Cardiovascular disease (CVD) is the leading cause of death in the United States, but African Americans bear a disproportionate burden from CVD. The reasons why African Americans are unusually susceptible to CVD and its complications are complex, multifactorial, and incompletely understood. Standard risk factors and subclinical atherosclerotic disease severity do not fully define the risk for CVD. Researchers have come to understand that vascular dysfunction contributes at both early and advanced stages in the pathogenesis of coronary heart disease and stroke. We propose to noninvasively characterize vascular function in 3,829 African Americans participants in the Jackson Heart Study by examining three related vascular phenotypes. We will measure (1) flow-mediated brachial artery dilation (FMD) and reactive hyperemia, (2) digital peripheral arterial tonometry (PAT) waveforms, and (3) aortic pulse wave velocity (PWV) and pressure flow relations. Our study includes four specific aims. We will: (1) Examine cross-sectional relations between CVD risk factors and FMD, PAT and PWV in African American adults;(2) Study the contribution of genetic variation to FMD, PAT and PWV in conduit vessels in African Americans;(3) Relate FMD, PAT and PWV to each other and to regional adiposity and to other markers of subclinical CVD;and (4) Assess the relation of FMD, PAT and PWV in conduit arteries to incident CVD events and mortality. The study will provide a novel opportunity to characterize the environmental and genetic correlates and the prognostic implications of abnormal vascular function in African Americans. By focusing on an African American cohort, the project will lead to innovative insights into health and disease in a population that is disproportionately at risk of CVD morbidity and mortality in the U.S. PUBLIC HEALTH RELEVANCE: Cardiovascular disease (CVD) is the leading cause of death in the United States. African Americans suffer from CVD at a higher rate than whites, and we don't fully understand the reasons for this phenomenon. This study will provide a novel opportunity to characterize the environmental and genetic correlates of abnormal vascular function in African Americans, and will potentially lead to improved prevention, risk stratification and management of CVD.