Clinical Implementation of Blood Pressure Polygenic Risk Score: A Randomized Clinical Trial - Elevated blood pressure (BP) is the single greatest modifiable contributor to premature mortality globally. The development of hypertension (HTN) and associated adverse cardiovascular (CV) events is contributed by an interplay of genetic and environmental factors. We constructed a genome-wide systolic BP (SBP) polygenic risk score (PRS), assimilating the risk for elevated BP conferred by over 1 million common genetic variations. In a US cohort, we have also demonstrated that the SBP PRS predicts the risk of adverse CV events beyond traditional CV risk factors, including clinic-measured BP. However, the high genetic risk for adverse CV events may be offset by controlling traditional CV risk factors and adherence to a healthy lifestyle. Young and middle-aged adults encounter unique barriers to sustained behavior change, including rapidly changing priorities with age. Young adults often prioritize education and social obligations, while middle-aged adults balance career demands and family responsibilities, resulting in a perceived lack of time for health-related goals and an underestimation of their risk for adverse CV events. Providing a comprehensive understanding of one’s genetic risk quantified by SBP PRS is likely to improve SBP control by enhancing adherence to a healthy lifestyle, which will eventually lead to a reduction in the risk of potentially fatal CV outcomes. However, this has not been evaluated in a cohort of hypertensive young and middle-aged US adults with poor CV health. We propose to conduct a randomized controlled clinical trial to assess the efficacy of SBP PRS dissemination on SBP control, adherence to a healthy lifestyle, and cardiometabolic profile. In the primary aim, we will enroll and randomize 300 adults (aged 18-55 years, including 50% females) to either receive SBP PRS results along with genomic counseling (SBP PRS disclosure arm) or routine care (regular care arm). Participants will be provided with educational materials on hypertension control at baseline in both arms, with only the SBP PRS dissemination arm participants receiving additional genomic counseling during the 3-monthly in-person follow-up visits. The main outcome will be the change in 24-hour mean SBP at 1 year between the two study arms. In our secondary aim 1, we will assess the change in diet (measured using the Healthy Eating Index), physical activity (estimated using actigraphy), medication adherence, smoking status, blood glucose, lipid profile, and body composition (lean mass and fat mass) and health-related quality of life between the two arms at 1 year. In secondary aim 2, we will assess the mediation of behavior change by SBP PRS dissemination and genomic counseling through each HBM construct. Overall, this study will evaluate the role of genomics in improving SBP control in a cohort of young and middle-aged adults with HTN and poor CV health and thereby mitigate the premature mortality burden secondary to elevated BP.
