Physical activity patterns, genetic susceptibility, and incident ischemic stroke: a population-based cohort study.

Background: Ischemic stroke is a leading cause of death and disability worldwide. Whether different weekly physical activity patterns confer similar protection remains unclear, and genetic susceptibility may further influence risk. We therefore examined the associations of physical activity pattern, polygenic risk, and their joint categories with incident ischemic stroke. Methods: In this prospective UK Biobank analysis, 84,006 participants with valid accelerometer data were classified by weekly moderate-to-vigorous physical activity (MVPA) pattern (inactive, active regular, or weekend warrior) and polygenic risk score (PRS) category (low, intermediate, or high). Cox models were used to estimate HRs and 95% CIs for incident ischemic stroke, including joint analyses across nine combined categories. Results: At ≥150 min/week of MVPA, both weekend warrior and active regular patterns were associated with lower ischemic stroke risk than inactivity, with no statistically significant difference observed between the two active patterns. High, but not intermediate, polygenic risk was associated with increased risk (HR 1.83, 95% CI 1.35-2.47). In joint analyses, excess risk was evident only in inactive participants with intermediate or high genetic risk. Conclusion: Physical activity pattern and PRS were both associated with incident ischemic stroke. Meeting weekly MVPA recommendations, whether regularly or as a weekend warrior, was associated with lower risk, whereas higher genetic risk was associated with greater risk.