DESCRIPTION (provided by applicant): My long-term goal is to become an independent researcher in cardiovascular epidemiology with a focus on the morbidity burden associated with cerebrovascular diseases, particularly stroke. I will use this Mentored Career Development award (K01) to fulfill a series of training objectives which build upon my prior skills, but also expand my expertise in ways which are essential to accomplishing my long-term goal. These include: learning to measure and analyze longitudinal stroke outcomes data; developing skills to assess, characterize, and measure white matter hyperintensity volume (WMHV) and cerebral microbleeds (CMBs) from magnetic resonance imaging (MRI) scans; learning about the design, conduct, and analysis of randomized clinical trials; and acquiring skills in mediation analysis techniques. To achieve my training objectives, I have assembled a comprehensive and complementary mentorship team which has worked together and with me for many years. My training objectives will also allow me to develop the skills needed to establish new datasets within ongoing studies during this award period. These subcohorts are necessary to achieve the research goals of the K01 and will provide preliminary data for future grant applications for independent research funding. I will apply my training to several important research questions during this K01 award. Recently, there has been growing interest in the role that vitamin D as well as omega-3 fatty acids play in the development of cardiovascular disease events. Given the high morbidity burden of stroke, determining the effect of these supplements on stroke outcomes is very important. The NIH sponsored VITamin D and OmegA-3 TriaL (VITAL) is an ongoing randomized, double blind trial testing vitamin D3 and omega-3 fatty acid supplementation in the primary prevention of cancer and cardiovascular disease. I will leverage this ongoing trial and collect additional data on stroke outcomes that would not otherwise be collected by the parent study. In addition, there is growing interest in discovering risk factors fr overall subclinical cerebrovascular disease burden in the brain as measured by WMHV and CMBs. Because WMHV and CMBs are associated with stroke outcomes, understanding risk factors associated with WMHV and CMBs in ischemic stroke patients may identify strategies to reduce the morbidity burden of stroke. I will collect MRI scans performed as part of routine medical care in participants with an ischemic stroke to create a database of WMHV and CMBs in VITAL and the Women's Healthy Study (WHS), a completed trial of the effects of low dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer with ongoing observational follow-up. By using data from both VITAL and WHS, I will have the unique opportunity to study how a wide variety of cardiovascular disease risk factors impact WMHV and CMBs in stroke patients. The training, mentorship, resear...