Yutong Wang, Yanwen Chen, Xinyang Song, Tao Xu, Chenxi Xia, Junsong Gong, Sixian Weng, Fang Wang
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Associations were examined using Kaplan-Meier (KM) curves, restricted cubic spline (RCS) models, and Cox regression.</p><p><strong>Results: </strong>Among 431572 participants with a median follow-up of 13.53-year, 29464 AF cases were identified. Higher eGDR quartiles demonstrated significantly lower AF incidence (log-rank P < 0.001), with L-shaped non-linear association (P nonlinear < 0.001). Each unit increase in eGDR was associated with a 9% reduction in AF risk (HR: 0.91, 95% CI: 0.91-0.92, P < 0.001), 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 < 0.001) compared to those with high PRS and low eGDR, indicating improved insulin sensitivity confers protection across all genetic risk categories.</p><p><strong>Conclusion: </strong>EGDR demonstrates dose-dependent protective effects against AF across all genetic risk categories, highlighting insulin resistance as a potential intervention target for AF prevention.</p>","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":" ","pages":""},"PeriodicalIF":5.7000,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Insulin sensitivity, genetic predisposition, and risk of atrial fibrillation: a prospective cohort study.\",\"authors\":\"Yutong Wang, Yanwen Chen, Xinyang Song, Tao Xu, Chenxi Xia, Junsong Gong, Sixian Weng, Fang Wang\",\"doi\":\"10.1016/j.hrthm.2025.10.015\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>To investigate the longitudinal relationship between eGDR and incident AF risk, and to assess the combined and interaction effect of eGDR and genetic predisposition on AF development.</p><p><strong>Methods: </strong>In the UK Biobank, eGDR was calculated using waist circumference, hypertension status, and glycated hemoglobin levels. 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引用次数: 0
摘要
背景：估计葡萄糖处置率（eGDR）是一种有效的胰岛素敏感性临床指标，可以预测心血管健康，然而，eGDR和遗传易感性在确定房颤（AF）风险方面的联合和相互作用关系尚不清楚。目的：探讨eGDR与房颤发生风险的纵向关系，评价eGDR与遗传易感性对房颤发生的联合及交互作用。方法：在UK Biobank中，eGDR使用腰围、高血压状态和糖化血红蛋白水平计算。通过AF的多基因风险评分（PRS）评估遗传易感性。使用Kaplan-Meier （KM）曲线、限制性三次样条（RCS）模型和Cox回归检查相关性。结果：431572名参与者中位随访13.53年，发现29464例房颤病例。eGDR四分位数越高，AF发病率越低（log-rank P < 0.001），呈l型非线性关联（P非线性< 0.001）。eGDR每增加一个单位与AF风险降低9%相关（HR: 0.91, 95% CI: 0.91-0.92, P < 0.001），四分位数间风险逐步降低（Q4 vs Q1: HR: 0.67, 95% CI: 0.63-0.70, P < 0.001）。与高PRS和低eGDR的受试者相比，低PRS和高eGDR的受试者AF风险降低74% (HR:0.26, 95% CI:0.23-0.28, P < 0.001)，表明胰岛素敏感性的提高对所有遗传风险类别都有保护作用。结论：EGDR在所有遗传风险类别中都显示出剂量依赖性的AF保护作用，强调胰岛素抵抗是AF预防的潜在干预靶点。
Insulin sensitivity, genetic predisposition, and risk of atrial fibrillation: a prospective cohort study.
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: To investigate the longitudinal relationship between eGDR and incident AF risk, and to 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 (KM) curves, restricted cubic spline (RCS) models, and Cox regression.
Results: Among 431572 participants with a median follow-up of 13.53-year, 29464 AF cases were identified. Higher eGDR quartiles demonstrated significantly lower AF incidence (log-rank P < 0.001), with L-shaped non-linear association (P nonlinear < 0.001). Each unit increase in eGDR was associated with a 9% reduction in AF risk (HR: 0.91, 95% CI: 0.91-0.92, P < 0.001), 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 < 0.001) compared to 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.
期刊介绍：
HeartRhythm, the official Journal of the Heart Rhythm Society and the Cardiac Electrophysiology Society, is a unique journal for fundamental discovery and clinical applicability.
HeartRhythm integrates the entire cardiac electrophysiology (EP) community from basic and clinical academic researchers, private practitioners, engineers, allied professionals, industry, and trainees, all of whom are vital and interdependent members of our EP community.
The Heart Rhythm Society is the international leader in science, education, and advocacy for cardiac arrhythmia professionals and patients, and the primary information resource on heart rhythm disorders. Its mission is to improve the care of patients by promoting research, education, and optimal health care policies and standards.
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