Abstract 12687: Evaluating a Coronary Artery Disease Polygenic Risk Score Screening Strategy in a Diverse Patient Cohort at UCLA

Abstract

Introduction: Recent efforts to predict and mitigate coronary artery disease (CAD) risk have incorporated polygenic risk scores (PGS). Few studies examine the clinical impact of these PGS screening strategies or quantify their performance in clinical terms. Here we estimate the number needed to screen (NNS) of a PGS screening strategy for CAD based using a diverse electronic health record (EHR) linked biobank at UCLA Health. Methods: We leveraged longitudinal EHR data to conduct a synthetic trial. We assumed PGS screening was performed on 6/1/2013 for patients established prior to 1/1/2013 or 6 months into follow time if established later. Patients with preexisting cardiovascular disease or strong statin indications (LDL > 190, diabetes or already on statins) are excluded. Patients with PGS scores in the top 5% of their genetic ancestry groupings (European, East Asian, African, Hispanic) are assumed to have been started on statins for the median 6.9 years of follow up. CAD diagnosis during follow up time was determined by ICD codes. NNS to prevent one CV event is calculated from cohort size and events assuming a statin number needed to treat of 50. Results: Of 33,789 adults, 17,074 were low risk and eligible for PGS screening (35% male with a mean age of 44). NNS to detect one CAD diagnosis was 351, 359, 814, 159 in the European, Hispanic, East Asian and African ancestry groups and NNS to prevent one cardiovascular event was 17,550, 17,950, 40,700, 7,950 respectively. Conclusion: Although PGS accuracy is lower in African ancestry individuals as compared to Europeans, the clinical utility of this PGS-based screening is highest in African ancestries due to increased baseline rates of disease in the African genetic ancestry grouping. Our results demonstrate that PGS accuracy is distinct from clinical utility of PGS-based strategies. Evaluation of screening strategies rather than accuracy alone will be required before PGS screening implementation.