Association of total and moderate-to-vigorous physical activity with stroke risk: A dose–response meta-analysis of 2,639,086 participants from 14 international prospective cohort studies

BACKGROUND: Stroke is the second leading cause of death and third leading cause of disability globally. The dose-response relationship between physical activity (PA), particularly moderate-to-vigorous physical activity (MVPA), and stroke risk remains unclear, with limited sex-specific evidence. AIMS: To examine the dose-response associations of total PA and MVPA with stroke risk, considering sex and subtype differences. METHODS: A systematic review and dose-response meta-analysis of prospective cohort studies published between 2013 and 2024, with follow-up durations ranging from 4.9 to 17.9 years, were conducted. PA exposures were standardized to MET-hours per week (MET-h/wk), and incident stroke was the primary outcome. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using random-effects models. Dose-response associations were assessed using restricted cubic spline models. Analyses stratified by sex and subtype were performed when available. RESULTS: Fourteen cohorts (n = 2,639,086) were included. Total PA showed a nonlinear inverse association with stroke risk: each 10 MET-h/wk increment reduced risk by 1% up to 130 MET-h/wk, corresponding to a 13% maximum reduction, after which benefits plateaued. MVPA exhibited an L-shaped association (P < 0.001), with the greatest benefit (19% reduction) at 19 MET-h/wk, followed by a gradual increase in risk. Sex-stratified analysis revealed a J-shaped pattern in females (optimal 10-15 MET-h/wk; 18% reduction). For males, the HR was 0.89 (95% CI: 0.70-1.13), and a nonlinear model could not be established due to limited data. In ischemic stroke, dose-response patterns paralleled those for total stroke. CONCLUSIONS: The study found a significant dose-response relationship between total PA and MVPA with stroke risk. Optimal prevention was observed at 130 MET-h/wk for total PA and 19 MET-h/wk for MVPA. Evidence in males and for hemorrhagic stroke remains limited and warrants further study.