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Insulin sensitivity, genetic predisposition, and risk of atrial fibrillation: A prospective cohort study
Yutong Wang1, Yanwen Chen1, Xinyang Song2
1Cardiology department, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Background:
The estimated glucose disposal rate (eGDR) is a validated clinical metric of insulin sensitivity that may predict cardiovascular health; however, the combined and interaction relationship between eGDR and genetic predisposition in determining atrial fibrillation (AF) risk remains unclear.
Objective:
This study aimed to investigate the longitudinal relationship between eGDR and incident AF risk and assess the combined and interaction effect of eGDR and genetic predisposition on AF development.
Methods:
In the UK Biobank, eGDR was calculated using waist circumference, hypertension status, and glycated hemoglobin levels. Genetic predisposition was assessed via a polygenic risk score (PRS) for AF. Associations were examined using Kaplan-Meier curves, restricted cubic spline models, and Cox regression.
Results:
Among 431,572 participants with a median follow-up of 13.53 years, 29,464 AF cases were identified. Higher eGDR quartiles demonstrated significantly lower AF incidence (log-rank P < .001), with L-shaped nonlinear association (P nonlinear < .001). Each unit increase in eGDR was associated with a 9% reduction in AF risk (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.91-0.92; P < .001), with stepwise risk reduction across quartiles (Q4 vs Q1: HR 0.67; 95% CI 0.63-0.70; P < 0.001). Participants with low PRS and high eGDR exhibited 74% lower AF risk (HR 0.26; 95% CI 0.23-0.28; P < .001) than those with high PRS and low eGDR, indicating improved insulin sensitivity confers protection across all genetic risk categories.
Conclusion:
eGDR demonstrates dose-dependent protective effects against AF across all genetic risk categories, highlighting insulin resistance as a potential intervention target for AF prevention.
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