Prospective associations of genetic susceptibility to high blood pressure and muscle strength with incident cardiovascular disease outcomes

Background: This study explored the prospective associations of genetic susceptibility to high blood pressure (BP) and muscle strength with cardiovascular disease (CVD) mortality, incident coronary heart disease (CHD) and incident stroke. Methods: This study included 349 085 white British individuals from the UK Biobank study. Genetic risk of high BP was estimated using a weighted polygenic risk score that incorporated 136 and 135 nonoverlapping single-nucleotide polymorphisms for systolic BP and diastolic BP, respectively. Muscle strength was assessed using a hand dynamometer and expressed relative to fat-free mass. Sex- and age-specific tertiles were used to classify muscle strength into three categories. Cox regressions with age as the underlying timescale were fit for CVD mortality (n¼8275), incident CHD (n¼14 503), and stroke (n¼7518). Results: Compared with the lowest genetic risk of high BP (bottom 20%), the highest (top 20%) had greater hazards of each outcome. Low muscle strength was associated with higher hazards of CVD mortality [hazard ratio (HR): 1.51, 95% confidence interval (CI): 1.43-1.59], incident CHD (HR: 1.16, 95% CI: 1.11-1.21), and stroke (HR: 1.20, 95% CI: 1.14-1.27), independently of confounders and genetic predisposition to high BP, compared with high muscle strength. Joint analyses revealed that the estimated 10-year absolute risks of each outcome were lower for high muscle strength combined with high genetic risk, compared with low muscle strength combined with low or medium genetic risk. Conclusion: Individuals who are genetically predisposed to high BP but have high muscle strength could have lower risk of major CVD events, compared with those who have low or medium genetic risk but low muscle strength.