Genetic Liability to Higher Muscle Strength Associates With a Lower Risk of Cardiovascular Disease Mortality in Men Irrespective of Leisure-Time Physical Activity in Adulthood: A Longitudinal Cohort Study

Abstract

BACKGROUND: Low muscle strength predicts premature mortality. We determined whether genetic liability to muscle strength is associated with mortality and whether this association is influenced by long-term leisure-time physical activity (LTPA). METHODS AND RESULTS: We estimated the effects of a polygenic score for handgrip strength (PGS HGS) on all-cause and cardiovascular disease (CVD) mortality risk in the older Finnish Twin Cohort (N=8815, 53% women). LTPA was assessed longitu-dinally using validated questionnaires. During the 16.9-year median follow-up (143 723 person-years), 2896 deaths occurred, of which 1089 were attributable to CVD. We found a significant interaction between sex and PGS HGS (P=0.016) in relation to all-cause mortality. In men, 1-SD increase in the PGS HGS was associated with a decreased risk of all-cause (hazard ratio [HR], 0.93 [95% CI, 0.89–0.98]) and CVD mortality (HR, 0.88 [95% CI, 0.81–0.96]), but was not statistically significantly associated with mortality in women (HR, 1.01 [95% CI, 0.96–1.07]; and HR, 0.96 [95% CI, 0.87–1.05], respectively). In men, associations remained after adjusting for LTPA and persisted for CVD mortality (HR, 0.85 [95% CI, 0.76–0.96]), even after ac-counting for other lifestyle covariates. This remained statistically significant even when non-CVD death was accounted for as a competing risk event. No PGS HGS×LTPA interactions were found. The predictive area under the curve estimates for PGS HGS alone were limited (0.53–0.64) but comparable to that of several lifestyle factors. CONCLUSIONS: Higher PGS HGS was associated with a decreased risk of CVD mortality in men. Long-term LTPA in adulthood did not potentiate this association.