Genetic Risk, Muscle Strength And Stroke Risk

Abstract

PURPOSE: Little is known about whether the beneficial impacts of increased muscle strength are consistent across all levels of genetic predispositions to stroke. The purpose was to examine whether the associations between muscle strength and stroke are independent of or vary by genetic risk for stroke. METHODS: We included 312,398 individuals of European ancestry in UK Biobank (a prospective cohort of >500,000 adults aged 40-69 years) who had no stroke at baseline and genetic relatedness. Genetic risk was assessed using polygenic risk scores, calculated by multiplying the sum of risk-increasing alleles at a given locus by the known effect estimates. Muscle strength was assessed through grip strength tests via a hand dynamometer. Values from both hands were averaged, then divided by fatfree mass. The outcome variables included incidence of overall (n=3,356), ischemic (n=2,632) and hemorrhagic (n=861) stroke over 9-year median follow-up. Overall, stratified and joint associations were estimated using Cox regression. RESULTS: Compared with the bottom tertile of muscle strength, hazard ratios [95% confidence interval] of stroke were 0.88 [0.81-0.95] and 0.80 [0.73-0.87] for the middle and top tertiles of muscle strength, respectively, after adjusting for confounders and genetic risk; higher levels of genetic risk were independently associated with higher hazards of stroke. Hazard ratios of stroke for the top muscle strength tertile were 0.82 [0.69-0.96], 0.78 [0.67-0.91] and 0.81 [0.70-0.93] at low, medium and high genetic risk, respectively: no evidence of additive and multiplicative interactions detected. Compared with the reference category of high muscle strength and low genetic risk, there was an increased hazard of stroke 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. Similar associations were observed for ischemic and hemorrhagic stroke, although for hemorrhagic stroke, confidence intervals were wider and inconclusive for some of the associations. CONCLUSIONS: Higher muscle strength was associated with lower risk of stroke, independently of genetic risk for stroke. The increased genetic risk of over