Polygenic Score Predicts Long-Term Blood Pressure Control and Resistant Hypertension

Introduction: Suboptimal blood pressure (BP) control remains a major cardiovascular disease risk factor globally. Whether genetic contributors to elevated BP independently predict long-term BP control and treatment-resistant hypertension is unknown. Objectives: We examined the associations of BP polygenic score (PGS) with long-term BP control and treatment-resistant hypertension among patients with hypertension. Methods: Using Mass General Brigham Biobank nested within the U.S. healthcare system, we identified 22,466 individuals aged 18-64 years with established hypertension between January 2018 and May 2019. Multiancestral BP PGS was fine-tuned using the external UK Biobank cohort. Longitudinal BP control was defined as cumulative duration above target systolic BP (SBP) ≥130 mmHg or diastolic BP (DBP) ≥80 mmHg in percentage over a 5-year follow-up. Treatment-resistant hypertension was defined as SBP ≥140 or DBP ≥90 mmHg despite the concurrent use of 3 antihypertensive classes, use of ≥4 antihypertensive classes at any BP level, or physician adjudication. Using multivariable regression, we assessed the associations of BP PRS with 5-year BP control and lifetime resistant hypertension incidence adjusting for traditional cardiometabolic risk factors and comorbidities. Incremental prognostic utility of BP PRS was assessed based on improvement in discrimination C-index or the likelihood ratio test. Results: The mean SBP/DBP (standard deviation) at index date was 132(18) / 75(11) mmHg, and 4126 (18.4%) developed resistant hypertension over a lifetime. In reference to the low (<20 th percentile) PGS group, the high (≥80 th percentile) genetic risk group was associated with 8.01 [6.68-9.34]% longer duration lived with above-target SBP and 6.19 [5.05-7.33]% longer with high DBP. In parallel, the high SBP genetic risk group had a 2.36 [2.07-2.68]-folds higher odds of developing treatment-resistant hypertension. Adding BP PGSs to traditional risk factors improved discrimination C-index [95% CI] for predicting resistant hypertension from 0.74 [0.73-0.75] to 0.78 [0.77-0.79] ( P <0.001). BP PGS consistently predicted longitudinal BP management in the validation population-based UK Biobank cohort in adherence to the UK clinical guideline. Conclusions: BP PGS predicts long-term BP control and treatment-resistant hypertension. Harnessing BP PGS may inform anticipated trends in long-term BP control to better enable optimal hypertension management.