PROJECT SUMMARY/ABSTRACT Cardiovascular disease limits the activity and quality of life of millions of adults every year, costing the United States billions of dollars, and accounting for more than 40% of all deaths among those 65-74 and 60% of all deaths for those aged 85 and older.1 Accurate assessment of atherosclerotic cardiovascular disease (ASCVD) risk is needed for effective primary prevention. More research on how SEP affects atherosclerotic risk is needed, particularly among gender minorities. Guidelines from the American College of Cardiology and American Heart Association (ACC/AHA) for prevention of ASCVD now uniformly include the assessment of risk of heart attack and stroke using risk calculators (the AHA/ACC Pooled Cohort Equations (PCE)) to determine the appropriateness of statin and anti-hypertensive medications, preventive therapies which are known to substantially reduce the burden of serious cardiovascular events and cardiovascular death. However, too little is known about the performance of standard cardiovascular risk factors in transgender persons. For several decades, researchers have been interested in better understanding cardiovascular risk among transgender persons, and among those receiving cross-sex hormone therapy in particular. Review studies have found some indication of increased ASCVD morbidity and mortality among transgender persons, particular transgender women, but these reviews also concluded that prior studies were of low quality, had small samples, a constrained number of measured ASCVD risk factors and too few cardiovascular events to enable robust conclusions about cardiovascular risk. This supplemental study, ?Cardiovascular Risk among Transgender Persons in a Regional Electronic Health Record Registry? is proposed in response to ?NOT-OD-20-032: Notice of Special Interest: Administrative Supplements for Research on Sexual and Gender Minority (SGM) Populations?. Our prior work indicates a significant degree of neighborhood-level variability in major ASCVD events (myocardial infarction, stroke or cardiovascular death), with low-SEP neighborhoods associated with event rates over three times that of high-SEP neighborhoods. Moreover, neighborhood SEP explained four times the amount of neighborhood-level variation in ASCVD event rates than that explained by the ACCF/AHA Pooled Cohort Equations Risk Model. The focus of this study is on examining and decomposing cardiovascular risk and underlying cardiovascular risk factors among transgender adults in a 20-year regional electronic health record registry. This work will provide (i) an understanding of ASCVD risk in transgender persons and (ii) support for clinical decision making for primary prevention of adverse cardiovascular events. This supplemental applications proposes to conduct our analysis in a transdisciplinary team-based environment, in a newly-established, cutting-edge regional research registry, based on electronic health data from Northeast Ohio?s two largest health systems, Cleveland Clinic and MetroHealth.