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April 24, 2026Journal of the American Heart Association0 citationsOpen Access

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

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YQYi QiWLWenhao LiuQGQing‐Yuan Gao

Key Result

Earlier onset of coronary heart disease is independently associated with greater risks of stroke, hemorrhagic stroke, and ischemic stroke, regardless of genetic predisposition.

Key Points

  • This research aims to evaluate the impact of age at coronary heart disease (CHD) onset on stroke risk and its interaction with genetic predisposition.
  • Conducted a prospective cohort study using UK Biobank participants without pre-existing stroke.
  • Assessed genetic susceptibility using polygenic risk scores and analyzed data with Cox models and propensity score matching.
  • Performed interaction analysis through bootstrap methods and likelihood tests for validation.
  • 11,180 participants developed stroke during an average follow-up of 15.1 years.
  • Each 10-year earlier onset of CHD increased the risk of stroke, hemorrhagic stroke, and ischemic stroke substantially (HRs ranging from 1.27 to 1.57).
  • No significant interaction was found between CHD onset age and genetic risk for stroke.

Structured PICO

Does earlier age at CHD onset increase the risk of stroke in individuals without prior stroke?

P
Population
UK Biobank participants without baseline or pre-CHD stroke
I
Intervention
Earlier age at Coronary Heart Disease (CHD) onset
C
Comparator
Later age at CHD onset or participants without CHD
O
Outcome
Incident strokehard clinical

Earlier onset of coronary heart disease is independently associated with a greater risk of subsequent stroke, highlighting the importance of age at CHD onset as a risk marker regardless of genetic predisposition.

Abstract

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.

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Cite This Study

Qi et al. (2026) studied this question. Earlier onset of coronary heart disease is independently associated with greater risks of stroke, hemorrhagic stroke, and ischemic stroke, regardless of genetic predisposition.

synapsesocial.com/papers/69eb092b553a5433e34b3b7dhttps://doi.org/10.1161/jaha.125.045895
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