Mediation effect of TyG-BMI, LDL-C, and CRP on physical activity-stroke risk relationship

While physical activity (PA) is known to reduce stroke risk, the unified biological mechanisms involving metabolic, lipid, and inflammatory pathways remain unclear. This study quantified the mediating roles of TyG-BMI, LDL-C, and CRP in the PA-stroke association using nationwide longitudinal data, and explored subgroup differences. Data from 6269 participants in the China Health and Retirement Longitudinal Study were analyzed. PA was assessed via IPAQ. Triglycerides, blood glucose, CRP, and LDL-C were measured enzymatically; TyG-BMI was calculated as log[triglycerides × fasting glucose/2] × BMI. Chi-square tests, generalized structural equation modeling (GSEM), and interaction tests were used for analyses. A total of 307 incident strokes occurred. In the crude comprehensive mediation model, the PA-stroke association was mediated by TyG-BMI (7.00%), LDL-C (2.21%), and CRP (1.32%). After full adjustment, only the TyG-BMI pathway remained statistically significant, accounting for 10.64% of the total association (OR 0.985, 95% CI 0.976-0.995), whereas the LDL-C and CRP pathways were attenuated and no longer significant. The direct effect accounted for 89.36% of the association in the fully adjusted comprehensive model. Subgroup analysis revealed more pronounced TyG-BMI mediation in adults ≥ 60 years and hypertensive patients, but not in diabetic patients. Greater PA was associated with a lower risk of incident stroke, partly mediated by TyG-BMI. LDL-C and CRP did not show significant mediation after multivariable adjustment. Personalized PA interventions for those at high metabolic risk are crucial for stroke prevention. Future research should elucidate the uncharacterized direct-effect pathways.