ABSTRACT The main goal of this project is to assess the contribution of epigenetics to cardiovascular risk in African American women. Cardiovascular disease substantially impacts African American women, who are at high-risk for mortality and complications. Genome-wide association studies have identified several genetic loci for coronary heart disease and stroke, but the epigenetic contribution to cardiovascular disease has been less studied, especially in African Americans and women. Epigenetic modification such as DNA methylation may better reflect lifestyle and environmentally induced risks, including risk due to lifestyle and behavioral factors, biological aging and environmental toxins. We propose to study epigenetic biomarkers of cardiovascular disease in a large sample of African American participants the Women's Health Initiative, a cohort of postmenopausal women with comprehensive clinical and lifestyle data, and large numbers of adjudicated clinical outcomes. We will identify epigenetic biomarkers of cardiovascular disease and its environmental determinants, and evaluate if epigenetic biomarkers contribute to risk prediction assessments of cardiovascular disease. The proposal aligns to goals set forth in the 2019-2023 Trans-NIH Strategy Plan for Women's Health Research and the NHLBI mission to reduce the burden of cardiovascular disease in populations with disparities in disease risk.