The epidemiology and common risk factors for cerebrovascular disease have been well documented by cross-sectional and longitudinal population surveys. These studies have generally involved unrelated individuals with little information on family history. Despite a significant role in cardiovascular risk, few studies have investigated familial contributions to stroke risk, and its importance is unknown. Recognition of the importance of hereditary influences on vascular disease of the heart has contributed, in large part, to the current emphasis on the molecular biology of vascular disease and a more balanced view that recognizes both genetic and environmental influences on coronary artery disease. Twin studies represent a simple and uniquely powerful tool for analyzing genetic and environmental contributions to complex human phenotypes(l). Studies of cardiovascular risk have shown the importance of heritable factors, and it is likely that similar genetic factors play a role in development of stroke(2). We will use the National Academy of Science Twin Registry to investigate stroke risk. This cohort consists of 31,896 twins born between 1917 and 1927 who served during World War H or the Korean Conflict. The twins have been surveyed periodically over the past two decades, most recently in 1985. Information obtained included questions on vascular risk factors, myocardial disease, and stroke. Our primary analysis will be an estimation of heritable risk. A comparison is made between monozygotic (MZ) and dizygotic (DZ) twins. If genes influence the prevalence of stroke, there should be more MZ twin pairs with stroke. Measures of concordence and heritability are used to estimate the size of the genetic contribution. Secondary analyses will focus on compound risk factors (e.g. hypertension ad diabetes), less well documented risk factors (e.g. diet and personality), and the heritability of individual stroke risk factors. With improved understanding of stroke risk factors (both genetic and environmental), early prevention measures can begin in high risk groups as early as childhood, an approach already applied to cardiovascular disease(3,4). Demonstration of a significant heritable risk for stroke should also prompt and help direct, further investigation into the molecular mechanisms of the genetic influences on stroke and may identify new approaches for stroke prevention and treatment, as it has for cardiovascular disease(5).

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Small Research Grants (R03)
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Special Emphasis Panel (SRC (OB))
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Yale University
Schools of Medicine
New Haven
United States
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Brass, L M; Hartigan, P M; Page, W F et al. (1996) Importance of cerebrovascular disease in studies of myocardial infarction. Stroke 27:1173-6
O'Brien, E R; Garvin, M R; Dev, R et al. (1994) Angiogenesis in human coronary atherosclerotic plaques. Am J Pathol 145:883-94
Brass, L M (1993) The design and appraisal of randomized clinical trials in cerebrovascular disease and CNS trauma. Res Publ Assoc Res Nerv Ment Dis 71:239-63