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Age at Coronary Heart Disease Onset, Genetic Susceptibility, and Subsequent Risk of Stroke
Yi Qi1,2, Wen-Hao Liu1,3,4, Qing-Yuan Gao1,3,4
1Department of Cardiology Sun Yat-sen Memorial Hospital, Sun Yat-sen University Guangzhou China.
Insights
Earlier onset of coronary heart disease (CHD) significantly increases stroke risk, including hemorrhagic and ischemic types. This heightened risk is independent of genetic factors, suggesting CHD onset age is a key stroke predictor.
Area of Science:
- Cardiovascular Medicine
- Neurology
- Genetics
Background:
- Coronary heart disease (CHD) is a known stroke risk factor.
- The relationship between age of CHD onset and stroke risk requires further investigation.
- Understanding genetic influences on stroke susceptibility is crucial.
Purpose of the Study:
- To evaluate how age at coronary heart disease (CHD) onset affects stroke risk.
- To determine if genetic predisposition to stroke interacts with age at CHD onset.
- To analyze associations with specific stroke types: hemorrhagic and ischemic.
Main Methods:
- Prospective cohort study utilizing UK Biobank data.
- Inclusion criteria: participants without prior stroke or CHD.
- Assessment of genetic susceptibility using polygenic risk scores.
- Statistical analysis via Cox models and propensity score matching.
- Interaction analysis using bootstrap methods and likelihood tests.
Main Results:
- Increased stroke risk observed in participants with CHD.
- Each 10-year earlier CHD onset correlated with higher stroke risk (HR 1.27).
- Earlier CHD onset (<57 years) significantly increased subsequent stroke risk (HR 1.33).
- No significant interaction found between CHD onset age and genetic stroke risk.
Conclusions:
- Earlier coronary heart disease (CHD) onset is an independent predictor of increased stroke risk.
- The association between earlier CHD onset and stroke risk persists regardless of genetic predisposition.
- Early CHD onset serves as a critical marker for elevated stroke risk.
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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