Coronary heart disease (CHD) has remained a major cause of morbidity and mortality in the United States, affecting nearly 13 million people and causing approximately one million deaths per year (Thom et al., 2006
). Although the incidence of cardiovascular diseases (CVDs) has gradually declined since the 1960s in the U.S. (Cooper et al.
, 2004), it is reaching epidemic proportions in many countries of Europe and the developing world (Yusuf et al., 2001
). In the 1940s CHD was recognized as the leading cause of mortality in the U.S. accounting for approximately half of all deaths (Kannel, 1990
). Nonetheless, knowledge of the factors that disposed individuals to CVDs was “virtually non existent” 60 years ago and was perceived to be an inevitable consequence of “aging or genetic predisposition” of individuals (Dawber and Kannel, 1999
). Fortunately, the U.S. Public Health Service (USPHS then and later NIH) recognized the necessity for understanding the causal factors of the epidemic and decided to establish a prospective longitudinal observational epidemiological study in 1947, in the town of Framingham, Massachusetts in collaboration with the Massachusetts State Department of Health and Harvard Medical School. The “Framingham Study” was formally established in 1948, to identify factors that contribute to CVD (Dawber et al., 1951
; Kagan et al., 1962
; Levy and Brink, 2005
The study, nearly six decades later and now known as the “Framingham Heart Study” (FHS), is the longest running, multigenerational longitudinal study in medical history (Butler, 1999). It has helped identify several “risk factors” and their cumulative influence on the manifestation of CVD. Indeed, the term ‘risk factor’ was coined by Framingham investigators (Kannel et al., 1961
Information collected on the participants enrolled in the study has aided in correcting a number of long held misconceptions on the role of blood pressure, lipids, diabetes, obesity, proteinuria, left ventricular hypertrophy, atrial fibrillation, smoking and exercise in the manifestation of CVD. Framingham investigators have also elucidated the pathogenesis of atherosclerosis and thus have laid a firm foundation toward preventive cardiology (Kannel, 1990
). Furthermore, the study has acquired an iconic status in public health and preventive cardiology and has been listed as the “fourth significant achievement in medicine” (after the development of antibiotic treatments, immunization against infectious diseases, and the understanding of the roles of vitamins; Anon., 1999
), and the second greatest discovery (behind electrocardiography) in Cardiology (Mehta and Khan, 2002
The investigators of the original protocol
of the “Framingham Study” recognized a wide range of variation among individuals in human populations in response to “stresses and insults” (Gordon and Kannel, 1970
). Instead of focusing on just one or a few independent causal factors that might influence CVD, they took an integrated approach and hypothesized that CVD may arise from “multiple causes which work slowly within the individual.” However, family history for CVD received the highest importance among many variables selected for studying its manifestation among the participants (Dawber et al., 1951
). In general, at least three major variables were assumed to contribute to the onset of CVD: constitutional (heredity), and conditioning (environmental) factors, as well as the length of time taken by the conditional factors to act on constitutional factors ultimately resulting in a clinically recognizable condition (Gordon and Kennel, 1970
). Thus, the founders of the study were cognizant of the fact that the biological basis of CVD may be complex and may be modulated by the interaction of heredity and environmental factors.
Although the role of hereditary factors in the development of CVD was acknowledged from the very beginning of the Framingham study, genetic studies did not receive much attention until the late 1980s. In the last twenty years, however, a number of investigators have utilized the rich resource available at the study and have attempted to understand the genetic basis of CVD using various approaches. In this review, we briefly discuss: a) some of the salient features of the Framingham Heart Study population, and b) approaches taken by the Framingham investigators toward identifying the genetic bases of CVD and some of its risk factors.