DESCRIPTION (provided by applicant): Increasingly, researchers understand that endothelial dysfunction and increased vascular stiffness contribute to the pathogenesis of cardiovascular disease (CVD). The Framingham Heart Study (FHS) has been examining vascular function in about 3600 middle-aged and elderly participants of the FHS Offspring and minority OMNI cohorts. The current proposal is to characterize vascular function by performing noninvasive studies of endothelial function with brachial ultrasound flow-mediated dilation, and of vascular stiffness with arterial tonometry, in 3850 adult offspring of the FHS Offspring and OMNI cohorts. The total of over 7000 vascular examinations in an extensively studied multi-generational community-based cohort will provide the opportunity to characterize the environmental and genetic determinants, and the prognosis of altered vascular function. The study hypotheses are: vascular function is determined by both environmental and genetic factors; endothelial function and vascular stiffness phenotypes are associated with each other: and vascular dysfunction predisposes to the development of hypertension (HTN) and CVD. Specific aims: Aim 1. To determine the cross-sectional relations of risk factors to vascular function in the community in young and middle-aged adults. Aim 2. To study the heritability of vascular phenotypes. Aim 3. To relate endothelial function and vascular stiffness to each other, and to other markers of subclinical CVD in early and middle adulthood. Aim 4. To assess the relations of vascular function measures to longitudinal changes in blood pressure. The third generation cohort provides a large, community-based sample of young and middle-aged adults with a wealth of risk factor data and the availability of longitudinal follow-up beyond the length of the proposed grant. The resultant data will complement data already collected on their parents, will increase the power for heritability analyses, and will permit the characterization of vascular phenotypes in a younger cohort, prior to the development of HTN, CVD medication usage and clinical CVD. The combination of investigator expertise and a well-characterized multi-generational sample will provide a unique vascular function data set, and will increase the understanding of the pathophysiology of HTN and CVD.