Physical activity lowers hypertension risk: A 2-sample Mendelian randomization study

This study aimed to investigate the causal effects of physical activity (PA) on hypertension risk and blood pressure using a 2-sample Mendelian randomization approach. We selected genetic variants with low linkage disequilibrium and strong associations with PA subtypes as instrumental variables, derived from genome-wide meta-analyses. Hypertension summary statistics were obtained from the FinnGen database (N = 2,18,754). Systolic blood pressure and diastolic blood pressure data were sourced from the IEU OpenGWAS project (N = 7,57,601). Causal estimates were calculated using inverse-variance weighted regression, supplemented by sensitivity analyses. Genetically predicted participation in heavy do-it-yourself (odds ratio [OR] = 0.24, 95% CI: 0.11-0.55; P = .0007), aerobic exercise (OR = 0.13, 95% CI: 0.06-0.31; P = 3.26 × 10-⁶), walking (OR = 0.23, 95% CI: 0.10-0.53; P = .0005), and vigorous PA (OR = 0.65, 95% CI: 0.49-0.87; P = .003) demonstrated inverse associations with hypertension risk. No significant associations were observed for light do-it-yourself or moderate PA. Aerobic exercise (β = -7.49 mm Hg, 95% CI: -11.78 to -3.21; P = .0006), walking (β = -4.17 mm Hg, 95% CI: -8.10 to -0.23; P = .038), and vigorous PA (β = -1.78 mm Hg, 95% CI: -2.95 to -0.62; P = .003) were associated with reduced systolic blood pressure. For diastolic blood pressure reductions, aerobic exercise (β = -5.21 mm Hg, 95% CI: -7.71 to -2.71; P = 4.50 × 10-⁵) and vigorous PA (β = -0.99 mm Hg, 95% CI: -1.89 to -0.08; P = .033) showed significant effects. Our Mendelian randomization analysis provides genetic evidence supporting PA as a protective factor against hypertension. The differential effects across PA subtypes highlight the potential value of targeted exercise interventions for blood pressure management.