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Contributions of the Framingham Heart Study to Stroke and Dementia Epidemiologic Research at 60 Years

PA Wolf - Archives of Neurology, 2012 - Am Med Assoc The Framingham Heart Study, the longest-running prospective epidemiologic study in history, was initiated in 1948 in response to the rising toll of coronary heart disease and hypertension. During the ensuing decades, the study of other diseases, notably stroke ...

It is key to highlight a number of important features of the design of the FHS that have unique pertinence for the study of neurologic diseases. Despite the focus on coronary heart disease and its impact on men younger than 60 years, women were invited to participate in the FHS in part to encourage their husbands to join. Women aged 30 to 60 years accounted for approximately half of the 5209 subjects in the original cohort in 1948. This resulted in large numbers of spouse pairs and extended families in this population of uniformly white individuals of European descent (Figure 1). To enhance the study of familial factors, particularly blood lipids and blood pressure, and to capitalize on the large number of spouse pairs, an offspring cohort (n = 5124) was recruited in 1971. These children of the original cohort along with their spouses provided 2 generations of subjects for the study of familial and genetic influences on disease and phenotype occurrence. The recruitment of families was extremely fortunate and resulted from an appreciation of clustering of cardiovascular and hypertensive disease in families. In this way, disease occurrence in parents in the original cohort could be related to disease or predisposing factors in their children in the offspring cohort. The advent of noninvasive testing including physiologic measures (eg, ankle-brachial index, imaging of the heart and carotid arteries) permitted identification of subclinical vascular disease in different arterial beds. Recruitment of 4095 children of the offspring cohort in 2002 has provided a further opportunity to explore genetic factors and identify earlier evidence of disease and premonitory factors of subclinical disease. This has important implications for our understanding of precursors of neurologic diseases and aging, which occur over decades and manifest in later life as stroke, dementia, and cognitive decline. The subjects in these 3 cohorts have shown allegiance to the study and cooperated with frequent telephone and in-person surveillance and examinations over decades. Participants of the original cohort have been examined every 2 years, with annual telephone health history follow-up, for 62 years; the offspring cohort participants have been examined approximately every 4 years during 4 decades of follow-up. Detailed and prolonged surveillance, standardized and quality-controlled measurements, and systematic and criteria-based disease reviews have permitted the study of risk factors, disease incidence, secular trends, and genetic studies of disease.