Invited Commentary: The Framingham Offspring Study—A Pioneering Investigation Into Familial Aggregation of Cardiovascular Risk

Launched in 1948, the Framingham Heart Study was a seminal prospective cohort study of 5,209 adult residents of Framingham, Massachusetts, that was designed to uncover the determinants and natural history of coronary heart disease. Data from this original cohort established the cardiac threat posed by high blood pressure, high cholesterol, smoking, obesity, physical inactivity, diabetes, and other factors. In the late 1960s, investigators conceived the innovative idea of assembling a second cohort that comprised the adult children of the original study population (and these children's spouses). From 1971 to 1975, a total of 5,124 individuals were recruited to form the Offspring Cohort. Studying successive generations in this fashion provided an efficient method for examining secular trends in cardiovascular disease and its risk factors, as well as an opportunity to assess familial aggregation of risk without the threat of recall bias. In a paper published in the September 1979 issue of the Journal, then study director William Kannel et al. (Am J Epidemiol. 1979;110(3):281-290) described the sampling design of the Offspring Study and presented selected baseline characteristics of the cohort. The scientific questions addressed by this research provided the impetus for a decades-long effort-still in full force today both within the Framingham Study itself and in the broader cardiovascular epidemiologic community-to quantify the independent and synergistic effects of genetic, lifestyle, and other environmental factors on cardiovascular outcomes.