Coronary artery calcium synthetic cohort and lifetime percentile project (CACSC-LPP)

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Coronary artery calcium (CAC) testing provides a direct measure of an individual’s atherosclerotic burden that is robustly associated with cardiovascular disease (CVD) risk. Accordingly, CAC scoring has a IIa recommendation in the 2018 AHA/ACC Cholesterol Treatment and 2019 ACC/AHA Primary Prevention Guidelines and is also recommended by many other national and international guidelines for the allocation of primary prevention medications. The clinical implications of the Agatston score can vary significantly based on the age, sex, and race/ethnicity population percentile score, which is particularly crucial for estimating long- term or lifetime CVD risk, especially for younger persons in whom a low Agatston score may commonly be reflective of premature atherosclerosis and significantly increased lifetime risk. However, current guideline- recommended CAC percentile scores were developed from only one NHLBI cohort comprised of predominantly middle-aged participants and there is no centralized website or resource with all the available tools to facilitate interpretation of the CAC score. Consequently, there is an unmet need to 1) develop CAC percentile data across the lifespan that is more representative of the US population and more diverse across racial/ethnic minorities, particularly South Asians, who have a significantly increased CVD risk yet are not included in current percentile score calculators and 2) create a centralized website and mobile app to aid in the interpretation of CAC at the point of care. Therefore, using standardized data harmonization techniques, we propose to pool data from 7 NHBLI cohorts and 3 real-world clinically-derived cohorts to create the gender- balanced, racially/ethnically diverse CAC Synthetic Cohort Lifetime Pooling Project (CACSC-LPP) of approximately 20,000 NHBLI participants with CAC data across the lifespan (age 30-95 years old) and an additional ~90,000 participants from clinical CAC cohorts. Harmonizing the individual participant level data will pragmatically leverage the enormous NIH investment (monetary and time) in these cohorts to create a new pooled dataset that expands the clinical impact beyond what was originally envisioned. It will also create an ideal foundation to iteratively expand the CACSC-LPP to ensure better representation for all persons living in the US, with an initial focus on South Asians. Additionally, we will build upon our prototype CAC-tools website and companion app so that clinicians and patients can enter a CAC score (plus any other available risk factor data) and retrieve their CAC percentile. This website/app will serve as the definitive source for all CAC related tools and would be well positioned to be endorsed by future national CVD guidelines (see LOS, Drs. Lloyd- Jones & Arnett). Through the creation of the 1) CACSC-LPP, 2) CAC percentile calculator across the lifespan, and 3) centralized CAC website/app this project will improve personalized CVD risk prediction, implementation of ACC/AHA primary prevention recommendations, while also creating the infrastructure for multidisciplinary and cross-institutional collaborations to further improve our understanding of CAC for CVD risk prediction.