Associations of muscle strength and genetic predispositions to high blood pressure with mortality and cardiovascular disease outcomes: Findings from the UK Biobank project

Abstract

PURPOSE: High blood pressure (BP) is a heritable risk factor for cardiovascular diseases (CVD). Whether muscle strength, a modifiable environmental trait, is associated with risk of mortality and CVD independently of genetic risk for high BP is unknown. The purpose was to investigate the associations of genetic risk for high BP and muscle strength with mortality from all causes and CVD, and incidence of myocardial infarction (MI) and stroke. METHODS: This study is based on data from UK Biobank, a prospective cohort containing >500,000 adults aged 40-69 years. We included 304,020 individuals of European ancestry without 2nd-degree genetic relatedness and prevalent CVD at baseline. Polygenic risk scores (PRS) for high BP were determined by averaging the standardized calculated risk scores for systolic BP (using 274 single-nucleotide polymorphisms [SNPs]), diastolic BP (278 SNPs) and pulse pressure (231 SNPs). Muscle strength was assessed through grip strength tests. The average grip strength values from both hands were divided by measured fat-free mass. Independent and stratified associations were estimated using Cox regression. RESULTS: Compared with the bottom muscle strength tertile, hazard ratios of the top tertile were 0.72 (95% Confidence Interval: 0.69-0.76) for all-cause mortality, 0.66 (0.59-0.75) for CVD mortality, 0.84 (0.78-0.90) for MI, 0.81 (0.74-0.89) for stroke, 0.79 (0.72-0.88) for ischemic stroke and 0.80 (0.67-0.96) for hemorrhagic stroke after adjusting for confounders and PRS. Higher PRS was associated with higher hazards of each disease outcome. At all tertiles of genetic risk for high BP, higher muscle strength was associated with lower hazard of mortality due to all causes and CVD (except at low genetic risk), MI, stroke, ischemic and hemorrhagic stroke (except for high muscle strength at medium genetic risk), compared with low muscle strength: no additive and multiplicative interactions detected. CONCLUSION: Individuals with higher levels of muscle strength have lower rates of mortality from all causes and CVD, and incidence of MI and stroke, independent of genetic risk for high BP. Increased muscle strength is, in general, protective against mortality and CVD in the whole population including those at increased genetic risk for high BP.