Zhang Hao, Huang Sizhuang, Fang Yanwen, Zhang Haihua, Yang Weixian, Yu Mengyue
Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, No. 167, North Lishi Road, Xicheng District, Beijing, 100037, China.
Cardiovasc Diabetol. 2025 Sep 11;24(1):360. doi: 10.1186/s12933-025-02860-z.
Insulin resistance (IR) has been recognized as a critical factor in the progression of cardiovascular disease (CVD), yet its association with cardiovascular-kidney-metabolic (CKM) syndrome remains incompletely understood. This study aimed to evaluate the impact of IR, as measured by the estimated glucose disposal rate (eGDR), on the risk of future CVD events in individuals with CKM stages 0-3.
This study included 325,312 participants from the UK Biobank with CKM stages 0-3. IR was quantified using eGDR, a non-insulin-dependent metric, with lower values indicating greater IR. Participants were stratified into quartiles based on eGDR distribution. The primary outcome was incident CVD, including coronary heart disease, stroke, atrial fibrillation, heart failure, and peripheral artery disease.
In the CKM 0-3 cohort, eGDR demonstrated the highest predictive value for future CVD events among non-insulin-dependent IR metrics. Incorporating eGDR significantly improved the predictive performance of the PREVENT Cardiovascular Disease Risk Equations (AUC: PREVENT Equations + eGDR 0.743 vs. PREVENT Equations 0.719, p < 0.001). Over a median follow-up of 13.57 years, 48,433 incident CVD cases were identified. The adjusted rates of CVD incidence (95% confidence interval [CI]) across eGDR quartiles (Q1-Q4) were 3.84 (3.62-4.07), 3.82 (3.66-3.98), 3.53 (3.41-3.65), and 3.37 (3.25-3.50) per 1000 person-years. RCS analysis revealed a significant nonlinear association between eGDR and CVD incidence (p for overall < 0.001; p for nonlinear = 0.020), with greater risk reduction at higher eGDR levels. A significant trend toward reduced CVD risk was observed across higher eGDR quartiles, with Q3 and Q4 demonstrating statistically significant reductions relative to Q1 (HR 0.920, 95% CI 0.871-0.971; and 0.883, 95% CI 0.827-0.942, respectively; p for trend < 0.001). Kaplan-Meier analysis further confirmed a graded decrease in CVD risk with increasing eGDR levels (log-rank p < 0.001).
This study establishes a strong association between IR severity and long-term CVD risk in individuals with CKM syndrome stages 0-3. The eGDR, a reliable surrogate marker of IR, independently predicts future CVD events and provides incremental predictive value beyond the PREVENT equations. These findings underscore the clinical utility of eGDR for risk stratification in CKM populations.
胰岛素抵抗（IR）已被公认为是心血管疾病（CVD）进展的关键因素，但其与心血管-肾脏-代谢（CKM）综合征的关联仍未完全明确。本研究旨在评估以估计葡萄糖处置率（eGDR）衡量的IR对CKM 0-3期个体未来发生CVD事件风险的影响。
本研究纳入了来自英国生物银行的325,312名CKM 0-3期参与者。使用eGDR对IR进行量化，eGDR是一种非胰岛素依赖指标，值越低表明IR越高。参与者根据eGDR分布分为四分位数。主要结局是新发CVD，包括冠心病、中风、心房颤动、心力衰竭和外周动脉疾病。
在CKM 0-3队列中，eGDR在非胰岛素依赖的IR指标中对未来CVD事件具有最高的预测价值。纳入eGDR显著提高了预防心血管疾病风险方程的预测性能（曲线下面积：预防方程+eGDR为0.743，预防方程为0.719，p<0.001）。在中位随访13.57年期间，共识别出48,433例新发CVD病例。eGDR四分位数（Q1-Q4）每1000人年的CVD发病率调整率（95%置信区间[CI]）分别为3.84（3.62-4.07）、3.82（3.66-3.98）、3.53（3.41-3.65）和3.37（3.25-3.50）。限制立方样条（RCS）分析显示eGDR与CVD发病率之间存在显著的非线性关联（总体p<0.001；非线性p=0.020），eGDR水平越高，风险降低幅度越大。在较高的eGDR四分位数中观察到CVD风险降低的显著趋势，Q3和Q4相对于Q1显示出统计学显著降低（风险比分别为0.920，95%CI 0.871-0.971；和0.883，95%CI 0.827-0.942；趋势p<0.001）。Kaplan-Meier分析进一步证实随着eGDR水平升高，CVD风险呈分级下降（对数秩检验p<0.001）。
本研究证实了CKM综合征0-3期个体的IR严重程度与长期CVD风险之间存在密切关联。eGDR作为IR的可靠替代标志物，可独立预测未来CVD事件，并提供超出预防方程的额外预测价值。这些发现强调了eGDR在CKM人群风险分层中的临床应用价值。
