Coronary Atherosclerotic Burden in AsA-NHPI: the Role of the Gut Microbiome - Cardiovascular disease (CVD) is the leading cause of death among Asian American, Native Hawaiian, and Pacific Islander (AsA-NHPI) adults, with rates varying across subgroups. However, the distribution of CVD risk factors in AsA-NHPI populations and how these factors influence CVD remain poorly characterized. Research addressing these gaps is needed to better understand CVD in AsA-NHPI populations. This study aims to investigate the relationship between the gut microbiome and coronary artery calcium (CAC)—a validated measure of current coronary atherosclerosis and a predictor of future cardiovascular events—beyond traditional risk factors. While animal models suggest a causal link between gut microbiota and atherosclerosis, human data, particularly in early subclinical stages, remain limited. No studies have examined this relationship in AsA-NHPI populations. Our preliminary data indicate that AsA-NHPI have distinct gut microbiome profiles, differing from White, Black, and Hispanic populations but also shaped by contextual factors. Additionally, our preliminary data indicate that some of these microbial species are associated with early atherosclerosis. Taken together, investigating the microbiome’s impact on cardiovascular health is crucial for guiding personalized, microbiome-informed prevention strategies. This study is the first to integrate bacterial, fungal, and viral microbiomes with CAC imaging, positioning it to transform both mechanistic understanding and prevention of CVD in AsA-NHPI populations. This study will leverage the NIH-funded MOSAAIC cohort of over 10,000 AsA-NHPI participants across five field centers, with baseline exams, questionnaires, biospecimens, and annual follow-ups. This R01 will generate critical data on CAC in 4,000 AsA-NHPI adults aged 40 and older. We propose two aims: (1) Characterize the current coronary atherosclerosis burden in AsA-NHPI adults, and (2) Investigate the relationship between gut microbiota and coronary atherosclerosis. Characterizing coronary atherosclerosis through CAC in AsA-NHPI populations will provide essential data to guide prevention strategies and improve cardiovascular health. Identifying gut microbiota associated with coronary atherosclerosis will enable early identification of high-risk individuals, laying the foundation for personalized prevention and targeted therapies.