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: Over a median follow‐up of 15.1 years, 11 180 participants experienced incident stroke. Patients with CHD exhibited higher risks of developing stroke, hemorrhagic stroke, and ischemic stroke than participants without CHD. Notably, each 10‐year decrease in onset age correlated with an increased risk of stroke (hazard ratio [HR], 1.27 [95% CI, 1.23–1.32]; P <0.001), hemorrhagic stroke (HR, 1.31 [95% CI, 1.20–1.43]; P <0.001), and ischemic stroke (HR, 1.28 [95% CI, 1.23–1.33]; P <0.001). Propensity score matching revealed that, compared with their matched counterparts with later CHD onset, participants with earlier CHD onset had an increased risk of subsequent stroke: <57 versus ≥57 years (HR, 1.33 [95% CI, 1.20–1.48]; P <0.001) and <66 versus ≥66 years (HR, 1.57 [95% CI, 1.41–1.75]; P <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.