Framingham Heart Study
The Framingham Heart Study is a long-term, ongoing cardiovascular study on residents of the town of Framingham, Massachusetts. The study began in 1948 with 5,209 adult subjects from Framingham, and is now on its third generation of participants. Prior to it almost nothing was known about the "epidemiology of hypertensive or arteriosclerotic cardiovascular disease". Much of the now-common knowledge concerning heart disease, such as the effects of diet, exercise, and common medications such as aspirin, is based on this longitudinal study. It is a project of the National Heart, Lung, and Blood Institute, in collaboration with (since 1971) Boston University. Various health professionals from the hospitals and universities of Greater Boston staff the project.
Thomas Royle Dawber was Director of the study from 1949 to 1966. He was appointed as chief epidemiologist shortly after the start of the project, when it was not progressing well. The study had been intended to last 20 years, but at that time Dawber moved to Boston and became chairman of preventive medicine, raising funds to continue the project and taking it with him.
By 1968, a fight was underway to keep the Framingham Study going in an era marked by protests, assassinations, the struggle for civil rights, and controversy surrounding America's military involvement with the Vietnam War. A committee gathered and considered that, after 20 years of research, the Framingham study should come to an end, since their hypothesis had been tested and extensive information concerning heart diseases had been gathered. Despite this conclusion, the study continued, and in 1971, it enrolled a second generation of participants. In 1994, a more diverse sampling of Framingham residents was enrolled as the "Omni cohort." In April 2002, a third generation was enrolled in the core study, and a second generation of Omni participants was enrolled in the following year.
Strong and weak points
Over 1000 medical papers have been published related to the Framingham Heart Study. It is generally accepted that the work is outstanding in its scope and duration, and overall is considered very useful. The initial population was 5,209 healthy men and women aged 30 to 62, not the whole of the town population, as is sometimes assumed.
It was rightly assumed from the start of the Framingham Heart Study that cardiac health can be influenced by lifestyle and environmental factors, and by inheritance. The Framingham Heart Study is the origin of the term risk factor. Before the Framingham Heart Study, doctors had little sense of prevention. In the 1950s, it was believed that clogging of arteries and narrowing of arteries (atherosclerosis, arteriosclerosis) was a normal part of aging and occurred universally as people became older. High blood pressure (hypertension) and elevated serum cholesterol (hypercholesterolemia) were also seen as normal consequences of aging in the 1950s, and no treatment was initiated. These and further risk factors, e.g., homocysteine, were gradually discovered over the years.
The Framingham Heart Study, along with other important large studies, e.g., the Seven Countries Study, Nurses' Health Study, Women's Health Initiative, also showed the importance of healthy diet, not being overweight or obese, and regular exercise in maintaining good health, and that there are differences in cardiovascular risk between men and women. It also confirmed that cigarette smoking is a highly significant factor in the development of heart disease, leading to angina pectoris, myocardial infarction (MI), and coronary death, along with other important studies about smoking, e.g., the British Doctors Study.
Recently the Framingham studies have become regarded as overestimating risk, particularly in the lower risk groups, e.g., for UK populations.
One question in evidence-based medicine is how closely the people in a study resemble the patient with which the healthcare professional is dealing. There has been discussion of the study in this regard.
Framingham Risk Score
The 10-year cardiovascular risk of an individual can be estimated with the easy to use Framingham Risk Score, including individuals without known cardiovascular disease. The Framingham Risk Score is based on findings of the Framingham Heart Study.
Major findings from the Framingham Heart Study, according to the researchers themselves:
- Cigarette smoking increases risk of heart disease. Increased cholesterol and elevated blood pressure increase risk of heart disease. Exercise decreases risk of heart disease, and obesity increases it.
- Elevated blood pressure increases risk of stroke. In women who are postmenopausal, risk of heart disease is increased, compared with women who are premenopausal. Psychosocial factors affect risk of heart disease.
- High levels of HDL cholesterol reduce risk of heart disease.
- Having an enlarged left ventricle of the heart (left ventricular hypertrophy) increases risk of stroke. Elevated blood pressure can progress to heart failure. Framingham Risk Score is published, and correctly predicts 10-year risk of future coronary heart disease (CHD) events. At 40 years of age, the lifetime risk for CHD is 50% for men and 33% for women.
- So called "high normal blood pressure" increases risk of cardiovascular disease (high normal blood pressure is called prehypertension in medicine; it is defined as a systolic pressure of 120–139 mm Hg and/or a diastolic pressure of 80–89 mm Hg). Lifetime risk of developing elevated blood pressure is 90%. Obesity is a risk factor for heart failure. Serum aldosterone levels predict risk of elevated blood pressure. Lifetime risk for obesity is approximately 50%. The "SHARe" project is announced, a genome wide association study within the Framingham Heart Study. Social contacts of individuals are relevant to whether a person is obese, and whether cigarette smokers decide to quit smoking. Four risk factors for a precursor of heart failure are discovered. 30-year risk for serious cardiac events can be calculated. American Heart Association considers certain genomic findings of the Framingham Heart Study one of the top research achievements in cardiology. Some genes increase risk of atrial fibrillation. Risk of poor memory is increased in middle aged men and women if the parents had suffered from dementia.
To what the study participants consented
The Framingham Heart Study participants, and their children and grandchildren, voluntarily consented to undergo a detailed medical history, physical examination, and medical tests every two years, creating a wealth of data about physical and mental health, especially about cardiovascular disease.
In recent years, scientists have been carrying out genetic research within the Framingham Heart Study.
Inheritance patterns in families, heritability and genetic correlations, molecular markers, and associations have been studied. The association studies include traditional genetic association studies, i.e., looking for associations of cardiovascular risk with gene polymorphisms (single-nucleotide polymorphisms, SNPs) in candidate genes, and genome wide association studies (GWAS). For example, one genome wide study, called the 100 K Study, included almost 1400 participants of the Framingham Heart Study (from the original cohort, and the offspring cohort), and revealed a genetic variant associated with obesity. The researchers were able to replicate this particular result in four other populations. Further, the SHARe Study (SNP Health Association Resource Study) uncovered new candidate genes, and confirmed already known candidate genes (for homocysteine and vitamin B12 levels) in participants of the Framingham Heart Study.
However, clinically, despite these (and other) efforts, the aggregate effect of genes on cardiovascular disease risk beyond that of traditional cardiovascular risk factors has not been established until now.
- Busselton Health Study has been carried out since 1966 in a high proportion of the residents of Busselton, a town in Western Australia, over a period of many years. A database has been compiled and is managed by the School of Population Health at the University of Western Australia. Although the results of the Busselton Health Study and the Framingham Heart Study are similar in many aspects, the Busselton Health Study investigated also the influence of some factors that had not been not investigated in the Framingham Heart Study, e.g., sleep apnea.
- The Caerphilly Heart Disease Study, also known as the Caerphilly Prospective Study (CaPS), is an epidemiological prospective cohort, set up in 1979 in a representative population sample drawn from a typical small town in South Wales, UK. The study has collected wide ranging data and has led to over 400 publications in the medical press, notably on vascular disease, cognitive function and healthy living.
- China-Cornell-Oxford Project, also known as "China-Oxford-Cornell Study on dietary, lifestyle and disease mortality characteristics in 65 rural Chinese counties". This study was later referred to as "China Study I". The successor study is named "China Study II".
- Mahmood, Levy, Vasan, Wang (2013). "The Framingham Heart Study and the epidemiology of cardiovascular disease: a historical perspective" (fee required). Lancet 27 (9921): 61752–3. doi:10.1016/S0140-6736(13)61752-3. PMID 24084292.
- 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., Epidemiological Approaches to Heart Disease: The Framingham Study Presented at a Joint Session of the Epidemiology, Health Officers, Medical Care, and Statistics Sections of the American Public Health Association, at the Seventy-eighth Annual Meeting in St. Louis, Mo., November 3, 1950.
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- Some lessons in cardiovascular epidemiology from Framingham. Kannel WB. Am J Cardiol. 1976 Feb;37(2):269-82.
- Applicability of cholesterol-lowering primary prevention trials to a general population: the Framingham Heart Study. Lloyd-Jones DM, O'Donnell CJ, D'Agostino RB, Massaro J, Silbershatz H, Wilson PW. Arch Intern Med. 2001 Apr 9;161(7):949-54.
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- Genetics of the Framingham Heart Study population. Govindaraju DR, Cupples LA, Kannel WB, O'Donnell CJ, Atwood LD, D'Agostino RB Sr, Fox CS, Larson M, Levy D, Murabito J, Vasan RS, Splansky GL, Wolf PA, Benjamin EJ. Adv Genet. 2008;62:33-65.
- Nutritional research within the Framingham Heart Study. Millen BE, Quatromoni PA. J Nutr Health Aging. 2001;5(3):139-43.
- Women and cardiovascular disease: contributions from the Framingham Heart Study. Murabito JM. J Am Med Womens Assoc. 1995 Mar-Apr;50(2):35-9.
- The health risks of smoking. The Framingham Study: 34 years of follow-up. Freund KM, Belanger AJ, D'Agostino RB, Kannel WB. Ann Epidemiol. 1993 Jul;3(4):417-24.
- Mortality in relation to smoking: 50 years' observations on male British doctors. Doll R, Peto R, Boreham J, Sutherland I. BMJ. 2004 Jun 26;328(7455):1519.
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- Atwood LD, Wolf PA, Heard-Costa NL, Massaro JM, Beiser A, D'Agostino RB, DeCarli C (Jul 2004). "Genetic variation in white matter hyperintensity volume in the Framingham Study". Stroke 35 (7): 1609–13. doi:10.1161/01.str.0000129643.77045.10.
- Elias MF, Sullivan LM, D'Agostino RB, Elias PK, Jacques PF, Selhub J, Seshadri S, Au R, Beiser A et al. (Oct 2005). "Homocysteine and cognitive performance in the Framingham offspring study: age is important". Am J Epidemiol 162 (7): 644–53. doi:10.1093/aje/kwi259.
- Herbert A, Gerry NP, McQueen MB, Heid IM, Pfeufer A, Illig T, Wichmann HE, Meitinger T, Hunter D et al. (Apr 2006). "A common genetic variant is associated with adult and childhood obesity". Science 312 (5771): 279–83. doi:10.1126/science.1124779.
- Hazra A, Kraft P, Lazarus R, Chen C, Chanock SJ, Jacques P, Selhub J, Hunter DJ (Dec 2009). "Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway". Hum Mol Genet 18 (23): 4677–87. doi:10.1093/hmg/ddp428.
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- A list of publications from the Busselton study
- Knuiman MW, Vu HT (Oct 1997). "Prediction of coronary heart disease mortality in Busselton, Western Australia: an evaluation of the Framingham, national health epidemiologic follow up study, and WHO ERICA risk scores". J Epidemiol Community Health 51 (5): 515–9. doi:10.1136/jech.51.5.515.
- Marshall NS, Wong KK, Phillips CL, Liu PY, Knuiman MW, Grunstein RR (Feb 2009). "Is sleep apnea an independent risk factor for prevalent and incident diabetes in the Busselton Health Study?". J Clin Sleep Med. 5 (1): 15–20.
- The Caerphilly and Speedwell Collaborative Group. (September 1984). "Caerphilly and Speedwell collaborative heart disease studies.". Journal of Epidemiology and Public Health 38 (3): 259–262. doi:10.1136/jech.38.3.259. PMC 1052363. PMID 1052363.
- Elwood P, Galante J, Pickering J et al. (2013). "Healthy Lifestyles Reduce the Incidence of Chronic Diseases and Dementia: Evidence from the Caerphilly Cohort Study". PLOS ONE 8 (12): e81877. doi:10.1371/journal.pone.0081877. PMC 3857242. PMID 24349147.
- Elwood PC, Longley M (2010). "My Health – Whose Responsibility – a jury decides". J Epidemiol Comm Hlth. 64 (9): 761–4. doi:10.1136/jech.2009.087767. PMID 19897471.
- China Study II, Cornell University.
- Daniel Levy and Susan Brink. (2005). A Change of Heart: How the People of Framingham, Massachusetts, Helped Unravel the Mysteries of Cardiovascular Disease. Knopf. ISBN 0-375-41275-1.
- Giroux Élodie (2012). "The Framingham Study and the Constitution of a Restrictive Concept of Risk Factor". Social History of Medicine 26 (1): 94–112. doi:10.1093/shm/hks051.
|Wikimedia Commons has media related to Framingham Heart Study.|
- Framingham Heart Study - official web site
- Heart Center of MetroWest - Cardiology group including William P. Castelli, MD - Former Director of Framingham Heart Study