Genetic Risk, Muscle Strength, and Incident Stroke: Findings From the UK Biobank Study

Abstract

Objective: To examine the associations of muscle strength and genetic risk for stroke with stroke incidence.

Participants and methods: We included 284,767 white British participants of UK Biobank without genetic relatedness and stroke or myocardial infarction at baseline between March 13, 2006, and October 1, 2010. Genetic risk was assessed with polygenic risk scores, calculated by summing the risk-increasing alleles, weighted by the effect estimates. Muscle strength was assessed through grip strength tests by hand dynamometers. Incidence of overall (n= 4008), ischemic (n= 3031), and hemorrhagic (n=1073) stroke was adjudicated during 11.5-year follow-up.

Results: Compared with the bottom muscle strength tertile, hazard ratios (95% CI) of stroke were 0.81 (0.75 to 0.87) and 0.76 (0.71 to 0.82) for the middle and top muscle strength tertiles, respectively, after adjustment for confounders and genetic risk; higher genetic risk was independently associated with higher stroke incidence. Stroke hazards for the top muscle strength tertile were consistently lower across genetic risk strata, with no evidence of interaction. Compared with individuals with high muscle strength and low genetic risk, stroke hazards were higher for individuals who had medium or high genetic risk combined with low or medium muscle strength but not for those who had medium genetic risk but high muscle strength. Associations were similar for ischemic and hemorrhagic stroke (although CIs were inconclusive for some of the associations).

Conclusion: Higher muscle strength was associated with lower stroke incidence in all individuals, including those with high genetic susceptibility. The increased genetic risk of overall and ischemic stroke was partly attenuated through increased muscle strength.