Progress in Cardiovascular Diseases 53 (2010) 55–61 www.onlinepcd.com

Progress in Cardiovascular Diseases 53 (2010) 55–61 www.onlinepcd.com

Framingham Heart Study: The First 20 Years Gerald M. Oppenheimer⁎

Brooklyn College and the Graduate Center, City University of New York Center for the History and Ethics of Public Health, Mailman School of Public Health, Columbia University

Abstract The Framingham Heart Study remains the most famous and influential investigation in

Statement of Conf ⁎ Address reprint

Associate Professor, C Mailman School of P NY 10032.

E-mail address: g

0033-0620/$ – see fro doi:10.1016/j.pcad.20

cardiovascular disease epidemiology. To generations of epidemiologists, it is a model for the cohort design. Here we revisit the origins of the Framingham Study before it became an accomplished and famous investigation whose existence and success are taken for granted. When in 1947 the Public Health Service initiated the study, knowledge of the distribution and determinants of coronary heart disease was sparse. Epidemiology was primarily focused on infectious disorders. Framingham’s pioneers struggled to invent an appropriate epidemiolo- gical approach to this chronic disease and to establish support for a new kind of research within a community. Thereafter they had to convince skeptical medical professionals that the results of epidemiological investigations of heart disease were applicable to their clinical practices. (Prog Cardiovasc Dis 2010;53:55-61)

© 2010 Elsevier Inc. All rights reserved. 

Keywords: Framingham heart study; Public health service; Epidemiology; Cohort study; Cardiovascular disease; Disease causation; Controlled clinical trial

The Framingham Heart Study (FHS) remains the most famous and influential investigation in cardiovascular disease (CVD) epidemiology. Since its inauguration in 1947, it has generated over 2000 peer reviewed articles. It has spawned two collateral investigations, the Offspring and Third generation studies, initiated in 1971 and 2002, respectively. It has served as the model for other cohort studies in Honolulu and Puerto Rico.1,2 Framingham has provided a unique database for researchers interested in testing a range of non-CVD issues, recently whether obesity and smoking are conceivably transmitted within social networks.3,4 According to Mervin Susser, epi- demiologist and historian, Framingham “is the epitome

lict of Interest: see page 60. requests to Gerald M. Oppenheimer, PhD, MPH, enter for the History and Ethics of Public Health, ublic Health, 722 West 168th Street, New York,

o10@columbia.edu.

nt matter © 2010 Elsevier Inc. All rights reserved. 10.03.003

of successful epidemiological research, productive of insights and applications…[and] the prototype and model of the cohort study.”5

The purpose of this article is to revisit the origins of the Framingham Study before it became an accomplished and famous investigation whose existence and success are taken for granted. I will describe the problems that physicians, statisticians, and public health officials confronted in order to create an epidemiological study and later to defend the initial clinical recommendations drawn from the path-breaking epidemiological results.

Framingham, however, was but one of several CVD cohort studies funded by the federal government in the wake of World War II. It was preceded by the Minnesota Business and Professional Men’s Study, headed by physiologist Ancel Keys, and quickly followed by investigations in Los Angeles, Calif; San Francisco, Calif; and Albany, NY. The United States Public Health Service was anxious to elucidate the causes of cardiovas- cular disease, to which it attributed 44% of total deaths in 1948, 20% higher than what it had been in 1940.6

55

 

 

Abbreviations and Acronyms

FHS = Framingham Heart Study

CVD = cardiovascular disease

PHS = Public Health Service

TB = tuberculosis

NHI =National Heart Institute

CHD = coronary heart disease

RCT = randomized controlled trial

56 G.M. Oppenheimer / Progress in Cardiovascular Diseases 53 (2010) 55–61

What those causes were remained amatter of spec- ulation. Experts on CVD were increasingly focused on the etiological role of arteriosclerosis and the importance of cultural factors.7 Unlike an alter- native model, aging, and degeneration as determi- nants of the disease, the new conceptualization permitted a role for pri- mary prevention.

Heart disease was part of a growing concern about chronic disease within the Public Health Service (PHS). In the first decades of the 20th century, the PHS, along with insurance companies and the Milbank Memorial Fund, had pioneered morbidity surveys whose results suggested that the burden of chronic illness and disability was rising. During the Depression, the PHS conducted a massive National Health Survey. Over one sixth of the US population suffered from a disabling chronic disease or physical impairment, the PHS found, and half of these individuals were younger than 45 years; chronic disease and disability affected many in their most productive years.8 The PHS recognized the rising prevalence of chronic disorders and called for public health research aimed at primary and secondary prevention of heart disease, cancer, stroke, and diabetes. World War II temporarily postponed that policy.

Launching the study

In 1947, epidemiology’s primary focus remained the study of infectious disease. At the PHS, JosephMountin, director of the Bureau of State Services, had recently created the Communicable Disease Center for that purpose.9 But Mountin, a master of public health policy, guided the PHS in a new direction. He championed the application of control programs, initially developed for infectious disorders, to chronic, non-infectious diseases.11 These generally included community-based screening and diagnostic interventions. In pressing for heart disease control efforts, Mountin added an epidemiological component.10 He subsequently selected Gilcin Meadors, a young PHS office, to initiate that epidemiological research, an investigation that evolved into the FHS.12

Precisely how epidemiology could be applied to CVD was unclear. Wade Hampton Frost, a pioneer in the epidemiological study of chronic disease, tuberculosis (TB) in particular, had investigated the factors responsible for TB transmission and susceptibility.13 But, in this instance, the necessary cause, the bacillus, was known, as was tuberculosis’ pathophysiology. How were epidemiol-

ogists to capture any of the determinants of CVD in the absence of such knowledge about heart disease? How were they to map a disorder which appeared to have a long, silent onset before it abruptly announced itself?

A number of issues made the launching of the Framingham study particularly difficult. The first, a unique factor, was the multiple authorities invested in the nascent project.12 The PSC worked with the Massachusetts Commissioner of Health, Vlado Getting, and David Rutstein, newly appointed chair of Harvard’s Department of Preventive Medicine. Rutstein who had previously been medical director of the American Heart Association, was the prime mover behind Framingham’s selection as the study site. Getting supported the idea, noting that the town, just west of Boston, possessed 28 000 inhabitants, sufficient for an epidemiological investiga- tion, and had a history of community participation in research, having been the site of an important TB study conducted from 1917 to 1923.14,15 (In addition, Framing- ham had a stable, locally employed and medically served populace; in 1947, it boasted two hospitals and a group of well-trained physicians interested in the possibility of a scientific study in their town10).

David Rutstein, a powerful and willful figure, had significant ties to the PHS leadership. After leaving the American Heart Association, he retained links to the academic elite that dominated the Association, drawing upon its Boston members to form Framingham’s technical advisory group. Rutstein16 sought to bend the new study to his own clinical purposes. To the Surgeon General, he suggested an evaluation of population screening tools like the electrokymograph, which recorded the movement of the heart.10,16 Both he and his advisory board of cardiologists particularly wanted to focus the research on diagnostic criteria and clinical performance.

Gilcin Meadors, by contrast, was a young Mississippi- born physician who had only graduated from Tulane Medical School in 1940 and just completed a masters degree in public health in epidemiology at Johns Hopkins.12 By July 1947, before the Framingham site had been selected, he developed the outline of a plan that proposed a goal recognizable to later generations of Framingham leaders:

“This project is designed to study the expression of coronary artery disease in a normal or unselected popula- tion and to determine the factors predisposing it to the development of the disease through clinical and laboratory examination and long-term follow-up of such a group.”17

Meadors envisioned a study composed of volunteers who would be followed for 5–10 years, periodically interviewed and tested to identify incipient cases of CVD among them. Subsequent analysis would measure the

 

 

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effect of heredity and psychic status, constitutional factors like body build and behaviors like dietary habits. Meadors17 hoped in time to develop “methods for examination of large population groups for heart disease,” but he was unclear as to how his variables were to be measured and analyzed. Some baseline factors he sought to capture, such as psychic status, were difficult to measure validly. He also wrongly believed that a self-selected cohort could give him an unbiased estimate of incidence and prevalence. Analytically weak, Meadors had problems substantiating his claims for the importance of clinical epidemiology to those like Rutstein who were skeptical of its usefulness or committed to alternative scientific goals. The scientific purpose and design of the Framingham study was thus contested terrain, pitting personalities, specialties, and research approaches.

Meador’s17 strength lay in his ability to draw the Framingham community into support of the study, whatever its subsequent shape. Ultimately of national and international importance, the FHS began very much as a local experiment bounded by the strengths and weaknesses of a single town (the first foreign publications using Framingham data only date from the mid- 1960s18,19). Meadors drafted town leaders to form the core of his Executive Committee. The latter, in turn, recruited critical constituencies, including the business, industrial and civic elite, and formed outreach and publicity committees. Meadors recognized that, to be successful, the study had to be adopted, if not truly “owned,” by the town’s citizenry. Only strong community support would stimulate voluntary participation and subsequent adherence. Meadors insisted that “the Heart Disease Study belongs to the community of Framingham [and] is a part of the local health program.”20 As such, he had to gain the confidence and support of Framingham’s physicians, assuring them that any information on participants would be sent to them and not divulged to their patients by the study’s staff.12

As a small, self-governing New England town with a prosperous economic sector and an unusually stable population, Framingham was an ideal site for a cohort study. But these features also made it highly unrepresen- tative. In particular, the Framingham Study sample consisted almost entirely of white, middle class Euro- Americans. Despite its impulse to scientific universality, the study lacked Blacks, Latinos, or Asians.

Over Framingham’s first year, Rutstein proved increas- ingly rash and proprietary, confronting the PHS, for example, over administrative control of the Framingham program. Thereafter, he urged a separation of the epidemiological and control projects, perhaps initiating the move of the latter to Newton, Mass.12 This split left the epidemiological study with greater autonomy, more so as

Rutstein’s influence faded as he made more demands the PHS could not accept.

Revamping the study

But another event proved more decisive. The epidemiological sophistication and validity of the Fra- mingham study was transformed in 1949, the year it was transferred to the newly created National Heart Institute (NHI). The first head of the NHI directed Felix Moore, his chief of biometrics, to evaluate Framingham’s methodology.21 Moore, a quantitative sociologist with considerable federal experience, brought to Framingham a talent for applied statistics, expertise in writing and scaling questionnaires, and the rigor of years of research work.22 During Framingham’s first year under the NHI, he was probably the principal architect of its scien- tific transformation.23

With Meadors’ assistance, Moore redesigned Framing- ham into a 20-year study of individuals, initially free of arteriosclerotic disease, selected randomly from the town’s adult residents, both male and female, 30 to 59 years of age.23,24 Because Moore underestimated the refusal rate among those randomly selected, he and Meadors had to fall back on volunteers; ultimately, they comprised 14% of the cohort study’s 5127 participants, adding a further bias to the study.10,12 Baseline variables were also reexamined. After some debate, cholesterol was included, as were weight and blood pressure and the consumption of alcohol and tobacco. From the study’s start, clinical variables predominated, with little interest in psychosomatic, constitutional, or sociological determi- nants of heart disease.25

Moore was particularly concerned about selecting those variables that could by validly and reliably measured. But other issues also intruded. As the Framingham study depended on the good will of its participants, he and the director who succeeded Meadors in spring 1950, Thomas Dawber, excluded those items they thought would deeply disturb people, for example, questions about psychiatric status, sexual dysfunction, and (perhaps given the conservative Cold War era) income and social class.10,26,27 Dawber, who led Framingham over the next 2 decades, was also skeptical about the value of the social sciences or public health in what he regarded as the domain of medicine. To him, epidemiology was “clinical investigation on a commu- nity level.”28 He strongly believed that his study should be defined by doctors, and that the outcomes it sought should those useful to practicing physicians.29

Finally, the study was guided by a manual of operations describing its “methods of examination and acceptable criteria for diagnosis.”30 The FHS was to correlate clinical and laboratory data and individual histories collected before the onset of disease with “findings related to and

 

 

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diagnostic of…degenerative cardiovascular disease.”30 In this way, it would “detect early signs pointing to probable development of disease” and uncover “etiological factors.”30 The manual also laid out 28 factor-specific hypotheses. Each of these expressed a possible link between CVD and degree of exposure to a factor, for example, “[d]egenerative cardiovascular disease appears early and progresses more rapidly in persons who habitually use tobacco.”30 In the logic of these hypotheses, one can already perceive the kernel of the “risk factor.” Although the term first appeared in a Framingham study article in 1961,31 the concept predates the heart study32

and pervaded its publications over the 1950s.

Risk factors, primary prevention, and the coronary prone patient

With its supportive cadre of NHI statisticians, always a source of Framingham’s strength, results came surpris- ingly fast. At the American Public Health annual meeting in 1956, Dawber et al26 presented some of the central findings of the FHS. They revealed that atherosclerotic heart disease was significantly associated with age and male sex. In men 45 to 62 years of age, for whom sufficient data existed, heart disease was correlated with hypertension, hypercholesterolemia, and obesity. Where two factors were elevated, probability of CVD increased greatly. The value of Framingham’s findings were enhanced by corroboratory results from the Los Angeles and Albany heart studies, reported at the same meeting.33,34 Over the next decade, these cohort studies would extend their findings. By 1960, for example, Framingham and Albany, by combining data to provide sufficient statistical power, showed a significant associa- tion and dose-response relationship between cigarette smoking and myocardial infarctions and heart disease– related deaths.35

The stature of epidemiology as a method for investigating CVD was heightened by the rapidity with which Framingham and other contemporary cohort studies reported their results. So too were the mortality data that emerged. Framingham found that through 1956, the case fatality rate for heart attacks was nearly 50%; almost a third of these were “sudden” fatalities (defined as deaths within minutes).26 With such stunning evi- dence, the test for epidemiologists became what to do with their information. Given the high coronary death rates and the absence of curative therapies, they took on the task of convincing their clinical colleagues, many of them skeptical of quantitative population-based data, to educate their patients about the value of primary prevention of CVD.36

The message that Dawber and others26 within Framingham like William Kannel sent to physicians focused on the notion of susceptibility. In this they were

joined by the heads of other studies like Ancel Keys and Jerry Stamler (who initiated a heart disease prevention trial in Chicago as early as 1957).36-38 Kannel and Dawber,36 starting in the early 1960s, advanced the concept of the “coronary-prone” individual, the patient already at greater probability of developing heart disease. Physicians were urged to intervene early, based on their diagnosis of their patients’ risk-laden signs and symp- toms, before sudden death, a heart attack or angina pectoris announced the disease’s existence.

From its earliest decades, Framingham sought to make itself indispensable to medical practice, allaying the indifference with which many contemporary doctors may have held it. Dawber and Kannel intimated that the “coronary-prone” patient could easily be identified using normal office procedures.36,39 Theoretically, that person was an obese middle-aged man, a heavy smoker with high serum cholesterol and blood pressure, low vital capacity and electrocardiographic abnormalities.40 In the office, the picture would be less clear, more nuanced, but doctors were warned that a combination of risk factors increased coronary heart disease (CHD) probability, doubling, tripling, or even quadrupling the risk.31

Finally, from epidemiological data, Dawber and Kannel warned that, contrary to physicians’ training, there was no cutoff in levels of blood pressure or serum cholesterol, below which they were “risk-free” or “normal.”31 In fact, given epidemiological observations, almost every patient was susceptible to CVD, especially in modern cultures like the United States. The art and science of medicine was then to determine, given patients’ composite of signs, symptoms and history, their degree of “risk.”

Causal uncertainty and epidemiological activism

By the early 1960s, the epidemiologists at Framingham and their contemporaries had begun to develop a new concept of chronic disease based on notions of probability and disease prevention.41 This model did not require much understanding of underlying disease mechanisms. It assumed that the disorders that were killing most Americans, heart disease, cancer, and stroke, were the consequences of a long induction period and generally multiple factors, some of which could be isolated. Often, certainly in the case of heart disease, none of these factors were necessary or sufficient. Frequently, they were of small statistical effect (the instance of cigarette smoking and lung cancer being an obvious exception). It was therefore difficult to predict who would be afflicted by the chronic disease, who would not. Although chronic diseases might be the consequence of “modern life,” there was little purchase, politically and socially, in advocating broad environmental reforms. In the 1960s, the response to heart disease, stroke, and cancer was

 

 

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primarily a medical one, advocating individual behavioral or “life-style” change, initially, at least, against the grain of market and cultural forces.

In making such life-style recommendations, epidemiol- ogists like those at Framingham were drawing inferences not yet supported by their evidence. They based their advocacy on observational research, their cohort studies, and not on controlled experiment. With the exception of cigarette smoking, there was no scientific confirmation at the time that by reducing risk factors—high blood pressure, cholesterol, or weight in patients—doctors would be able to lower the risk of heart disease, producing outcomes like those in persons with habitually lower numbers.40 And there was no way of predicting whether the correlations between heart disease and risk factors, based on current studies, would hold true in future ones. Most importantly, epidemiologists were still without tested scientific knowledge of the underlying causal chain of events that led to heart disease. If they knew anything, they knew correlations.

Without evidence of causality, Framingham and other clinical epidemiologists fell back on the need for good clinical practice and for action. William Kannel argued, for example: “If physicians were to wait for unquestioned proof of efficacy of every therapeutic measure they are called upon to employ, they would never treat cancer, arthritis, or most of the degenerative and metabolic disorders. In short, they would be reduced to therapeutic nihilists.”40

Certainly, any physician could read and act upon the risk characteristics of his or her patients, even absent proof of the efficacy of such actions. Doing so—reducing blood pressure or weight—was consistent with standard medical care. And the hazards involved here were small compared with the potential benefits.

In 1964, the Surgeon General’s Advisory Committee on smoking and health added its considerable scientific and political status to the position taken by Dawber, Kannel, and their colleagues. Interestingly, in the famous report, Smoking and Health, which authoritatively out- lined for a generation of epidemiologists the criteria necessary for judging causality, the committee addressed the need for precautionary action against heart disease risk factors, despite the absence of demonstrated causal association. Referring to cigarette smoking, high blood pressure, serum cholesterol, and obesity, it argued, “The causative role of these factors in coronary disease, though not proven, is suspected strongly enough to be a major reason for taking countermeasures against them.”42 Here a lower level of proof seemed apt, given the consistency of evidence across epidemiological studies and the enormous toll wrought by CHD.

Despite the advocacy of the Advisory Committee and the persistence of CVD epidemiologists, many physicians in the 1960s were reluctant to accept the need for primary

prevention. There was still controversy over whether to treat essential hypertension or wait until a patient’s pressure became very high or complications had set in.43

Doctors were unsure whether serum cholesterol was a factor in CHD.43,44 Such questions persisted, despite the consistency of the results produced by the growing number of CVD cohort studies.

Constructing a consensus

The inability of the epidemiological cohort studies to allay doubts about the importance of most risk factors spawned a drive to field randomized controlled trials (RCTs), a relatively new technology. Beginning in the early 1960s, researchers sought to show under controlled conditions that, by reducing such factors, they could measurably diminish CHD events. To do so required the resources of the US government, the NHI in particular. At that time, the NHI, unlike its peer, the National Cancer Institute, had little experience with such trials. Yet, over the 1960s, the NHI produced two significant double-blind RCTs focusing on the possibly causal role of cholesterol: the Diet-Heart study and the Coronary Drug Project.45 The Diet-Heart study undertook the seemingly impossible task of testing the “coronary-genic” effects of the contemporary American diet. More conventional scientif- ically, the Coronary Drug Project assessed the effect of 5 cholesterol-lowering medications on CHD. Although neither, for different reasons, succeeded, they were followed by additional controlled trials. These helped establish a broad consensus within the NHI that, like smoking cessation, reducing blood pressure and choles- terol lowered rates of CHD events; RCTs in the United States and Europe played a pivotal part in shifting the position of many physicians and policy makers toward favoring primary prevention as a weapon against cardio- vascular disease.

Population-based studies, particularly randomized con- trolled trials and observational cohort studies of CHD, helped effect a major change in American culture and marketplace in the second half of the 20th century. Throughout that period, as investigations waxed and waned, one scientific venture ceaselessly continued on its prescribed course, producing a massive, corroboratory base of data on the natural history of CVD. Beyond Meadors’ imagining, the Framingham study he initiated in 1947 still seeks, in his words, “the factors predisposing [a normal population] to the development of the disease through clinical and laboratory examination and long-term follow-up of such a group.”

The Framingham study and its longevity were only possible because of federal commitment to the project, financially, politically and intellectually. It was a product of the purposeful US government that emerged from the

 

 

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Great Depression and World War II. Subsequently, this intensely local study, initially of indefinite shape and purpose, has become an icon of modern epidemiology, both here and abroad. But it remains very much an American story, a linkage of government, science, and community, midway in time between the New Deal and the Great Society.

Acknowledgments

This work was supported in part by a National Endow- ment for the Humanities Fellowship Award (FA-53395) and a Professional Staff Congress-City University of New York Award (#610940039).

Statement of Conflict of Interest

The author declares that there are no conflicts of interest.

References

1. Garcia-Palmieri MR, Feliberti M, Costas R, et al: An epidemiological study on coronary heart disease in Puerto Rico: the Puerto Rico Heart Health Program. Bol Asoc Med PR 1969;61:174-179.

2. Kagan A, Rhoads GG, Zeegen PD, et al: Coronary heart disease among men of Japanese ancestry in Hawaii: the Honolulu Heart Study. Israel J Med Sci 1971;7:1573-1577.

3. Christakis NA, Fowler JH: The spread of obesity in a large social network over 32 years. N Engl J Med 2007;357:370-379.

4. Christarkis NA, Fowler JH: The collective dynamics of smoking in a large social network. N Eng J Med 2008;358:2249-2258.

5. Susser M: Epidemiology in the United States after World War II: the evolution of a technique. Epidemiol Rev 1985;7:147-177.

6. Moore F. Minutes, October 14-15, 1949, in Records of the National Institute of Health, National Advisory Heart Council, Box 21, National Archives, College Park, MD.

7. Keys A: Nutrition in relation to the etiology and the course of degenerative diseases. J Am Diet Assoc 1948;24:281-285.

8. Fox DM: Power and Illness: The Failure and Future of American Health Policy. Berkeley, CA: University of California Press; 1993.

9. Etheredge EW: Sentinel for Health: A History of the Centers for Disease Control. Berkeley, CA: University of California Press; 1992.

10. Dawber TR: The Framingham Study: The Epidemiology of Atherosclerotic Disease. Cambridge, MA: Harvard University Press; 1980.

11. Mountin JW: Changing concepts of local public health services, in Selected Papers of Joseph W. Mountin, M.D. Joseph Mountin Memorial Committee n.p., 1956.

12. Oppenheimer GM: Becoming the Framingham Study, 1947-1950. Am J Public Health 2005;95:602-610.

13. Frost WH: Risk of persons in familial contact with pulmonary tuberculosis. Am J Public Health 1933;23:426-432.

14. Aronowitz R: The social construction of coronary heart disease risk factors. In: Aronowitz R, editor. Making sense of illness: science, society and disease. New York, NY: Cambridge University Press; 1998. p. 111-144.

15. Framingham Monograph No. 10: Final Summary Report, 1917-1923 Inclusive. Framingham, MA n.p., 1924.

16. Rutstein D: Correspondence to T. Parran, October 10, 1947, in Papers of the National Heart, Lung and Blood Institute, Epidemi- ology Correspondence Folder.

17. Meadors G: Correspondence to B. Boone, July 19, 1947, in Papers of the National Heart, Lung and Blood Institute, Epidemiology Correspondence Folder.

18. Rose G: Familial patterns in ischaemic heart disease. Br J Prev Soc Med 1964;18:75-80.

19. Kannel WB, Widmer LK, Dawber TR: Gefahrdung durch coronare Herzkrankheit; Folgerungen fur die Praxis aus 10 Jahren Framing- ham-Studie. Susceptibility to coronary heart disease; preventive implications of 10 years of observation in the Framingham Study. Schweiz Med Wochenschr 1965;95:18-24.

20. Meadors G: Correspondence to B. Boone, May 6, 1948, in Papers of the National Heart, Lung and Blood Institute, Monthly Report Heart Disease Epidemiology Folder.

21. Meadors G: Correspondence to E.W. Ford, March 1, 1949, in Papers of the National Heart, Lung and Blood Institute, Monthly Report Heart Disease Epidemiology Folder.

22. Gordon T: NHI statistician, oral communication; 2001. 23. Moore F: Memorandum, August 1, 1949, in Papers of the National

Heart, Lung and Blood Institute, Framingham Heart Disease Epidemiology (General) Folder.

24. Giroux E: Cohort study and multivariate analysis: An epistemolog- ical and historical analysis of the Framingham heart study. Revue d’Epidemiologie et de Santé Publique 2008;56:177-188.

25. Moore F: Correspondence to C.J. Van Slyke, August 26, 1949, in Papers of the National Heart, Lung and Blood Institute, Framingham Heart Disease Epidemiology (General) Folder.

26. Dawber TR, Moore FE, Mann GV: Coronary heart disease in the Framingham Study. Am J Public Health 1957;47:4-24.

27. Schrecker E: No Ivory Tower: McCarthyism and the Universities. New York, NY: Oxford University Press; 1986.

28. Dawber T: Risk factors in young adults: the lessons from epidemio- logical studies of cardiovascular disease—Framingham, Tecumseh, and Evans County. J Am Coll Health Assoc 1973;22:84-95.

29. Dawber TR, personal communication, November 2001. 30. National Heart Institute: Heart Disease Epidemiology Study, manual

of operations, 1949, in Papers of the National Heart, Lung and Blood Institute, Historical Folder.

31. Kannel W, Dawber T, Kagen A, et al: Factors of risk in the development of coronary heart disease—six-year follow-up experience, the Framingham Study. Ann Intern Med 1961;55: 33-48.

32. Rothstein W: Public health and the risk factor: a history of an uneven medical revolution. Rochester, NY: University of Rochester Press; 2003.

33. Doyle JT, Haslin AS, Hilleboe HE, et al: A prospective study of degenerative cardiovascular disease in Albany: report of three years experience. Am J Public Health 1957;4:25-32.

34. Chapman JM, Goerke LS, Dixon W, et al: Measuring the risk of coronary heart disease in adult population groups. The clinical status of a population group in Los Angeles under observation for two to three years. Am J Public Health 1957;4:33-42.

35. Doyle JT, Dawber TR, Kannel WB, et al: Cigarette smoking and coronary heart disease: combined experience of the Framingham and Albany studies. N Eng J Med 1962;266:796-801.

36. Dawber TR, Kannel WB: Susceptibility to coronary heart disease. Mod Concepts Cardiovasc Dis 1961;30:671-677.

37. Keys A, Taylor HL, Blackburn H, et al: Coronary heart disease among Minnesota business and professional men followed 15 years. Circulation 1963;28:381-395.

38. Stamler J, Berkson DM, Young Q, et al: Approaches to the primary prevention of clinical coronary heart disease in high-risk, middle- aged men. Ann N Y Acad Sci 1963;97:932-951.

 

 

61G.M. Oppenheimer / Progress in Cardiovascular Diseases 53 (2010) 55–61

39. Kannel WB, Dawber TR, McNamara PM: Detection of the coronary- prone adult: the Framingham Study. IowaMed Soc 1966;56:26-34.

40. Kannel WB, Kagan A, Dawber TR, et al: Epidemiology of coronary heart disease. Implications for the practicing physician. Geriatrics 1962;17:675-690.

41. Oppenheimer GM: Emergence of coronary heart disease epidemio- logy in the United States (1947-70). Int J Epidemiol 2006;35:720-730.

42. U.S. Department of Health, Education and Welfare. Surgeon General’s Report, Smoking and Health: Report of the Advisory

Committee to the Surgeon General of the Public Health Service. PHS Publication No. 1103. Washington, DC: Government Printing Office; 1964.

43. Dawber TR, Kannel WB: Application of epidemiology of coronary heart disease to medical practice. Mod Med 1962;30:85-101.

44. Kannel WB: personal communication, July 11, 2002. 45. Marks HM: The Progress of Experiment, Scientific and Therapeutic

Reform in the United States, 1900-1990. Cambridge, England: Cambridge University Press; 1997.