Age at Coronary Heart Disease Onset, Genetic Susceptibility, and Subsequent Risk of Stroke

BACKGROUND: Coronary heart disease (CHD) has been established as a risk factor for stroke. The study aimed to assess how age at CHD onset influences stroke risk and interacts with genetic predisposition to stroke. METHODS: This prospective cohort study included UK Biobank participants without baseline or pre-CHD stroke. Polygenic risk scores assessed genetic susceptibility. Cox models and propensity score matching investigated the association between CHD onset age and stroke. The interaction analysis was performed using the bootstrap method and likelihood tests. Sensitivity analyses were conducted to ensure robustness. RESULTS: <0.001), as well as subsequent hemorrhagic stroke and ischemic stroke. However, no evidence supported an interaction between CHD onset age and genetic risk for stroke. CONCLUSIONS: Earlier CHD onset is independently associated with greater risks of stroke, hemorrhagic stroke, and ischemic stroke, regardless of genetic predisposition. Earlier onset of CHD may serve as a strong independent marker of elevated stroke risk.