PROJECT SUMMARY At least 60 million (one in every five) Americans live in rural areas, among whom harbor a disproportionately high burden of cardiovascular disease (CVD). The worsening disparity in CVD mortality between rural versus urban America has created a need to improve our understanding of atherosclerotic resilience for the promotion of cardiovascular health in rural communities. The absence of coronary artery calcium (CAC) is a highly specific marker of atherosclerotic resilience, as CAC=0 is consistently associated with an exceedingly low risk of future CVD events and mortality regardless of traditional risk factor burden. Despite the prognostic importance of CAC=0, the risk factors underlying this protective phenotype are not well understood, especially in rural populations. To address this knowledge gap, we propose the first epidemiologic study to determine the prevalence and correlates of CAC=0 in rural communities. We will leverage clinical and socioeconomic measures, as well as non-contrast cardiac computed tomography among 4,000 participants (44% White, 45% Black, 10% Hispanic) enrolled in the Risk Underlying Rural Areas Longitudinal (RURAL) Cohort Study. Notably, RURAL is a NHLBI-funded study that examines cardiovascular health in rural communities across the Southeastern United States, providing an ideal setting for the proposed work. The primary definition of atherosclerotic resilience will be CAC=0, but we will also examine absence of thoracic aortic calcium and a normal ankle-brachial index for a more comprehensive definition of atherosclerotic resilience in secondary analyses. In Aim 1, we will determine the prevalence of atherosclerotic resilience (CAC=0) according to age (<45 versus >45 years old), sex (women versus men), and race (black versus non-black) in rural persons. Regression models will calculate prevalence ratios for CAC=0. We will then use collected information on clinical CVD risk factors, diet, physical activity, and psychosocial adversity, to determine their association with CAC=0 in rural participants (Aim 2). Multivariable regression models with sophisticated adjustment strategies (sequential, individual, and leave-one-out) will calculate prevalence ratios to study the individual and combined relative impact of clinical, lifestyle, and psychosocial measures on differences in atherosclerotic resilience across groups of age, sex, and race. We will then contrast prevalence ratios and the effect estimate attenuation after performing the various adjustment strategies. In sub-aims of Aims 1 and 2, we will perform the above analyses for CAC burden (CAC 1-99, CAC 100-299, CAC >300) and premature CAC (any CAC among individuals <45 years old or >90th percentile according to age, sex, and race) to facilitate a better understanding of atherosclerotic resilience. In total, the proposed research will provide important insights into the biopsychosocial pathways underlying atherosclerotic resilience, and aid in understandin...