O O glom ruloneph ti acute 8 () () (plomerul nephritis hron 9 ((() chron CT al d sease unclas of 1 10 ( ( ( d abetes m ll tus, e tabl bed 11 0 0 () diabetes mell tus presumpt se 1 () ch onic al olol sm 13 (1) O portal c roh si 14 () () O b liary curth is 151) () () rheumatic heart disea e 16 (10) Oyphil t1 heart disease 1. 10 ( hypothyro d m 18 11 ( hyperthyro d m 19111 () other end x inopathe WOD k OCTOBER, 1960 ·Span D 11TH DIIC From the ciche ter County Medical Framiner Coronary Artery Siuly and Brade VE Ethnic Date lleight Weight Somatotype Panniculus Расс Case No Ser Age Immediate Cau e of Death Circum lances Basic Cause of Death Occupational II tory Ir Streak I laqu falification Ti rom us AORTA Ileart Weiglit Valves Pericardium O tia Infarcts Location Size Age Lelt CA. PCA Grading Aorts Coronary Arterres VOL. 50 NO 10 AJPH ·COMMITTEE ON DIET, PHYSICAL ACTIVITY AND BIOCHEMICAL MEASUREMENTS James Hundley M.D Chairman are 1m D IETARY intake and the expenditure of energy through physical activity are two components of the nutrition bal ance sheet of an individual or of a group of people Methods of measur ing dietary intake and energy expendi ture are the subject of reports of two subcommittees Biochemical mea.urement portant in the analysis of dietary intake in the analy is of the relationship of phs ical activity to cardiova cular di ea es and in diagnostic studies in general The u es and standardization of brochemical mea urements are con idered by a third subcommittee SUBCOMMITTEE ON METHODOLOGY FOR DIET APPRAISAL Vartha T ulson ScD F4PH 4 Chairman Introduction pected relationship between diet and and atherogene is have increasingly be come an integral part of the design of cardiovascular epidemiological tudies The Subcommittee on Methodology for Diet Appra al was establi hrd to ex amine the exi sing procedures for collecting and proces ing food intake in formation to study the deficiencies in rurrent proredures and to make recom mendation for future research The methodology con idered in this report is limited to the tody of food consumption of individual rather than for an average for groups of people Thus problem of obtaining and proe essing information at the family or national level are not included Di CUL ions of computation and laboratory determinations will relate only to caloric values protein content and fat content After a di cu sion and summary of the problems encountered in the collec tion and proces. ing of individual food data, a second portion of the report wall present everal recommendation aimed at improving and clarifying the status of dietary surveys in relation to epi demiological tudies Methods in Common Use in Dietary Surveys There are eneral different dietary tudy method in current ue in epi OCTOBER 1960 ·demiolognal ausies In order to yield meaningful information they mut all include certain minimal facts about the subject such as age er orcupation height pre ent weight weight changes oses i period of years activy health tatus (including inte tinal para itic in festation in subjects from certain areas) the usual number and time of daily meals and where the meals were eaten and current medication or dietary upplements The evaluation of dietary intake in volies two procedures (1) the record ing of the foods caten during the period of ob ervation and (2) the conversion of the intake record into units of food or nutrients naire Collecting Food Information There are everal technics in com mon u e for preparing a food record The outline below presents an arbitrary classification of the e procedures in terms of characteristics which have im portant methodological implications The e characteristics are the time period covered the timing of the recording proces and the method used to de termine amounts of foods In the e terms the method most commonly nised or mot rea onably considered for epidemiological studies are (a) Intake at specific meals rerorded con currently in terms of eights household mea ures or estimates of quant ty (b) Intake at specific meals reported by re call in terms of emate of quantity or frequency of occurrence of food stem (c) Current usual intak reported either in term of estimates of quant ty of specifi food or by frequency of occurrence of food items (d) Pat changes in intake reported in terms of frequency of occurrence of food items When there are concurrent record ings of intake at pecific meals (method (a) above) the conyer ion of the intake record into unit of specifir nutrients may he accomplished by chemical analysis of amples of the foods or by calculation from tables of food value When the obseration involves recall (methods (L) (c) (d) inclu ie) nutrient values can be estimated only through the food value table The concurrent dietary data can be recorded by the ubject by the per-on Tespon ilile for the subjects food or lov a trained ob ener Although the re call method utilizing either an inter Viewer or a elf administered que-tion IS one of the mo t convenient method of obtaining uch data at has its limitations For example whereas a diary or record will yield factual data an interview will yield only the ub jective average of an individuals re called food intake This is subject to a large human error factor-perhap the mot important variable and certainly the most difficult to estimate This error may be minimized by en 1ting the subjects fullest cooperation ind al o by the hill and talents of the interviewer The interviewer mut be well trained in method of collecting and treating data He mu t be able to establi h rapport with the subject He mu t have knowledge of the cultural and socioeconomic factors operating in the community and peak the language or have a very competent interpreter He must develop technics of eliciting dietary information and of a embling this information If the subjects are to fill out questionnaires by themselve then the questionnaire mut be pre tested under condition comparable to those of the survey area The tress or apprehension cau ed by the survey it elf may bring al out a change in the subject s dietary prac tuces He mas temporanly alter hus intake to conform to his conception of what he hould be eating If the subject is receiving public financial as istance he may report fewer or different foods than he normally eats becau e of fear that the stipend will be reduced In 40 YOL 50 NO 10 AJPH ·CARDIOVASCULAR DISEASES and COCIO other situations the ubject may eat better than he usually does to impress the workers Arterio clerotic heart di ea e and hyperten von develop over a period of Year Ideally the entire past hi tory of nutritional and other environmental factor should be as essed The value of dietary tudier of individuals actual current intake for hort periodone day one week or one month-1s que tionable unless it can be e tabli hed that the hort term tudies reflect usual eat ing patterns of the pat R w of L terat e Studies of daily food intake have re Sealed marked variations even in the same individual 13 Yudkın 4 using the daily records of postgraduate dietetic tudents at hing Colleve de igned a tudy to provide data on the adequacy of dietary tudies taken for period of le than even days He found that caloric intake of an individual can differ by as much as 68 per cent from week to week h data howed that the fat intake was largely respon ible for thi variation Thomp on weighed the daily food intakes of a group of preg women and reported that the profile for the nutrient content of the indivdual diet appeared to retain its main characteri tics two widely eparated weeks Chappelle weighed her own food every day for more than a year She concluded that an ob ervation period longer than one week has little ad Vantage over horter ones if only an average estimate of nutnents is de ired A more accurate estimate could be ob tained from three weekly record of weighing cho en casonally throughout the seat IcHenry after studying the foot intakes of a mall group of normal per on at intersal throuch out a sear reported that the variation I ere of such magnitude that uf the intakes for that group had leen recorded for a single week s period the results would have varied con iderably depending upon which week was u ed Young and co workers concluded that hen daily diane are used aver ages for groups did not appear to vary sufficiently from week to week to war rant more than 1 even day record in contra t to adequately study the intake of an individual it would appear that for some individual more than a single week s record would be desirable Variations in the dietary intake de pend upon many factors especially food supply ea onal change economic factors Religious and cul tural patterns alter intakes of certain food at pecific periods of the year The degree of internal variability and its relation hip to the design of the total tudy must be con idered in elect ing the time pan over which the dietary information will be collected E timates of nutrient intahes calcu lated from the food table vary with the method of collection of information on food intake even when the same indi viduals and the ame food intakes are being studied Experience in compar ing nutrient values resulting from three different method of collecting data are ummarized by Young' as follows 1 The detary h2 tory (defined by Burke as a era e food stake sad rable period 10) was compa ed with the 2-hour recall and the se en day record with thour recall, as method of est mating the nutrient intake of an ind: sidual and of a group Data for th sp comp cons were obta ned f om threr dit fer nt population gro P grade school chuift (New to ki h k chont and of lege stud nts (Rhode I land) and pre nant women (Vassachusetts) 2 For an ind sidual in any of the thee popu) t on oups studied the thour re call did not peth Samue estimate of dietary 1 take as th dietary history 3 For an dutul in any of the thee population group tudi d, the "+hour re call d d not gte the same estimat of detary ntak as the eyen day r cord To descr he the intake of id dualth nant in ver & con OCTOBER 1960 41 ·dents and pregnant women Under certain circumstances the 2 thour recall can be substituted for the seven day record in estimating group istakes. two methods could not be tised interchange ably 4 For the mean of a group the dietary hi tory gave distinctively higher values for grade scbool children and for pregnant women than did the estimates obtain d by a 2+hour recall The history and 2+ hour recall gave results which were in better agreement for the college group studied 5 For the mean of a group the seven lay record and the 2 hour recall tended to give approximately the same estimates for the dietary intake for mot nutrients. This was true for all three population groups to which the two methods were apphed grade school high school and college stu Bransby also reported that the values calculated from weighing hou ehold measurements and questioning of the children were in broad agreement for energy and nutrient content There did not check clo ely with chemical analy es of the foods (Tables 1 2) Mornicon found that the memories of eight scientists for a 21 hour recall of food intake were extremely un atı Talle 1. Hverage Daily Energy and Nutrient Intakes Found by Four Methods of Survey in the Maljonal Children Home Harpenden (49 Children) Vethod of Survey Weighing Value SD Homely Measures Value SD Item Que tioning Value SD Chemical Analysis Value SD Calories Protein gmt Fat M CHIộ gt 7 760 83 96 366 507 18 22 69 2 72 89 107 363 423 16 21 52 2604 81 95 35. 197 18 19 68 2 381 89 81 394 718 16 14 These are standard deviations for a single child and were calculated from the actual thre day intakes of nutrents the resulting values bein, divided by three to obtain the above fi ures. I rotein--NX60 as the dets contain both animal and cereal protein The starch values determined by the method adopted sere increa ed by "1 per cent to permit comparison between analytical and calculate I results. Adapted from Bran by ER Daubney C G and Aung J Compari on of Result Obtained by Different Methods of Individual Dietary Surses Table 5 Bat j Nutrition 2 101 1948 Table 2--Correlat on Coefl cienty Between Energy and Nutrient Values Found by Four Met ods of Dietary Survey in the National Ch Idren s Home Harpenden Methods Correlat Calories Protein Fa: Carbohydrate WHI WI WXA HxQ нх А 094 094 087 091 085 0 80 090 094 099 087 08_ 088 093 091 0.57 0 87 053 0 43 093 093 081 091 071 075 *V=Weighing QuQuestionmg Hellomely measures A-Chemical analysis Adapted from Bransby E R. Dautney CG and kino J Comparison of Results Obtained by Different Methods of Individual Dietary Surrey Table 8 Brit. J Nutrition 2 103 1948 YOL 50 NO 10 AJPH 42 ·CARDIOVASCULAR DISEASES factory on an individual la How ever the averages for the group were similar to the calculated averages of the Weighed food There is ? paucity of published data on methods of tudying long range eat ing pattern Trul on and McCannt in Ve tigated the patterns of 39 Italian American male factory workers using a research hutory method and repeated the study after a two year interval The mean intakes of the group for calories Protein and fat as estimated from the two surveys did not differ significantly but there was considerable individual Variation The correlation coefficients between the two urveys for the intake of protein fat and carbohydrate were approximately 05 The error in the method and changes in food supplies economic status occupation etc could have contributed to these differences The information collected may be a closer approximation of current eating practices than it 13 of long range pat tern Marr13 examined the dietary records of middle aged male British bank officers obtained by the weighing of food for two periods The «cond period was selected approximately ir months after the first period in an attempt to mea ure seasonal variations as well as reliability of reporting The data from 25 men are reported in Table 3 There appears to be considerable stability in the nutri tional habits of these men during this si month period For energy value and for the nutrients calculated (protein and fat) correlation coefficients for the two period ranged from 0 72 to 087 The co fficients for fat fland animal marine animal and vegetable) ranged from 081 to 087 (Table 3) From the preceding di cussion it is evident that more knowledge is needed regarding the reliability of the results obtained by different methods in com mon use for collecting dietary informa tion It is not yet pos able to utilize intahe results obtained by one method for predicting results expected from another method Further re earch $ needed on individual food consumption to identify the character tics of a diet pattern which are con tant and not greatly affected by daily and weekly Variation The problems encountered in the proc e sing of dietary data will be presented and discu ed in the next portion of this report Table 3—Twenty fve Ind dual Repeat Weeks Weighed Diet Survey (Bank oflicers males 40-55 years inclusive) 1957–1998 A erage Daily Consumption Correlation Coeffic ent First Surrey Second Survey Calories (Cal ) Protein (gm) Carbohydrate (gm) Fat total (gm) an mal (m) marine (gm) veg table (m) Calones from fat (c) (69 82 3 6 197 93 6 78 41 819 83 338 196 92 081 07 089 0 85 0 80 081 087 083 27 40 Pepeat Indi dual Heghe I Mart J W Heady J A and "forrs J Diet Surveys Proc Nutr tioncrets 18 1 1999 OCTOBER, 1960 ·Table Calculated Intakes of Food Components Comparison of Inalysis of Puplıcale Samples of Diets and Calculation of The r Contents Day Vutrient Vethod 2 3 5 6 Energy (calories) Analy is Sample a Sample b Differente Estimation 1,521 1,968 1911 97 152 1991 2.37 20 2,260 2 512 2 553 41 269 2018 2015 57 2,238 2051 2,032 19 2.288 2,384 7411 77 2.339 1,516 Protein (m) 56.5 74 4 Inalysi Sample a Sampl b Dullerene timanont 538 760 160 69 7 6.3 959 614 676 32 6 870 85.5 15 81.5 680 72.8 48 811 862 83 7 0.5 836 27 65 6 16 837 lleat of combu tuon tValues denied from standard tables by multiplying total intales of protein fat and carbohydrate by factors 565 9 40 and 41 respectuely Thomas R U et al Autritional Status of Chuldren. YIN Accuracy of Calculat u Intakes of Food Compon nt with Respect 10 Inalytical Values. I am Dietet. A 26 11 891 1990 Processing Dietary Data There are three method wuch the re earcher may ue to evaluate the dietary data (a) chemical analysis of representative amples of the food con umed (b) calculation of individual nutrient using food tables and (c) classification of information according to food usage Each of these method will be examined briefly methods suitable for obtaining valid alıquots and for the analysis of food samples Tablt how differences in the analy 1y of duplicate amples a reported hi Thoma 10 Difficulties were de cribed in obtaining consistent results from the analysis of duplicate ample from nonhomogeneous dishes uch a meat stew The greate t "ariation oc curred when uch foods as fried pota toes or green beans cooked with bacon fat were on the menu The bet data on nutrient intake for a specific time segment are probably ob tained by weighing and analyzing food items or aliquots of the diet as eateni Expen e and practicality may make uch detailed observations infea ible This technic has the further limitation that it can be ued only for pro pechive studies which cover a pecific time pan and require concurrent observation As with other methods the po ibility {x1 ts that weighing and sampling may influence the kinds and amounts of food the subject eats by focu ing his atten tion on his diet Laborato y Analys s Acceptable methods have been land ardized for the analy is of food for a few nutrients Procedures for pyridox determination remain unsatis factory Analy is of food for total fat continues to present problems while the be method for analysis for pecific fatty acid remain to be selected Work on these problems continues currently in the US Department of Agriculture as well as in many other laboratories A committee appointed by the Interdepartmental Committee on Nutrition for Mahonal Defen e is work further landardization of ing ine on YOL 50 NO TO AJPH ·CARDIOYASCULAR DISEASES The main u efulness of direct anals sis of foods in epidemiological tudies is for establı hing the reliability of re sults obtained from other methods which Calculat on from Food Tabls Dietary intake obtained by recall technics and meal recordings are fre quently converted to nutrient intake by use of the standard food talles There are a number of tudte in the literature compare chemical analy 15 to calculated report Table 5 presents a ummary of the differences re ulning from treatment of the same dietary data by laboratory analys and calculation from food table 114 Caloric and protein values were within 10 per cent in more than half the cases hut only 23 per cent of the fat de terminations were within this range Only 15 per cent of the calculated values for calories and protein vaned from laboratory analısı figures by more than 20 per cent while more than 50 per cent of the fat determinations were outside this range Mot of these differences can be at tributed to the calculation of the protein and fat content of the meat Tables of food composition prior to 1950 and ome of the more recent tables express the values for raw meat on the ba is of carcass or whole-ale cut and have little or no information on trimmed retail cuts either raw or cooked It has been cu tomary to use the data for the raw meat in entinating nutritive values When meat is cooked there is con ider able lo s of fat into the dnppings re ulting in a large reduction in calores and very little los in protein Fat adhering to the mu cle frequently i trimmed from the meat after it is cooked thereby reducing the calones further Therefore it i to be expected that the values for meat as calculated from the tables will be high for fat and consequently for calories but will be within a rea onable range for pro tein If meat constitutes a large propor tion of the diet the calculated values for fat and calories for the diet as a whole probably also will be too high A recent publication concering the nutritive value of cooked meat helps to elucidate some of the apparent discrepancies between analy is and calcula tion of meat fat Future revision of food table are planned to provide more Table 5-Comparison of Calculat ons from Food Tables wth Chem cal Analys . Per cent Differ nee.Calculation vs Ch n cal Analysis r - 30 Mor - Oto -10 to _99 -199 +10 to +n to +199 +999 +30 or More +99 Total 92 Clories No of a es er of ca es 0 0 8 21 29 77 21€ 577 73 193 398 1000 58 Fat No of cases of c 20 77 10 38 36 139 66 255 21 9.3 37 13.5 68 6.3 259 1000 es Prot in No of case of es 1+ 13 41 14 1.0 535 ng 91 8 2.4 318 1000 21 Bed n 29 tud es Two of the tud es are Canadian fare Bth and the rem nde are American Th re are 23 d flerent studies report as comparisons of cal nies, as of prote a d'l of fat. These tud es were publihet from 1937 t 1957 See eferences 1 S and 15 to 49 OCTOBER 1960 ·Table Calculations of the Same Weighed Diets by Workers in Fighe Different Suales-Based on 21 One Day Diet Records Means and Standard Deviations for Celonies and Protein MO W 15 Iowa NIL Mich Vinn S D (a) S D (5) Calories Mean Sd Range 1,893 1 875 1994 19.8 432 1,295 1,820 329 1 026 1,872 387 1 410 351 417 1936 390 1,388 1 901 398 1 616 1,233 1 711 1,567 Protein (m) Mean Sd Range 6. 6 172 68 9 619 199 639 572 154 687 09 331 1378 619 155 67.3 55 9 15 3 61 7 624 159 681 57.2 169 748 * Standard deviation Unpublishe i data furnished by Dr Wilma Brewer lased on a pilot study conducted by the NC5 Tech Committee compilation of data by Harriet Roberts tices The nutrient salues in the table repre ent average values throughout the year a detailed descriptions of cooked meat Accuracy of calculations till depend to a large extent on adequate descrip tion of a food item as it is actually eater It is recognized that direct chemical analysis is the best available method for determining the exact amounts of nutrients supplied by particular food sample at a particular time How (ver calculations using the best avail able tables of food compositon when applied to a detailed food record com piled over a long period of time may be more repre entative of wual intake than chemical analysis of samples of foods eaten during a short period In this connection reference is made to the background of the figures on nutrituse value of foods publi hed by the Department of Agriculture The values shown in the e tables of food composition are not necessarily arith metical averages of all analyses avail able for each nutrient in each food Many factors are taken into considera tion in deriving the particular value shown such as variety seasonal and geographic differences production and consumption statistics shortage and manufacturing and preparation prac The use of food tables for determin ing nutrient content of mixed dishes requires very pecial care since recipes will differ from day to day from hou e to hou e and from region to region Unpublished data from a pilot study 18 show wide variations in the calculation of nutrient content by eight different nutritioni ts using the same weighed drets and food tables (Table 6) The lack of adequate description of food mixtures places an added burden on the calculators judgment in selecting the appropriate item in the food table Calculation of the nutritive value of carefully obtained food records from appropriate food tables has many ad vantages The researcher has great latitude in selecting the pecific com ponents to be calculated The only limi tation is the data in food tables With improvements in food tables the oppor tunities to search for possible interrela tion hips between different components of the food intake and other a pects of the subjects condition will be greatly extended VOL 50 NO TO AJP H 46 ·CARDIOVASCULAR DISEASES portant relation hups between food in take and cardiovascular disease Food Usage The third method of processing the dietary material is according to food usage Cla sification according to the frequency of use amount type of prepa ration periodic intervals of fea ting or fasting patterns of alcohol consumption and use of condiments may help de scribe the subjects nutritional environ ment A regional publication of the US Department of Agriculture describes homemakers meals (Table 7) Caloric and protein intake for the Birmingham and Minneapolis women were in clo e agreement However when the diets were classified according to food groups considerable differences were observed Mo attempt has been made here to review the literature but results from this and similar reports suggest that further study and experimentation with the raw data in this ca e intake in terms of food items, may uggest im Discussion A major defect in the collection and processing of dietary data lies in our inability to make precise or even approximate statements concerning the reliability of the various procedures in current usage Until such information is available it is difficult to evaluate the u efulness of dietary appraisal in epidemiological studies Mechanical inaccuracies can be de creased through greater use of auto matic devices for the processing of data, while vanations due to subjective judgments will be reduced to measur able proportions only through tand ardızation of each procedure For every dietary study con dera tion hould be given to establishing the degree of reliability for each tep in the Table 7-One Day Food Intake of Homemakers Average nutrient content Burm gham Moneapol s (261 Subjects) (245 Subjects) Calories 1,80 1 720 Prote n (gm) 57 61 Fon intake accord ng to food groups Per cent calories contributed by 11 i od grups Bmngham M nneapol s ( 61 Subjects) (245 Subjects) Per cent Per cent tik cream ice cream and cheese 96 11.3 Fats oils 233 10 Eggs 32 2.8 Meat poultry and fish 169 21 4 Dry beans pea and nuts 34 1.2 Potatoes and sweet potatoes 41 42 Ctru fruit and tomato 16 28 Leafy green and yellow vegetables 1.5 1.6 Other vegetalles and inits 34 64 Sugars and oth e sheets 92 61 Gran products 238 n90 Adapted f om Clark F and Fincher LJ Nutriu e Content of Hom makers Meal Fur Cities Winter 1918 USDA Agncultural Information Bull Mo 112 (Mar) 1954 pp 3 and 30 OCTOBER 1960 ·collection and proces ing of dietary information Such te ting of the repro durability of results should begin with a demonstration of the dependability of the instrument and procedures selected for obtaining and for processing the in formation Equally important will be the reliability of the subject as an in formant He should be able to report repeatedly the same factual information The interviewer mut have the ability to interpret diet information objectively For each procedure which depends upon a subjective interpretation results from two or more workers hould be compared Through repeated interviews with the same subject and through the use of built in cro checks in a ques tionnaire procedures can be pretested for a selected ample prior to the wursey of the total population to be studied Attention to the areas for which re liability is poor or for which reliability appears difbcult to check will more clearly point out the deficiencies in presently employed methods In addition to the reliability that is the error variation in methods of collect ing and proces ing dietary data the validity of a method i an important criterion of t u efulness The validity of the method will be judged by the extent to which the data it yield are a true mea ure of what the investi gator wishes to describe In other words do the data obtained answer the question that is a ked or satisfy the purpose of the insestigator? The primary problem is to evaluate how accurately any method of collecting in formation measures dietary intake keeping in mind that reliable data for a specific period such as a week or two may not be a valid measure of the char acteristic diet of an individual described in the main body of the report There is need for dietary data on in dividual which can be related to other informalion about them In planning dietary studies certain decisions mu t be made 1 What are the objectives for the dietary tudy 2 What hypytlesis is under consideration' 3 What shall be the time span involved in the dietary study? (a) Intake for a specific time (b) U ual characteristic intak for some defined period (c) Combinations of these 4 What meth ds hall be used for collecting data? (a) Record (b) Recall (c) Compo ite of duplicate meals 5 How will amounts be reported? (a) Weighing (b) Mea uring (c) Estinating 6 Who shall be the informant? (a) Subject himself (b) Per on re ponsible for the subjects food (c) B th (a) and (b) (d) Observer 7 Who will record the information or sample and collect the food (al The in rmant (b) A trained interviewer (c) (1) A nutrition st or other profes su nal person in food or nutrit on or losely related field (2) Other persons knowled eable about food 8 How certain i the in e tiator that he method i steurin, the information de lred? & (a) The schedule mu t be pretested unless it ha ben tested under sim lar con d tins (6) Interviewers should undergo tho du h training per od wh ch in cludes actual collection and treat ment of data in trial situation and info mat on on th culti al and cio e onom c factors operating in the commu ty 9 What additional information concerning the subject is ne ded? (a) Ce tajn minimal basic fa ts about the subject must be known &ge sex physical activity an data on physı cal mea urements and present and Summary The principles of dietary studies cur rently in use in epidemiological insesti gations of cardiovascular di ea e are 48 YOL 50 NO 10 AJPH ·CARDIOVASCULAR DISEASES B Preservation of the Onginal Dietary Dato The committee su ge is that a means of pre ervation of dietary data le ex plored Government agencies can use the facilihes of the National Archive For other arrangements through ap propriate journals with a repo itory the Library of Congren will allow for storage and later u tem well collected dietary material from numerou earlier studies, reported only in terms of carbohydrate protein and calories for example could now be proceed for other nutrients uch a past health satus that are to be studied in relation to the dietary data Some social and econom data may also b u eful 10 How can the data be proces ed? (a) Chem cal analysis of fod composites or inddual foods (1) Computation of energy value and nu frient i om tables of food compo 1 tron (c) Cla incation accord to food usa or Patterns 11 What information can le obisin d ſom the dietary intale! (a) The insestigator may search for p sible terrelat onships between differ ent components of the fol intake and between the food intake and nutritional health or oth r a pect of the subjets condition 12 What ar the gaſs or I cks in method ology? (a) Lacks or lim tation ha e been discused in the main tody of the pape and the followin, recommenda tions to h lpump ove r ethodolooy for diet appra sal have b en bad by the committee uch a Recommendations 15 The members of the committee recog nize that ways mu t be der eloped to minimize Current problems noted in the present methodology of ecuring infor mation on food con umption of indı viduals for u e in epidemiological tudies of cardiovascular disease They make the following recommendation C Continued Study and Development of Methods of Chemical Anolysis Food Composition Tables and Classification and Patterns of Food Usage (1) Chemical Analysis -The commit tee recommends continued research on the chemical analysis of food and the standardization of methods Analy for fat techntcs of collecting and com po iting food methods of analysis of such como ites as well as better ana lytical methods for nutrients such as fatty acids and pyridoxine may be uited as areas for inve tigation (2) Food Talles-lhe committee recommends tht expan ion of the tables of food compo ition currently available Activities are under way to improve and extend several of these However more information is needed concerning compo ition of recipe di hes or mixed dishe regional dr lies and commer cially prepared or partly prepared ready to eat food or food mires One po ability for covering regional variations in nutrient composition of locally grown and locally con umed foods would be to hate the US Depart ment of Agriculture collect, compile and publi h uch information when avail al le (3) Cla sification of Food-It may A Assembling of Published and Un published Work Relating to Method ology of Dret Appraisal The committee recommend that a collection compilation and critical evaluation be made of publı hed and unpublished work relating to meth odology for diet apprai al particularly material on validation and reliability of methods currently being u ed It is recommended that uch an evaluation be publi hed and be made available to workers in the field of epidemiological tudies of cardiova cular di ea e OCTOBER 1960 ·ferent ways he as important to instigate the intake of certain foods types of food or groups of food as it is to estimate the consump tion of nutrients they supply The com mittee recommends that additional study be devoted to this area particularly to accommodate the testing of current hypotheses in epidemiological studies of cardiova.cular disease D Processing of Dietary Data To standardize and expedite the proc essing of dietary data the u e of ma chine computation should be further explored The committee recommends that more systematır effort be devoted to utılızıng modern machine devices to calculate dietary intake information into nu trients food groups meal patterns etc This has already been done for a few studies but there is no standardized pro cedure The saving of time and money as well as the increase in accuracy make this most important E Research in Methodology (1) Sh rt Mothod for Obtain g Detary Inform ton The committee recognizes that there is need for new approaches to methods for obtaining dietary data that can be u ed in epidemiological studies Since the objective of cpidemiological tudies is to search for evidence of possible association between a dependent vari able (such as ischemc heart di ease) and an independent variable such a study usually is concerned with a rela tively large number of persons who are to be classified into subgroups which will differentiate the persons arcording to the independent variable When food intake is the independent variable to be examined there are major difficul ties to be overcome because unlike such variables as age hours of sleep or even number of cigarettes smoked per day food intake 18 a multifactor variable which can be cla sified in many dif In any study in which diet or level of consumption of pecific commodities or nutrients is to be one of the independent variables one or more methods of classification must be decided upon and then the data collected in such a way that this classification will be practicable If an hypothesis about the relation of a specific nutrient food or group of food to a disea e is to be toated this will determine the aris on which persons will be classified In many recent studies of ischemic heart disease association of the disease with amount and types of fat and with the percentages of total calories obtained from such sources have been of principal interest The results of such studies in the United States have not proved definite as ocia tions Con equently there is a desire to take a new look at the total problem of food intake dietary patterns eating habits etc and to correlate this with calorie balance If this is carried out with no hypothesis to guide the collec tion of data what steps can be taken to develop procedures for searchung for evidence on which to base some hy pothesis for more intensive and con trolled insestigation? Es entially the problem is to find and describe the major differences among individuals with respect to foods eaten and to develop practical methods for obtaining information needed for clas ifying people according to selected dietary characteristic If groups can be clearly differentiated by use or non use high or low r e of any food item or items or other dietary character istics then such characteristics can be tested for a sociation with the disease It is propo ed therefore that a short, simple schedule for collecting informa tion about types of foods used and meal patterns be prepared and used for ques tioning persons in several samples of selected populations The populations studied should be from communities YOL 50 NO TO AJPH

·CARDIOVASCULAR DISEASES
known to differ with respect to mortality
or prevalence rates for ischemic heart
disease The e also might be groups
with different rates within a community
The objective would be to compare
either mortality or prevalence rates for
persons in various diet classifications
REFERENCES

·Sd I Child U S DP 1 C N 859 (M) 191 40 alk BI # km NS | | | C D F C41 IL Am D A 35 l. 197 (Fb) 1959 01 W dwa E 1 MG RA ты —ТЬ Sp 1 Limit LA H 30 3 (FB) 1913 4 Lojk! ME с C. Р S A Cmp 1 D d C110 AM 1 Echt IT ty Sb UL LY IM Ag #p s Amh BIN 469 9 US 13 Y ma 1 B P E 4 к R Sny IP APH 3 1311 139 (D) 19: 4! 1 1 R 11 du CY Th N f Coud d 4t Oklh m SLI 17 AR EPS M 11 I b ( MP 49) ( MIB 4 dat 11 A стр 1 F1 -R P #d Po LSD A 1 Jdbrook 8 5 c 4 CIk F L. C $ MI F Ci 1948 Ilm F M It IR á Sny U SDP It Ag BI 11 1956 1 A o SUDCOMMITTEE ON METHODS FOR ACQUIRING INFORMATION ON PHYSICAL ACTIVITY AND BODY FORM Harwood S Belding PSD Chairman 1 The Task UFFICIENT suggestive evidence has tween level of physical activity and de velopment of cardiovascular disease to encourage a rah of hypotheses regard ing the mechani ms involved Mean while further epidemiological studies are required better to define the rela tionship Such studies will continue to be complicated by interactions of physi cal activity with body form (con titu tion) and with diet It is obvious that any one of these factors may influence the other two The fact that the subject of dietary measurements is handled by another subcommittee should not be taken as indication that relationships of any one of these factors can be under stood without attention to the other two The task of this subcommittee is to consider means by which the phy ical activity and body form of population groups or of indinduals within such groups may be asse sed the con dera tion of hypothe ey and the evaluation of evidence now available beyond the scope of our a signment We deal here only with methods of assem ment of physical activity and body form Our approach to this problem was first to decide what it that we should know about physical activity of a popu lation under tudy then to indicate and discu s means for acquiring the in formation This approach was repeated in dealing with body form physical activity 2 Physical Activity We are agreed that whether the pur po e be to describe two homogeneous population groups having different ac tivity habits or to de cribe individual in a population under study it is neces ary to know (2) what the physical activities have been and the environ body form diet 52 VOL 50 NO 10 AJPH ·CARDIOVASCULAR DISEASES in mental conditions under which they have been conducted (ie what have been the stre ses) and (b) what phy 10 logical demand the activities have made (ie what have been the strains A Description of Physical Activities (The Stresses) Of ue (11 A crage D fy Energy E pe df. This is essential information for even the most primitive classification into ac tivity groups namely relatively active and relatively edentary It will also tie mo t closely to tudies of effects of nutritional factors Such information ba ed on activity level in the immediate pa t of ubjects will probably be inade quate for epidemiologic purposes Ideally information will be sought over the lifetime and at the leat it will be needed for the adult years Exactness of estimate of average daily energy expenditure cannot be expected from technics applicable to epidemiologi cal studies of long term physiological changes It seems likely that the general It is beheved th t classifying workers wth reasonable accuracy into three categor es of physical actity requires vi ts to the job s te by e p rien ed observes and unde id al ci cumstance mea urement of the energy re quir ment of any tasks wth whi h the of s unfamtiat It hould h reco nz that when such clas fic tion rest p m rily on occupation the es umption is made that lei ur time a tvit a ent d tributed that the ene gepnd ture f the ede tary group in rea ed enough to compromi e the differe ce in erersy els lietu en the ce fentary and mode ately actie group It may b th t th wa actually the case n the tudy of miner and cle kg at Fife Scotland in 1959 wh te twa foun i that in 19 colmn the en toy e perd tu en acti atres not at utk 14%0 calo le pr nan pr day while # 10 cek it ws ) 410 aloes C Cm mon sen cł ks if at ons will ple e the } 4t ech ry & P i mits in BOP hich requ es heasy phys cal act sity t the t tal e rgy expend ture Imers wa 3.670 calories and that of cle ks 2,800 The differ nc 860 calories is it eally la ge ad means onttal nem e penditure of that i to denn a top mploy din mod rat physc1 ctity on is attempt to d lin un differences of the order of only 300 or 400 calo les. To do ths with preci non level of physical activity can only be de cribed terms of about three grades light moderate and heavy For uniformity in usage of these terms we suggest that light be used to describe daily activities involving up to 2400 calories of energy expenditure per day for a man of averaget size moderate be u ed for 2 400 3 200 calories and heavy be u ed for expenditures in excess of 3 200 calories Since the energy re quirement for rest is about 1 800 calories/day light represents up to 600 calories of work moderate up to 1 200 and heavy abore 1 200 Assessment may te by interview or more accurately by study of the characteristics of the job performed and supplementary in formation from available sources on activities during off job hours in these connections are summaries that have been publi hed on the energy cost of various ta ks (see Pas more Rand Burnin J F G A Physiol Rey 35 801 810 (Oct ) 1955) However come common ta ks have not been studied Furthermore published values may be ob ously requires a good deal more than just a ual question ng hn the observr does n t have fi chand knowledre of actual job condit ons it is te lexed tb 1 a satı factory classıh ation of the actt ty ! el b mad by using two lasses a signated sedentary and physically it! a third group de gnated as md rately active and/or uncertain the kind of cla incat was used by Morris J N Heady J 4 Raf! PAB Rolp ts CG and P tks JW Lancet 265 1053 1057 (No 211 1993 n cla fying dath c 16 ate data an act ity ups bas en la i kn wa ocu pat on dły w kers in the Minnesota Lah oratory of Physiolow ca] Ilygiene study g raul road employers. Amn of a e age sel one who weigh 18 at:o 1 118 cm tall and has a urf ce area of 1.85 m For most pu poses, 1o dy ght? an adeg ate mau f rest ng nervy e pen lite Its a curacy a a mea ure of A erage daily esoy e penditure varies som what th the mount and kind of work do e caloric I for & ades of wok may be a lju ted downward or up id ac o dan e with percenta e d at on of an ndo iduals weight from 70 kilograms the degree of a cura y required and the ange 1 Wok ene by beina studied my in bcat the urse of more nearly pec se formulae serve notes wa kilo ram 1 in th Tha 1 trary ler 1 1 OCTOBER 1960 ·mi leadıng berause the energy expendı tures for a particular job may not be equivalent from country to country due to differences in methods for example EH Christensen s values (Symposium on Fatigue Floyd WF and Vellord AT (Ed) London H Lewis 1953 pp 93 108) for various jobs in the Snedish steel indu try do not cor respond to those of Cord A B Heller stein II and Turrell DJ (Cir culation 20 537 518 (Oct) 1999) for these jobs in Cleveland For relatiely homogeneous popula tion groupe with establi hed and con sistent patterns of activity (eg pri on populations or fishermen in a Neet) it would be worth while to make sample measurements of oxygen utilization and to maintain an accurate log of time spent in various activities as a means of improving the estimate of total energy utilization A little anthmetir will show that the large t errors in estimat ing work calories are in the e timation of time spent at any particular task Probably the most accurate index of total energy expenditure (for such popu lations) may be acquired by careful assessment of the caloric value of the diet Meticulous application of existing method for estimating over all daily energy expenditure cannot be expected to have accuracy better than + calories This degree of accuracy will not be required for most epidemiologic studies pattern between work and reat may affect his long term well eing Desirable knowledge includey cus tomary peaks of energy expenditure and their frequency The types of mu cular activity al o may be rertinent e 8 whether static or dynamic (becau e static heavy effort affects cardiac filling --the Valsalva effect) whether heasy or light whether involvin, lew or many mu cle groups (ee Lehmann G Prak ti rhe Arbeit physiologie Stuttgart Ceorg Thiem Verlag 1953) Inlorma tion on activity during and out ide of gainful employment including exual activity and leep babit is nerded for a reasonably complete picture Methods involved in as e ment of activity reals and pattern of activity are generally similar to tho e utilized for determining the total daily energy er penditure The emphasis here is on determination of the history of heavy demands on the circulation and on dis tinguishing between situations involv ing free filling and retricted filling of the heart The likelihood of bias in the subjects evaluation of his maximum efforts is not known Error of e timate is encouraged by the fact that most ac tivities (whether they be brick laying climbing hill or playing tennis) may he accomplı hed at widely varying speed Data on current on and off jol activi bies of subjects can often le quite ac However uch will not be re garded as sufficient for purposes of studies of on et of chronic disea e Collection of data on the lifetime of prior activity by interview of subject relatises and associates is necessary despite the fact that such data will be les accurate In taking a detailed activity history one mut inquire carefully regarding the principal energy consuming tasks on the job and the time spent doing each one (See Appendix 2 for check list of items to be covered in quescurate (2) Variety and Pattern of Act vity This information may be is important as that on average level of activity Relatively brief but frequent bursts of activity may be significant for entab lishing or maintaining mu cular power and cardiovascular capacity among those classified as less artive on the basis of average daily energy expenditure Furthermore man being thythmic as re gards activity level the very rhythmic 54 YOL 50 NO 10 AJPH ·CARDIOVASCULAR DISEASES off the job tionnaires regarding phyical activity ) placed in a eparate category It is Attention hould al o be paid to rest believed that these men are easily identi pau es ind activities requiring little or fied if the obsener will take time to no energy the mode of transportation make a di tinction between men who go to and from work and the activities to the gym for companionship and only during recreational periods Ouestion a token amount of exercise and those hould be directed at the amount of men who spend three to four hours a time spent walking both on the job and week in participation in high energy Care should be taken to level conte ts see that the subject does not confue It should be empha rzed that there has standın, with walking In all cises an been practically no systematic effort to attempt hould be made to obtain ome validate an activity history When one estimate of the time spent in each task actually examines the available data it Each subject should be asked to IS found that very little is actually de cribe the most trenuous ta k which known regarding physical activity pat he performs and the frequency with tems and energy expenditures of the which he performs it It is believed Amencan wage earner Living in large that this question should be left to the urban centers end of the interview since it is a lead Since walking is an activity which ing que tion which sometimes leads to requires more energy expenditure than overstatement and bousting Under that found for many production workers ideal circumstances then an interview in indu.try (Hellerstein HK and would vield an estimate of the total Ford A B JAMA 161 225 231 (May energy expenditure in three grades plus 18) 1937 Ford and Hellerstein Cır an indication of the intensity and fre culation 18 823 832 (Nov ) 1928) the quency of the significant peak loads time pent in walking by sale men and Again under good circumstances office workers in large banks and indus pecial que tioning into leisure time ac trial concerns is of real consequence tivities should be carried out Expen Very little is known concerning walking ence has shown that the majority of patterns of such men whose work would energy consuming leisure time activities be claed superficially as light, but are of the type which demand a low whuch may actually fall into a higher rate of energy expxnditure and center category around gardening home The time di tribution of activities is hobbies requiring tools or ports such important but it may be just as im as golf (except on hilly course) which portant to identify the man who always do not require peaks of high energy walks rapidly and prefers walking up It should expenditure However stairs to ridin, an elevator there is be noted that increasing the peed of group of men who spend time in gyme walking on the level from 20 to 40 participating in bona fide high peak miles per hour increases the calories er energy expenditure ta. ks uch as squash pended per minute (but not per mile) and handball requiring the utilization for a man who weighs 160 pounds from of a good deal of anaerobic energy 32 to 58 In this context it may be Anaerobic exerci e of this kind is noted that there is no information on quantitatively and qualitatively different the distribution of walking peeds from the u ual phyical activity of the among American men Walking peed average wage earner with or without might be u ed as an index of drie hobbies and in those situations where in tudies where this was a parameter of it 13 fea ble men of this type hould be interest repair and a OCTOBER 1960 perk ·on Pulse rate and pulmonary ventila tiont are correlated with the energy demands of aclivity If a higli degree of correlation were established for such physiologic re pon-es data obtained from 21 hour u e of monitoring appara tus could be converted to values for peak and daily energy expenditure Sce Appendix 1 for ources of infor mation method for objetivo measurement of therg) utilization (3) En ronmental Factors Certain components of the environ ment may enlarge or diminsh the stress of activity Of mot obuous importance is the thermal environment Work in heat is accompl hed at greater cardiac cost (eg Robin on S Turrell ES and Gerking S D Am J Physiol 143 21 31 (Jan) 1915 l'elding HS and Hatch T F Heating Poping and Air Conditioning ASHAE Journal Sec tion 127 pp 129 136 (Aug ) 1955) and with di tribution of a sub tantial fraction of output through cutaneous vessels habituation to cold insolses dif ferent utilization of the cardiovascular system The general thermal environ ment should be a matter of record par ticularly if compari on i to be made between population groups from geo graphical areas with widely difierent climatic condition For subjects ex posed to proces heat in performance of their jobs the fact of exposure should he recorded Ohjective data on physiologie re ponses to work (vide infra) should be collected under tindardized thermal conditions if this is not fea ihle the ensironmental conditions should be described Other environmental factors of po ule consequence and interest include barometric pressure hole and vibra tion The Ociologie and cultural environ ments in which life activities are con ducted may be of importance in poten tiating or canceling effect of phis Ical activity per se It is hardly within our phere of competence or re pon builts to point out methods of describin, the e environment in terms of the trees (ten ions or drives ) which they present Nevertheless we recognize that om jobs involve threat of cata trophic con equence for mi takes in judgment or performance (eg piloting a plane or other public tran portation high level decision making, and that induidual workers on such jobs may or may not be affected by these stres depending on temperament but the pre ence of uch tress should be a matter of record in epidemiologic studies In other in stances personal drive from competition This may be re Rected in average daily energy expendı ture (pace of physical activity) but if the drive is nervous rather than phy: cal in it expression it may not be mea urable by available methods may result B Description of Physiologic Strains of Activity very heavy Christensen (loc cit) cla sfis the heat ness of work as follows Cal/hr Pulse/min unduly heavy 750 above 175 600 150-175 heavy 430 125 150 moderately heavy 300 100-125 lucht 150 75 100 These values apply for the work it 18 They do pot includ ret pau es Deselopers of the MP (see Aprendi 1) believe that re piratory m nute volume 1 closely prop yrt onal to energy expend ture over a wide ran e of activities The JVP direct ipformation respiratory minute volume (1) C stom ry Act ty Descriptions of the work pattern and environmental conditions of a tudy population are no more important than Know ledge of the phy rologie re pances of the population to the strens of life activities Significant lead toward identifying cau es of cardiovascular (CV) disea e may be found in comparı On yeld 56 YOL 50 NO 10 AJPH ·CARDIOVASCULAR DISEASES 503 (June) 1912) The Waters stepping exerci e might be modified for this purpo e but probably will not be suitable at standard pace becau e it repre enly heavy work (cla sfication of Christen en loc cut ba ed on data of Ford A B and Heller tein HK JAVA 361 1868 1871 (Aug 21) 1957) in which & teady tate ordinarily not be achieved to most sul jects cons between populations having 3p parently Rumitar actuity levels but er hibiting different degrees or types of physiologic respon es Heart rate blood pressures blood volume and compose tron cardiac output and respiratory te spon es to cu tomary activities represent only a few of the parameters potentially important in relating work to CV disea e The work plnışıolog, i relies on work and recovery pusle rates as important Indicators of oier a!? CV stram pro duced by activity A lower pule tale is held to be consistent with less CV strain and greater cardiovascular fitnes Cardiologists rightly point out type of CV al normality in which such interpre tations may be erroneous Actually we cannot recommend sole reliance on pul e rate or any other single parameter as a measure of CT strain Purgher has again pointed out (Burgher GCE and Vatten CA Proc VII Internat Cong Occup Health 3113 118 1937) the desirablass of using pul e presure during activity in conjunction with pule rate and has demon trated how uch valve may be utilized to dent an index of heart work (3) Max mum Ast ty knowledge of the maximum capaci ties and limitations of the C6 tem would be useful in comparing popula tions and especially m studies of the isme course of change : capacity among groups with different actiety patterns Such information could also provide an objective check against ac ceptance of subjet is exaggerated claims of phy scal prowes The problem of estimating maximum capacity for work for maddle aged and older subjects is difficult becau e we will not accept risk of injurs and to require maximum effort may or may not mohe such rish The need is for a means of <etermining capacity without requrring maximum effort lule there is 330 established relial le means for ac comık hing the leads have been pro vided Astrand (Thesis from Gym nastika Centrahnstitute Stockholm 1952) in his studs of working capacity of normal subjects in relation to age showed that heart rate al submarimal work levels can be uwd to predict may mal lesels of work output with fasr ac curacy Hus ubequent research has been de igned to evaluate this concept for lese fit and older populations (re sults not yet available) German (Vuller FA Frerburger Symposium llentielt erg Springer Ver lag 1998) and Dutch workers have been pndicting maximum level of us tained work by mea unog puke TM one to increments of work on the (2) St nd d Aet ty In comparing populations having dif ferent actus levels it will often be ue ſul to know ihr rp pon es to a sand ardized level and kind of actually I're sumably uh artxuty would be sekreted to le Mither the competence of mot meml ers of th population under tuds Tallin on the level or up a moderate grade probably the les actity for the e purpo e The mot meaningful in siologie valu sl} le olfamed after subjects have been exercising for ime and have acqusred uch a sleady state Flecovery pule sore eic 31 als have ome meaning cf Johnson R E Brouha. L and Con plazıo Res Canad Biol 191 ome blood pres OCTOBER 1966 57 ·bicycle ergometer The exerci e may be terminated at a level predetermined as safe (eg 125 or 150 beats per minute), or on the ba is of ECG changes The cune of heart rate against work is then extrapolated to 180 beats per minute (or a lower value for an older subject inferred from Robinson S Arbeit.physiologie 10 251 1938) The validity of such predictions depends on the degree of extrapolation that is required We would endorse support of studies further to develop and define the arcuracy and sensitivity of predic tions of work capacity based on heart rate and/or respiratory ventilation The extra circulatory burden of ex posure to warm ensironmental condi tions during a performance test may be considerable (vide supra) For ex ample our computations using Robin son s data (loc eit 1915) indicate extra demands of 15 liters per minute or more for cutaneous circulation when men are resting in heat and up to 30 liters or more when they are working It 15 clear that thermal stress mu t be mini mized or controlled in application of tests such as those des ribed above Re search may be warranted to determine the usefulness of responses to thermal stress (in lieu of exerci e) as a measure of cardiovascular status and capacity tion is chosen afterward The cost of the two types of approach 13 not our direct concern but since the prospective type of study costs much more the te sults of our deliberation on this ub ject may be of intere t. It seems to us that the possibility of collecting accur ite data regarding lesel and type of phyical activity is much greater while the subject is well The present average and peak levels of ac tists and the physiological repon.es to work are directly ob ertable After sickney is recognized these advantages of direct ob eration are lost and the prospect of obtaining an unbrased ac counting of prior total physical artıyty from the subject or observers is le cened because of the vagaries of memory To the extent that there is a long term em ployment record on members of the tudy population this disadvantage will of course be le s important (2) Two Approches in Study of Phys cal Acti ity The information needed and the methods in attempting to find relation ship between phy ical activity and CV di case will vary with the type of ap proach that i intended We recognize two major approaches study of two or more population groups a sumed to differ in physical activity and tudy of a single population suppo edly with duerse activity levels and attempting to cla ify its individuals as to physical activity (3) St dy of Populat o s Sel cted by Occupatio When the tudy is of the first type the energy demands and type of work should be ascertained by direct obsers a tion by a work physiologist using technics for sampling oxygen consump tion of pecial activities and time study as required with view to ascertamıng average total energy requirement and peak energy requirement and distribu tion of deviations from average Such C General Observations (1) Prospective vs Retrospect Ye Stud os The working group spent some time in weighing the opportunities for gather ing information on physical activity in relation to development of CV disease (1) when the population is chosen for a longitudinal study in advance of major CV incident and (2) when the popula See also Contelat on of Static and Physical Endurance US 4F IA A Test of Physical Performance Based on the Cardiovascular and Respiratory Respons to G adually Increased Work Bruno Balke USAF School of Avia tion Medicine Randolph Field Tex Project No 21-37 004 Rep No 1 1959 58 YOL 50 NO 10 AJPH ·CARDIOVASCULAR DISEASES moderate to high level peak activities at may be useful to differentiate primary requrements of peed (intermittent muscular contraction) endurance (for extended periods) and strength (lifting pushing carrying and so forth) Minimum acceptable mea urements of body form will be needed on all mem bers of the population Comments made above regarding de sıralality of measures of CV function and capacity through exercise tests are equally applicable in this type of epi demiologic study data are necessary to show how differ ent the two populations really are Sufficient data on employment history must be examined to a ure that em ployment has been (or in prospective tudies will continue to be) stable A representative sample of each popu lation should be chosen (minimum re quirement) for adminı tration of an interview designed to establ h average and deviations from average total daily activity as well as maximum activity levels over the adult years The same sample should be subjected to body measurement so that homogeneity or differences in build may be establı hed for groups that are to be compared (vide infra) It would be desirable to hare total activity and body build data on the total por ulation as a ba is for sorting out subjects who are atypical It is al o desirable to have information on current cardiovascular status of the sample or the full population whether available exercise tests can de fine cardio vascular tatus ufficiently for purposes of epidemiologic studies is not known I ut we con der the likelihood promis ing (5) Retro p ct vs St des Some parts of these observations have been applicable only to prospective studies It is recognized that direct measurements will have reduced useful ness in studies of factors related to onset of CV di ease using populations in which heart disease is already pre ent When the interest is in progress of CV disease after its fir t manifestation ome of the direct measures will still be ap plicable (4) St dy of N hom g sous Pop lotios When the study is of the second type of a population which is apparently nonhomogeneou as regards activity level and type it becomes necessary to cla sıfy each individual on the basis of physical activity This should be ac complı hed by interview of all members of the group In addition it would be desirable to tet the validity of inter view data by admini tration of the same Interview to a sociates at work and to friend as well as by examination of employment records Categories of work that may be differ entiated are light moderate and heavy as n gards average play ical activity Peak level may be clasified as high moderate or low For tho e haung 3 Body Form* A Information to Be Sought Body form may be related to the oc currence of cardiovascular disease (a) directly through some un uspected or uncontrollable mechanı m (genetic link age) or (b) indirectly via ome other factor(s) now thought to be a ociated with cardiovascular di ease such as oc cupation biochemical tatus phyical activity or diet Even if the primary association of body form with cardiovascular disea e 1> stronger than its a ociation with other atherog nic or hyperten ogenic factors the causality is obylou ly not direct that i body form does not in The W lag Group expresses als apprecis Lion to IT E llertzberg wil wells and w Mrogman for suggest ons wa chapper in this section OCTOBER 1960 57 ·esther I enign hypertension or no known di eu e 1tself cause di ea e As in all epi demiologic tudies the underlying meclian m will till have to be sought in the laboratory Uy in The rocks mu cular phy que re portedly prone to holh types of cardio sa cular disea e coronary leart di ea e and hypertension thus contra t harply with the lean phs que found more ceptible to tuberculo 1 in recent large cale pro pectuse tudies both Fnland and the United States (Berry TC and Mach FA Tul ercle 36 161 171 (June) 1935 Palmer A Jallon S and Edward PQ Am Rex Tubprc Pulm Di 76 517 539 (Oct) 1957) So once more Hippocrates may have been right in contra ting the phtht and apoplectic habitu (1) R lat on to Card ovascular D sease Other committees be ide this one pecifically those on pathology and genetics-have cited the evidenre for an a. ociation between body form and coronary heart di ca e Such esidence comes from two ets of investigators ung the omatotype technic for de cribing body build Gertler M M and White PD (Coronary Heart Disea e in Young Adult Harvard Uni versity Press 1991) working with clini cal material characterized young cor onary patients as predominantly meo morphic (bony muscular) and econd anly endomorphic lround fat) Spain D M Brade s VA and Huss G (Ann Int Med 38 251 277 Feb) 1953) on autopay material called such patients predominantly mesomorphic In a later tudy Spain D M Bradess VA and Greenblatt I J (Am J MI Sr 229 291 301 (Mar) 1955 ) ported that among endomorphs and mesomorphs but not ectomorphs (linear a thenic) coronary clerosis paralleled serum beta lipoprotein levels The concı tent results of these two ets of investigators require confirmation with additional measures of hody form and with better controls For example 27 of Gertler and whites 100 coronary patients but very few of their un matched controls were Jewish Many reports too numerous to cite relate hypertension to stocky rather than lean builds Hipportates was merely the first to note apoplectic habitus Malignant hypertension has however been said (Pere ra GA and Damon A Arch Int Med 100 263 265 (Aug) 1957) to orcur in women ignificantly leaner by the height cube root of weight inder than women of the same age from the same clinic with re (2) Relation to Bo hem cal Facts Since Mia nikow (1851) many in vestigators have reported that choles terol is higher in those of tochy than lean body build This has recently leen uggested as an a sociation with body fat rather than muscle (hey A Ander on IT Fidanza F hris V1 H and Swahn P Clin Chem 1 3152 (Feb ) 1935) (Miller DC Trul on MF McCann M B White PD and Stare FJ Diet Blood Lipids and Health of Italian Men in Bo ton Ann Int Med 19 1178 1200 (Nov ) 1958) and (I anner J M J Physiol 115 371 390 (Dec ) 1931) To dis tingus h fat from muscle keys and Mller u ed kinfold Tanner u ed both skunfolds and comatotype The consistent relation hip noted be tween body fat and erum cholesterol is low with a coefficient of correlation at best 0 10 though tatistically signifi cant However muscularity of build said to characterize persons particularly su ceptible to coronary heart disea e has with equal consistency hown no relation whatever to erum chole terol les el This is puzzlıng in view of the well documented elevation of the erum 60 YOL. 50 NO 10 AJPH ·CARDIOVASCULAR DISEASES chole le rol among patients with coro nary heart di ease Perhaps Dr Spain hypothesis of a lower threshold for athero clerosis among mu cular persons aliord an explanation Alore re earch 14 obwou ly needed on this point (3) R lato + Occ pat on a d Phys cal At ty a Since Morris work (Morris ) N Heady J Alalle F AB Robert с с and Park J W Lancet 2 103 1057 (No 21) 1933) on British bus drivers and conductors and on postmen and telegrapher occupa tional differences in (oronary heart di ea e have been attributed to energy expenditure However there is a real pos.sh ility that self or job selection re sult an concentration of certain type phy ical or constitutional in certain occupations Morris himself recognized this possibility finding that bus drivers had larger waist than con ductors on entering ervice with the bu company (Morn J N Heady J A and Paflle PAB Lancet 2 569 570 (Sept 15) 1956) I revious independ enl work on American bu and truck drivers howed that they were more mesomorphic and tockier than the gen eral population (Damon A and Mc Farland RA Am J Ihy Anthropol 13 711 742 (Der ) 19,5) authors indicate that conse tent physical differences have leen reported among occupation and adduce evidence that the { are not cau ed by the orcupation (Damon A and McFarland RA JANIA 153 622 625 (Oct 17) 1933) In a recent letter Dr Morris informs us that further analy 19 of morbidity and mortality data among bus drivers hous plenty of heart di ea e among both fat and thin However fat doners have more heart disea e than tht con ductors and thin drivers have more than thin conductors Here again i an Area which needs further tudy B Methods for Obtaining Information Descriptions of body form for study ing correlations with cardiovascular di east are obtained from height weight and other anthropometric di men ions skinfold thickness somato types strength tests and physico chemical analy es of lody compo ition The last four technics attempt to supplement the u eful height weight rela tionship by apportioning total weight or hulk among various ti sue and com partment particularly distingui hing mu cular bony from fatty components (1) Hght d Wight Height and weight are minimum e entials and should be taken as nearly nude as poible The practice of per mitting light clothing and footgear has vitiated everal large and expensive tudies If omp clothing mut be worn --and ock hort and bras lere may have to be permitted-several represen tative clothing amples should be weighed to gue an accurate subtraction constant These hasic dimen ons should be taken with the care expended on the ECG and cholesterol determination Sloppy technic ly untrained or unsuper ved technicians is all too common Height should not le taken with the bar attached to some medical balance cale but preferably again t a Nat wall without a molding at the ba e with the subject in tructed to stretch to his maximum height and to take a deep breath Printed engineering trips med in inche and tenth or in centi meter are san factor for pa ting on the wall A cigar lor or other night angled I lock can be lid down the wall until firm contact is made with the head oriented in the horizontal eye-ear plane (top of external auditory meatus and inſerior margin of lont orut) 11 a scale bar mut be used it should be calibrated firt and again the subject urged to tretch and tapped in the lum The same OCTOBER 1960 ·An an 28 as ince bar region to facilitate the thropometer is acceptable but only in the hand of a trained person Weight hould be taken preferally on a medical type of balance scale to the nearest pound height to the near est millimeter on an anthropometer tenth of an inch on printed strips or quarter inch of the scale bar is so cal brated Almost important current weight is weight hi tory as detailed as possible Inquiry hould be made and checked by objective records of po syble--as to maximum weight age when attuned its duration and caue (in activity illness pregnancy) rea on for weight loss of any and durabon of cur rent weight It would be desirable to reconstruct weight during each decade of adult life Weight can often be re called in connection with athletic par ticipation military service marriage or pregnancy Each figure should be pecified as with or without clothing Of course such ubjective data involve considerable error A rough check on reliability is afforded by asking the subject his current weight before weigh ing then comparing the two figures standards of dubious applicability to the populations being studied ) Skunfolds These are u eful correlating about 070 with body fat and with endo morphy An excellent in trument the I auge skinfold caliper is available from the Venner Gren Aeronautical Laboratory of the University of Ken lucky The two preferred sites for mea ure ment are triceps and subscapular Technic is extremely important slight sariations in method and location of site can make major differences in readings The technician mut be trained and at least initially checked by a skilled professional The ame tech nician should take all the mea urements in a gien urvey of possible (4) Circ mferences Upper arm circumference at the level of the skinfold chest circumference in males) waist circumſerence eat (hip) circumference and maximum calf cir cumference are desirable Of thewe only the first is recommended a minimum essentral (but ee below) by the National Research Council Commit tee Nutritional Anthropometry (Brozek Body Measurements and Human Mutrition (Ed) Detroit Mich Wayne Univer ity Pres 1956) These are all horizontal with minimal pre sure and made with a millimeter teel (not cloth) tape Keuffel and Ecser Wyteface or Lufkin cumferences are measured three times as are skinfolds recording the best single figure Chest circumference is mea ured during quiet breathing (5) 8 actomial and B Tac D meters Though recommended by the NRC Committee on Nutritional Anthropome try and though theoretically useful in indicating laterality of build these two skeletal dimensions alone have so far proved much less relatable to behavior 2 on All cir (2) Index of Body B Id Ue of the data once obtained is not strictly within this subcommittees pur view but the utility of the ponderal Index height/cube root of weight, as a simple generalized description of body build is worth noting Though not dis tingu hing between the fat and bony mucular components of body bulk ats distribution is known in several izable population amples and Promising correlations have been reported with occupational choice physiology and Attention should al o be drawn to the widespread but unfortunate cus tom of exprensing perfectly good nude heights and weights as percentages under or oterweight based on clothed di ease 62 YOL 50 NO 10 APH ·CARDIOVASCULAR DISEASES B Acta Pychiat et neurol Suppl 86 pp 1 163 1953) Strength may also be relat d to energ) expenditure physiology or disease than ratings of morphological masculinity and femi ninity based on additional criteria Thi is true whether these dimen.jons are analyzed separately added related to tature separately or combined or when related to one another as an index of morphological masculinity (Seltzer CC Psychosom Med 8 75 97 (Mar Apr ) 1916) (Damon A and McFar land R A JAMA 153 622 623 (Oct 17) 1953) (Miller DC Trul son MF McCann MB White PD and Stare F JAnn Int Med 49 1178 1200 (Nov ) 1958) Further more they require anthropometric kill and are wore than useless unless so taken Since these measurements are currently being taken in several veys it may be premature to di card them until all the evidence is in For the present it seems be t to retain them along with upper arm circumference as on the borderline between minimum ac ceptable and desirable until their value 19 prosed or disproved Unless bacromial and bieliac di ameters can be measured accurately and reliably whirh requires training the y should not be taken at all ur (8) Photographs These provide a permanent record of what the subject looks like From photograph reliable measurements of body diameters can be made especially if the anatomical landmarks have been marked on the subject One may also obtain somatotypes hair patterns mas culinity rating and planimetric de termination of body areas and even volumes of front ende and back poses are available Since the strongest evi dence for an as ociation between body form and coronary artery disea e comes from somatotyping it seems logical to recommend this photographic technic (Sheldon H Varieties of Human Physique 1910 Atlas of Men New York Harper 1951) Other photo graphic technics may be as good or bet ter but none has received so extensive a trial (Tanner J M and Weiner J S Am J Phy Anthropol 7 115 186 (June) 1919 and Gasan J A Wash burn SL and Lewi PH Am J Phys Anthropol 10 331 353 (Sept ) 1932) The important point to photo graph at a tandard di tance with a known magnification fartor and with the subject carefully posed in the three tandard views A 900 turntable is desirable (6) SH ng Hoght This is a desirable measurement, since it varies with sex race and body build and since-by subtraction from stature -t provides a melure of leg length a u eful tailoring dimension along with chet warst and eat circumferences In retrospective studies such as those current at the Johns Hopkins and Al bany Medical Schools (Paffenbarger and Krueger this conference) clothing size may provide data not otherwise available on body dimensions With height and weight such data permit an approximation to body build (7) Hnd Grp St ngth This correlates about 057 with fore arm girth largely mu cle (Lindegoard (9) Res arch T hncs Research technics well worth investi gating but not as yet suitable for epi demiological studies include method for analyzing body composition in the lis ing uch as den itometry gas and dye dilution body water partition and radiography (hey A., and Brozek J Phy tol Re: 33 215 323 (July) 1933 ) The ultimate logical tep 18 to study the mechan: m underlying tho e as ociations between body form and cardiova cular di ea c which with fur OCTOBER, 1960 ·ther work remain firmly establı hed One such research area being studied by Dr Spain is the correlation between body build and endocrine statu Another is the correlation between body build and organ or to sue morphology men are Summary Subject to later reve ton if warranted by experience the following measure ments of body form are proposed for epidemiology tudies of cardiova cular di ea e Minimum fcceptable Veasurements Herghz Weight -plus weicht h story in as much derail as posible Sk nfolds subscapular and triceps B acromial and bl liac diameters Circumferences upper art chest (in men) Desirable Measureme is tate of oxygen uptake (or the energy equivalent of such uptake) 13) Our definition of energy expen diture lesel in terms of light moderate and heavy with caloric expenditure les els designated for each is useful in epidemiologie studies The description of the tandard man to whom such caloric values apply and a method of finding the equivalent caloric values ap plicable for nonstandard pelled out (4) When fea ible record of diet ary intake hould be u ilized to check estimates of total energy expenditure ob tained from analy 19 of phyical activ ties (5) The cardiova cular tress of physical activity may be more directly represented by an index which utilizes heart rate and blood pressure than by an index of caloric expenditure In other word energy expenditure does not always reflect heart work How ever one mea ure is not a sub titute for the other When an hypothes, call for investigation of relaton.hip between heart work per se and degenerative (V changes a heart work index will pro vide the information that is most di rectly relevant However when bio chemical or phy ical concomitants or by products of muscular action are being examined in relation to cardio vascular change energy utilization is the information that will le most di rectly u eful (6) We reiterate that minimum ac ceptable measurements neces ary for description of body form are height weight (with hi tory) skinfold thick ness and key circumferences and di ameter Such information on mor phology hould probably be a matter of record in all tudies of concern to this conference The information will of course be esential in studies where the focus is on diet or activity Other measurements of the ghen l t are desir able when it is ſea. Ihle to obtain them Seat wait, call c rcumferences Sutin, her_ht Hand grip tren .th -Collins-type dynamometer carefully al brated Narta ansett Gym nasium Equipment Co Centralia Vo Photographs-front side and back po es Conclusions (1) We reiterate that when physical activity is of concern in epidemiolog cal tudies knowledge will be required of aserage daily energy expenditure the pattern of actruty as regard peak les els and timing and the phy ical environ ment in which activity is performed all over a period of years (2) In many tudre it will be de irable to know the phy lological re pone of our populations to physical actvity in terms of cardiovascular strain insoled in performance of accustomed actavities and of a tandard work tah The best available single index of effec tue cardiora cular capacity is maximum VOL 50 NO 10 AJPH ·CARDIOVASCULAR DISEASES Recommendations for Research on Methodology (1) Method should be ought for determination of blood pres ure durinn work This would enable derivation ot u pful indexes of heart work based on appropriate combinations of heart ralt and blood pres. ure values (2) Methods should be des eloped for monitoring and recording blood pre ure and heart rate over ett nded period Chis would give information of value in judging cardiovascular cost of the complex ta ks which make up a obtained by various technics of ques tioning and interviewing on physical ac tivity should be verified by direct ob eration (1) Means hould be desploped and validated for predictin maximum or} gen utilization without requiring mati mum work Fyrst efforts should be di rected toward finding the reliability of prediction of maximum work capacity ha ed on phytological respon es to sys tematic increa es in work load from light to moderate (5) Statı tical procedures for work sampling should be developed a means for determining energy require ments of various occupations a days activity (3) The reliability of information APPENDIX 1 Outl ne of Methad for Measu ement of Pl y cal Act v ty (with Key Reference) 1 Energy Expenditure (respiratory volume oxygen utilization - Estimate from oxygen consumption (with or with out CO production) Method insolves metering of expired air rollection of total volume or alıquot sumple mea ure ment of oxygen content (CO content) computation of energy consumption as orygen utilization 19 (approximate) -calories enery Weir has provided a refinement of computation which takes protem metabolism into account? I recautions Arrange apparatus to encumber subject as little as possible In de cribing energy requirement of a tash obtain repeat mea urement possible on different subjects Attempt Showman hip on part of subject can markedly alter level of activity and timin of tak to point where repre en tative value are not obtained for lugh level activitie mea ure o upisle ly the o called integral method at rest before and during work and recovery o that anaerobic a well as aerobic cot of effort may le lexed Cont of work depends on the mu dle groups in solsed energy cot of locomotion de pend more on Fody mass than surface area so expression in Cal per unut weight is preferable (8) Classical method nvolves collection of exp red air in Douglas Bag or sp rometer later meter ng and collect on of sampl for analysis, analysi ot kamp for O2 and Co with Ilal dane apparatu 34 (1) The Max Planck In tytute at Dortmund has developed a device 5 & which meters ex pired ar w thdraws 0.3 to 06 per cent of total for analysi Dev ce requres cal bration at ariou rates of air flow (c) Wolff has a veloped an integrating Motor Pneumotach gaph (IMP)7 R for meas uring volume and collect ng sample It 18 the h htest device available a dh s been used continu usly for period, of ma y hours Sampiin pe nod should be more than 10 N 2utes (d) Paul n 30 has de elop 1 $mple me ns for determ nation of O n expired air depending on pa ama nete prof rties of ga es. Dial reads dir ctly on per cent or par tial pressure of orygen Fatr and requi les skill th the I[alda e method a curacy i suthi ent but ot a good as Hald ne (e) If qud Co n expired air can be alyzed ly iní are i gas analyzer 11 (1) Time me cht n of indi dual tasks w 11 u ually he necessary to drie valu for total e ty ot of jo! Fample of procedures : I osad I by Horna! at תו OCTOBER, 1960 ·2 Pule Rate (a) By manual palpation Radial pulse may not be accessible without disturbing work in which case carotid may be convenient site of palpation Po texertional pulses have meaning for certain tests of fitness but should not be relied upon as index of grade of work previously performed (b) By EKG or cardiotachometer Heavy muscular efforts and sweating make accurate measurement by these means diff cult. of chest lead helps reduce static" (c) By pickup from photensensitive clement which follows changes in opacity of the car (d) A general reference on these systems 13 provided by Dill 13 Cros Uise Lehe CP 15 phylla Statt fit C t IE + 1: 1953 3 C 3 C F S RE dYk E. MD: Mbd St L M Mby 191 4 WE VIR Edi dbs 1 Comroe J 11:SI II Yu Book P blib. 5 MEATSHM at ho E Ciri b Traprod Rpt tort с вль phy 1 14 199 195 64 TL in Zurkdec BA me lo Coiz 7 #18 HS Рос А Soc Lo a 15 77 1955 bl fm Lgh m Th mpso Ltd в ъг Я ь н Eelt 9 P13 Wood d S d t Ck to $ 68 9 1946 10 Åil bt 110 AC d 6 V DC mod 4 1JOB km So Punad C! 14 I of Sp Di 1 It 3 m CPPIA CI! (too 1 M # KM Tb App! I E TEY R 9 m D in Edith wk Lod ( F. + FC d SO Pa Agr EPS 1959 13 D1 DB R! (1b BtR + Poc F W ns C! d ь н (1957) NwYk Hoebe HP 195) TO ית Pard REFERENCES W B dv NW M thod I M1 b] R Wib Sp 1 R Mblm J Phy: L 109 1 1949 C1 Pt PP 60 73 APPENDIX 2 Check Last of Items to Be Covered in Que tionnaires on Plive ral Activ tv Off the Job Activities On the Job Activities Rouune current activities-hours and maxi Present job duration mum effort Hours vacations lay offs Regular exercise--sports walkın, ama Title teur professional competition Job description-what do you actually do Home maintenance Maximum efforts-rest periods-periods of Hobbies Intense activity Transportation (walking to work etc ) Proportions of sedentary standing walk In clubing etc Attitude toward exercise Heavy lifting-Heat stress Amount of sleep Previous jobs general type and details as Hi tory of phy cal activity above-priods of unemployment School and college changes since-relate More than one job 10 weht history Attitude toward job VOL 50 NO 10 AJPH 66 ·SUBCOMMITTEE ON BIOCHEMICAL MEASUREMENTS Forrest Kendall PHD Chairman are HE Subcommittee on Biochemical TH Mleasurements con iders that its ta.k In this conference is I To di cuss the place of brochemical mea urements in epidemiological tudies of cardiovascular dı-ea en II To et up criteria for judging the suitability of any pecific biochemical mea urement for uch a tudy III To outline the procedures re quired to achieve comparability of mua urements made in various partici pating laboratories throughout the dura tion of the study and IV To recommend a plan for im plementing a system of controls neces ary to achieve this comparability between laboratories I The primary purpo e of any epi demiological tudy is to evaluate the influence of diver e genetic and en vironmental factors upon the occur rence and severity of a di ease We all recognize that the achievement of this purpose in the field of cardiovascular disease in of the utmo t importance and of the utmo t difficulty This is par ticularly true for athero clero is and hyperten ion No one ha succeeded in demonstrating pecific etiological agents for these di eae However marked differences in the occurrence and everity of these di eases in different population groups upport the hope that epi demological tudies may ucceed in de fining the factors shich cause them Two obviou difficulties of applying epi demiological technics to the fudy of the e di ea e are the chronic character of the di ea es and their presence in occult form in 1 con iderable portion of the population factors leading to the deselopment of these di ea es may be operatie over a period of many years before clinical manife tations recognized The problem would be simplified if at could be hown that a cardiova cular di ea e produces ome character tur bio chemical change which appears before clinical ymptom become manifest and which di appears when the cau e of the di ea e is removed Much re earch in the field of athero clerosi has been undertaken in the hope of showing that the concentration of some substance in the blood i as useful diagno tically in this di ease as the level of gluco e is in diabetes mellitu The presence of ab normal depo its of cholesterol and other lipids in the lesions of athero clerotic arteries has focused attention upon the relationship between serum lipid level and the pre-ence of diagno ed athero cleroi Studie have been made of the relation hip hetween coronary athero clerosis and the erum level of cholesterol of pho pholipid of cho lesterol pho pholipid ratios of alpha and beta lipoprotein of triglycerides and of chylomicron Some degree of cor relation has been found to exit between the level of each of the e factors and the ease Although the differences betsseen the mean lesel in diseased and control group tati trcally ignifi cant the values for the two groups are di tributed over very imilar ranges and have little diagno tic or prognostic 18 nificance for any guen individual It is intere ting that this tatement could hase teen made immediately after the publication of the fir t tudy of the di tritution of sprum cholesterol lesel in the erum of patient with coronary heart di ea e and a control group It hown at thut time that the erum are wa OCTOBER 1960 ·chole terol values were di tributed over similar ranges in both groups although the di tribution curses teniled to be kesed in favor of high levels in the coronary patients Sul-equent surveys have only erved to confirm the original ob ervation they have added more points on the cure but the curves have not changed it unlikely that addı tional work to increase the accuracy of the methods for either ampling the population* or of determining the serum cholesterol levels will add ustantialls to the refulness of serum cholesterol levels as a means for diagno ing the pre ence of atherosclerosis Surveys that seek to relate biological lesels with the disea e are not strictlı epidemiologi cal tudies in pite of the fact that large groups of the population are being surseyed Thry sull remain in the category of clinical investigations be cau e they do not relate the disease to pecific emironmental or genetic factors which characterize the population under investigation The biological level of a substance in an indruduał 18 not neces sinly a characteri tic of that indu adual but may reflect environmental factors In many studies a brochemical de termination ha been ubetituted either for an adequate tudy of these factors or for an adequate apprai al of the clinical manife tations of the disease This procedure is vald only if it is known with certainty that the di ease a directly related to the hological level of the ub tance mea ured At the present tage of our know! edge the a umption that the biological kie) of any ub lance an ebolica! factor in the deselopment of athero sclero is mas obscure rather than illu minati the snitcance of an epi Choice of population samples for study of arbarrosrlero is poses many prol lemn Genera) populatiors are depleted by deaths due to atherosclernsis and other du ea re but include many person who have atherocl ro is without c'in cal manifestation Bit r diagnostic tests 1 ould simplily sample select on demiological ludy Thu populations consumirl, high fat dicts tend to show an increat in serum lipid level as well as an inerea ed incident of coronary athero clerosis These two phenomcha may le related to each other only ? occurring simultaneou ly in man, indi viduals The Ingh serum hjad levels may len direct result of the pre ence of large amounts of fat in the diet, while the development of the lessons may be due to one other environmental fartor which varies si temajically with changes in the lat content of the det An epidemiological study should be o designed that the biochemical data are not introduced into the scheme of the study as an intermediate factor B 25 ocrating A the environmental and genetic factors with the di ea e 4 BC Evaluation of a possible relationship between B and C may be one of the pur po es of the study but the survey should be et up in such a way that the effect of A upon B and C 19 a ses ed unde pendently B The placing of clule terol between the environmental far tors and the divea e has resulted in a widespread tendency in the medical profesion to treat thic hyperchole trrolemia in their patients as though they were treating atheso sclero 18 It has been found that variou types of medication will result in a re da tron of serum chole terol levels Nicotinic acid for example will reduce the serum chole ferol level and many other thing will do it equally well Ep-om salts is as effective perhaps as nicotinic acid Persi tont diarrhea rp duces erun cholesterol levels sers well indeed but does it cute athero sclerosis? An out tanding contest recently made the statement that he thought our preoccupation with erum cholesterol 68 YOL 50 NO 10 A JPH ·CARDIOVASCULAR DISEASES levels had resulted in the mot flagrant example of tubular u ion he had en countered in the field of medicine and that he felture that thi preoccupation had presented u from eeing and recog nizing relation_hip that certainly exit between environment and the disease It is poible that the most valuable function of biochemical measurements in studie of thi type 1 to permit the clection of certain egm nt of the population to be subjected to a far more complete analy is than can le applied to the whole population Thus studies of the background of the individuals who develop symptom of coronary athero sclero is in the presence of low levels of cholesterol and beta lipoproteins in the serum or of individuals who do not develop symptoms of the disea e in spite of persistent high level may succeed in helping to define the epidemiological factors re-ponsible for the di ease II To be u eful in an epidemiological tuds a biochemical measurement must fulfill certain minimum requirements (a) The level of the substance measured hould not be subject to wide fluctuation dependent upon factors which rannot be controlled under the conditions of the study lo cite an en ample The level of the une terified fatty acid in the blood which may turn out to be a very important factor in thi 13 o dependent upon the dietary intake physical activity and emotional status of the subject that tudy of this important biochemical factor could not be expected to yield signifi cant information in an epidemiological study without extraordinary care in setting up basal conditions (b) The concentration of the sub stance in the biological sample hould not be subject to ignificant chance be tween the time the ample 1 collected and the time when it is analyzed Thi would perhap rule out many deter minations which might yield valuable information of proper preservative tech nics are not available This is par ticularly true of the concentration of variou enzyme sul stances in the erum (c) Analytical methods must be available that will yield reproducible results under all the working conditions likely to be encountered geographically throughout the tudy Some methods which are atisfactory in temperate climates fail completely under abnormal conditions of temperature and humidity (d) The method elected should give valid results over the entire range of amples that might be encountered Thus some methods for the deter mination of serum chole terol levels yield invalid results when applied to lpemic or hemolyzed era or to samples where the concentration les outide a small restricted range (e) The method selected hould be one that can be performed with techni cal adequacy by the laboratory person nel atailable Many methods which yield reproducible results in the hand of a highly killed investigator are too dihcult for the average technician III The problem of in uring com parability of biochemical measurements made at different times and ly differ ent laboratories is not oled by the selection of a valid method Report comparing the values obtained by differ ent laboratories for the concentration of various serum con tituent in replicate amples of the same serum reveal that intolerable differences occur unle sy tematic effort is made to in ure com parability This dificulty is not one that 1 unique to epidemiological tudies It er to wherever brochemical mea ure ments are made It may le due to in ternal factors exiting in individual laboratories that result in failure to obtain con 1 tent re-ults from analse performed on the ame sample on dir lerent days It may be due to external factors leading to differences in the analy es performed by the various par ticipating lalıoratones Prerre informa disea e proces 3 OCTOBER, 1960 ·out tion concerning the cause of these difficulties is urgently needed In 1958 the National Heart Institute and the Communicable Disea e Center initiated a pilot standardization pro gram with the cooperation of five labora tories untere led in epidemiological studies The purposes of this project were (1) to investigate the usefulness of statı tical methods for the detection and control of factors which contribtite ngmuficantly to variations in total cho le terol values within and among lab oratories and (2) to determine the practicability of u ing lyophilized human serum as a standard reference material for total chole terol determinations The study showed that statistical analysis of the results obtained by introducing a small number of previously analyzed amples in each day) workload permits rapid recognition of failure to achieve internal reproducibility The participating laboratories ana lyzed duplicate samples of lyophilized serum from each of four erum pools containing graded concentrations of cholesterol The analyses were repeated every three weeks for a 15 week period In this time three of the laboratories did not differ significantly among them selves the fourth con istently reported higher values than the others No secu lar changes were observed sults sugget that lyophilized human serum can serve as a reasonable refer ence standard IV Up until the present time every epidemiological tudy has had to find an independent solution of the prob lem of 17şuring comparability of bio chemical measurement The commit tee is of the opinion that the time has come when it would be economical for the organizations that pon or this con ference to take some action toward set ting up a s tem to help achieve this We bebeve that this would be done bet by the establi h ment of a central laboratory which would have the following five purposes 1 To act as a central intelligence agency in order to maintain communi cation between laboratories and in terested organizations carrying specific measurements 2 To prepare characterize presene and di tribute tandards which can be used in the calibration of particular methods This is a particularly im portant function that should be taken over ly a central organization We all remember how a few years ago the ervice performed by the Bureau of Standard in prouding accurate pri mary tandards in many different field of analy is played an important role in the development of chemistry in America This function is no longer nece ary in mot field- but it is till needed in the field of biological chem istry It may not be pos able to buy a sample of chole-terol that I pure enough to defend upon as a working standard for the determination of cholesterol Each individual laboratory seems to be expected to know just how to prepare this necessary primary tandard from commercially available cholesterol Pro 11310n of a chole terol standard would help obtain comparable results from different laboratories Trustworthy standards are even more important in other fields eg reliable tandards for mei uring prothrombin time If this central organization did nothing but provide standard materials to enable the participating laboratories to check their results, it would an important function 3 To furnish Consultative advice on biochemical method to interested and qualified laboratories 4 To compile and publish the experi ence and performance records of calt bration studies 5 To act as an international clearing house for the exchange of biochemical information pertaining to the solution of methodological problems These re erve comparabilty VOL 50 NO TO AJPH 70 ·COMMITTEE ON CULTURAL, SOCIETAL, FAMILIAL, PSYCHOLOGICAL, AND GENETIC INFLUENCES Harry Kruse MD F.AP.II 4 Chaman Introduction fi lency OT This committee of the Conference on Methodology was concerned with cul tural societal familial psychological and genetic influences in relation to cardiovascular divease This postulated association is commonly based on the following as umption cultural societal and familial situations may create stress in the individual leading to or adversely affecting cardiovascular disease Why some persons react pathogenically to stresy and why only certain of them have their cardiovascular system in volved are questions usually explained by attributing this electivity in part at leat to genetir influences Implicit in this hypothesis is the be lief that stress may either contribute to the development of coronary disease or at least, adver ely affect the clinical cour e of the e tablished disease Al though at present there appears to be no con ensus on the relevance and im portance of stre» in heart disease this po sibility must continue to merit con sideration until tres and its related circum tances have been demonstrated unqualifiedly to have little or no sig nificance Unfortunately the concept of causa tion--and of tress for that mattermay be so sague or olersimplified as to be mi leadıng Today cau ality of di ea e is eldom visualized in the old simple relation hip that A produces B Rather a holistic concept of cau ation enyisioning a constellation of diverse factors is held Esentially these factors fall into three main groups (1) tho e in the environment using the term broadly to cover both the physical and social environment (2) those in the host or individual and (3) those as sociated with the adver e agent or process whether it be an excess a de an interference The multiple indıvidual factors subsumed under these headings vary in their on et Tute intensity and duration Thus they have their own particular characteristics and functions in the con tellation and mnahe distinctive contributions to causa tion Various names l ave been proposed to designate their charactenstics and functions for example predisposing provoking precipitating perpetuating and conditioning factor and antecedent circumstances These names are of course not equivalent But one of the most important points to be borne in mind is that a factor that alone cannot produce disease can determine whether the di ea e is produced With that in mind it should te obtous that, in the present tale of knowledge the flat statement that tres has a minimal ignificance in heart dı ea e is enou ly mi leading Until it has been irrefut ably demonstrate whether stress 18 an active component in the cau al con tel lation and until the nature and extent of its participation have been clarified it is impo sible to evaluate its ignifi cance with finality in it nature and its expanse the sub ject of this committee po e seu charac ten tics unlike that of any other com mittee of the conference First, it com a OCTOBER, 1960 ·a The e pairs pri es varied topics each of which falls under eparate discipline Each discipline lies its distinctive group of specialit vocabulary and meth odology Second de pite this diversity all the topic in this subject are inter related For example here are natural pairs phyical environment and the individual the group and the indi vidual omatic and pychological in vironment and heredity are interrelated not only horizontally but al o vertically and diagonally This complex interrelation hip poses a prob lem These topics are so clo el as souilted that it is a most imposible to discuss each eparately without some di tortion ari ing from incompletenes On the other land discussing these in terrelation hips neces arily involves repetition Actually we hould talk on all points imultaneou ly But for pres ent purposes that procedure would create grave disorder Thus the discussion started with the individual then moved to group phe nomena and finally rctumed to the indı vidual In each topic clarification and cry tallization of content was sought before methodology was discussed From the standpoint of methodology it is useful to re tate at this point the sequence of events in the thesis to be investigated It is de irable to a certain whether cultural ocietal and familial influences produce stres that may be linked with cardiovascular di ease A two tage operation would probably prove bel (1) the relation of cultural societal and familial factor to trees and (2) the relation of stress to heart disea e Of course it is pos able to de vise a one stage operation which by pa ves stress namely the relation of social environment to heart di ease Such a study would doubtle s produce u eful data however if the evidence were po itve the essential intermediate steps would be mi sing Stress and Adaptation Because it occupies a central place in the cour e of events the fate of stress is the logical topic for first considera But there were also practical reasons Enough is known about stress to warrant the supposition that it can erie as a valuable indicator of influ ences to be looked for in the environ ment Furthermore i{ stress is demon strated to have any ignificant relation to heart disea e this fact becomes of utmo t practical significance in the pre vention and treatment of coronary disea e In considering stress we are mediately confronted with its meaning and the number of terms associated with it and ometimes u ed synonymou ly strain load pressure tension It is hy no means certain that stress is the proper term for the phenomenon under dis cussion but it would erve no u eful purpo e to cavil over terminology or to Third although this is a Conference on Methodology it was impossible in this section to exclude content The de sign of any study depends on its objec tive in turn both the design and objec tive depend upon a hypothesis which must be constructed from content Then too inclusion of content was even more e ential I ecause of the multidisciplinary as well a intradı ciplinary differences in subject matter terms and meanings In consequence this section had to be concerned with both the substantive and procedural pha e of the ubject The basic assumptions of the subject its diversity the interrelations and mul tidi ciplines of its parts and the opera tional equence all these considerations dictated the approach of this ection The ubject was divided into four major topics and the order of discu ajon fol lowed the equence outlined in the hy pothesis describing their interrelation The e four broad topics were tres en vironment (especially ocial environ ment) type of per on and genetics tion im YOL 50 NO 10 AJPH 72 ·CARDIOVASCULAR DISEASES eries of draw di tinctions in meaning Never theles its developmental history 1 in formative Twenty five centuries ago Hippocrate used the term stress in relation to di ea e and in general the current bio logical concept is remarkably similar to his view In the late eventeenth century the concept of stres came into promi nence in phy is in defining the proper ties of gases and olid borlie On the biological side Cannon brought tre s from the philosophical into the clentific realm by analysis of the biological re action His reaction tent however wa limited From observations on experi mentally induced stre s Selye greatly er tended the boundaries of the concept with his demonstrations and ews of the alarm reaction general adaptation syn drome and local adaptation syndrome Wolff and Hinkle further expanded the concept and filled in missing areas by their tudies on the ocial environment its effect and mans reaction to it Currently the term tre > is applied biologically to indicate the state in an organism which results from reaction to noxious stimuli or di turbing situations However the group expres, ed ome re ervations over this interpretation In the groups opinion stres itself is concept combinin, both an abstraction and a generalızation As an ab tract quality it characterizes a number of bodily states But the fact that treso 1 an abstraction is no rea on to avoid con sideration and u e of the term As it i usually descriled it is well recog nized Hence it wa agreed that as the term is u ed in biology and med cine it ha understandał le meaning man is facing difficulty To impart that meaning the term has vefulne It was decided however that it would not erve present purposes to attempt to differentiate and separate different type of trees uilh as acute or chronic emo tional or physical It is useful to describe the nature of stres its meaning its production the adaptrse reaction which it elicits and its effects It cannot be overemphasized that the topic encompasses a events with a potentiality for multiple processes at each tage Nan 15 exposed to two different kind of external environment physical and ocial Each in its own way exertats influence on him and each producen a different type of effect Here we are concerned with the di turbing not the heneficent influences The physical environment including what we call nature has certain prop erties which affect man heat cold elec tric shock rays pathogenic organu m and toxins By and large as iclas they have a distinctive mode of rela tionship to the body of action and effects (1) They impinge directly upon the body (2) they di turb energy transformation by bringing about an increase or a decrease by withdrawal or interference and (3) they may de troy cellular form and function Quite different is the ocial environ ment in its mode of affecting man Its influence ari es in ituations and per sonal interaction It is transmitted with out direct phy ical contact with the body Instead stimuli are recelled by mans en ory sy tem Out of the mul tiplt impul-es in an experience are selected and unmated The ensu ing ensation arou e a Ociation ories and feelings in hort perception and evaluation occur As an ideational proces evaluation may not take place until some time after an experience L ually there is a succes. jon of idea tronal prore es with temporal projec tion both retro pective and pro pec tire memories other imagerie loth imaginative and anticipatory and thought Meaning and value judg ments enter into the thought tate and feelings are aroused An attitude of di satisfaction may des elop in an affec tive tate of unple i antne a ome mem OCTOBER, 1960 ·ome In evaluating a situation man takes into account the demands upon him and in turn his needs urging satisfaction all organized in a setting of circumstances and conditions for a variety of reasons the per on may regard a situation as unfavorable To him it may appear to be threatening alarming overdemand in restrictive frustrating conflictive or unsatisfying It is well to reiterate that whether a situation in the social environment imposes a train on a per son depends upon his conception and evaluation of it Similar situations do not have the ame meaning for all per sons Indeed, a situation rated by a detached observer as undisturbing may not be so regarded by a person involved in it The opposite trangely enough is equally true To unfavorable influences from both environments the body responds Either a di turbing physical factor or social situation may act as a signal whereby the body reacts in an effort to neutralize overcome and nullify the unfavorable influence to avert its further operation and to restore the body to its usual state This is the process of adjustment or adaptation in which the body re sponds as a whole physiologically bio chemically and psychologically through hodily function mood thought and behavior Depending on the type of disturbance the reaction is mediated at various levels of the central nervous system For signals from a social situa tion the brain acts as an adaptive organ directing the mitigating oppos ing and restorative efforts of the body Since all parts of the human system are subject to participation in this adaptive reaction the tremendous potential of the brain for altering Lodily function and behavior can scarcely be overestimated The capacity for adaptation is not the same in all persons hence success in How well man reacts to a situation in the social en pironment depends in part upon his con ception of it When he perceites a life situation as oppressive ob tructive or unsatisfying he may not be able to make a favorable adaptation Somatic and psychological alterations occurring during adaptation may lead to disea es designated di eases of adap tation Thur production has been variou ly explained It has been sug gested that they occur as a result of in appropriate or overly ustained adapta tion Another view is that disturbances of bodily function mood thought and behavior which occur during periods of adaptne effort make po ille appear ances of disease proces es which might not otherwie manifest themselves Acherman has described in detail his views on the psychological processes compri ing adaptation and the times pathological consequences Three levels of phenomena are involved in the interaction between the individual and society the structure of the environ ment interpersonal relations and the Inner psychic life of the individual Personality and society cannot be con sidered apart Human behavior 19 shaped both by the organization of the internal forces of personality and the external forces of society Social forces do not operate in a human vacuum nor does personality exist ocial Social forces are mediated through that phase of personality which achieves expression in group relations Hence in studying social phenomena the most serviceable definition of per sonality is that which emphaizes the orientation to social participation The functions of personality oriented in two directions (1) toward the internal processes of the organism and (2) toward the social environment There I continuous interplay between the two relations Together they con stitute total personality In its position of interchange with the environment personality has a relative unity Society is the medium in which the ie in a Vacuum аге adaptation is variable YOL 50 NO 10 AJPH 74 ·CARDIOYASCULAR DISEASES ones a 15 identity of a per on gradually emerges As the individual matures he achieves an identity which is at once both indi vidual and social He has an indısidual elf and a social elf The individual component of personal identity is rep Tesented in the more durable less modi fiable aspects of character tructure It 15 the core of the personality the more personal private relatively fixed aspect of elf It reflects behavioral tendencies which have been conditioned by Inter action of biological di po itions and family environment The ocial rom ponent of persons identity represented in the less durable inore modifiable layers of character It is less personal less private less fixed It re flects behavioral tendencies which have been acquired later It is these relatively Inore external layers of character which permit the greater degree of penetra tion by ocial forces The social identity of a person reflect the continued inter dependence of individual and society For pre ent purposes we are primarily concerned with this ocial self ripre senting those functions of personality which are externally oriented Thone operations of the social elf in the context of a given life situation may be called social role Social role is the Intermediate between intrapersonality life and group behavior being that in tegrative a pect of the total per onality which is expressed in ocial action It amplies the capacity of the per onality to make fluid changes in form in ac cordance with the adaptational require ments of the individuals po stron in ociety In a given time and social situation certain components of the total elf are mobilized into action and moved into a dominant position while other components are temporarily subordi nated In essence this is the process of social adaptation By definition ocial role is the adaptational unit of person ality in action The psychic proces es and combined components of behavior make up the configuration of social role Orienta tion in this action pha e of personality presupposes a set of goals and values commensurate with the individual s posi tion in a given group The e values which provide directives for social action are derived partly from the indi vidual personality and partly from group organization they are oriented toward both self and ones relations to other persons Their dual ori ntation involves (1) personal attitude toward individual triving and (2) quality of apperception of culturally dominant patterns of interpersonal re lations Out of the orienting coordinating functions of personality and the ur rounding group forces there is crystal lized a specific pattern of action which 19 reflected in the form of a particular social role Some of the components entering into the integration are apper ception of patterns of interper onal re lations attempt to achieve gratification of inner need assertion or subordina tion of self compliance with or protet against social pre sure effectuation of means for control of the environment election of particular defenses against anxiety an effort to find olutions to personal conflict projection of inner conflicts into the social role These components determine value orientation and the corresponding configuration of the ocial role The relative success or failure of adaptation in a given social role is the re uit of coincidence or conflict between character di po ition and ocal environ ment There are numerou vicis itudes in the relation between ocial role and individual personality First, it is as sumed that the normal per on ha the capacity to effect flexibly a sariety of ocial roles in accordance with adapta tional requirements But persons iary in the patent of their repertoire and they may be required to a. ume roles OCTOBER 1960 ·ecre The per beyond their range or out of character Second the degree of pychic distance between the individual and ocial elves is significant In emotional content the ocial role may be peripheral or central to the individual self hence it may lave central or peripheral significance in relation to the individual s emotional life Such relations will determine the degree to which an individuals identi fication with a group is enume or false spontaneou and healthy or forurd and anvety ridden Third the mount of anxiety gen erated is influenced by the degree of harmony or conflict between individual identity and social dentity on inner concept of self either may coincide with the a pect of self projected into a particular ocial role or may clash with it In the event of conflict anxiety 19 generated with profound effect on social role It may induce increa ing in tability and a tendency to rapid change of roles induce increasing ngidity In either event adaptive efficiency is impaired Thus the personality performance in a given social role is affected by the rela tive harmony or conflict between the ocial expression of self and the inner evaluation of self In this proces of ocial adaptation the individual may react to social pres sure in four ways compliance protest withdrawal new integration It is the latter reaction which i of particular in teret New integration occurs when social pressures are overwhelming and exceed the individuals resources for pliable adaptation Sometimes the di lemma of more than one role brings on the crisis This situation occurs when a person faces two antithetical roles and is incapable of a suming either or when he must perform two roles but their conflicting nature presents per formance of them The consequence of the unre olved conflict between the emo tional content of antithetical roles i Or it may adaptive breakdown of the characteris tic and usual social role Then the per on rt pond with integration of a new form with di tinctive properties of its Oun Thu proce seems to occur in the des elopment of the so called psycho somale di order Through physiological arrangement in the coure of adaptive reaction any hodily function subject to the regula tion of the central nervous system might be influenced to a ignificant de Srce That regulatory influence might be mediated directly by any of the nervous pathway hy internal tion or indirectly through changes in the over all leltavior of the individual Al o the physiological changes brought about during adaptation to life situa tions may include release or production of conditioning factors contributory to the occurrence of di ease Hence the association Letween adaptive reaction and incidence of allness may he ex plained on reasonable ground This recognition of the adaptive reaction to a social ituation as either a precipitat ing or perpetuating factor in disease imparty to this relation hip an impor tance in prevention and treatment Whatever the explanation have been produced experimentally as the consequence of adaptation Simi larly incidence of illness in person has been associated with life ituations con ceived by the individual as disturbing and involving the adaptive reaction In one study it was found that at leat one third of all episodes of illnes were in fluenced in their time of occurrence or in their cour e by the attempts of per ons to adapt to situation From this same investigation came the new that the majority of all occurrences of illness in adults are influenced to some degree by efforts to adapt to the ocial environ ment Hence it has been concluded that mans susceptibility to illness i to a large degree inſtuenced by his relation to society d: eases an 76 YOL 50 NO 10 AJPH ·CARDIOYASCULAR DISEASES This conclu ion is not surprising inas much as the state of the host has long been recognized to have an inſluence on the occurrence of illnes Exposure and extreme fatigue are conditions be lieved to be conducive to the occurrence of disease or to adversely affect its court Reaction to a disturbing situa tion surely alo repre ents an altered tate of the hot To carry the equence of events to completion it hould be stated that not all per on reacting to a situation con tract the same type of illness Just as a similar ituation does not affect all per on alıke those who do react with an as ociated illne s do not develop the ame disea e Although mans relation to his social environment exert a major influence on the occurrence and cour e of illne it has relatively little influ ence on the type of the di ease Rather the type of disease is believed to be de termined by various other influence (1) The physical environment and op portunity for exposure to particular pathogenic agents and conditions ex fant at that time and previously (2) the genetic constitution of the per on The variability in the e factor could te re ponible for the differences in the type of disea e developed Enumerating a few of the various duea es a ociated with adaptive re action uch a ulcers colitis a thma and cardiac d ea e probably brings the I ord psycho omatic to mind Actually no qualitatne differences have been found between di eases in their relation to ocial adaptation Whatever differ ence may ex t appears to be quantita tive that certain di cases appear to be more readily and therefore more fre quently and more profoundly influenced in their coure by the physiological effects of adaptation than are other The e have gained the name omatic di ea e Thi account pre ents a working hy pothe that fits the available ob er ration It can form the ba is for establishing a number of objectives in investigations de igned to test the propo sition that a relation hip eut between ocial environment, phy ical environ ment genetics and coronary disease Methodology –With this background the group turned to con ideration of ob jectives and the methodology most ap propriate for achieving them Specifi calls it di cued the detection of stren and means for mea uring its intunity When it is con idered that stress may be induced by a variety of mean that stre sors impinge or gain entry to the body at very different point that in reaction the body u es various y tem and proce ses-physiological biochemi cal and pychologi al-t 1 by no means certain that tress is a imple homogeneous quality Certainly recog nition of its possible heterogeneity and complexity gue no encouragement to finding a ingle tet let alone a quan titative method It wa agreed that tre s cannot be directly di tingui hed It was admitted therefore that there is no measure of the late of stress per e in the body The problem was then approached by con idering the relations of tre One 15 the reachion to it Can tres be de tetted by its effects? Thı question wa di cu ed in different term namely the measurement of inten ity of stre hy indexe or indicator Reaction to stres it will be recalled comprc numerou functional changes insolung phy iological procee and behavior Some of the e change have been pro po ed and used a indicators of tre Changes in metabolic rate blood pre ure pule rate orygen con umption I lood clotting mood or behavior were mentioned But it sa decided that none of these inderes mea ures Corticoid erorttion and blood kvel were regarded as being more related to Ire and therefore letter indicators 1 at their limitations were acknowledged tres Picho OCTOBER 1960 ·It was thought that exten ile mca ure ments of the indicators in relation to tre > would not be productive in the opinion of the group there is no simple indicator which provides an objecture mea ure of the inten ity of stress It was pointed out that future research may provide such an indicator for en ample changes in the hypothalamus «cem to be clo e expressions of stress But a method for evaluating these changes is not now ready The group then turned to the ante cedent relation to stress namely the factors producing it A te t was cited in which type and load of work were used as indicators in measurement of tres Hinkle proposed that a combination of loth relations the antecedent tressor and the subsequent reaction be studied Here the tressor was designated the challenge It was proposed that the challenge be di covered in the constella tion of circumstances in the environ ment both physical and social that this challenge be evaluated and that the reaction to the challenge be studied In an investigation of the relation of athero clerosis and hyperten ion to per onality and the ocial environment the complexity of this area and the use of the term stress hould not obscure the fact that the epidemiolo,ical methods here are essentially no different from those used in other medical studies At the tart a hypothesis should be formu lated about certain events or processes within the cardiovascular system which are thought to be relevant to athero clero is or hypertension and about the way that these processus may be modi fied by nervou endocrine or behavioral influences as the individual reacts to his total life situation As the dependent variable come mea ures of the cardio vascular reactions are u ed As the independent variable one can inea ure objective features of the life situation features of the indusdual which indi cate that he percentes a guen situa tion in a certain manner or features of the individual (whether socially cul turally or psychologically determined) which make it likely that he reacts to his hlt situation in a certain manner The experimenter counts classifies and sechs as ociation as in any other epi demiological study The ame con iderations of experi mental design selection of sample and reliability of indeves that apply in other tudies apply here The experimenter should try to avoid nause a sumplions (such as that primitive societies are le s complex and less stressful) He hould try to clasify like with like (and not to a sume that Neyro school teacher are the same as Negro laborer») He should try to call phenomena by their precise name (and not to call anxiety tress) He hould try to report re ults in terms of observations (eg respon es on ? Psychological test) rather than as conclu ions or diagno ey (eg hysterical personalities) With the help of killed behavioral and social cientists pecific answers to pecific questions can be obtained In the same vein Ackerman ngge ted that the paychosocial representation of stre s might be approached operation alls in the context of the individual functioning within the family family within the community This ap proach requires procedures for systema tic psychodynamic study of the ongoing interactional proce ses of the individual patient with his family group It is as sumed that the individual patients would undergo traditional forms of p ) chiatric and psychological study Be yond that however there would be systematic examination of the family phenomenon its internal organization and external adaptation to the surround ing community The individual patient is then viewed as a living unit within that group Necessary to such an ap proach is a dynamic concept of the in the 78 YOL 50 NO 10 AJPH ·CARDIOVASCULAR DISEASES di ease a tegration of personality into required family roles The phenomenon of break down and illness may be seen both as a function of the individual organism and as a function of the familial organ 1 m Ofpecial sigmficance in this connection is the relationship between the emergence of lness and the inter play of individual and family group delense against anxiety In an attempt to correlate specific defen e operations anxiety and omatic pathology it is necessary to look into the conflict ten ion and anxiety arou ed by a threat to a persons in tegrity Perhaps particular configura ons of subconscious conffacts and frus trations may be found to be related to But the experience of conflict alone is no index of functional break down with illness It is essential to note how man perceives a threat in a situa tion and how he considers which of his resources might be mobilized to protect him and control his tension Every human being experiences func tional distress in a particular way Hence 1t 18 no urpri e to observe certain re actions in the inner organ system When there can be no relea e of tension in the voluntary mu cles it may flow over into the sympathetic and para ympathetic systems That is an inappropriate kind of mobilization of defense again t ten son a failing type of mobilization Such inappropriate mobilization sugge ts that there might be a relation hip belween acting out and acting in The phrase acting out ignifies a situation in which a per on is esperiencing a con flict in & distre ing way he cannot cope with it and in an irrational and inappropriate way elements of that con flict pill over into society in such a manner as to get him into trouble be cau e his action does not fit the social ituation Although the consequences may be unplea ant for the moment the individual has ucceeded in relieving the exce me ten ion and has e tablı hed an equilibrium for his internal life However it is possible to concene of a situation in which the individual would like to act out but does not dare Such a ituation would elicit different types of deſen e behavior some indicatrie of well being and come which are patho genic exther pychically or omatically or both It would be profitable to con duct tudies on the mobilızation of healthy or pathogenic defenses and their po zble relation to disease Pather than attempt to work out the sequences of changes in the development of coronary disease with special inquiry into stres Dr Selse would go directly to a tudy to determine whether wb tances found experimentally to protect animals from cardiopathy would confer like protection again t coronary di east in man He reported his ex perimental observations recommending that they be put to clinical test Dr Selve a werted that combined treatment with certain teroid and electrolytes produces a cardiopathy characterized by necroses The steroid was regarded a conditioning factor ie it condi tioned the heart for production of the cardiopathy by the electrolyte Among all steroids tested only certain corticoid had this capacity As a conditioner 2 methyl 9 chlorocorti ol (Ne CI COL) po ce sed the highe t potenry Following conditioning of animal with the effective steroid certain electro lytes could induce the necrotic cardı opathy Only certain sodium alts pecifically monosodium pho phate dium sulfate and sodium perchlorate had this ability Other odium alts Here inactive It was concluded that both the cation and the anion po e en this sen ittzing potency Certain other electrolytes actually pre jented desclopment of the necrotic cardiopathy when they were gnen multaneou li with en itizing electro- Iytes to animal uitably conditioned ith teroid Among all the alt a 0- OCTOBER, 1960 ·rat tested pota tum chloride and magne sium chlorid were the most potent protectors In all experimental animals usedguinea pig monkeys and dogsthus reaction has been produced It is fair to as ume at least that a chemical mechanism for it exists in man Di tinct from the cardiopathy pro dured gradually by the persistent action of corticoids plus certain actii ahng odium salt is the sudden eliciting effect of tre Although pretreatment of rats with thre hold dose of Me Ci COL plus MaH POproduced little or no cardiac damae sub equent expo ure to the stress of neuromuscular effort immediately elcited severe and e ten ne cardiac necro es in all experi mental animal Under the same ex perimental conditions of pretreatment, various atre. creating maneuvers kimi larly induced a high incidence of myo cardial necroses Neither Me CI COL nor stres alone produred cardiac ne But after pre treatient with Me CI COL alone ie without sodium alts numerou quite unrelated agent creating tres had a cardiotoxic effect Hence the eliciting action of stress wa regarded to be nonspecific cipitation of infarct like myocardial lesions by sudden exposure to stressors is of pecial interest in view of its clini cal implications After pretreatment of rats with Me CI COL a ingle intratenous injection of papai extract produced myocardial necro es more readily than otherwise It is highly significant that hcl and MgCl are effective in presentin, the various forms of cardiopathy produced by the following different means (1) corticoid and sensitizing Na salts (2) corticoid conditioning followed by ex po ure to various tres ors and (3) in travenou injection of a protea e These ob ervation rai e the hope that they may al o le leneficial in presenting cardiopathies in man It was stated very clearly that the erperimentally induced cardiopathies do not reproduce all the histopathologic changes presently regaruled as a ine qua non for the development of coro nary di ea e For example there is no athero ck To S Hence pathologically none of the experimental cardiopathies in animals 13 an analog of coronary di ease in man Nevertheless since both potas cum chloride and magnesium chloride exert protective action again t various types of myocardial pathology induced expen mentally by different means Dr Selye believes that this fact warrants te ting of their efficacy in preventing coronary thrombos Furthermore t would be a afe and sumple procedure The re are three types of procedures commonly u ed in ascertaining etiology and treatment of a disea (1) experi mental production of the disease u ually in anım ils (2) test treatment of the naturally occurring di ea e in man and (3) test prevention of the natural Il patient studies on the pro tective action of the electrolytes were undertaken the preventive type would provide critical data In addition many Ines might be saved that uch tests are ju tified even if the likelihood of success eems small מנמן מבר cro : di ease 0 The pre Environment Culture Having considered tress We now turn to its environmental source It is ohsous that both the physical and social environments may cause stre Becau e the influence of the phy ical en vironment was scheduled to be di cu ed by another section our attention was focused primarily on the social en vironment as a source of stres Yet o intertwined are the two environ ments that the phyical environment was mentioned at appropriate points It mu t be remembered that ociety cannot be considered separately froni personality Human behavior i haped YOL 50 NO 10 AJPH 80 ·CARDIOVASCULAR DISEASES in both by the organization of the internal forces of personality and the external forces of ociety Indeed the two are interrelated throughout life Environ ment has a molding effect on character structure which vanes with the distinc tive features of each society At each age level and at each stage of per on ality organization the environment re quires distinct types of ocial function from the individual Hence ocial en vironment contributes to the haping of adaptive behavior by determining the path along which the individual may ucce fully adapt to his surrounding It reinforces come individual drives and subordinates others Current factors in the environment influence the social level of personality integration and may even penetrate to the individual per sonality The ocial environment is also the medium for situations which are the ources of stress But again the stua tion cannot be con dered separately from the participating personality The situation derives its meaning from the participants interpretation It has been found that a participant in a ituation evaluates its tres provoking quality differently than does a detached ob server It may have a meaning and ignificance for the participant that does not enter into the ob erier s evaluation Hence the problem becomes How may per onalized tress creating ituations in the ocial environment be detected and identified and how may their rela tion to cardiovascular disea e be tudied Specialization has brought about a dov ion of the social environment into culture society and the family It is therefore mo ! convenient to con ider the nature and methodology of each divi ion eparately yet the three be come commingled when any one is subjected to tudy Culture compres the cu tom man ners way of life and conventional s dom of the group This way of life includes innumerable details of be havior which repre ent the normal anticipated respon e of any of the ociety s members to a particular situa tion Norms of behavior and opinion constitute a culture pattern Culture as a whole is a more or les organized aggregate of such patterns It provides members of any society with an indis pensable guide in all the affairs of life It would be imposible either for them or for society to function effectively without it It operates with a back ground of ocial approval and social pre ure There are many types of culture in the world Broadly speaking they differ in their homogeneity and implicity Even within national border whether ections or in smaller ubdivi ions such as district variants of the ba sc culture may appear Since the anthro pologi t in hi tudie 15 often con cerned with the cultural homogeneity of a ample he sometimes ha to sepa rate population group into ubculture and even into further fractions Becau e of cultural heterog neity tudies in the United States were regarded a mo t difficult by the late Ruth Benedict New York City it elf offer an impra ile array of subcultures Dr Shapiro empha azed that the mot important property of culture 18 the learned patterns of behavior By that is meant the patterns that people live by the expectations they have in the behavior of other people in their own community These cultural patterns confer the ability to carry on a rela tively large series of behavioral patterns in a emiautomatic way By providing a way of routine living thee patterns pare man the nece ity of con tant de ci ion Decau e once a pattern 15 estal I. hed and expectation bult up for most of the events in daily life man can pro ceed in a predetermined was without giving much thought to it Thi prore OCTOBER 1960 ·eries dure is of coure a caver of time and of emotional wear and tear on the indi vidual for having to make fresh deci sions for every item of behavior would indeed be time con umin, and eners at ing Man comes to take his cultural pattern o much for granted that mot of the time he does not think about ita operation Then when he encounters a ituation which is different he thinks of it as being very odd strange and peculiar No matter how well regulated a ociety may be how well understood the cultural patterns may be by mem bers of the community there is always a residuum of conflict which may ari e anywhere in the ocial order to provoke emotional stress It was Dr Shapiro s belief that a highly educated society in which the people have a variety of rules and statutes to contend with may con tain many more stres-creating tua tions than does a primitive organization For example being a member of a minority group or exclusion from a ocial clas or operation of economic factors that are flexible and open to manipulation beyond what the cultures might be expected to control all these things as they appear in the more highly developed society give rise to ituations which could produce tress than occur in a bushman ociety where there is not much economir dis tinction between the members of the society where there are no clases and where there are no minority groups Obviously even there ome situations which would lead to stress would occur but the numher would he fewer Methodolog) ---It is appropriate to de cribe briefly the way a cultural an thropologi t works his methodological approach, once he has elected his popu lation sample His objective is to pro de an account of group behavior in all activities of living But such an area of observation is vast and compler Cul ture itself has a multitude of component each compri ing numerous details Το add to the difficulty an individual may differ in his behavior if ever so slightly from time to time and individuals may differ even more from one another Thu a real culture pattern is a of varying behaviors although the range of variation is usually within moderate limits This variability of behavior yielddata that are much too bulky and un wieldy to be descriptive and workable Hence the anthropologist develops a cul ture contruct pattern by establi hing the mode of the series of variations within the effective range of a real culture pattern he then uses this mode as a symbol for the real culture pattern The total culture construct is obtained by combining all the culture con truct patterns This procedure provides a concise and convenient approximation of the conditions existing within the real culture It is a serviceable method for summarizing group behavior in the activities of living has been repeatedly emphasized that whether a situation is stres provok ing depends on the conception of a per son involved in it not on the judgment of a detached observer Since the situation thus derives its value from the participant the anthropologist as a de tached observer cannot directly erringly and a suredly detect and iden tify stress bearing situations At bent he can study each culture separately and select those situations that might Le stress provokin, Cultural patterns of behavior are the concrete expressions reflecting general ized meanings or values Because of their influence on behavior value onen tations play an important function in the lives of indıvıduals Professor Clyde Kluckhohn defines value onentation 1s a generalized and organized concep tion influencing behavior of nature of man s place in it of mans relation to man and of the desirable and nonde ir more un VOL. 50 NO 10 AJPH 82 ·CARDIOVASCULAR DISEASES able as they may relate to man environ ment and interhuman relations Florenre Kluckhohn has developed a conceptual cheme which will permit a sy tematic cla fication of cultural value orientations as they pertain to uni Ter al human problems This scheme et forth central types of value orienta tions and the ranges of their possible variability It is based upon two as sumptions The firt is that there is a limited number of ba ic human proh lem for which all peoples at all times and in all places have had to find some solution Five of these common human prob lem regarded as being of key im portance were tated in the form of que tion 1 What are the innate predup tions of man? That is what i his bas e human nature" ? What is the relat on of man to nature? 3 What is the signifcant time dimension 4 What is the val d personality type 5 What is the dominant modality of the relat nship of man to other men? hich might be a ource of tress wherea in our society with its mother in law jokes the situation is not the ame On the other hand social mo bility is probably a ource of much difficulty in our own ociety but it does not exit in Polyne ia There the naties are not fired with ambition to become tycoon Polynesia has no tycoon the native have no particular de ire to be one Indeed Polynesia has no ocial cla es and corporation hence it ha no high pre ure executives Prestige and sexual jealou y occur in both cul tures but in quite different character Certainly tress occurs in all ocieties What should be underscored is that the origin of the stress may vary not only with the conception of the affected per son but also from one ociety to another Even when ocietres are apparently imilar they may not be becau e of the different overtones Dr Hinkle recounted ob ervations from a cross cultural study of health patterns in groups of Chinese Hun garian and American college tudent Cultural differences were ob ered in their attitude toward work, relation ship to father and getting ahead He raised the question whether the type of attitude might be a ociated with a cardiova cular reaction pattern related to the development of atherosclerosi Dr Shapiro pointed out the danger of overgeneralızıng on the basis of ob er 1ations from a subculture For example getting ahead has a very high value rating among a very limited portion of the Chine e population kut it is ly no mean typical of all Chine e Mor are all Americans driven by overaultino ambition and high a piration Since there are ubcultures in both China and the United States it 13 i ky to u e ub cultural patterns in making broad gen eralizations about Chinese and Amer) can Iti neces ary to a certain how general a pattern 1 in a culture Three other types of tudies were re The second assumption underlying the heme that solutions found for the problems are variable but that the variability is within a range of pos able solutions She recognizes three types of solution for each univer al human problem 'This scheme permits a sys tematic compari on of societies or sub groups on the basis of man conceptions of fundamental and universal relation hips Dr Shapiro acknowledged the ya lidity of the types of value orientations However he felieved that their ap plication in observations on individuals might be difficult becau, e they are al tract A a more u eful procedure he prefers to deal with pecific everyday ttuations Dr Shapiro enumerated everal ex amples of likely ources of tress in cul tures Vlother in law avoidance in ome American Indian societies & & cu tom OCTOBER 1960 ·ie garded as likely to yield significant in formation Because of inadequacies in published data it ould be desirable to conduct cross cultural studies on blood pressure Concernin, hypertension it would be useful to study cultural groups in which persons have a desire to act out but fear to do o because of the consequenres as contrast d with other cultures in which it 14 permissible to act out freely Interrelationship normally provides the indı vidual with some degree of protection In our society this sy tem is not orking as well as at might It would be helpful to study groups in which the culture normally provides Yaned degrees of reinforcement The individual should be studied in relation to the family and to the larger culture In this comparı son of cultures posible relationships with cardiovascular disease should be tested To Dr Shapiro the paramount ques tion in methodology was how to eval uate stres in one culture in comparison with tres in another It is a difficult problem because the personal reaction appears to outweigh the particular it mation For example is the Chinese boy striving for cholastic pre tige under the same kind of tension and pre sure as an American Joutlı attempting to climb in a business organizition? It is con rentable that the two situations require different types of adaptation Whether one might be a sociated with a signifi cant change in cardiovascular function a matter for testing Above all it would be helpful to have an objective physiological measure for evaluating the stresa provoking potency of ituations Then they could Le more readily identi fied and compared in different cultures Some caution should be exercised in the con aderation of broad cultural fac tors a sociated with stress a pos ably related to heart disease Specifically the following conceptions and practices are investigations to make ob ersations on more limited and pecific phenomena fear rage dilemmas of deci ion ordeals of endurance or tolerance 2 I ailure to differentiate a far as possible between the phenomenon of culture and the phenomenon of ociety ror research purpose there i an ad vanta,e in keeping them conceptually and somewhat operationally separate 3 The popular and largely false as umption that the relatively primitive and preliterate societies are simpler and le tressful than are our sophi ticated and civilized societies Their stres ors may be more intense than ours and some of their components may be more complex (language hinships tems and so forth) We can be certain of finding wider cultural contra ts in Primitive societies but not so certam of finding greater simplicity of components or potential stresors for per onal ex perience 4 The easy as umption that culture and society are primarily offenders rather than befrienders to persons sub Jected to stress (fear etc ) The primary function of culture and society is to olve or re ole a people s problem Most sociocultural systems do a reason ably adequate job of it 5 A tendency to neglect or ignore the utility of a balance between tres induction and stress reduction mechan within ociocultural tem (gho t fear) 6 Failure to properly differentiate between a homogeneous and table cul ture and a heteroceneous and/or chang ing (ulture There is an apparent tend reduction mechani ms of culturally induced stress to break down more rapidly than the induction mechani ms 7 Failure to recognize and account for the fact that culturally induced stres is subject to modification by the 18 nificant reference group members and - im a ency for the to be avoided 1 Lumping all threats or strain upon the individual under the encompa ing tres or challenge It would be better in any anthropological term of load 84 YOL 50 NO 10 AJPH ·CARDIOVASCULAR DISEASES by individualized per onal experience (famıly ) 8 Failure to allow for or to take ad vantage of the phenomena of cultural electivity in socially conditioned tre s induction and stress reduction 9 Po ible lack of adequate recogni tion and utilization of existing sociocul tural variation in family tructure 10 Posible lack of recognition of the re earch potentials of cultural sariation for te ting the hypothesis of acting out and acting in of stress fru fration ize and 1 i lic source of tre > Yet it was obvious that in their lues the natives experi enced much stre mo tly cultural in origin Certain ituations also had stres productive a pects that did not seem to make sense Deeper investigation re Tealed that the natives had been con ditioned to fear particular ituations It was then posible to place much of the eemingly illogical and unintelligible in the category of culturally realı tic stress hearing situation Furthermore it was oh erved that although the native are subjected to culturally determined stre potential their tres resolved by other cultural provisions Thus the cul ture creates stres provoking situation but it alo provides protectie mea ures again t them From these observations Profe or Simmons concluded that it is nece ary to look searchingly into both the culture and the per ons liſe history to di cover what patterns conditioned lu fear It may be necessary to slice the culture into uch subcultures as orcupational ethnic religiou and familial aspect in oriet The u efulnes of social variable in ociety for epidemiological tudiey might be con idered on the basis of their po ible relevance to tress or cardiova cular di ea e eg the nature of the o cial system ocial tatus with procene of ocial tratification ocial interaction and social mobility and ocial roles whether they be a cribed achieved adopted or a umed Other sociological variables u ed in various tudies and found to be ignifi cant are ocial clans type of re idential area occupation identification in the general population authority leader hip re-pon ability and affectional tres To thee may be added the following van alles ize of group forms of inter nal communication rules determining right of mem! ers method of a igning ta ks and handling grievances program of sociological research Environment Society Concurring in the statement that no societies are free from sources of tre Proſe or Simmons went even further in aying that it probably would not be po zble for a ociety to survive without source of stress As enciety means to timulate and control action stress has a urvival function Profe or Simmons de cribed a procedure for identifying tre a provoking situations by peeling off layers of perceptive interpretations of them A list of critical ituation with I potential of creating tress in the life of man in his culture is prepared for a particular ociety Three questions are then applied to each ituation Would it induce stres becau e of its physical element? I its treny-inducing nature rea onal le only in the light of the cul ture? Is there any a pect of the tua tion provoking tress that i not explain able by either the phy ical environment or human culture and dependent upon the pecial experience and dio yncra ses of the participating indudual? In hort the e que fions eel to a cer tain whether the tre inducing nature of the atuation has a bai of phyical or cultural realism as hard ly other members of the ociety When applied to the Hopi Indian it was urpri ing to find little in the phs cal environment that ined a a giren a real OCTOBER 1960 ·on into the epidemiological factors po sibly a ociated with cardiosa cular disea es might profitably follow the plan which 13 outhned by Dr Simmons with teps taken omewhat in the order named If undertaken by sociologists at hould be under the constant counsel and guidance of a medical tr am of per who are recognized as experts in cardiova cular di orders A general ecological approach would be recommended as preferable partic ularly in the initial tages of the study Study should be concentrated on a par ticular geographic area containing a rer onably wide range of factors sus pected to be significant in predisposing per ons to cardiovascular di ease In addition the factors considered (biologi cal ocial cultural familial psychologi cal etc) should be tho e for which fairly reliable technirs of differentia tion and/or measurement are available It would al o be preferred that an area where a considerable number of good ecological studies have already been made he chosen in order to take advan tage of the accumulated ecological knowl edge existing on the area Good examples would be New Haven Conn Prov dence RT Framingham Mass Evans County Ga Other areas might be selected later to serve as areal con trols or for comparative purpo es The cho en area hould be sufficiently repre sentative to make possible the gathering of data on the various factors listed below or at least a plection of them A repre entatie sample should be taken of the entire population of the area as of a pecified date This sample would erve as the base line and popula tion from which all the succeeding data would be drawn for analysis and cor relative tet Every member of this sample (with prou ion for ubstituting members for drop outs or tho e failing to cooperate) hould le ubjected to a competent med acal diagnot to determine the presence of cardiovascular di ea e both in clear cut in tances when there is no doubt of the actual pre ence of the di ea e and in ca es of border line incipient or po tential existence of the di order Others should be medically adentified as clearly free of any recognized symptoms or in dications of incurning the li ea e The e would serve as controls or for panel or cohort studies in long term per pective The ill and potentially all would be clasified according to degree or type of complication age and other categorie to be studied as the re earch progressed Probably special attention would be given to the middle aged and younger categories and only general at tention paid to the aged persons Some order of priority or sequence hould be e tablished in the making of statistical checks on incidence or preva lence of the disorders as correlated with existing social factors. An order uch as the following might be followed sex racial or ethnic grouping rural or urban re idence ecological areal place ment in the region studied immigrant generation religious afilation social clase position as pecifically or opera tionally defined family structure ta bility and status as operationally de fined extent of social mobility a operationally defined etc When these gross statistical correla tion have been carried as far as fea ible on the basis of findings inten ive inter viewing of tratified sampled and perhap paired respondents should begin for much more detailed ind definitie studies These could be made on a shot Crosectional basis and on a lon term periodic panel basis Such far tors as shifting age tatu economic stability family equilbrium ocial mobility diet stres components and so forth could then be studied in the context of case history and life bu tory as well a the sociological context This is perhaps as far a it is at all u eful to ugge t po sıhle design for an or one YOL 50 NO 10 AJPH 86 ·CARDIOVASCULAR DISEASES ecological study Next steps all along the way would be influenced primarily by the findings from the steps previou ly taken own Environment Family In the vat social structure a hey unit is the family It is a primary group intermediate between the individual and wider society Here in this smalle t and clo el ocial group culture, society and the genes meet Family bond are made up of a fusion of factors biological Pychological social and economic The family has a natural life history of its on the other hand every person in his lifetime has several different farm lie one for each period of his life Among the number of social purpo es that the family serves two will be par ticularly mentioned (1) It determines the form of behavior that are required in the fundamental and prominent roles within it and (2) it provides training toward integration into a wide range of social roles and acceptance of ocial re pon ability Specifically famıly rela tron hip controls the qualty quantity and direction of emotional expresion it regulates and patterns the form and range of opportunities for security pleasure and self realization it develop a sen e of responsibility for the welfare of others It teaches evaluation of u pected danger in a situation it in ten ifie or les ens anvety and it in fluence the choice of defen es again t it Obviously to fulfill these purposes tability of the family! important The tability of the family and it members hinges on a delicate pattern of emotional balance and interchange The behavior of each member is affected hi every other member The degree of tability in family relation hip is the end product of complex interdependent proce es for it is governed by the interaction of family meml ers in their respective family role ment for stability Is maintenance of con tinuity of identity Against this are balanced the requirements of capacity to change through receptivity to new experience and learning to achieve further development and to fill new life roles Effective adaptation requires a favorable balance between this pro tection of continuity and accommoda tion to change The homeostasis of behavior--the balance between con tinuity and change the clinging to the old and receptruity to the newis influenced in turn by the capacity to cope with conflict Operating to prevent a conflict to establish a protective equi librium or to compen ate for conflictual effects is the pattern of famly role relations called complementarity Failure to find an effective solution for control of conflict leads to adaptive breakdown which engulís all members of the family Through faulty functioning the family may become a source of tres or fail in its support of a member already under pressure outside the home When a family becomes di abled and its opera trons impaired its stability 14 threatened Usually such impairment in performance is not total but partial Some compo nents of family functionung maintain their integrity while others are disabled Families exhibiting deterioration may be thought as of progressively failing to carry out their e wential family function Acherman ha devi ed a system of grad ing familie which expres en quantita tovels the extent of their disability Break down in the paychological oper ations of the family group does not occur all at once Initially it may be rela lively localized and may be manife-ted in impairment of the family s capacity for problem olving and deci ton mak ing In the beginning the di integra the effects of hreakdown may be rela tisely uhtle fut hy d grees they pread progre els to affect mon and more of the family sla ic function At this point manifestations of treak down One require OCTOBER 1960 ·disorganization are so unmistakable as to be easily detectable isolation of family members critical barriers to communication conflict and hostility di integratın, family unity With the e developments the family as a group can no longer fulfill even its minimum functions During the cour e of deterioration efforts may be exerted to halt or re vere it Families vary in their capac ity to contain those problems for which they cannot find a olution while on deavoring to make some tolerable reti tution Such compensatory behavior 1» posible only when despite conflict and alienation some family pairs are able to maintain a atisfying pattern of complementarity In one way they may damage one another yet in another they may proude material upport and at faction of mutual needs Not to be overlooked is the relation hip between family conflict and psycho logical conflicts within a member This relation hip is a basic influence on both individual and family stabılıty for the tability of the individual per onality is pirtly dependent upon the stability of the family Here again complemen tarity in family role relations funda mentally influences the course and out come of per onal conflict Stres in the family has focal point that are readily recognizable As a group the family develops a major pat tern in its difficulties In ome the major area of stres centers in the marital relations in other in parent child relations tall others in the truggle to reconcile the requirements of multiple roles or to establi h the po ition of the family in the wider community Stress and conflict emerge when the behavior of a member in one family role fails to complement the needs of the member in the reciprocal tre s or somatic allne - unless the refer ence group is also interpreted for mot influences upon the individual are regi tered through the intersening network of interpersonal relations The family is one of the most influential group Accordinely the individual should be studied not in isolation but within the framework of his ongoing experience and interchange with the family group In that context personality and life histories of individuals may be studied in relation to stres and somatic illnes In an examination of the family in its relation to stress and somatic illnes it is clear that all elements mut be in cluded the individuals the family group and the various interrelation hips In particular this examination should cover the following areas each members per onality his interactions both within his family group and out side with the wider social unit the in ternal organization of the family it performance of functions which in fluence «ach member by inculcating both family roles and the social re pon sibility which comes with wider ocial roles and the external adaptation of the family to the surrounding com munity When a person concerves of a atua tion as di turbing or threatening he reacts with ten ion and anxiety this circumstance he con iders which of his resources may be mobilized to protect him and to allay has anxiety In order to understand the personalized disturbing element in the atuation and the individuals reaction to at it 15 necessary to look into the individuals personality conditionng and delen es But the individual is an interacting member of his group hence it is es ential to study him and his life in the context of his group In a tudy of the family as the related certain points hould be ob seried major areas of tress pre ence of conflict tate of tahility or deteri in role group Methodology-—It is difficult to corre late culture or personality with either YOL 50 NO 10 AJPH 88 ·CARDIOVASCULAR DISEASES goes on in.ade the individual (2) what goes on between this individual and other significant family members and (3) psycho ocial patterns of the family as a whole Several reported investigations on all ness in relation to the family have con centrated on one or another a. pect of family life eg the role of cultural values ituations of cry oration performance of ba ic functions e pecially support of a member who mas have anxiety, and interplay of andısıdual and family group defenses again t anxiety it is necessary to mea ure the extent of pychic resources for control of anxiety both in the indı vidual and in the family group and to correlate the defense behavior of the individual with that of the network of clo e relationships since the latter compo ate plays an e sential part in the mobilization of defense against the effects of anxiety Somatic breakdown J> related to the success or failure of the e defen e operations In fact it i impre 11e to note the apparent cor relation between crises in somalıc fung tioning and the relea e of acute anxiety I ecau e defen es break down Thus when the individual is studied within the family group it is possible to relate the occurrenre of illness to an epi ode of anxiety and to breakdown of de fenes Ackerman has developed a method of evamınıng the family and has pub 1 hed a detailed guide for at applıca tron His examination include the following behavior components the relative autonomy of the individual his emotional integration into family group that i the adaptation of hi personality to the required family roles the fit or lack of fit for the ame individual of ignificant familial or extrafamilial role the extent to which the reciprocal role Hehavior of other family members support or threaten the stability of the individual and the psychological identity and value orientation of the fannls group and its external adapta tion to the community Data obtained on three points provide the bar for determining the nature of three inter related ets of processes (1) That The Individual His Personality and Psychological Reactions We now return from the environment to the individual his susceptibility to both stress and heart di ea e It ha been postulated that certain individuals are more vulnerable to stres of these a certain number appear to be prone to develop coronary di ea e or its cir culatory precursor For two rea on this subject has practical significance (1) the elucidation of factors re pon sible for the development or precipi tation of heart di ease and (2) the ability to predict the probability of the occurrence of heart di ea e and to make early identification of probable victim as a basis of prevention Vulnerability to stres and vulner ability to coronary di ea e are two dif ferent characteri tics Yet becau e of their possibly significant a ociation they may profitably be tudied either eparately or jointly A persons rela tion to stress exhibit two a pect (1) his ensitivity to tren the appro priatenes frequency and inten it with which a penon concerves of situa hons as d, turbing and (2) the nature of his reaction to that tre JE poible that a particular type of reac tion to tress may be one of the factor influencing the occurrence or court of heart disea e Such a equence would explain in part ans vulnerat ility to the cardiac compler Is there a particular per onality type :ociated with deselopment of heart ie A lerman NB Life Stress an) Bels Deae Character Structure in Ilyperten e Ison R. Pit1 A Ners & Vient Du 9900 9 8 Balta re Will ams & Wat hi 1950 OCTOBER, 1960 ·те di ea-e? That are the characten tics of such an individual? These seemingly simple questions open a very large and complex area The meaning of per onality itself has been an elusise ub ject Allport has compiled more than 55 definitions of personality which have been propo ed at one time or another Since the method of distinguishing per onality types depends upon conception of the nature of per-onality it is theo retically po sible to have a different method for every definition Actually four tudies have reported on personality type and heart disease or ome a sociated sign such as hyper tension U ually these tudies were conducted after signs had developed Accordingly the significance of the re ported observations has been quentioned Did the ob-erved per onality pattern precede or follow the occurrence of coronary diseasp or hypertension. Or did the same factor or et of factors that produced heart di ea e also bring ał out the per onality change? It may be said at this point that investigators believe that the personality structure has been laid down long before the appearance of heart di pase It will be recalled that Wolff and Hinkle found that whether a situation is capable of inciting stress in a person depends upon his perreption of the ituation its meaning and its value for him This point of view is in harmony with the possible vulnerability of an individual to stress After reviewing those ob ervations and conclusions which bear upon the topic of vulnerability and characteristics of the vulnerable Dr Hinkle propo ed a type of procedure to obtain further knowledge People differ in their su ceptibility to illness regardless of its nature Tho e who became ill most frequently were found to be more likely to deselop both more varied illne es and more esere illnesses than tho e frequently All type of illness seemed to occur ome what more frequently during period when the indısıdual was having diffi culty in adapting to the total configura tion of his life It is to be cyperted that a mans adaptive reaction pattern will exhibit a variety of alteration depending upon his own constitution previous conditioning and the circum tances he encounters Con equently it at understandable that he would develop a variety of illnesses It is rea onable to assume that cardio vascular di ea e might be among the di orders arising out of mans inter relation with his environment As he goes through life man might have an adaptive reaction pattern that flected in the function of his cardio va cular system and if continued over a sufficient period of time this pattern might produce disease Thus men de veloping cardiac pathology will not nec e sarily be different from those con tracting other illnesses except po sibly in one or two characteristics of the specific adaptive reaction pattern rele vant to the cardiovascular system Hinkle pointed to the need to find out more about the characteristic both physiological and psychological of per cons with cardiac di order and their reactions to ituations More specifically he proposed trying to identify (1) the nature of the challenge in the situation (2) any peculiarity in the evaluation and (3) the nature of the cardiovascular reaction pattern He pointed out the desirability of taking general hypo the e developed on evidence from the laboratory out into the field Unfortu nately in athero-clerosis and heart di ea e the laboratory evidence on which hypothese may be built is quite limited Possibly the best hypotheses at hand were derived from limited laboratory ob en ations on persons placed in rela tusely acute situations to which they responded In these tudies mea ure ments were made over a rather hort who became ill le YOL 50 NO 10 APH 90 ·CARDIOVASCULAR DISEASES period of time on a limited number of variables One such hypothesis would be in hort term experiments persons may be subjected to situations which are de igned to threaten them As part of their reaction some of them will de elop elevation of blood pressure Some persons perceiving their life tuations a threatening to them alo exhibit an adaptatue reaction which includes an increase m peripheral resistance with elevation of their blood pre sure If thi adaptatrve reaction were carried on over a long penod of time it might ultimately produce hyperten ile cardio va cular di ease How does one identify persons who are prone to this type of reaction? A proportion of the people who react in the way seem to have a ingular mental pattern which makes them easily threat ened by a variety of circumstances They react to this situation with an aggressive feeling which they have dif ficulty in expres ing Mot all of these persons nece-sarily have anything abnormal about their cardiovascular apparatus Many people in the population who have this person ality trait do not have hypertension On the other hand a ignificant number of hyperten ives do not have this trait Nevertheless it is probable that this trait occurs more frequently in hyper ten ile One say to test thi hypothesis would Le to study cardiac morbidity rates in ropulations which differ in their conception of certain threatening curcum tance se whether they see them eles 7 threatened For this it is necesary to turn to the anthropologit It is a rea onable a umption that certain cieties facilitate in their members reads cypre ion of the agres e re pon e elicited by such threat while other so cieties hinder it Some people are in a ituation in which their treatment by ociets bhely to arou e in them a great deal of ho tile resi tance which they cannot expres becau e that would only make the tuation wor e Another hypothesis may be cited When certain people are faced in life with situations that they regard as threatening the biologic re ponse will include a significant rise in the blood cholesterol If this metabolic reaction pattern is u tained over a period of time it is concert able that it facilitates the development of athero clero is In a certain number of people thi type of adaptative reaction is as ociated with mobilization Thi rai es the po ibility that it is the triving member of our society who are particularlu ceptible tho e who get up earlier work harder and longer and keep going all the time To test this thesis again we turn to the anthropologists to identify ocietie in which this pattern seem to be preva lent and other ocieties in which it i not From studies over a number of years of the personality character tic of hyperten ire patient Ackerman ha developed a hypothesis In evaluating the character structure of these patient he ha placed pecial empha is on their defen e behavior and role adaptation They exhibit he has noted a pyra miding series of specific hoch reaction in the per onality representing the re pon es to experiences conveying real or symbolic threat In these reaction the proces es for control of emotion are acutely oscrwhelmed and the adaptive functions of the personality tolerzo im. pairment or breakdown Specifically the defen e mechanim of repre ion proses ina lequate auxiliary defene hich are then mobilized al o are in uf ficient With this parals is of the adaptive processe tate of temporary emotional disorganization induced There 1 a loss of balance in the inte gratise functions of the peronality at all lesel Thus inadequacy 1 reflected in a OCTOBER, 1960 ·He 1 2 UIT IS 0 the failure to maintain a character fic ocial role which is significant in the prevervation of ecurity in interpersonal relations It is assumed that the poten Lality for this particular form of shock reaction depends on the specific pattem of emotional predispo iton conditioned by the vici itudes of experiences during the formative tages of personality Thus there is believed to be a basic factor of vulnerability in the personality which long antedates the emergence of overt symptoms of hyperten ion The generalızed impairment of adap tive capacities in this shock reaction is tran itory The lo s of emotional control while profound 1 brief equilibrium is quickly re tored After a series of such critical episodes precipitated by trau matic life experiences which symbol ically pell a danger the pre ence of hypertension is often revealed Its on et is associated with a pyramiding series of pecific hock reactions in the per onality in the later tage fixation of the di tortions of adaptive function of the per onality is involving in crea ing rigidity of the psychophysical mechanı m of the personality The com ponent of conflict which is primarily re lated to the hypertensive reaction is that luch occurs between the person and the enuronment rather than the per ons conflict with self In um it is believed that a exis vulnerability in per onality plus the reactions to trau matic life experience produce the con dition in which blood pressure elevated at fort reversibly later perma nently From hus study of hyperten ive per Ackerman has gained impresions of their per onality Their behavior ug ge! that they would like to act out and to behave like roychopaths but do not dare Acting out ignifies a situation in which a per on is experiencing a con flict which cau e him dietres and which he cannot cope with in a rational and appropriate way Thus his manner of re olving this conflict is likely to get him into trouble because his action does not fit the social situation From that action unpleasant consequences may en sue but for the moment the individual has ucceeded in relieving the excesive tension and has established an equili brium for his internal life ſhe behavior of a psychopathic per sonality illu trates acting out highly egocentric person who is antı ocial gets into trouble with his rounding ocial group againt everything lud down by prescribed cial behavior defies tradition and gets into trouble with the law The psycho path acts as if he were more powerful th in the forces of his environment He acts en ele sly as if he had some magi cal power to make him-elf tronger than anyone else in his sorial group In characterizing the personality of the hypertensive patient as a would be psychopath Ackerman stated that such a per on is motivated in phantasy by a desire to live like a psychopath But he doe not dare The fear of retalation is overwhelming So he does not have the ability to master the environment with hostile aggressive power On the other hand he is not able to accept ind execute a role of submission to and de pendence on the environment Obviou ly the two roles are incongruous and irre concılable That is his dilemma Hence he acts in It is no surprise to ob erse reactions in the inner organ y tem Then tension cannot be relea ed in the soluntary muscles it may flow over into the sympathetic and parasym pathetic systems It however an in appropriate failing type of mobilization of defen e against tension Ackerman has explained the psycho logical proce es underlying this be havior One prominent manifestation in a hypertensive person is the overten e conflict experienced in the effort to con trol aggre ute impul es and the ten een . 15 son VOL $0 NO 10 AJPH 92 ·CARDIOYASCULAR DISEASES dency to suppress the translation of such impul es into action Suppression occurs because the usual defenses are un uta ble and defective Attempts to cope with impul es through represyon are un uc cessful and auxiliary defen es also are inadequate It is not clear that thi pattern of defective repre, ioni pecific for hypertension it may prove to be a common pattern in a variety of psycho o matic disorders Con cious suppression of emotion represents the final defense again t the threat of loss of control If the La ic impulses were to break through the control mechani ms and be dis charged into action it likely that the resulting behavor would be either psy chopathic or psychotic When pycho o matic phenomena appeir instead it is believed that they represent a substitute for a break through of emotional control with direct translation of impul e into action The component of conflict which is critical in the hypertensive phenome non and possibly in other psychosomatic disorders as well 1 that which takes plare largely at the level of translation of conscious or precon riou emotional experience into action ie the level at which the patient struggles with ome degree of consciou nes to act against the presumed dangers of the environ ment The patients reaction reflects a strenuous effort to control or even ac tively reshape the environment whether at the level of reality or at the level of omnipotent mastery The implied urge is to mobilize magic power in order to coerce significant persons mo a pro tective and upportive role It therefore seems that the externalized rather than the internalized component of conflict is pecific and crucial for hyperten uses In the proces of adaptation ocial role may repre ent either a po tre er role pre ion of indusiduality that i and per onality may coincide or a nega tive function of defense In the latter case the effort to execute a particular social role may exact an exces ive price in the terms of conflict and anxiety within the indusidual Or the inner con flict may be such as to damage or ac tually present the execution of a given ocial role The relative success or failure of adap tation in the context of a given role is artly the re ult of coincidence or con flict between a particular character dis position and a particular group environ ment with its status and role For the e rea ons the relations be tween personality and environment have much significance in the development of hyperten ion It would appear that the link between emotional reactivity and the hyperten re response ie psy chological pecificity is to be sought, not in the content of conflicting drue nor in the total per onality configura tion but rather in the pecific pattern of defect of the mechanı m of control of emotion in a situation of undue tres between the person and the environment All that has been sail sugge ts a focus of interest on the structure of the ocial environment and on the ego regulatory mechanisms of personality in hyperten e pecially the precie defents which they employ against impul e di charge and anxiety Accordingly any Pychological specificity is to be ought in tho e mechani ms of the hypertensive per on which integrate emotion and con trol tran lation of impul e into action in the performance of a ocial role in hort the emphasis 15 on role adaptation and defense behavior It thus becowes Decesary to uces (1) the particular ego infegration patterns and defenr employed in a given tole (2) the degree of adaptive eflicacy or failure (3) the manner in which such defen es are periodically overwhelmed (1) what forms of com pen atory defen e are erected in the pha e of recuperation following a tem porary break through of emotional con trol 11e tain OCTOBER 1960 ·To obtain this information in testing the validity of the hypothesis the u ual Pychoanalytic approach is inadequate It does not proude a sufficiently accu rate cro section appreciation of total character in particular tho e patterns of character integration that in a given time and given environment are pro jected into a gren ocial role Actually psichoanaly is not oriented toward examining the social self hather it has tended to emphasize a denuding by the patient of the social layers of his identity in order to gain access to the unconscious and biologically con ditioned drives Thus it keeps in abey ance the very ego integration that would be a principal object of study in hyper tensive per ons Ackerman has devised a guide for the evaluation of total personality function in the context of the pre-ent time and the pre ent liſe ituation It tresses pat tern of ego integration onented to the maintenance of a given social role or role in a given environment He empha size that the personality should not be disas ocated from the environment Rather the two hould be treated as a functional entity The picture of the pi tients per onality hould be unified and dynamic and his functional relation with his environment hould be pre served Ackerman hogests that this mode of analy is might profitably be ap plied to a larger group of hyperten ves Profes or Carney Landis offered still another approach to determining the characteristics of person who develop cardiar disea e He pointed out that mot cientific discoveries have resulted omeones a king the rght ques tion For effective results from direct interrogation a et of relevant que lions mille de igned for the occasion If he were to undertake such a type of tudy on cardiac disea e he would first obtain from a number of cardiologi t what they thought were the relevant questions Then he would design the internet The biggest obstacle to such an in quiry by direct questioning is the scarci ty of swtable interviewers It should be strongly stated that interviewing cannot be turned over to unskilful and un trained persons It takes a long time to find and train competent interviewers In order to di coier the characteris tics of per ons vulnerable to heart disea e Profesor I andis would question two groups (1) per ons with undoubted hypertension and (2) those who had had a coronary attack He would all them pertinent question to find what their life experience psychological prob lems and social relation hips have been To the prote t that many coronary patients could not or would not submit to an interview Proſessor Landıs main tained that any question can be a ked if it is asked in the right way and under the proper circum tances and it will be answered He recommended that the application of any tests should come only after com pletion of the survey by interview never before Only after the relevanre of ques tions in the interview has been con firmed is it possible to prepare tests for the inte ligator mu t apply te ty that are relevant to the intended u e in his opinion there is no available psychologi cal test which has any relevance and therefore any primary value in cardio vascular disea e On these ground he would not apply the Army Alpha Rohr schach or Thematıc Apperception Tets Nevertheless he thinks that after the urvey by interview has indicated the pertinent questions it hould be possible to design texts with the requisite rele sancy for cardiovascular disease Worth noting is Profes or Landis e limate that to properly conduct a study by direct questioning would require from 15 years Genetics At the out et of con ideration of gene tirs in relation to heart di ease two YOL 50 NO 10 AJPH 94 ·CARDIOYASCULAR DISEASES points hould be kept clearly and em phatically in mind In a en e they are the prevent day doctrines of genetics One principle is that what is inherited for the most part is a potentiality not an neuitability Whether this poten tiality develops into an actuality depend primarily upon environmental circum stances Thus genes do not exert an ab olute control but determine potential development in particular environmental situations The second principle which is really a corollary of the first recog nizes that gene and environment are interrelated that an interlocking net work of hereditary and environmental influences determine the outcome Concervably genetics may influence in several different ways the develop ment of coronary di ea e it may act tructurally or functionally at various stage of pathogenesis. This po sibility rares a number of questions for investi gation In general the numerous rela tions and que tions concerning them may be grouped in three major cate gorie The paramount question goes right to the crux of the matter Is there a hereditary predi po ition to coronary di ea e? To answer this question re quires a direct over all approach which does not nece arily cast any li_ht on the mode of relationship But its an wer would provide fundamental information which would have practical application in the prevention of heart di ease A ide from its value per se the an wer might dovetail with knowled,e of pe cific points in the hypothesis of the equence in pathogener Determination of whether there is a vulnerability to cardiac dt ca e for which genetics has at lata hare of the respon ability might complement exi ling partial evi dence on the equence of event pathogen in consequence to that er tent it might place the hypothest and its parts on a more ul tantial footing Out of the group of person with an adaptive reaction leading to frequent illness from a variety of di ea es why do only ome person contract heart di ea e? What is the bası of this selec tiytty? To answer this question it is Important to find out whether certain persons inherit a potentiality for de veloping coronary di ea e Surely it would al o stimulate a number of inves tigations on pecific point for the over all approach available method, such as study of hereditary lines or twins are well known The econd large question concerns the posible di tinctiveness of person who will develop coronary disease and the genetic transmis ion of this quality Can uch individual be characterized in a prototype? Are there recognizably di tinctive characteristics associated with a per on who tend to develop coronary I order? Are the e features tran mis ible? Demon tration of an aociation between a distinctive type of person and bi vulnerability to heart dra e rai es the que tion whether his charactertacy have any hereditary ba is There have been a number of efforts to type jer on who develop or have coronary di ea e for valid typing would be extremely u eful it would proude an inden for identifying potential coro nars victim so that preventive mea ures might be in tituted Furthermore al though typical characterı tics might not explain the pathogenesis of Preart di ea e they might furnih a clue to the ignificant features of the proces JE the characteristics were found to be un der genetic influence the u cfulnes of typing would be enhanced on loth score For present purpo e iti de tralle to know whether well defined ea ily recognizable characterı fics validly nificant and pecific for coronary di-ea c are available for u e in genetic tudies Attempts have been directed at troba pus of de tingu hing person fody type and personality Gertler and White have re OCTOBER 1960 ·structural functional and metabolic Hence genetic methods must be applied in ronjunction with morphological phys nological and biochemical technics Only four changes were considered in detail by the group adaptive re action a lesion at the junction of the intima and media in the coronary ar tery lipoprotein and blood coagula tion ported that coronary di ease occurs more frequently in persons with endomorphic me omorph body build Technics of physical measurements and a number of systems of classification of body type were developed long ago The selertion of significant physical measurements and the validity of the systems of class fication have been the objects of critical comment and difference of opinion Four tudies have been conducted on the per onality type as ociated with per sons having hyperten ion Briefly tated the present attitude is that it is less promising and less profitable to establish per onality type associated with coro nary di order than to investigate the pychological reactions especially role adaptation and defense behavior of per ons who develop hypertension and coronary disease as The third area of investigation by genetics has to do with the various pathological changes in heart disea e sugge ted reputed or demon trated to be under genetic influence They may be arranged in four groups psycholog cal physiological biochemical and his tological At one time or another enght different changes have been specula tively a ociated with genetic influence It is to be borne in mind that for the mot part the relation of these changes to genetics is at present a postulation These changes are shown in the follow Thy ome persons react to tre , with illnes but why only certain of the e de velop cardiova culır disea es are ques tions u ually explained by attributing this selectivity in part at least to genetic influences These que tion male perti nent the inve tigation of the ro ble relation hip of two separate phenomena to genetics One of the e phenomenanamely genetic influence in the selection of the heart a the vulnerable point-has already been di cus ed Now the non pecific adaptive reaction comes under con ideration Here the ob jective is to ascertain whether the adap tive reaction and its apparent re ponsi bility for vulnerability to illnews indicated by the frequency with which it is a. ociated with illness in particular individual as determined at leat in part by genetic processes For present purpo es vulnerability to allness is of intere t only in so far as it indicates the type of adaptive reaction that is responsible It i assumed that this re action could lead to cardiovascular disea es or any of a number of others depending on different factor As uch it may be regarded presumptively as one stage in the pathogenesis of cardiovas cular disease If this type of adaptive re action is conducive nonspecifically to heart di ea e it is important to ascertain whether this reaction has a genetic bais whether certain persons inhert a potentiality for developing it But to es tabl: h a gent tic relation to any charac teristic one mut have a reliable means of identifying that distinctive feature At pre ent there is no quick and sure ing tabulation L poprotein P-ycbolo ica] Bioch mical Role adaptation and Hypercholesteremia d fen e behavior Blood coagulat on Phy 101 scal Hi tolol al Vascular hyperactivity Tran jent hyper Arterial wall width ten on and Defect at unction of tachy arda intime and med a 1€ From examination of this tabulation it is obvious that geneties may be related to three level of cardiac disease ac cording to the nature of the pathology YOL 50 NO 10 AJPH 96 ·CARDIOVASCULAR DISEASES an primary factor means of accomplishing this identifica tion Hence application of a genetic approach awaits perfection of identifying method Next to be con idered were the proc e es relevant to the development of athero clero 13 and thrombosis and conceivably affected by genetic influ ence In de cribing the formation of the athero clerotic plaque Dr Wilkinson pointed out that two theories have teen proro ed to explain the origin of the early depo it One postulation is that there are always circulating in the blood tiny thrombe which may attach them elve to the vessel wall one does attach ut elf and starts to organize during the pro es of organization fatty infiltration and calcification occur The econd po tulation about the process of athero gen is alled the infiltration theory has wiler acceptance on the continent Ac cording to thi theory there is a con tant flow of fatty particles from the inside to the out ide of the ve sel But for some Tea on atherogenesis infiltration Iuild up at the junction of the intima and media of the coronary artery and lipid material collects to constitute a formation in compo ition the material at fir t rlosely resembles the circulating lipids of the hlood ie the lipoproteins As the lipid infiltration ages its compo itron changes relatively more cholen terol and less of the other lipid are pre ent If this infiltration progres es it becomes 1 yellow or lipid plaque As thi lipid plaque age rarring and calcifi ation may occur until very little lipid materials leht The resulting pearly plaque i compo ed of fil rous ti sue and calcium Athero clero 1 is widely prevalen! mo t adult are found to exhubut it in the two exes there is prolably no dif ference in the total amount Iut there a difference in da tribution in the male the coronary artery} more frequently inyolsed in the female at i eldom affected until after the menopau e It 15 po tulated that atherogenesis in the coro nary artery is as orated with an in herent defect at the junction of the intima and media and that this defect 19 an inherited charactenstic Despite the widespread prevalence of atherosclerosis it is only when a com plication such as the formation of a thrombu on the eroded surface of the plaque sets in that clinical di ea e may be aid to have occurred For this rea on the amount of athero clero i is not 50 important a the chance di tribution of it Various factors influence atheromene $18 The rate and manner of formation of the plaque us affected by priraary and econdary factors Age and sex are With age there as a tendency toward increa ed athero.enc SI Quite apart from the effect due to hormonal differences are the anat mucal effects of ex on atherogene is At birth differences may be di tingui hed be tween male and female roronary arter ie both in thickness and in anatomical configuration in the heart The e pri mary factors favoring the female would probably account for from 2 to 3 per cent of the difference in death rate for coronary di ea e between males and fe males if there were no rcondary factor Among the econdary factors affecting athero enesis may le mentioned hyper ten jon dial ele renal di ea hypothy roidi m hyperlipemia an i hypercholen tu remia Hyperten on prol ably the mot important factor in the lit Of the remaining factor hyperlipemia is of pecial sole case of a relation to the clinical di orders in eficct those metal olic di ei es that increa e the rate of athero_ene 1 remove the female ex prolection For example female dia Ieties at an age are jut a likely a nondial etic males to have athero clero The one common denominator in the metal olic condition that remove the female e protection ra mon lary h rấn mua in 1 OCTOBER 1960 ·It may Genetically determined hyperlipemia appears to be indistingui hable from Secondary hyperlipemia With the hope of comparing within family groups the effect of hyperlipemia nine genetic types have been po tulated in setting up genetic studies it is important to find the carrier tate Hyperlipemia is noticeable in the homozygou al o be observalsle in the heterozygous individual by the time he is 30 Dr Wilkinson emphasized that if every per on between the age of 25 and 35 merely had his blood inspected and his diet adju led if he were found to have hyperlipemia from 3 to 10 per cent of potentially fatal coronary di eases could he prevented When all the posible econdary factors in the development of the athero clerotic heart are studied it may he that one of them will be found to be jut as important as hyperlipemia or even more so Medical genetics is in the midt of an extraordinarily active and fertile period largely the outcome of investi gations into the biochemical back grounds of disease Accordingly Dr Block pre ented the biochemical ap proach to menetics with pecial con sideration of lipoprotein patterns and heart di ease Before indicating promis ing lines of investigation he reviewed the brochemi try transport and inter mediary metabolism of lipoprotein Total lipid in the blood compre neutral fat chole terol chole terol e ter and pho pholipid in the blood tream the e lipids are carried in combination with protein The e lipoprotein make up from 12 to 15 per cent of the total protein in normal human plasma Se rum protein itself i compo ed of two heterogeneous groups of proteins--al humins and globulins--but it may be further fractionated Electrophoretic an alysis of erum protein yields a dtagram containing five to ten protein bounda ries depending on the type of fractiona tron Each boundary is indicative of a eparate group of proteins The first boundary represents albumin the re maining boundaries globulins In order the latter are designated alpha 1 alpha 2 beta and gamma Ahout 75 per cent of the serum lipids are carried in combi nation with the protein in the beta glob uhin fraction Only a small proportion of lipid is carried with the alpha protein fraction How lipid and protein are combined and how tightly they are bound are not exactly known It has been sug gested although not proved that there ? 1 core of protein with actre groups of amino acids on its urface This core holds these molecules together through attractive forces between non polar peptide residues such as leucine and phenylalanine and the fatty acid of the lipid moiety "I hat happens to lipoprotein in the blood stream in the utilization of lipids? It has been postulated that there is a normal level of lipoprotein in the blood That level is exceeded when lipoprotein is unable to take up more neutral fat that point is the high level of lipopro tein {at combination Then from tis ue an enzy me or clearing factor lipoprotein lipa e is released When it comes into contact with the lipoprotein it plits off the neutral fat fraction mn glycerol and fatty acid thereby regenerating the protein to be available to pick up more lipids In the hiochemical approach to the study of genetic influence in any disea e it is nece sary to select a specific charar i fic to be inve tigated In the pre ent instance it may be a lipid con tituent of the blood uch as neutral fat Whatever its validity and significante is usually e tablished through its occur rence in patients with clinical signs of a particular di ease Alo blocks and aberrations may occur in everal ways and in various stages in the metabolism of a sub tance For one thing the meta holic block may be found to be a so its VOL 50 NO O AJPH 98 ·CARDIOVASCULAR DISEASES an I olalıd t ог or 01CI ciated with an enzymatic aberration Whatever the detectable abnormality the pecific characteristic is traced genet cally Somehmes the tracing is best undertaken genetically groups Bloch pointed out that a metabolic abnormality may Le found in either of two stages biochemically manifest or latent In some per ons it may ta readily detected by an appropriate ho chemical method in others it is 111 o called carrier state which may be revealed only after special measure For full and complete application of genetic principles detection of the carrier susceptibility tate is highly important Perhaps one way to reveal this state is lo impo e an appropriate stre load upon the subject Two examples illustrate the point when a family is being studied for occurrence of phenyl ketonuria the abnormality will be found regularly in the urine of some members but will not be detected in others However Jervt has indicated that the adminitration of shenylalanine to patients with this di order may lead to an abnormal phenylalanine tolerance cune Another means of detecting enrly evidence of di eases which develop late in life is a technic devi ed by Conn and Fajans which utilizes stres for the recognition of su ceptibility to diabetes In both examples the u repti Bality which would otherwie go un noted is detected by a form of fres Empha ized was the posible u efulne s of detection of the carrier tate in tudies of hcart disease Practically de tection of the carrier tate open the po ibility of delaying or preventing the mnfet den e Block propo ed three tudies in a bro chrmical genetic approach to heart du ea e In one the objective would be to mea irre the clearing ahılıtı of the era of per ons with lyperlipemia Normally the en7 me lipoprotein lipa e cannot le detected in the blood but if heparin i injected into the subject h blood hon within five minutes a rapid in trea e in its ability to clear neutral fat ne turbidity and hyperlipemia dis appear from these and other observa tions it ha been concluded that hepa un produces a profound alteration in the lipoprotein pattern If this lipemia cleanin, test were applied to patients with hyperlipemia it might be po sible detect whether they have a normal re pon e to heparin with liberation of the ti sue enzyme which in trumental in the utilization of neutral fat or whether they have a di turbanre in the relea e of the clearing enzyme A a cerond study Bloch sugge ted that the level of lipoprotein fractions in the I lood of per on in family groups hould be determined and the results genetically analyzed There i some eva dence to indicate that a carrier state may exist in hyperlipemic persons which as detected in the alpha lipoprotein frac tron From tudies on a large family through eseral generations Adlersberg hi reported an aberration in the alpha lipoprotein Third Block recommended that de tection of the carrier tate by Llochem cal method be applied to genetically isolated group It is here that the pro cedure has its greatest effectivenes. As an example he described it application in the tudy of primary temic amyloi dosi in a genetic i olate Upon ultra centrifugal analy is of erum lipoprotein from 66 cul jects 29 hou ed an ah normal pattern on the alpha 2 globulin region which corre-ponded approxı mately to the postion of an atypical ſeak in electrophoretic diagrams AL thuch biochemical anal i of lipopro tein from andisidual with clintcal igns 11 important of only to e tal li h the Climcal significance of the re ult 1L Ereatet u eluinee wa an dere line the ul clinical the so-called carrier tate For the e rea on I look recommended tudies of the relint : tochemical char OCTOBER 1960 ·"1 nº 1 ILAT111 LACTOR 11 ROMBOL TASTINOY (OVI111 I ROTHROMBIVO(1) 11 IHROVONI AS'I + ACCISSORI + ( + 'ROTHROMBI 11CTORS movemento TISSU "I HROMBONASIIT (ATH!!".. ICTION .. TIROVI + 1 IBRI\00 1111 IRI 1 IBRI II(TITUTO BIVOT IBU ISO 11101 Figure 1--Schema of Blood Coagulation acteristics of heart discase in genetically 1 olated groups One of the most significant des elop ments in the pathogenesis of coronary disease is the formation of a thrombus which may lead to occluion This pos i bility--an actuality all too frequently rai es everal questions whether the blood of some persons is in a hyperco agulable tate whether that state is mea urable whether it is attributable to an abnormality in the blood and whether it has a genetic association In approaching the subject Dr Quick pre sented such evidence dy is available Then as an aid to understanding both his explanation of his observations and the rationale of his sub pquent opinions he reviewed hemo tasis the process of blood coagulation and the probable events in the formation of a thrombus In an attempt to determine whether a thromboplastic tendency could be demon trated Quick conducted a bat tery of te ts on the patient with throm bophlebitis The e tests revealed no real abnormalities that would indicate a thromboplastic tendency Unfortunately mot available tests were not designed to detert coagulability but the opposite hemorrhagic tendenry For example in hemophilia the clotting abnormality can be attributed to the lack of a specific factor thromboplastınogen (Factor VIII antıkemophilic globulin) But available methods useful in the tudy of bleeding tendency do not provide such reliable and complete information on hypercoag ulability Because of their limitations when applied to coa, ulability the results yielded by these methods are open to question In Quich s opinion hypercoag ulability is measurable neither by the clottin, time nor by any other test rou tinely u ed in the laboratory In view of the technical limitations Quick turned to a different approach In raising and answering for himself the question what is hypercoagulability he reasoned that essentially it mut in volve a greater amount or an increased rate of formation or reaction of throm YOL 50 NO 10 AJPH 100 ·CARDIOVASCULAR DISEASES bin for after all it is thrombin that converts fibrinogen into fibrin in the formation of a clot Avoiding the more difficult and uncertain course of search ing for ways to rai e the thrombin lesel by influencing factors that control its formation he went directly to the er perimental production of a clot by in jection of thrombin When thrombın in high concentration was injected rapidly intrava cular clotting throughout the vascular system encued But such large amounts of thrombin were necessary that obsously the experimental pro cedure was not comparable to the natu ral occurrence of any hypercoagulable tate Then too the clotting o far ex ceeded the extent which might be presumed to occur from a natural hyper coagulable tate that it did not repre ent an analog I ut when thrombin was injected at a low constant rate re ults oppo ate from what might be expected were ob tained Instead of the clotting time being hortened it was prolonged One of the reasons for this spemingly paradoxical reaction that thrombopla tino en drops to a very low concentration The level of Factor V is al o reduced What 1 actually produced a hypocoagu! alle state which acts as a natural pro tector mechan m preventing the build ing up of a hypercoagulable state IS F gure 2 HEMOSTASIS C o Injury 4 2 Reflex contraction & retraction a Nar owing of the lumen b Decrease of blood flow 용 상 e ce 3 Gluing effect of injured endothelium 4 Platelet thrombus formation (clou hemostatique) Liberation of a diffusible vaso constmctor principle from platelets 5 Fibrin clot Continued liberation of vasoconstrictor principle OCTOBER 1960 ·Direction of blood flow Injund area ce le Serum New clot It hould le emphasized that it is thrombin which is the all important sub tance in coagulation There are tho ways in which it is formed (Figure 1) In one it is produced in the blood per blood completely 1 olated from tis ue This process requires a complex reaction a platelet factor and a pla ma factor the thromboplastınogen complex form thromboplastin this then reacts with prothrombin accesory factor and calcium to produce thrombın In a test tube it takes at least from five to eicht minutes for that reaction to occur The slownese of the reaction rate makes it mot unlikely that the body develops a hypercoagulable state by thi route Quite different is the formation of thrombin from another ource tis ue thromlopla tin and by another route Ti ue thrombopla tin does not have to be manufactured during the clotting reaction It is widely di tributed in the tis ue When it comes into contact with other factors in the clotting sys tem there 15 rapid clotting in 12 econd It is ti ue thrombopla lin that could be the ource of hypercoas ulability The first tep in arrest of bleeding hemo ta is 14 vascular con friction (Figure 2) It is a factor in intra vascular formation of a thrombus But the thrombus doe not form in the blood stream in tead it has its rigin at the site of an injury to the vascular wall (Figure 3) This clot get its tart from tissue thrombopla in which leaks out the thrombus form rapidly be cau e of the quick action of true thromboplu tin Then the thrombus can organize especially if the blood tream or the clot may attract platelet undergo contraction and extrude erum The crum contributes to further thirom boss with a new clot I rovided it is not swept away by the circulation it 13 sliperimpo ed on the original throm bu a result there may le ucces ile growth of new thrombi Figure 3--Probable Events in the Forma 110 1 of 11 e Thrombo ie It is important to reiterate that the clot which is a sumed to play an im portant role in heart disea e does not originate from the blood it clf but from the vessel wall It is then coordi nated with the clotting factor Con sequently in Quicks opinion Jattle knowledge concerning thrombo 1e to le gained by study of the blood for coagulation changes. Certainly the re ported re ult from studies on the in Auence of lipid on clotting are open to quention Since the clot ori inates in the lensel wall it] there that the search hould be directeel in studying coronary thrombo 1 Heredity plays 7 more important role in hemorragic dt ca e than any other group of di orders Perhaps it may al o evert an unfitence over throm But the chance are rather re is fat А bol * JOZ YOL 50 NO 10 A ·CARDIOVASCULAR DISEASES 101 en mote of findin, Ilood changes indica inle of a hype icoagulable state that may be relevant to coronary thrombosi and po shly attractie for genetic analy 1 Focu ting on the level wall eemt more promise Dr Jannik drued the ps ble re Jarion Imp of genche influeme to heart di ea e at various tages in the Ru pothr szed eguence of it production Conceivably there may be genetur la tion line with both the eneral and specific a pects of the proce From the studies of oft and Herzkle st ha been concluded that hen per un have illne-s a ociated with an adaptive reacron ta et durinn: Huation They may develop any of a vanets of di ea e including cardsos i cular di ea e une they may be regarded a Teing u ceptible to many kind of d, Thene person may have a gen erakzed constitutional weakne From this conclu son it may be further in ferred that all art capable of developing athero clero is provided that they lue long enough and are expo ed to appro prate environmental influence In re labon luip to general con tatutional wenk Dr Jarvik likened atherosclero is to tul erculo x Bith uficient exposure everyone can contrart tut erculos Set there appears to be a genetically deter Inined variation in te istance to this ome people uccumłoby more ray than other The ame relation ship mi.ht hold for heart de ea e On the other hand geneties may be more precifically related to the produc tion of heart i es e do deselop afhero clero is Many people dhe & 90 or 90 wsth no evidence of it Onls anine perons luase the capacity Allproceso can le tles eloped only Is tho e lo have the potentiality pre umably on As in chizophrenia on heart d, only tho e who hare the proper parte con tractat That both the conditutional ani the ific procee base a genetic rela pon upis po ihk indeed probable (once zably all person may have a Kennality for deseloping certain types tardiovaxcular dene whereas only the per ons with a specific combina tin of vents sucum 10 other types Perhap the psychological reacton pal Um of certain prople la ed on a partu ular combination of genes which may be a ousated with a tipe of phy 10 local actrusty that produce hyperten It would be important to deter mine the points because at present there is no gentile esidence for the stre genetic influence may be relatet in two way 0 ) Cenene efforts may be largely respon able for the tua non creating trees (2) genetic influ enre may affect the indusidual lity and reaction to tres Situation creating tres ma) exit 161 certain {amhrs because genetic factors have contributed to the production of other In families with mentally de fertue members or chuszophrenics the group is expo ed to a greater degree of stress than 18 uual It would be informatise to determine the incidence of heart di ea e in familie pxperiencing this adchlonal stre A tuds NOW being conducted to find out whether die trece created by uch a diablin condition ay deaine s wluch im part gu nelically determined increases the in cidence of chizophrenia in the family In the search to a certain whether the vanou pasiiologscal changes to heart dsscar have a gnetic relation bapth asordance of one particular pullar? hould ir emt ha szed An di atler that is genetically determined had it counterpart on an environmental lase The entironmentally produced di or ler which is called a plienocopy mints the genetically determine form clo els that the manfestations of the two tje are in l, tingin halle Vethodology-on onler 10 » ATT question conceming the bearing of di ea es de ea e Tof all persons a genetic ba 1 OCTOBER, 1960 ·nics genetic influences on heart disease both twin and family studies are needed One of the mot important objectives hould be to ascertain whether genetics exerts an influence on cardiovascular di ea e and if so whether it would be po able to identify individuals who are particularly vulnerable to the disorder Then it would be u eful to apply studies of twins in a somewhat different way than is usually done Once vulnerable individuals can be identified it would he profitable to search in the environ ment for significant vanables that affect them and bring them down with cardio va cular disea e Becau e it would be rea onably certain that such a group has the potentiality of developing the di ease it would be the only group in which the influences of environmental factors could be so readily studied Originally twin studies were de signed to reveal the importance of genetic factors by comparing the rates of preva lence of a di ease in twins and iblings Jut as valuable if not more so would he twin studies in conjunction with experimental exploration of environ mental factors When u ed in conjunc tion with the application of therapeutic method twin tudiey could be very u eful in investigating physiological and biochemical variables In exploring the environment for rele vant and significant variables it 15 helpful to follow clues By the same token it is more important to ask the right question than to test a random erie of correlations Studies alreads under way have indicated a greater corre pondence of levels of blood con tituent letween identical twins than between siblings On the ba is of the e ob ervations it is uogested that when the individuals who are most vulnerable to cardiovascular di ease have been identified at be 1 certained hether levels of blood pres ure and lipoprotein in the blood are at lea t in part genel calls determined A genetic evaluation should be a part of any epidemiological tudy A number of simple test factors exit that enable the iniestigators to detect gross genetic differences within the group or groups being studied The application of genetic technics to cardiova cular di case may be druided into three broad areas 1 Gathering of Information - Cum plete famıly hi tors (including infant deaths) an objective descripłon of the subjects physical characteristics identi fication of the subjects with their hrown relatives pre ence or absence of con anguinity hi tory of exposure to radia tion In countries where reg trien exit these hould be utilized 2 Mass Screening Laboratory Tech Electrophoretic anals is blood typing pecific antigen antibody reac tions chromotography urnarv amino acid excretion patterns (urinary tests for alcoptonuria ci tinuria galacto una and pentosuria) enzyme determinations cytological and ser determinanon Par ticularly u eful in term of mass surveys would be the application of carefully designed overload tests to detect the latent state or the carrier state of cer tain metabolic abnormalitie s Studies of special group genetici olates and twin famıly agte gate Lilienfeld has recently publi hed re Sults on 1 methodological problem in the tudy of familial agregation of In particular he inve tigated the application of a binomial test determine the consi tency of ob erva tions with a reces ive gene hypothesi His re ult indicated that this method hid a low ability to discriminate be tween genetic and non,enetic hypo theses In accord with the publi hed opinions of everal geneticist he drew attention to the difficulties and pitfall in determinin, whether a disea i herited uch as disea e to in 104 YOL 50 NO 10 AJPH ·EPIDEMIOLOGIC METHODS IN CURRENT CARDIOVASCULAR DISEASE RESEARCH Rol h S Paffenbarker Ir ID FAPILLO Ehrue er UT 2 cez DW ERING the six month penul inding in Varch 1939 we have fun loppor tunits to review 1 enes of epidemiole v tudies of cardiovascular di La rently under way a to thu natin Tuents one of these fudiex deal with ome a pert of hyppien son os arterio sclerotic heart di ea e and thus their tuds method may le of intere to the mornhers of the Lenſerence over all view of thesr tudo method 1 ghen as well. Inel de criptions of each of the 21 tudies Al traris of eicht whirh perhazm have been les widely s cu ced than the well known endeavors at Framinghans Alluny etr exemplify the range nf method ploved and are incorporated in the body of the resort Al tracts of the main ing 13 are mcluded as an ardendum נגן * mental factor and the freçu ncy of di eu e are cach determined Popula ting thing udred are drunded into tho e with and those without diseae und in taleh group the proportion with common per onal aiinbutes tuined Al o the proportions of dreaweł and of nond erved pupulations that en gage in a common practice enrounter imilar maden or are exposed to similar potential nks are mea ured lui In the experimental approach fu man volunteers are inducrd to chance their habits of erronmental factors are altere and th effect of these changes on di ea is measured Regardles of she approarh used the purpo-e to determasne wither indi widuals characterized in one was uch ay by a phy cological or socioenwron mental factor are differentiated in a econd w21 & ht & di pa e For ex ample one mehr determine whether a difference in the frequency of coro nary heart 0141 CUID) axity or ti een a group with premature pres byopia and aroller group without it The e ence of the approach i company son and it i encouraging that invali gators are greatly concerned with tandardırıng theit of crations and accurately cla ifying pers 3n by the pre nice or al ence of two yanables the factor in que fion and vir die notier to make and comparson po ille The cientific requirement of a es in the 0100nvironmental part ał le independent of the clinico-labora tors variul le leing met For the most Tit attention ; flent to other influencing vanalle throueh splection Study Methods The application of epidemiologic methods to the tady of an rionclerotic heart di ease (ASHD) and hyperten Bisc heart d spa e (JUD. is taking three approaches decriptase analytical and experimental (1) In the de criptive approach ob ervation on recognized ds ra e are made in tertos of clirono look and yeographic distributions and the character tics of patient Ier-onal altert ute of patient are contra ted with similar alimbutes determined from cen Su$ figure of some other available source for residents in the patients com munsts (2) In the analytical approach Independent sanalles are utentified and Telated to the occurrence of ch case Thr frequ ney of pecific host or environ OCTOBER, 1940 ·of study subjects or through adjustment by accepted statı tical technics Un certainties in diagnosis of disease lead to ue of probable or borderline clasifications and mo t Rocioenviron mental factors are measured on a gradi ent scale Thus comparison of the dış ease variable and the sociocnvironmental variable u ually is not limited to a two by two correlation The tarch for association between either ASHD or HHD and any of a number of host or environmental fic tors u es one of three methods First contemporary tudies of disea ed and do ease free persons are providing nap hots or prevalence figures of the specific factors under study Sec ond studies that are longitudinal in time are picturing flu hbacks to an earler period by measuring (through interview past medical record and sular data) the proportions in the dis ea e group and in the disease free group that have experienced the ame specific factor La t longitudinal studies are fol lowin., individuals through a period of time in motion picture fa hion and hy mean of appropriate clinico labora tory te ts are making initial and un cessive determinations of the frequencies and magnitudts of the diseases and the factors Populations being studied include (a) ho ptal or clinic patients (b) clo ed populations in in titutions and (c) groups of persons in communities at large The e populations or linarily are chosen to meet a specific require ment of the study design The abstracts of study methods re viewed here are necesarily brief Re ponsibility for omissions inconsisten cies or inaccuracies in the e abstracts is ours and not that of the inve ligators who upplied the infortnation Current Studies 1 Navajo on Reversation—The firt tudi to te de-crit ed is being conducted out of the Western Navajo Hospital in Tubı City Arz The frequencies and distnbution of cardiova>cular di ea es (CID) particularly coronary heart di ease (CHD) among the Navajo art being ob erved Specific aims are to determine (a) the prevalence and inci dence of CHD (b) the erum lipid patterns of adult Navajo males (c) the make up of the Navajo dietary and (d) the geographic and demo graphic characterı tics of Navajo ub groups on the reservation Thent en deavors were prompted by prevailing clinical impresions and publi hed reports to the effect that the Navajo experience le CHD than the white or Negro races The design of methods includes the examination of 150 adult Navajo males who were con idered healthy and without clinical or labora tory evidence of diabetes renal disea c or thyroid disea e Clarico laboratory examinations of snap hot type are being performed and for comparative pur poses amilar measurements are being made on a selected eries of healthy white males seeking routine medical checkupy in a medical clinic in Albu querque In addition the heart and aortas of Mix njo and clinic patients coming to necropsy are being examined for atherosclero 1c (Approximately 50 per cent of the Indians who die in the Fort Defiance Navajo Medical Con ter or in the Western Navajo Hopital come to necrop y) 2 An example of the motion picture method applied to an open population is the study in Lvan County Ga The study ha been activated in search of precursive factors of athero clero and its sequelae The total county census by age yer race addres and place of birth) has been determined from vital records list of utility subscribers new paper solicitations and house to house canvasses The census is being kept current by periodic recheck using these same counting devices Morbidity 106 VOL 50 NO 10 AJPH ·CARDIOVASCULAR DISEASES a The race and mortality data are obstained through amination All overt attacks of CHD phy ician vital record and ho pital and deaths from this caue will be data The county with a population of recorded as they are recognized Bien 7500 and a two to one white to legro nually the health tatu of each partici di tribution is largely rural andi erved rant will be reukwed through telephone by two practicing physicians One of or personal contact Through record of the phy ician is the pon or an priner uch repetituse oh ervations and labora pal nie rogator in this tud; and the tory deteminations it is erpected that other cooperates clo ely Vasked rap ome of the precur ors of CHI) may port exit among the phy ician and rome to light their patient who comprie entially The influence of ex race and treas the total county population le rog le factors (physical and psychological) on are requeste on the death of each serum lipid level of children from county re ident and are performed by birth through preschool ages is being con ulting pathologist on approxi determined Umbilical cord Flood am mately 50 per cent of dece dents ples are being collected at mot deliv Pelative rates of CHD by race and eries in the county and repeat blood ex groups are bein, determined longi amples are drawn at ix month in tudinally from (a) phy ician ho pital terval These specimens are being autopsy and vital record and (b) te-ted for levels of cholesterol alpha successive censu es of Evan County and Feta lipoproteins, and the lipid Thi phase of tudy will continue mobılırıng factor ex and through calendar year 1960 birth weight of euch infant are re Blood specimens for erum lipid de corded together with weight and illness terminations are being drawn from 1p hi tories at each ix month inter al proximately 1 200 adult li ted on the Studies of chool aged cohorts are Fan County cen us regi lry Subjects patterned after the newtom tudien are cho en throu.hu e of a stratified with effort being made to eolit all samplin, technic Laboratory testing school children in the county More of specimen permits comparlon of than 95 per cent have recered parental Lipid level by age ra e sex and spa approval to participate and are being son of the year in which the emples entered in the tudy as rapidly a labor were collected atory facilities permit Repeat blood For one physicians office practice samples are being drawn at annual in all patient aged 30 years and over tervals and pecial interest centers on who rek medical advice or treatment the influence of puberty on eru lipid for any illneas are being followed over level a he year period (mod 1958 through 3 The napshot method . Keing u ed mid 1963) for the orcurrence of CHD at Loun iana State Unserity School To the degree that bu) practi e of Vedicine in tudy of athero clerosi Procedure base teen tandardized for permits the following data are being recorded on each patient at least once taining arterte with Sudan I\ and for annually (al family and pronal his preserving them in flat tran parent tory of heart di esse b) result of a durable pla hic bacs Aka a method of grading human aorta ts which der general shy scal examination and (c) findin from ferent pathologi ts secure imilar result alpha and leta lipoprotein tent Then has been developed and used to estimate patients do not return within 1 year macro copically the extent of fatty they wil le contacted and lipid deter treaks fit rous plaques ani complicat mination repeated a minimum ex ing In Ion (hemorrhage ulceration erum cholesterol and OCTOBER 1960 ·over cau e thrombo is and calcification) Current tudies eek information on pathogenic mechanisms through description of aortas and other arteries from necrop les on individuals aged one year and Specimens are received from general ho pitals and medico legal erv aces in New Orleans Guatem ila Puerto Rico and Colombia Special attempts are made in these geographic areas to necropsy all deaths regardless of All aortas mot coronary arter le and more recently cerebral arteries are graded as to intimal lesions Physi cal studies (photographıc hght refrac tion and colorimetnc) and chemical studies (quantitative and qualitative determinations of lipid) are in progress on a sample of pecimens to (a) develop a grading scheme that does not require per onal judgment and (b) search for age ex and racial differences in patho logic lesions An endocrine project in cluding urine a says is being developed to permit correlation studies with ath erosclerotic lessons As a econd study observations on zoo reared baboons have suggested that this widely prevalent ape which is fir t order below the anthropoid might lend it elf as an ideal experimental ani mal for atherogenic studies African expedition was undertaken in the summer of 1958 to obtain baboons from their native habitat A total of 163 animals was captured and sacrificed for pathologic examination Specimens permitting estimation of chronological age und degree of atherosclerosis were hipped to New Orleans for study (Age e timates are being made from kull teeth and bone pecimens together with measurements of body weight and size ) 4 Out of the Georgia State Health Department a motion picture study of two circumscribed populations is in Since October 1957 senal obversations have been made on resi dents of two mona teries in tudy of dietary regimens as they may relate to arterio clerotic heart disease (ASHD) One monastery quarters members of the Trappi I order whose religiou dictates Tequire a meat free lactovegetarian det The second monastic population com Prises Benedictine monks who are om nivorous and consume a diet e entially comparable to that of citizens at large in the United States Quantitative and qualitatie dietary records are collected on elected fast feast and regular days in order to compute average intakes per monk per day Yearly clinico laboratory examinations and medical records during any period of ho pital: zation permit (valuations of illne ses Including ASHD Blood Tecimens drawn quarterly are subjected to 1 battery of testy for lipid and protein determinations Participation in this ongoing study is voluntary with more than 90 per cent of the Trappi t com munity and a comparable percentage of residence stable Benedictines enrolled Eighty two Trappists ranging in age from 20 to 80 years (median age=35 years) are participating The e monks live rigorou lives in primitive physical ething without modern conseniences Their work is largely of heavy manual types which is inter per ed with seden tary hours for meditation There is es entially no verbal communication among the monks On days elected for determination of diet intake each monk keeps a record of his consumption by noting during meals the amounts and types of food inge ted Uniform ery ings and the u c of tandard puon sizes facilitate accurate reporting Tobacco and alcohol art not u ed these monks Sixty five Benedictine monks of an older age range (median age=10 years) than their Trappa t peers are partici rating They live in modern dormitory type structures engage in relatively less phy ical exercise and are largely a teaching order Their diet permit little frecdom of choice qualıtatnıely but Hence an progress VOL 50 NO TO A JPH 108 ·CARDIOVASCULAR DISEASES contrary to that of the Trappi t allows for more quantitative election A food model demonstration is pre-ented at the monasters to a sit the monk in making quantitative e timates of their Intake A small proportion of members of this order u es tobacco anla ome what larger proportion ves alcohol 5 A combination of snap hot flah back, and progres ne motion picture methods i in ue at Deth El Ho pital Brooklyn NY In progres per the pa t two years this study is de igned to determine whether pecific somato types are as ociated with a coronary diathesis and if so for what rea on Members of a fraternal organization are invited to a cancer and heart di ea.e detection clinic for specific clinico lab oratory te ts that permit classification by body type coronary heart di ea e tatus Socioeconomic stratum and cholester olemnia and estrogenuria levels The base population from which subjects volun teer to participate consi ts of 33 000 residence stable Brooklyn males who carry health insurance Participants are somewhat health con cious adults who largely lead a sedentary lıfe and eat high fat diets Sixty per cent are salesmen and 95 per cent are married They are queried as to dietary and social habits and cla sified into types of body build by the ame examiner A econd examiner evaluate their car diar status through admını tration of a medical history physical examination and electrocardiogram (ECG) tracing Their attack rates of CHD are being as essed through (a) annual reexamina tions and (b) reports on cardiac mor bidity and mortality from their health insurance plan which includes phy 1 cian and hospital coverage One hun dred elected subjects in each of the three basicomatotypes (ectomorph mesomorphs and endomorphs) being examined for estrogen lesel by analysis of 21 hour urine ample As an independent tudy the degree of coronary atherosclero is and the type of body huld are being a essed for all indasiduals dying suddenly and coming to medical examiner s autopsy in the t che ter County NY The collection represents a 10 year experience and compri es largely deaths from automo bile accident 6 Sometimes referred to a a human population laboratory studies in prog ress at the Unıver its of Michigan School of Public Flealth maintain a current inventory of people place and things Over an 18 month period nearly all residents of Tecumseh, Vich and adjacent residential area have been characterized by demographic and other factor The prevalence of 11 chronic di ea e conditions has been de termined for this group through elf administered questionnaire form The total population of approximately 8300 person has been identified by hou e hold (N=2 400) familial and kindred (N=3 400) aggregation An additional 1 000 per ons from neighboring com munities who are relevant to the blood line aggregates have been identified Through even con ecutive monthly reports received by mail from each hou ehold new occurrences of illnes have been determined Alo tudy ha been made of the phyical facilities and of the receptiveness of lay and medical groups to future more inten site studies in this population The collected data hase been analyzed a lead eeking device and to determine the suitability of the population for ub equent epidemiologic tudy of a vanety of chronic di ea e entities On the ba is of the e analyes the inves tigators are satisfied that the commu nity lends itself to pro luctue future tudi ince (a) the ingle large industry in Tecum eh is relatively table and the population 1 nonmigrating (b) adequate numbers of indivdual over the entire are pectrum are avail alle (c) a high prevalence of numer 1 are OCTOBER 1960 ·ous chronic diseases exists and (d) new cases of CVD orcur with a fre quency which permits testing of many hiypothescs over a everal year period Early identification of individuals as to their usceptible or immune status in reference to heart di eases through both nap hot and motion picture tud 10% is under way (Other chronic dis ea will be studied in similar fa hion ) Specific aims include (a) identification of individuals with heart di ea e and a ociated condition (b) earch for a ociations between factors of hot environment and pecific types of heart di ea e (c) analysis of data by kin dreds in earch of familial influences and genetic patterns (d) description of the frequencies and distribution of cerebrovascular accidents (CVA) and determination of their relationship to heart di ea e (e) examination of heart di <a e patterns for relation hips among congenital rheumatic arterio clerotic and hyperten we heart di ease and if) Initiation of similar studies of chronc di ene other than heart disea e Pro cedures entul the examination Terum eh inhabitants re ident of sur rounding area and kindred in neigh boring communities (N=approximately 9 500) Method include taking detailed medical hi tories by trained lay inter Viewers reuew of these hi tories by physicians who perform phy ical exami nition and laboratory examinations As another tudy lesel among Bahama Negroes hale been mea ured to determine prevalence ratios of hyperten ion and to compare the findings with similar data available for Megroes living in the United State One tudy is based on the clinical record of the single phy ician on the Grand Bahama I land and pertains to approximately 60 per cent of the in habitant A third study relate to blood pre eure determinations made by an er demiologit and medical students from the Untersity of Michigan on 3 000 indinduals cho en 19 a probability im ple of Mas au City on Providence Island Demographic social and cultural data have been collected on these sulyject a large proportion of whom ar Negroen Drinking water samples from elected communities have been collected for odium determinations ince the water frequently is brachi li and as ociation betsten water of high odium content and hyperten ion will be looked for 7 At the Johns Hopkins Unnverity School of Medicine and School of Hy giene and Public Health two different methods of tudy and two different types of population are being u ed in earch of factor 7 ociated with CID Since 1916 medıcıl tudents at the Johns Hopkins University be been u ed as subjects in a study de igned to identify tho e characteri tics which may be of value in predicting and in pre venting an early on et of CVD Το date nearly 1000 student have l een cla sified by 11 ariety of genetic phy 10 logical psychological and metabolic characteri tics in earch of tho e traits which are asocinted with CHD or HHD The CVD heritage of each student 14 as e sed through family hi toris taken on parent grandparent uncle and aunts in the student them selves in their third and fourth years at Hopkin On the fifth and tenth anniversaries of graduntion cach tu dent is reevaluated by mail question naires concerning hi health tatu and sociophysical habit The health tutus of his parentale is redetermined Under the as umption that tudents ex perience greater rid of de seloping CID if they have an unfavorable CVD heri tage con titutional differences between low and lush r k student group have been identified Bard on ob ervations to date a four way grouping of healthy tudents according to parental hi tor) and student character tic 1174 l een pro posed as 1 har for eketing mghly blood pre sute 110 YOL 50 NO 10 AJPH ·CARDIOYASCULAR DISEASES disea e traits u ceptible indisidual The individual marriage and reproduction po tive traits in this grouping in and psychic and physical stre - Through clude (a) higher erum chole terol cro s correlation analyses tho e factors levels (b) nonectomorphic body build of host which are associated with early (c) higher blood pres ure lesel (d) death from ASHD are being ought In tachycardia and (e) blood pre sure search of pri cursors of ASHD erum hyperreactivity to cold or eterci e cholesterol and serum uric acid deter tudent with two or more such po tive minations are being made on a ample is cla ified as haun, po tire of the decedents children and pounes individual characteri tics The parental in each of the four groum po itise traits signify that one or & Two tudies are being conducted both parents ha a history of coronary by worker affiliated with the Health or hyperten ne di ea e Follow up data In urance Plan of Greater New York on health will be related to these char and Columbia University College of acteristics Phy icians and Surgeons The fir t 15 As an independent study the death armed at determining the influence of certificates of Baltimore residents aged female gonadal function on the devel 45 years and le who died between opment of CHD The method employs 1931 and 1959 have been rategorized the measurement and compari on of by cause of death in earch of factors CHD prevalence in oophorectomized and Predi po ing to ASHD Subjects with in a control group of non oophorecto death ascribed to ASHD have teen sub mized hysterectomized women White da ified into one of three categories female gynecological ward patients aged following validation of death certifica 45 63 years from the Columbia Pres tion through review of hospital phy I Lyterian and Mt Sinar Ho pitals are cian and autopsy records These cate being included in the tudy Other gories are (1) definite ASHD (2) ho pitals will be added if neces ary uncertain ASHD and (3) definitely to realize the population of 700 oopho not ASHD In the period under tudy rectomized and 1 300 non oophorecto death certificates with dagno es of mized ubjerts e timated to be needed ASHD included nearly 200 ubjects with in order to determine whether there a validated diagno is of ASHD 1 a difference in CHD prevalence Te t (Group 1) 250 with uncertain ASHD and control group are being matched (Group 2) and approximately 10n with by (a) period of operation within diseases other than ASHD (Group 3) three year grouping (1) age at opera All other Baltimore decedent in this tion and (c) nationality or country age clas (15 year and less) ercept of ongin Patients with hypertension or those dying of accidental cau es diabete at time of operation are elimi cla ified into a fourth category (Group nated from the tudy Study ubject 4) Individuals who e death are identified through medical record a cribed to ASHD (Group 1 2 and review and then contacted through one 3) are then matched by age er race or another of the following methods and date of death on a one to one basis ta) telephone (1) attending gynecolowith individual cla. ified a having git (c) ocial enice erchange (1) died from other than ASJID (Group 1) return United States mail (Form 331") Survisor ( pou es or sibling ) of the (e) Welfare Department or (1) site li a retail credit agency deceased are interviewed by nur ey mak When noti Sed of a death the investigator ohtain ing lome survey for pecific and de tailed information on famils hi tory of a copy of the death certificate Surs nors ASHD alcohol and moking other are invited to the hospital for medical are was OCTOBER 1960 ·are and laboratory examinations A history of e trogen administration is obtained from the patients family physician The criteria for diagnosis of CHD rest largely on history of episodes and cur rent ECG tracings The study will con tinue until interpretable results are ob tained The second study is that of CHD survivor hip and repeat attacks It has been activated only as a pilot under taking thus far utilizing new cases re ported from three HIP Medical Groups Patients are invited for examination by a single physician and for approprate laboratory examinations Serial medi cal checks are planned at six month intervals for two years and brennially thereafter Attention will be given to clinical manifestations that develop as well as to mortality to Discussion most effective when they are u ed in combination The investigators interviewed aware that the mere demonstration of statistical a sociation between a given factor and a given disepse does not establish the link of causation between the two events Rather such an asso ciation simply indicates that a change in the frequency or magnitude of one event is accompanied by a change in the frequency or magnitude of the other A given event shown to be directly associated with a given di ea e may repre ent only an index of a second event which is in fact a true cause Procedures to distinguish temporal association from causal relation hip must be designed to fit specific situa tions and conditions Such differentia tion requires a thorough knowledge of biologic concepts of the disea e gether with the conduct of studies that would test specific hypotheses Pro cedures would seek to verify by further facts to establish ancıllary evidence to reproduce results under different cir cumstances or to develop alternative hypothe es Uncertainty exits as to whether the factors presumed to be related to CVD represent primary or econdary etiolo gies--that 18 are they definitive cause or in contrast do they provoke clinical attack in individuals harboring a pri mary cause? Do such factors as hyper cholesterolemia hypertension obesity and the bke compr) e definitive or only predi posing etiologies of CHD? These questions thus far unanswered may prove analogous to the interactions between primary and secondary etiolo gles in acute poliomyelitis In this dis three immunologically distinct viruses comprise e sential cau es and such factors as pregnancy oropharyn geal surgery and the intramuscular inoculation of antigens have been e tab lished as contributing causes ease In general the studies reviewed here employ methods which have been devel oped and extensively applied in the study of infectious di eases. The process is that of measuring and comparing the frequencies and di tributions of dis ease within defined populations The aim is to identify or unmask those factors and conditions that caue dis In regard causation it is recognized that the inability to ee the dynamic pro esses of pathogenesis in human subjects calls for use of the epidemologic method and the inductive reasoning on which it depends Of the three methods being used in earch of associations between cardio vascular di ea e and host or environ factors-termed snapshot flashback and motion picture for convenience of description--it is gen erally agreed that motion picture studies provide the most comprehensive and 'The three study types are complementary however and are mental ease accurate data VOL 50 NO 10 AJPH 112 ·CARDIOYASCULAR DISEASES Current and Proposed Study Factors The 21 studies which we have re tewed are mea uring a variety of en vironmental and phy ological charac teristics in addition to tho e on which information is obtained in the course of a routine diagno tic examination, medical history ocial history physical examination and laboratory te-t. Table 1 hows a partial hst of these additional factors the number of investigators cur rently mea uring each factor and the number of other investigators among the 21 principal investigators who were proposing but had not yet begun to measure the respective factors at the time of our review in early 1959 Deci non to measure a particular fac tor implies that ome hypothesis about that factor and the occurrence of dis ea e is being te-ted For any given fac tor different measurements are being made from tudy to study Diet is the factor of intere t to the large t number of investigators ten are currently measuring diet and seven others propose to do o Four are now using ome measure of psychic tress and five others plan to measure it The items physical tress and cupation require some explanation Physical stress refers to the admin tra tron of ome test of reaction to exertion uch as an ECG after exercise whereas occupation refers to a job classification as an index of physical activity Environment change as used here means an attempt to alter a specific characten ticeg dietary intake and to measure the effect of this change on the occurrenre of de ease A deci ion to undertake environmental change rets not only on confidence that an anoria tion exists between an environmental characteristic and occurrence of di ea e but also on the idea that a change in the environment will be accompanied by a change in the occurrence of dis ea e The problems of measurement of the factor still exi and may be made more difficult because of the fact that the investigator ha induced an ecologic change It apparent from this hit of factor being measured in current and propo ed re earch that the ubject area of meas urement elected for attention in thi Conference on Methodology are of im mediate and major importance in epi demiologic studies of CVD OC a Table 1-Ens ronmental and Physiolog cal Facto s Mea u ed in 21 Selected Popular on Stud es Summary The methodologies being employed in eries of epidemiologic studies have been reviewed By means of measure ment and comparison the aims of these tudies are to determine whether per ons manifesting pecific phy hological or socioenvironmental factors expenence a different nuk of cardiovascular dis ea e than do persons without uch fac tors A ociations are sought between a specific di ea e and a pecific factor through (a) contemporary tudies pro viding a nap hot of the two esents (b) chronological tudies picturing fa hbacks to an earlier period and (c) long term tudies of progres, ne motion picture type Group under tuds in clude clo ed or open mpulations that are cho-en at random or lected on the las come preeri ling condition Factors Measured Populat on Stud es Current Proposed 7 0 Pych c stress Physic) sress Dietary Occupation En ironment ch nge Lung function Skin fold Clothing Endoc ia 4 3 10 8 1 3 5 2 5 OCTOBER 1960 ·It is recognized that the success of hoth current and propo ed epidemio logic tudies will rest on standardized ob enations and on preciee classifira tions of persons according to the pre ence or ab ence of two variables a pecific factor and a specific disease Follow up studies will attempt to dis tinguish between a sociations that are only tatistical and tho e that reflect & (au ative relation hip To this end epidemiologic studies will complement clinico laboratory efforts by providing collateral eudence by verfying ampli fying or modifying prevailing concepts or by developing alternative hypotheses It is anticipated that application of epi demiologic methods to the tudy of chronic disea es will lead to evidence consistent with a causative hypothesi as have such method, in the study of acute diseases Addendum pecific factors of host Foremont among these factors have been hyper cholesterolemia hypertension and obe ity NIore recently other factors have been added and include dietary habit alcohol consumption tobacco usage edu cational levels lipoprotein measure ments and di trict of residence in Framingham Plans call for exten ion of the tudy over at lea t ten more years 10 Connecticut State Health Depart ment-Studies began early in 1997 with the initial aims of (a) measuring the prevalence and incidence of CHD and CVA in Middle er County and (b) te ting specific hypothe es concern m, causation of myocardial infarction (MI) a related to particular dietary habits and to orial and per onality correlates of stress Ca e finding has been achieved through report from practicing physicians and ho pita! coupled with death certifications A 10 per cent probability sample of the popu lation was queried through Bureau of Cen us interviews to provide population e timates for rate denominator an in dependent estimate of clinically inanifest CHD and controleries for the com pari on phases of the study ie the nu trational and sociopsychological phases The ociopsvchological pects of the tudy contrasted a sample of white male patient aged 55 61 year who surved an attack of MII with an equal number of patients suffering from an acute evere allness other than heart di ea e and matched with the test group by (a) age to within five year (1) race and (c) orcupational level and (d) ethnic origin traditionally similar to that of the te t subject The e tudies continue and are currently directed at refinement of both hypotheses and tools of mey urement 11 New York State Department of Health--A long term project began in 1933 a repetitive ob ervations on nearly 2000 mal Civil Service employce aged 39 50 year from the Albany or 69 9 Framingham Mass - This longitu dinal tudy began during the period of 1948 to 1950 and has run continuou ly to date Serial ob ervations have been made on over 1000 individual per cent of an initial randomly cho en sample that repre ented two third of the Framingham population aged 30 to 62 year Biennial medical hi tories physical examinations and laboratory tests have provided the data for tuds Peports from local practicing plıysi cians and ho pitals have complemented the e record The study s initial aims were to obtain descriptive information on CVD and to measure prevalence and incidence of the e di ea es in the popu lation Secondary purposes were to test elected hypothe es concerning cau a tion of heart disease the e hypothe es being con tructed from clinical impres or the epidem:ologic findings of others To date major effort ha been directed to ASHD and HHD and to a ociations between these di ea es and $ion YOL 50 NO TO AJPH 114 ·CARDIOVASCULAR DISEASES area ca es Participants represented 89 per cent of the population invited into the tudy Primary objective have been (al to evaluate established methods of early detection of all forms of heart di ea e (b) to evaluate new technics for thi purpose and (c) to look for etiologic factors of CHD Annual phy 1 cal examinations and medical hi tories by phyican ay well a self adminis tered questionnaires have provided the data for tudy (linico laboratory meas urement have permitted a wide earch for factors a sociated with all types of CVD Special empha is has been placed on the study of potential nutri tronal influences on the e di eases The tudy proceeds in tandardızed fa hion with more inten ive clinical observations being made on suls ample of the study population A econd project began in early 1953 and continues to date It compri es a tudy of con ecutie autop ies from a general hospital and the comparison of cardiac pathology with ante mortem characteristics and environmental en po ures of the decedents The principal purpo e i to search for etiologic factors of coronary ocelu ion and MI Oliser vations at necrops include measure ments of the lumens and thicknees of coronary vessel Ob ervation concern ing the autop ied subjects are made through medical tudent interview with a clo e relative of the decedent Other ocial and environmental detail are oltained from the u ual family phy 1 cian and life insurance medical records of the decea ed Selected characteris tics being tudied include nutritional factors usual occupation weicht alco hol con umption tobacco u age and o forth Compari on on these charac ten tic are made between individual dying of heart di ea e and individual dying of other di ease It i expicted that the tuds will be extended leyond the current population of approximately 900 autopies A third tudy is being started which confrat by retro pective mean of Ml with matched control ubjects The ca e population is being obtained by a carefully developed and vigorously monitored reporting sy tem from all phy ician in Albany County Peport Ing inrludes ca es with other manifesta tions of CHD but detailed tudy is heing limited to survivors of firt in farctions Control subject. matched on five characteri tics (are ex race Socioeconomic tatu and urban rural residence) are drawn from a 5 per cent census of the population It) estr mated that 500 case matched with an equal number of control will be col lected hy 1961 Compari on of the e population will be directed primarily toward the variables of diet physical activity and chronic emotional tres although a number of other charac ter ti are being studied 12 Columbia Unuier ity College of Physician and Surgeons Harvard Med ical School and Lniversity of Britih Columbia Vedical School--For the pat 12 years a group of 100 sympathec lomized Smuthwich operation) hyper tensives and an equal number of un treated hyperten wes have been followed to as ens the effect of thus operation on survival Fairs of test and control subjects were elected from hyperten ne clinics in New York City Bo ton and Vancouver They were matched by (a) age race and tv (b) aser age and range of blood pres ure read ing (c) cerebral symptoms and complı cations (d) cardiar ize and ECG pat tern le) hi tories of angina or cardiac failure and (f) other factor including degrees of proteinuria eve ground chan and renal damage Each of three ine-tigators reviewed clinical and sunnal data on all pair in a blind fa hion at two five and ten years after ut jert were entered into the tud; Independent tudies of imilar OCTOBER 1960 ·matched control type are heing under then at Columbia u ing groups con sisting of 25 patients each to te t specific hypotheses These groups will provide information on relative sur vival rates of (a) patients with malig nant and essential hypertension and (b) drug treated and untreated hyper tensiles 13 New York City Health Depart ment-Thi project began in February 1957 to determine (a) if it were feasi ble to achieve dietary control in a free lumg population and (b) if such dietary management would reduce total cholesterolemia and lower coronary heart morbidity and mortality Male Volunteers willing to follow tailor made dietary patterns were solicited through two new paper announcements They were included in the tudy after attend ing an orientation lecture if they ex pres ed willingness to follow a pre scribed ( prudent) diet over many year perhaps until age 65 years Ongi nally the study included males a ed 50 59 years but thi has since been broadened to include age classes from 20 through 59 years When a subject enters the study a medico laboratory examination is con ducted and a comprehen ive diet his tory covering the two preceding weeks is obtained by personal interview with the subject and his wife The interview permits an estimate of all nutrients as well as the intake of total calories and calories from fat If the ubject is judged by clinical means to be over weight he is put on a weight reducing diet When a normal weight] achieved the subject is placed on a prudent diet that includes a fat intake providing about 30 per cent of total calories Fats are divided half and half into aturated and unsaturated of fat (Part of the latter is given in ay h forms as specially prepared margarine containing 80 per cent un altered com oil and a milk con tructed from a homogenized mixture of fat free powdered milk vegetable fat and water ) Serum cholesterol levels are measured at weekly intervals at the outset to establish a base line which is computed as an average of two or more determi nations within 10 per cent of the lowet Follow through is attained by (a) annual medical examinations with ECG trac ings (b) erum cholesterol measure ments and diet and weight checks every four weeks and (c) sessions with a board of review (phy icians) every ten weeks to discuss the individual progres Subjects provide medical data at the ten week check and hospital in formation where it exista complement thuis Subjects are told that they will he followed personally until ane 65 Years and thereafter through Social Security records 14 University of Pittsburgh Graduate School of Public Health-The mortality experience in (1) the Arsenal Health District of Pittsburgh during the inter Val 1951 1956 and (2) Donora Pa from 1918 to 1957 has been reviewed Mortality has been examined in rela tionship to prior findings of morbidity surseys in each area (The Donora ur vey of 1918 inve tigated the health effects of mug exposures in October of that year The Arsenal urvey was undertaken to measure the frequency of chronic illnesses and medical care in 1951 ) Together with these mortality studies the surveys of these populations have permitted prevalence estimates of Various chronic conditions including heart diseases Findings have convinced the workers of a need for (a) more detailed ob ervations recognized {ases of all di eases and (b) a better understanding of the timing of onset of overt heart di ea e and its progres sion Forthcoming tudies in a group of industrial employees will give atten tion to these problems 15 Presbyterian St Lukey Ho pital on types YOL 50 NO TO AJP H 116 ·CARDIOVASCULAR DISEASES -A fire year tudy of heart di east's among a large group of industrial em ployees began in the fall of 1937 with particul ir emphasis on CHD Study ubjects were men aged 40 55 years who had been employed two years or more in a Chicago electronic indu try and who on review of the company medical record were lelieved not to have had either MI or angina pectoris when the study started A total of over 3000 men was randomly cho 1 from the complete ro ter of company em ployees and invited to participate Over 2 100 (70 per cent) rompud have been examined and are now in the econd round of examinations The aims are (1) to determine the cardiovascular status of ubyerts at the time of the Initial examination (2) to measure in cidence of heart dı-ease through four annual reexaminations and (3) to re late the incidence of heart di ease to various physiological measurements and other characteristics of the subject Data gathered at the initial examina tion included (a) a family hi tory pre pared by the subject (1) a medical hi tory and physical examination by one of 25 volunter physicians as Isting in the tudy (c) clinico laboratory te is including somato typing with photog raphy (d) diet a sessment by detailed interview with the subject and a ques lionnaire completed by the spouse (e) Jhy ical activity measurement by analy is of job requirements and an inter view concerning off the job phy ical er ertion and (f) personality traits deter mination as revealed by the Minne ota Multipha ic Personality Inventory These procedure are leing conducted in facilitie at the plant and require about two half days for which the ub Ject is given time off with pay 16 Tulane University-Sinre 1911 the influence of hot and humid ( ut tropical) environments on play bologic and pathologic reapons in man ha been under tuds Obsersation Leing made hoth in hospital wards and in experimental chambers using normal ubject and patients with chronic con go the heart di ea e Nea urements of cardiac function are being contra ted Fetween study population and temporal compan on are being made within the e populations 17 South Carolina College of Aledi cine-Clinico laboratory procedures hase been des eloped and standardized to per mit screening of large numbers of ub jects for (a) blood lipid lesels (b) whole blood coagulation and (c) in travascular agglutination of erythrocytes ( ludging) Interrelation hips among the e variables are being sought for everal contra ting groups including (a) elected di eased and normal popula tron and (b) samples of white and Negro residents of metropolitan Charles ton A battery of lipid tests are being run on all blood erum, including those for cholesterol pho pholipid tri glyceride and alpha and beta lipopro teins Microscopic ob ervations photo graphs and cloned circuit televising of the capillary circulation in the bulbar conjunctiva allow estimation of the de gree of erythrocyte aglutination and arteriolar plugging with ludged ma e Blood coagulation is measured by con ventional technic 1P California State Department of Health-In 1918 a total of 577 healthy individual aged 50 years or more were selected from 813 regi trants who vol unteered to participate in a tudy of nutrition as related to aging Selection from the regi trants trove to include only individuals who were phy ically and mentally capable of participatina in good health not under a physcian care within the three prior month ane not food fade Selection attempted to achieve an equal er di trilution and a range of age and eco nomic cla es Initial tudy of the group included (a) a nutritional hi tory and a record of seven day fond ure OCTOBER, 1960 ·(om mntakt (b) a detailed medical hi tory and complete phyical examination and (c) a series of laboratory re ults from blood and urine analy es and from che t rays bone density determina tions and vaginal (Papanicolaou) mears Follow up phyical examina tions and dietary evaluations of as many uljects as were available were made in 1952 and again in 1954 Data that have been analyzed pertain to mortality morbidity and disability (both for CVD and for total di ea e) in relation to the original (1948) phyical find ing blood analyes and diet patterns The health tatus of subject till avail able for examination and interview is being reevaluated after a total of 11 years of oh ervation In 1951 a multiphasic creening er amination was given to 1000 long horemen who volunteered to partici pate out of a total of 6 000 such worker in the San Franci co Buy area Te ts included measurements of age height weight hearing blood pressure hemoglobin blood sugar glycosuria al buminuria a che-t xray and an ECG tracing The ub equent mortality of the 4000 volunteers and the 2000 nonpar ticipant has been followed through death certificate analy es and union health insurance record This tudy continues as a routine operation offer ing a potential for testing a hypothees of cau ation A health survey of a representative ample of Californian ka conducted in 1951 1955 whereby information was obtained for nearly 32 000 induiduals by Bureau of the Cen u interviewers A total of 250 individuals (150 male ind 100 females) gave history of some form of CHD A substantial propor bon of the e indusduals was matched with di ea e free control ubjects of the ame age and ser cho en from the unes population Interviews were held with d: ea ed and control ubject to determine the relatie frequencies of various characteristics that might be related to CHD (Next of kin were interviewed where subjects in the sample had died ) Special attention was given to (a) smoking habits (b) pre byopia (c) physical exertion at work (d) par ticipation in athletic events ie) occu pation (f) urban versus rural resi dence and ig) native versus foreign birth 19 Mt Zion Hospital San Francisco Calif -The role of specific behavior patterns as they may predispo e to CHD among elected population groups is under study In general these efforts measure independe ntly (a) per onalty and behavioral patterns and (b) histori cal experiences with CHD Subjects many of whom are industrial executive were selected if they gave evdence of highly developed aggres. 11 eness petitivenes and a tendency to accel erate all activities or if on the other hand they pemed to lach these at tribute Evidence of previous experi ence with CHD was obtained from medical historie and ECG tracing Competitive ubjects (N=83) were matched with noncompetitive ubjects (N=33) by similarities in age ethnır group diet heght weight and the amount of physical activity quired by their job A total of 12 linemployed blind subject al o were tudied The latter re embled the non competitive group in per onality pat tern but had the complicating factor of continual anxiety At the time of ob ervation electees first were cate gorized by one examiner as to whether their behavioral pattern which had been elected to repre ent the extreme of contrast between driving and easy going per onalities were com pletely or incompletely des eloped (This was done for purpose of subela sıf cation ) A detailed medical lu tory was taken and a physical examination per formed Then a second examiner dreu blood for determinations of chole terol race re eries of YOL. 50 NO 10 AJPH 118 ·CARDIOVASCULAR DISEASES u mean e and clotting time measured bleeding time and took FCG tracing A third examiner gave detailed in tructions that would permit selectees to record qualı atre and quantitatre information on dietary intake by daily dian technic for one week Short term studies on mall -Tolip of CHD patient and elected control ubjects are under way to refine cur rent technics and to develop new and hetter method Endocrine CHD hy pothe es are being teated throuch utılı zation of data from urinalsce Other tudies now in progress are de igned to mea ure personality trait by objective A lze detector that imul taneou l records amplitude and rate of respiration body movement and car diac function is under study Al o a psychophy hological te being de vi ed in search of a predictor of the occurrence of CHD in pecific group of individual 20 North Dakota-- In 1936 1937 a longitudinal tudy of CHD was tarted in a ix county area surrounding Grand Forks AD to determine the fea ibilty of certun inte ligatise inethods and to test pecific hypotheses concernung cau ation of this di ea e (This area wa elected for tudy because vital record had indicated that North Dakota re ported the lowest death rate from CHD in the nation) Patient developing acute manifestations of CHD either a new or recurrent events were reported by practicing phs icians to the tudy center a, the primary ca e finding device Alo phy ician provided clinical and ECG findings on their CHD patient to a il a review committee of internist in de ciding whether reported ca es hould be con dered CHD for purpose of the tudy and in cla ifying them into ub groups Monthl, uit 1ere made is an epidemiologi t to earh phu tcian in the tuds area and limonthly vits mere made to phy ician dering the counties to improve the degree of reporting and to collect col lateral information Hopital record and mortality tati ties were reviewed periodıcılly to check the completenes of thi ca e finding method 4 10 per cent probability ample of dwelling unit. was chosen and resident therein vere intervened through Bureau of the Cen enumerators for demographic and elected personal characteri tics Theme characteri tics included data on occu pation moking and food habits a the principal area. of interet and were determined through personal in terviews with all males aged 35 years and over who came into the probability sample A mngle dietitian made detailed dietary a ment of each recognized CHD patient together with uch a es ments of two age matched control ub jects chosen for each patient from the probability ample Attempt was made to e-tablı h the dietary pattern of pa tient for the month preceding overt disease and of control ubjects for the month prereding the interview If the CHD patient had died hi wife or near et kınas interviewed a in uch in tance were comparable relatives of the matched control ubjects Thereafter tandardized procedures were followed in estimating qualitative and quantita tise intake of pecific nutrient 21 Chicago Board of Health-An on going tudy has been conducted in a Chicago utility company in earch of factors of hot and environment that pred, po e to or precipitate cardiova cular renal mort idity and mortality particularly ASUD and HD 'The health tatu country of birth social cla and occupational experience of 736 employees imed 50 39 years (96 per cent of the plant employees in the age cla. ) were determined as of Janu 1951 from preexi tin record Ling erjal ostnation from annual eraminations conducted throu,h lant facilities a (rien of de ter ninatue analı ces ! In progne (in art phy scal in area hor OCTOBER 1960 ·Various ch Telate la intake (1) a detailed medical hi tory and complete phy ical examination and (c) a eries of laboratory result from blood and urine analyses and from chet x rais bone density determina tion and vaginal (Papanicolaou) Sineurs Follow up physical examına tions and dietary evaluations of as many ubjerts as were available were made in 1952 and again in 1951 Data th it have been analyzed pertain to mortality morbidity and disability (both for CVD and for total di ea e) in relation to the original (1918) physical find ing blood analyses and diet patterns The health tatus of subjects tall avail al le for examination and interview is being reevaluated after a total of 11 years of observation In 1951 a multipha le creening er amination was given to 1000 long horemen who volunteered to partici pate out of a total of 6 000 uch workers in the San Francisco Bay area Te ts included measurpinents of age height weight hearing blood pressure hemoglolun blood sugar glycosuria al huminuria a cheat ray and an ECG tracing The sub equent mortality of the 1000 volunteers and the 2000 nonpar ticipant has been followed through death certificate analyes and union health insurance records This tudy continues as a routine opt ration offer ing a potential for te ting a erie of hypotheses of cau ation A health curvey of a representative ample of Californians was conducted in 1951 1935 whereby information was obtained for nearly 32 000 individuals by Bareau of the Census interviewers A total of 200 indnuduals (150 males and 100 females) gave hi tory of ome form of CHD A sub tantial propor tion of the e individuals was matched with di ea e free control <ubjects of the ame age und sex cho en from the sure population Interviews were held wyth di ea «d and control ubjects to determine the relatne frequencies of Calt patid among under measure ind behai cal experit many of who were selected highly deselop? petitivenes and erate all activities hand they seemned tribute Evidence o ence with (HD was medical hi torie and Competitie ubjects matched with noncompetiit, (N=831 by similarities in ethnic group diet height neu the amount of physical actik quired by their jobs A total unemployed blind subject also studied The latter resembled the competitive group in personality tern but had the complicating facio of continual anxiety At the tip of observation electees first were cate gorized ly one examiner as to whether their behavioral patterns which had been elected to repre ent the extreme of contrast between driving and easy going personalitie pletely or incompletely developed (This was done for purposes of subcla safi cation ) A detailed medical history was taken and a phy acal examination per formed Then a second examiner drew blood for determinations of chole terol were com 118 YOL. 50 NO 10 AJPH

·No text on this page.

·January 1958 the study was enlarged to include the entire labor force aged 40 59 years approximately 2 000 indı viduals ) Specific aims include the test ing of hypotheses concerning associa tions between CVD and the following ho t and environmental characteristics (a) place of birth (native or foreign born) (b) dietary habits and nutrition (c) marital status (d) physical activity (e) psychologic stress and (f) other factors A second study concerns the com parison of Negroes and whites with respect to patterns of cholesterolemia and incidence of CHD Other correlates include age sex height weight occu pation indu try and duration of resi dence in northern states A third tudy employing method of experimental epidemiology is de signed to met ure the effect of a nutri tronal hygienic regimen on rik of de veloping CHD Several hundred middle aged men without evidence of CHD but presumed to be at high risk by yırtup of high levels of (a) body weiht (b) blood pre sure and (c) serum cholesterol have been induced to follow a prescribed regimen and are being examined serially They are being con trasted for coronary disease with appro priately matched control ubjects from the Chicago utility company 120 YOL 50 NO 10 A ·he no ticularly in heart disease there are spreral things that need to be said about the viewpoint of those who work in CO CHAIRMAN'S ADDRESS* Herman E Hilleboe VDF 4.P14 THIE «es sons of fi onference I hendalls definition of epidemiology have not beard mir hl 1 epidemi (Report of the Subcommittee on Bto ology or what epiden It eem chemical Veasurements ) I would like to to me we need to r the rather repeat it because it is tated perhap broad background of th 110 are better than many definitions made by con idering I woulin rel r to epidemiologi ts them elves Dr hendait Paul Sears a commer bout a ien aid that the purpo e of any epidemiotist FIC and Disc it and coinmu logical tudy is to evaluate the influence rucation are the two pume oblı atı ns of duerse genetic and environmental of a scientit Ano a ion such a this factors upon the occurrence and everits gives a scientit an opportunity to ir of di ease I think this is particularly amine some broad ues in the light pertinent in the field of heart di ease of the pecial knowk doe and experi where hare demon.trated ences of tho e who are not epidemic lospecific etiological agents gists The other remark he made that I hope that even though our truck home had to do with differences major concert is the epidemiological method applied to varius types of heart in the mean level of particular factors disease we shall endeavor to think in that might be tatı tically ignificant brond terms abnut applying such di ci among di eased and control groups He pointed out that values for the two plines as mathematics physics chemis try and other sciences to the problem groups are scattered over the same ranne and have little diagnostic or prognostic at hand We hould al o bear in mind that ignificance for any given individual I would like to reempha ize that, trctly we need to know something about biology in general and ecology in par peakınguneys of characteritoare not epidemiological studies they do not ticular if we are to learn more about relate the di ea, e to specif environ mnans relation hip to his environment mental or genetic factore which charac We have not heard much about ecolo terize the population unter Invest 1 gi ts here but I think that epidemiolo tion He pointed out that in many gits come close to being ecolom! In tudies biochemical determinations have their method An ecologi, been ub tituted either for an adequate know has a newpoint jut a httle dif juds of the factors or for an ultimate ferent from others in the apprai al of the clınıcal manifestations field For one thin, he seen man a of the disease a corial being in a cultural matris, In the area of epidemiolons and par and powerfully affected by population dynamics Getting down to the pecific point of epid miology I am delighted with Dr epidemiology and who hate epidemie lorical tudies in on in area On the third day of the Confrnce 8 OU cientific OCTOBER, 1960 ·uch as heart di ea e cancer anto mobile accident cerebral pal y und birth defects All the e tudies have a rommon denominator I think it is parhcularly important that we talk about thr methods of epidemiology because intrin ic in the € tudies is the ve of statistical method Infortunately certain groups in our country feel strongly that tatı tical tudies on man are of relatively little value and inconclu lie These groups believe that the true facts can be a cer tuned only by animal experimentation and clinical ob ervation This is not and in critici m this is merely an oleration We are often urged to take no public health action untal lab oratory and clinical tudies have gien ultimate an were ahout the nature of nch di ca e as cancer This attack on the public health approach e pret es 1 belief that is widely held I think perhaps for that ren on it is important to point out that epidemiological studies on man have been highly productive of scientific knowledle and of practical application in the advance of medical cience This does not in any way dep recate the value of animal experimen tation in the laborators or clinical in Testigation in the ward I think there things are ind pen alle and certainly nece art for medical progres But we mut empla ize the true value of the epidemiological approach with its heas reliance on tatt tical compilation in the analy is of events that occur in human population I would like to mhe another point here that has not been mentioned in the lat two days of discu sion and that is the interchangeability of medical tatı ticians and epidemiologists The medical stats tician is u ually called a ho tatı tician and is first of all a mathematician who adapts his knowl edge to the tads of di ea e demiologi I on the other hand is killed in medrine I ut ha learned to adopt a mathematical approach in the fuds of disca e among groups of people Certainly whene ser posible the two work together in the proces thu tati tician becomes a better epidemiologit and the epidemiologi t a better stati to cian so that the two ultimately approach one another clo «ly in their skills Since thie di tinguishing feature of an epi demiological study is its ue of numbers and their analysis by stati tical method and logic it seem permi aible in the present di cusion and in our future di (u sions in this area to u c the word bio tatistics and epidemiology almot interchangeably Without going into great detail i think it would be wise for all of u intere ted in epidemiology to go back to the era preceding knowledge of the bacterial and voral cau rs of di ease to ee the way in which some of the carly workers 1 ed epidemiological methods When Jenner did his work on mallpox 161 year ago he handled his accounts and compiled his cases in uchi a way that he really carried out a neat epı demiological study Ile knew nothing about the cau e of the di ea c and yet he found out how to present the di ra e John Snow s chic tudies on cholera in 1851 arr a parallel with what we are facing today in heart di ease Many of the same puzzles were faced by John Snow in hi attempt to work out the relationship betwein cholera and the way in which the disease was trans mitted Michael Taylor in England tudied epidemies of typhoid fever in 1957 and traced its transmission through milk Again he knew little about the but he knew how to develop meaningful a ociations So as we tracr epidemics brch through the last century we find many individual inve tigators confronted with precisely the same types of problems that we are facing at the present time in heart di case To bring this viewpoint up to date I lould like to point out that our cau e The epi 122 YOL. 50 NO 10 AJPH ·we can IS we almo tuner aliy among our adult pop disea e is almost unser a! the com rart on of ca es and honcases become CARDIOVASCULAR DISEASES knowledge of carcinogenic agents and more often. to paucity or inaccuracy the mean of preventing certain type of of data or to fal e logic in their inter neoplastic d ease to the extent that pretation largely the product of epi Finally I would like to say that in demiological studies Certainly the early talking ahout epidemiology we mut be studies on scrotal cancer in chimney cautious about the use of the word sweeps on cancer from contact with We hear about shoeleather epidemi pindle oil on canrer of the bladder ologi ts who go out into the field and of aniline workers and on hin cancer learn things by doing their own work from arsenir are all examples of the We hear about armchair epidemi epidemiological approach Vany of you ologi t who have others gather their are familiar with some of the recent data Nou ke have heard recently reports on the des elopment of leukemia about clinical epidemiology Dr John among tho e treated with rrays for Paul of Yale has ju t publi hed a hool spondyliti the effects on children of with that title We hear al o of experi irradiation of the thy mu and the in mental epidemiology The point I wh crease of congenital deformities among to make he Is that we need to con ider babies who e mothers had pelvic v ray epidemiology in it total context examination during pregnancy Again We also need to realize that many the e are examples of the method heart di ea. e tudies labeled epidemi are talking about ological do not actually follow epi I would like to read a hort quotation demiological methods in their design or from Dr Frot one of our foremot execution There is no ren-on why epidemiolog l who was my professor elery study which ets out to de cribe of epidemiology at the Johns Hopkin characteri tics of person with heart School of Hygiene and Public Health di ea e hould He called an epidems He aid The opinion is more or les ological tudy Iti my hope that when prevalent that inference based upon ep clinical and laboratory researchers de demiological argument cannot te truly sign an} carry out epidemiologiral conclu ne becau e the evidence is studies ther take care to tudy carefully purely circum tantial Such opinion has and follon epidemiological method frequently failed to take account of the Onls when a tudy employ epidem: whole ma of evidence and to follow ological m thod hould it be labeled the argument which is neres anly built epidemiological up step by tep in its apmewhat com Good epidemiological tudies are very plex and perhaps tediou way Given difficult in coronary heart di ca e be suffirient cope and accuracy of observa cau e the preclinical stages of athern tion a conclusion as to the nature and clero in the precursor of coronary pread of d ea e may often be e-tab heart disea-e-appear to be occurring 1. hel quite firmly by circum tantial evidence well in advance of experi ulation in the United State mental confirmation Voreover many problem of disea e tran mis ion which almo timpos ir le except in po t mortem are highl important from the tand tudie let the companion of ca point of prevention are of a type that with ronca e comprises the last can le soled only by investigation of this kind The weaknese in conclu ions method of epidemiolog Difficulties notwith tandına there te drawn from currum tantal tudien is u ually chargeahle not to la ir defect Paul Jahn RCI in the method of inte-tigation but rests of Ch apa Pese 1928 When a al Eritme logs U f OCTOBER, 1960 ·YOL. 50 NO 10 ALPH 124

·No text on this page.