SUMMARY This application will provide the Principal Investigator, Dr. Pamela Lutsey, with protected time and other support to 1) accelerate a successful record of mentoring junior clinical investigators and graduate students engaged in cardiovascular disease (CVD) patient-oriented research (POR), 2) obtain additional training in pharmacoepidemiology, -omics and mentoring best practices and 3) advance her ongoing CVD pharmacoepidemiology research program. Pharmaceuticals play a crucial role in the prevention and treatment of CVD and other conditions. To improve the effectiveness of pharmacologic interventions on CVD outcomes, we need junior clinical investigators conducting POR who have rigorous training and mentorship in the areas of pharmacoepidemiology, clinical epidemiology of CVD, translational research methods and the use of complex data sources. An expert in these areas, the candidate, Dr. Lutsey, proposes to apply K24 funds toward the mentorship of POR scholars at the University of Minnesota who are committed to a research career that will reduce the burden of CVD in the population through building rigorous evidence regarding how to optimize use of pharmaceuticals in order to prevent CVD in at-risk populations and reduce risk of recurrence among individuals with CVD. Aim 1 involves conducting pharmacoepidemiology POR comparative effectiveness research to prevent CVD in at-risk populations and improve the outcomes among CVD survivors. State-of-the-art pharmacoepidemiologic techniques will be applied to large administrative data sources, specifically MarketScan and the Medicare 20% sample. Aim 2 will harness rich data from deeply phenotyped cohorts to understand behavioral characteristics that influence the effectiveness of medications, and glean added understanding of the physiologic mechanisms through which pharmacotherapies act. These analyses will use data from the Atherosclerosis Risk in Communities (ARIC) study and the Multi-Ethnic Study of Atherosclerosis (MESA). Findings from the proposed Aims will advance understanding of the role of specific pharmacologic treatment strategies on CVD risk, and have potential to directly impact clinical practice, reinforcing or leading to reconsideration of existing clinical guidelines. This proposal is structured to allow trainees the flexibility to pursue their own hypotheses, motivated by their clinical experiences and interests. With support from this K24, Dr. Lutsey plans to expand the breadth of her POR research activities, recruit new junior clinical scholars into POR, and prepare them to make major scientific advances and launch their own independent research careers.