Vol. 41

Epidemiological Approaches to Heart : The Framingham Study* THOMAS R. DAWBER, M.D., GILCIN F. MEADORS, M.D., M.P.H., AND FELIX E. MOORE, JR. National Heart Institute, National Institutes of Health, Public Health Service, Federal Security Agency, Washington, D. C.

THE use of the word " " cal diagnosis. Thus, today, the epidemi- and the concept of what epidemi- ological approach is used to explore ology as a discipline may encompass has certain relationships in health and disease varied widely since the days of Peter which, with present technological meth- Panum and . There are today ods, cannot be observed directly. In many differing definitions of the word, addition to the many studies of the infec- but nearly all workers in the field will tious , there have been epi- agree on one element of the definition: demiological studies in the fields of The word " epidemiology " by etymology nutritional imbalance, metabolic dis- refers to the study of something " which orders, occupational hazards, accidents, is thrust upon the people." There are cancer, and rheumatic fever-to mention still some who insist that epidemiology only a few. deals only with epidemics of infectious In the field of cardiovascular diseases, diseases, but current usage suggests that studies using the most workers would now agree that epi- have led to findings of considerable prac- demiology deals with " the fundamental tical importance for prevention and questions as to where a given disease is treatment. Mention may be made, for found, when it thrives, where and when example, of the studies of nutritional it is not found . . . in other words it is diseases, such as beriberi, pellagra, and the ecology of disease " 1 without regard scurvy, and of the infectious diseases to whether the disease is believed to be such as syphilis, hemolytic streptococcal infectious. infections, and streptococcus viridans Frost gave an analytical definition bacteremia. Rubella and other virus when he wrote that epidemiology " in- diseases have been implicated as etio- cludes the orderly arrangement of facts logical factors in congenital malforma- into chains of inference which extend tions of the heart, but further epidemio- more or less beyond the bounds of direct logical study is still required to establish observation."2 His definition might be these relationships beyond the possibility called the essence of the " epidemiological of reasonable doubt.3 Even in rheumatic method " except for the fact that it has fever, where fundamental etiology is still been used by the physician since the obscure, epidemiological studies have time of Hippocrates to arrive at his clini- helped to demonstrate the relationship of streptococcal infection to subsequent rheumatic activity, and this has led to * Presented at a Joint Session of the Epidemiology, Health Officers, Medical Care, and Statistics Sections the adoption of control measures which of the American Public Health Association, at the show Seventy-eighth Annual Meeting in St. Louis, Mo., great promise:4 November 3, 1950. It should be pointed out, however, [279] 280 AMERICAN JOURNAL OF PUBLIC HEALTH March, 195f that except for rheumatic fever, the dis- At this point it is well to present in eases mentioned above account for only outline the principal considerations a very small proportion of morbidity or which guided the development of the mortality from cardiovascular disease. study, and led ultimately to its location Of the epidemiology of hypertensive or in Framingham, Mass. arteriosclerotic cardiovascular disease al- The study is focused on arteriosclerotic most nothing is known, although these and hypertensive cardiovascular disease, two account for the great bulk of deaths because these are the most important of from cardiovascular disease. The scanty the cardiovascular diseases and the least epidemiological knowledge of these dis- is known about their epidemiology. As a eases which does exist is based either on working hypothesis it is assumed that the study of mortality statistics, which these diseases do not each have a single in the investigation of long-term diseases cause (as is the case in most infectious are often not very revealing, or on clini- diseases), but that they are the result cal studies, which have the disadvantage of multiple causes which work slowly from the epidemiologist's point of view within the individual. It is recognized of being based on the study of those who that, for the most part, specific and un- already have the disease. Clearly, what ambiguous tests for precise diagnosis of is required is the epidemiological study the early stages of these diseases are- of these diseases based on populations of lacking. normal composition, including both the Based on these general considerations, sick and the well as they are found in the following research plan was devel- the community. oped. A group of randomly selected per- These facts have long been recognized. sons in the ages where arteriosclerotic- Sir James Mackenzie, one of the great and hypertensive cardiovascular disease pioneers in cardiology, over 30 years ago are known to develop is selected for began what was intended to be a long- study. Based on as complete a clinical term study of disease in the entire popu- examination as feasible, there are selected lation of the town of St. Andrews, out of this initial group those persons Scotland.5 Because of Mackenzie's re- who are free of definite signs of these tirement a few years after the start of diseases. These persons will be termed the study, it was never completed, how- the normals, and they will be observed ever, and since that time there have been over a period of years until a sizable no other attempts to study heart disease number are found to have acquired the- in a large population of normal composi- diseases. At that time a search is made tion over any long period of time. The for the factors which influenced the expense of such a study and the necessity development of disease in the one group of guaranteeing its operation for a span and not in the other. of many years puts it beyond the ca- As one by-product of this investigation pabilities of the individual investigator. it will also be possible to study the effi- If such a study is to be done, it is clear ciency of various diagnostic procedures that it must be carried out by the com- in finding heart disease or as indicators munity health agencies. In the light of of the subsequent development of heart this situation, and with the g'rowing disease. (These findings, of course, have interest in chronic diseases, the U. S. important bearing on the question of Public Health Service began in 1947 to including tests for heart disease in mass lay plans for setting up an epidemio- screening programs.) A second by-prod-- logical study of the cardiovascular dis- uct will be data on and eases in cooperation with state and local of cardiovascular diseases. health agencies. With these aims set up, it was then Vol. 41 FRAMINGHAM STUDY 281 necessary to define the population on State Health Commissioner for Massa- which the study would be carried out. chusetts, offered to cooperate with the Ideally, perhaps, epidemiological investi- U. S. Public Health Service in setting up gations of cardiovascular disease should the study in that state, and after con- be set up in a number of widely separated sideration of a number of possible areas areas simultaneously, so that various the Town of Framingham was selected. racial and ethnic groups will be repre- Framingham, lying 21 miles west of sented, and a variety of geographic, Boston, is an industrial and trading socio-economic, and other environmental center of 28,000 population, and is al- factors can be considered. The results of most independent of Boston from the a study of a single area will have gen- standpoint of providing suburban resi- erality only in so far as the population dence for the city. As is true of New of the area is representative of some England towns, it includes not only the larger population. Many thousands of built-up business and residential areas persons should be included to allow for but also the outlying rural area within numerous axes of analysis, and it would the town limits. Other points of interest be profitable to follow a cohort of indi- are that Framingham has the town- viduals from birth to death. Because of meeting form of government and the the expense of examination and follow- people are accustomed to and well versed up, however, it is not practicable to carry in the group approach to their problems. on studies simultaneously in several It was in Framingham that the first com- areas, nor to observe more than a few munity study of tuberculosis was under- thousand persons for a limited number taken-a program sponsored by the of years. It was concluded, therefore, National Tuberculosis Association and that the study should be set up in a the Metropolitan Life Insurance Com- single area, and that coverage would pany, which began in 1917 and continued have to be limited to approximately successfully for six years.6 This latter 6,000 persons in a limited age range, who fact, together with an indication of would be observed for a period up to 20 interest in response to the initial ap- years. A town of 25,000 to 50,000 popu- proach influenced to some extent the lation will supply this number of adults, selection of the town. and it was felt that a town of this size The problems involved in setting up would be more desirable than a larger the study fell into four categories: pro- city for the type of community approach fessional, administrative, organizational, required to secure full co6peration and and technical, and all will be discussed coverage. This limitation in geographic in some detail. A program which in- coverage clearly limits the generality of volves medical examination of large conclusions which can be reached. There numbers of people requires the respect, is, however, reasonable basis for the be- endorsement, and support of the medical lief that the distribution of arteriosclero- profession. The plans for the project sis and hypertension in the white race in were given the endorsement of the the United States is such that within- Massachusetts Medical Society.7 In community variance is very much greater Framingham the medical groups which than between-community variance, and center around the two local hospitals a wide range of type-situations influenc- offered their active support to the pro- ing development of these diseases may gram as proposed. be found in any community. This hy- From an administrative standpoint it pothesis can only be tested, of course, by was necessary to secure clinic facilities similar studies in other communities. and recruit a professional and technical In mid-1947, Dr. Vlado A. Getting, staff. A centrally located residential 282 AMERICAN JOURNAL OF PUBLIC HEALTH March, 1951 building was remodeled for clinic and study in a way which would be understand- laboratory space, and diagnostic equip- able to all elements of the community. ment installed. A staff was 3. To bring recognized and potential leaders organized, of the community into active participation in including, the examining physicians; a the organizational aspects of the study. clinic nurse; x-ray, electrocardiography and laboratory technicians; statisticians; After analysis of the community interviewing and administrative clerks; organization requirements of the study a health educator; and visiting consult- by the Executive Committee, six sub- ants in the fields of cardiology, electro- committees were set up: Arrangements, cardiography, roentgenology, pathology, Publicity, Industry, Business, Civic and biochemistry. Organizations, and Neighborhood Organ- The organizational problems are those ization. The Arrangements Committee involved in bringing into the study the *has assisted in the operation of the study cross-section of the population which it by providing clerical assistance and is desired to study. The mechanics of transportation. The Publicity Commit- selecting that cross-section are described tee, composed of residents who are in a later section; at this point the focus specialists in the areas of press, radio, of interest is the method of bringing advertising, and associated fields devel- about community participation. The oped a plan for publicity media to be work of building a community organiza- used in placing the program before the tion began months before the start of community. The Industry, Business, and clinic operation. Civic Organizations Committees brought As a start, a health educator was the study to the attention of their special placed in the Health Department with publics. the assignment of studying the com- Perhaps the most important of the munity. This meant not only learning committees, however, is the Neighbor- about the history, resources, and govern- hood Organization Committee. It has ment of the town but, more important, been the aim that every participant in getting to know the people-their na- the study should come into it on the tional origins, economic conditions, and basis of an invitation from someone he lines of social stratification; their reli- knows, and in whom he has confidence, gious, fraternal, and civic organizations; and further that the- invitation should and their recognized and potential lead- come from a person who has been ers. From this study grew plans for the through the clinic. At the start, there- appointment, by the Town Health Offi- fore, examinations in the clinic were cer, of an Executive Committee of 15 offered to all members of the committees persons for the study-a committee and these, in turn, passed word of the which was broadly representative of the study on to other members of the com- various groups in the community. munity who were encouraged to volun- Parallel to, and integrated with, the lay teer for examination. From these volun- Executive Committee, there was organ- teers a set of neighborhood committees ized a Professional Committee of physi- has been selected. To those committees cians and dentists under the chairmanship falls the all-important job of inviting the of a cardiologist. Together, the Execu- initial participation of the selected indi- tive Committee and the Professional viduals and later stimulating co6peration Committee accepted the following re- in return for follow-up observation. sponsibilities: Up to the present time, use has been 1. To assist in planning a program which would made of standard publicity channels to be acceptable to the community as a whole. inform the people about the program. 2. To interpret the aims and objectives of the However, as we discovered from sam- Vol. 41 FRAMINGHAM STUDY -X83

pling of opinion of persons volunteering Advisory Committee appointed by ithe for the study, the most valuable public State Health Commissioner and made up information has come through word of of eleven physicians from the Boston mouth. The community has accepted area expert in the fields of cardiology the program as its responsibility, and and public health. This committee aided recognizes that when people participate in setting up the broad outlines of the they make a real contribution to medical study by proposing hypotheses as- to research. It should be added that the suspected etiological factors for testing. nature of the examinations provides a The committee assisted also in suggest- service to the selected individuals, and ing specific items for examination and this has undoubtedly motivated many in laboratory study, and in advising on the community to participate. It should criteria for evaluating these criteria. be noted parenthetically at this point, The procedures which are carried out on however, that the service aspects of the each person admitted to the study may study are limited to diagnostic informa- be summarized briefly as follows: tion which is furnished to the only per- 1. An extensive medical history including: sonal physician of the person examined. a. Family history of cardiovascular disease Where there are abnormal findings, the in mother and father, siblings, and children. individual is referred to his own physi- b. A detailed past medical history of diph- cian for interpretation of the findings theria, scarlet fever, sore throat, rheumatic and treatment if The fever, various chronic diseases, operations, necessary. clinic thyroid diseases, presence of transient or per- staff does not provide treatment, nor manent hypertension, heart murmurs, and offer advice on treatment. "heart attacks"; previous diagnoses of an- The technical problems of the study gina pectoris, limitation of activity due to may be considered under two headings: heart disease, congenital heart disease, heart failure, vascular disease of any kind, enlarged medical and statistical. The medical heart, " nervous heart," pericarditis; and the problems involve selection of diagnostic history of any previous kidney disease, renal procedures and methods of measuring or hypertensive complications of pregnancy, the various characteristics of the people, or of any menopausal symptoms. and the establishment of criteria for c. Careful questioning for any current symp- interpretation of toms of heart or pulmonary diseases including these tests. Statistical cough, dyspnea, hemoptysis, smothering sensa- problems include the development of a tion, palpitation, chest pain and discomfort, method for sampling the population, and edema, and phlebitis, etc. of methods for recording and analyzing d. Personal habits of the individual, includ- the data obtained. ing number of hours of sleep, amount of to- To determine the presence or absence bacco and alcohol consumed. e. Average weight at five year intervals, be- of cardiovascular diseases and to record ginning at age 25. those items in the patient's past history f. History of peptic ulcer, chronic colitis, ner- that may have a bearing on the devel- vousness, headache, and other symptoms sug- opment of disease requires a rather ex- gestive of emotional upset. tensive study of each selected individual. g. Use of drugs or medicines. Within the framework of this type of 2. A careful, detailed physical examination per- formed independently by at least two phvsi- study, it is also necessary that the exam- cians, aimed at detecting cardiovascular ab- ination be organized in such a way that normalities or diseases related to the cardio- the whole procedure can be done in a vascular system, and measurement of charac- reasonable length of time, and without teristics which may be related to such disease ,discomfort or risk for the person being including: examined. a. Height, sitting and standing, weight, an- tero-posterior diameter of chest, chest circum- All medical planning for the study was ference, waist circumference, vital capacity, done in consultation with a Technical estimate of body build, color of eyes and hair, 284 AMERICAN JOURNAL OF PUBLIC HEALTH March, 195I and distribution of hair and degree of bald- biennially for a period which it is hoped ness. to extend for as long as 20 years. If b. Skin color and degree of freckling, the presence or absence of sweating, clubbing of they move from Framiungham, an at- fingers and toes, cyanosis, exophthalmos, arcus tempt will be made to bring them under senilis, xanthelasma, thyroid enlargement or a comparable examination elsewhere. If tumors, chest deformity, and evidence of pul- they die, an attempt wil be made to monary disease. secure autopsy data, and, at the very c. Examination of the heart itself including description of heart sounds, murmurs, abnor- least, complete description of cause of mal rhythm, blood pressure determinations on death, and data as to the existence of admission and at time of discharge, and at cardiovascular diseases at time of death. intervals during the examination by each of The choice of a sampling plan for this the examining physicians. by a number of con- d. Examination of abdomen for tumors, liver study was dictated enlargement, or palpable spleen. siderations, some of which have already e. Examination of the extremities for pres- been suggested. The number of cases ence or absence of femoral pulse, dorsalis pedis which could feasibly be studied-6,000 and posterior tibial pulsations, ankle edema, -was much smaller than the adult popu- varicose veins, and phlebitis. had to 3.X-ray examinations, teleoroentgenogram on lation. Therefore, some method 14" x 17" film and on 70 mm. film with two be introduced to select persons and avoid meter target distance. the unknown biases of self-selection. The 4.An electrocardiogram using twelve leads. total sample had to be allocated in such 5.Electrokymographic tracing at 12 points on a as to yield the maximum informa- the cardiac silhouette. way 6.Examination of blood sample for: tion over the period that the study was a. Hemoglobin to be carried out. And the plan had to be b. Serum cholesterol such. that it would be acceptable to the c. Serum phospholipid comnmunity, and could be carried out d. Sf 10-20 fraction (of Gofman) through the community organization. e. Uric acid One important decision which had to. f. Glucose level g. Serologic test for syphilis be reached concerned the age range of 7. A routine urinalysis the study population. Clearly, if only a very young group was studied, only a The aim of securing information on all very small number would develop ar- of these items of history, physical exam- teriosclerotic or hypertensive cardiovas- ination or laboratory test is twofold. cular disease even in 10 to 20 years' First, it is desired to record, in as full time. On the other hand, in the very old detail as possible, the characteristics of group there would be too large a propor- each individual which are considered tion with preexisting cardiovascular relevant to the presence or absence, or disease. To balance these two effects, the the potential development of cardiovas- age group 30 through 59 was selected for cular disease. Second, it is desired on the study. The population in this age range basis of this examination as a whole to was approximately 10,000. If 6,000 of classify the population studied into two this group were taken into the study, groups: (1) those with definite signs of with the age-sex distribution existing in arteriosclerotic or hypertensive cardio- the town, it could be predicted (on the vascular disease, and (2) those appar- basis of the criteria of the study and ently free of these diseases (who may be tentative data available from a small termed "normal" for the purpose of volunteer group) that roughly 5,000 this discussion). would be free of cardiovascular disease It is the " normals " who are the prin- at the time of initial examination. Of cipal focus of interest of the study. They these 5,000 it was estimated that ap- will be brought back for reexamination proximately 400 would be found to have Vol. 41 FRAMINGHAM STUDY 285 cardiovascular disease at the end of the be available when the initial examina- 5th year after the initial examination, tions have been completed early in 1952, 900 at the end of the 10th year, 1,500 and this will increase as follow-up exam- at the end of the 15th year, and 2,150 inations are carried out through the at the end of the 20th year. (These years on the normal group. Analysis of numbers include, of course, persons who the data will proceed at each stage of would be dead of the disease at the end data collection. When initial examina- of the specified period.) These numbers tions have been completed, it will be appeared to be large enough to insure possible to abstract prevalence data of statistically reliable findings, though it considerable interest. It will also be pos- is recognized that even this number of sible to proceed with a study of the cases will not be sufficient to carry out contribution which various elements of all of the detailed analyses which will the total examination make in the deter- suggest themselves in the course of the mination of a final diagnostic impression. study. Analysis of this type will, for example, There remained the problem of secur- give a basis for determining the relative ing an actual listing of persons who efficiency of the miniature chest x-ray, would form the sample. Under ordinary or of certain electrocardiographic leads, circumstances, it would probably have as diagnostic tools as compared with the been desirable to use some form of area total examination. In this area, some sampling. The Town of Framingham, tentative data based on the group of however, publishes annually a listing of volunteers already examined will shortly all residents 20 years of age and over, become available. Another important based on a local census, and it has been type of information will be -data on the possible to use this list as a basis for range of values- of various' diagnostic sampling. (An independent check of tests for " normal" populations, which the completeness of the listing is being have not hitherto been available in medi- made by the Bureau of the Census.) cal literature. The Executive Committee advised that The more truly epidemiological parts it would be desirable not to break up of the analysis are essentially retrospec- families-that is, if one member of a tive and must wait the passage of time. family was to be brought into the sample, At the end of 5 years a portion of the all other family members resident in the base population, which was normal at same household should also be brought the time of initial examination with re- in, provided they were within the eligible spect to the diseases studied, will have age limits. This has been arranged, and passed the borderline into definite ab- the sample has been drawn in systematic normality, and a few will have died. At fashion from a list which is first strati- that point it will be possible to study the fied by family size and by precinct of differences, as of the time of the initial residence, and then arranged in serial examination, between those who re- order by address. mained essentially normal, and those The sampling ratio is two-thirds, who subsequently became abnormal (or which will yield approximately 6,600 diseased). From this study it should be names. This is 10 per cent over the possible to test a number of hypotheses number required for the study in order with respect to factors associated with to provide for losses through refusal or the development of arteriosclerotic or by movement out of the town before hypertensive cardiovascular disease. As examination. the abnormal group increases in size with As the description of the examination the passage of time, such differences as suggests, a formidable mass of data will are found to exist can be determined 286 AMERICAN JOURNAL OF PUBLIC HEALTH March, 1951 with increasing statistical reliability. For Frost, M.D. New York: Commonwealth Fund, 1941. p. 1. the group which becomes abnormal, the 3. Hill, A. Bradford, and Galloway, T. McL. Maternal rate of progression of disease can be Rubella and Congenital Defects. Lancet 256:299- 301, 1949. measured, and from the entire group 4. Jones, T. Duckett, et al. Rheumatic Fever and there will be data which will yield esti- Rheumatic Heart Disease in Proceedings, First Na- tional Conference on Cardiovascular Diseases. New mates of incidence of arteriosclerotic and York: American Heart Association, 1950. pp. 66-77. hypertensive cardiovascular disease for 5. Mackenzie, Sir James. The Basis of Vital Activity; Being a Review of Five Years' Work at the St. a more representative population group Andrews Institute for . London: than has hitherto been studied. Faber and Gwyer, 1926. 6. Framingham Community Health and Tuberculosis REFERENCES Demonstration, National Tuberculosis Association, 1. Paul, J. R. " Epidemiology " in Green, David E., Final Summary Report. Framingham, July, 1924. and Knox, W. Eugene (Eds.), Research in Medical 7. Massachusetts Medical Society, Proceedings of the Science. New York: Macmillan, 1950. p. 53. Council, Annual Meeting, May 24, 1948. New Eng- 2. Maxcy, Kenneth F. (Ed.), Papers of Wade Hampton land J. Med. 239, 4:130, 1948.

New Jersey Local Health Units Bill The first bill introduced into the 1951 affiliated with the county government but its New Jersey State Legislature is a per- jurisdiction would extend only to those missive health district bill. Developed municipalities included in the district. out of the recommendations of the Gov- The central idea of the bill, according ernor's Committee on Local Health to its sponsors, is that qualified, full- Administration, it gives communities a time public health personnel can take number of choices in organizing their care of the public health needs of a local health services. These are: population much larger than is found in most New Jersey communities. By com- 1. Separate municipal organization as at bining with other communities and present. contributing its reasonable share of the 2. A consolidated health district made up of cost, a community will be able to obtain two or more municipalities. This would be independent of county government. the benefits of expert public health 3. A county local health district to include service, and often without substantially some or all of the municipalities of a single greater expenditure than at present for county. In this case the district would be service that is often inadequate.