Abstract 14508: Association of Multi-Ethnic Genome-Wide Blood Pressure Polygenic Risk Score With Adverse Cardiovascular Events

Abstract

Background: Traditional cardiovascular (CV) risk factors and the underlying genetic risk of elevated blood pressure (BP) determine an individual’s composite risk of developing adverse CV events. We evaluated the relative contributions of the traditional CV risk factors to the development of adverse CV events in the context of varying BP polygenic risk score (PRS) profiles among multiethnic population-based cohorts (ARIC, MESA, JHS, FHS, CARDIA, and CHS cohort). Methods: Multiethnic genome-wide BP PRS was constructed among participants with WGS data through TOPMed program and were stratified into high, intermediate, and low genetic risk (>80 th , 20-80 th , <20 th centile). Based on the ACC/AHA Pooled Cohorts Equation (PCE), participants were stratified into low and high (10y-ASCVD risk: <10% or ≥10%) CV risk factor profile groups. Cox regression was used to assess the risk of adverse CV events (incident HF, CHD, and stroke) and its components. Results: Among 21,899 American adults (mean age: 56 years; 56% women; 36% non-White race), 1 SD increase in the BP PRS computed using 1.1 million variants was associated with systolic BP (β: 4.7, 95% CI: 4.5-5.0) and HTN (OR: 1.09, 95% CI: 1.09-1.10), respectively. This association was robustly seen across racial/ethnic groups. Each SD increase in BP PRS was associated with a higher risk of the primary outcome (HR: 1.08 [1.05-1.11]) after controlling for ACC/AHA PCE risk score. Among individuals with a high BP PRS, low ASCVD risk was associated with a 69% lower hazard for the primary outcome (HR: 0.31, [0.27-0.35]) compared with those with high ASCVD risk. A similar pattern was noted in intermediate and low BP PRS groups. Comparable results were noted for all the secondary outcomes. Conclusions: In a multiethnic cohort of >21,000 US adults, genome-wide BP PRS was associated with BP traits and adverse CV events. Adequate CV risk factor control may reduce this increased predisposition to adverse CV events by 69% in those with high BP PRS.