DESCRIPTION: Stroke remains a major public health problem with a disproportionate impact on Blacks and Hispanics. Studies in Northern Manhattan have demonstrated that Blacks and Hispanics have a greater stroke incidence and more frequently have intracranial atherosclerotic stroke than whites. The reasons for this race-ethnic disparity are not entirely clear. Cross-sectional and case-control studies have identified racial-ethnic differences in modifiable stroke risk factors, however definition of exposures in these studies has been looked upon as prone to measurement errors because of retrospective recall and selection biases. The Aims of this competitive continuation application are to evaluate the reasons for race-ethnic differences in stroke incidence, confirm the case-control findings of the protective effects of leisure-time physical activity, alcohol use, and HDL-cholesterol, and test new hypotheses regarding HDL subpopulations and homocysteine. To accomplish these Aims a population-based, prospective cohort study is proposed. Community subjects free of stroke will be ascertained through dual frame random-digit dialing and a cohort of 3000 White, Black and Hispanic adults over age 55 living in the same tri-ethnic community of Northern Manhattan will be followed. Approximately 1400 subjects will have been enrolled by the time this application begins and another 1600 subjects will be enrolled in the first 2 years. Socioeconomic, demographic, and risk factor data including dietary assessments will be gathered through direct interview of the subject or family. At baseline, all subjects will have measurements of anthropometric indices, blood pressure, and EKG, and blood will be drawn for total homocysteine, related metabolites, B12, folate, creatinine, and lipid profiles (cholesterol, LDL, triglyceride, HDL, and HDL subpopulations). Subjects will be followed by annual telephone interviews to ascertain stroke, myocardial infarction, and death. In-person assessment will be done for all subjects with suspected outcome events and a 10% random sample of the cohort. Community stroke surveillance will be maintained to insure stroke detection among the cohort. Kaplan-Meier curves and Cox-proportional hazards models will be used to calculate adjusted relative stroke incidence rates and to evaluate the dependence of the exposures of interest on stroke adjusting for age, gender, race-ethnicity, socioeconomic status and other risk factors. This study will be the first prospective cohort study of stroke to focus on risk factors in Whites, Blacks and Hispanics living in the same community and will help fill the gaps in our knowledge of the epidemiology of stroke in minority populations.