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

Abstract

BACKGROUND: Suboptimal blood pressure (BP) control remains a major cardiovascular disease risk factor. Whether genetically predicted BP independently predicts long-term BP control is unknown. We examined the associations of BP polygenic scores (PGSs) with long-term BP control and treatment-resistant hypertension. METHODS: We identified 22 456 Mass General Brigham Biobank participants with hypertension. Longitudinal BP control was defined as the percentage of time above-target systolic BP (SBP) >= 130 mm Hg or diastolic BP (DBP) >= 80 mm Hg over 5 years. Using multivariable regression, we assessed the associations of BP PGS with duration above-target BP and lifetime treatment-resistant hypertension incidence. Incremental prognostic utility of BP PGSs was assessed based on the discrimination C-index, Brier score, and net reclassification index. Validation was performed in the population-based UK Biobank cohort using the SBP/DBP >= 140/90 mm Hg threshold. RESULTS: Among 10 853 (48.3%) were female, the mean SBP/DBP (SD) at index date was 132 (18)/75 (11) mm Hg, and 4126 (18.4%) developed treatment-resistant hypertension over lifetime. In reference to the low (<20th percentile) PGS group, the high (>= 80th percentile) BP PGS was associated with 8.01 (95% CI, 6.68%-9.34%) longer duration with above-target SBP and 6.19 (95% CI, 5.05%-7.33%) with high DBP. Each high SBP and DBP PGS conferred 2.36 (95% CI, 2.07-2.68) and 1.75 (95% CI, 1.55-1.99)-fold higher odds of treatment-resistant hypertension. Adding BP PGSs to traditional risk factors improved treatment-resistant hypertension prediction from C-index (95% CI), 0.74 (0.73-0.75) to 0.78 (0.77-0.79). BP PGSs consistently predicted longitudinal BP management to a comparable extent in the UK Biobank. CONCLUSIONS: Harnessing BP PGSs may inform anticipated trends in BP control to warrant vigilant monitoring and augment prioritization of intensive therapy.