The American Heart Association(AHA) first defined cardiovascular-kidney-metabolic syndrome (CKM) in 2023, elucidating the complex association between metabolic risk factors, chronic kidney disease (CKD) and cardiovascular disease (CVD), and emphasizing that early intervention in CKM stages 0-3 can reduce the risk of end-stage cardiovascular events. Triglyceride glucose index (TYG), as a novel marker of lipid metabolism, has been shown to be associated with CVD in the general population, but its association with CVD in the CKM stages 0-3 population still needs to be supported by evidence-based medical evidence.

To explore the association between TYG level and CVD risk in patients with CKM stages 0-3.

From a baseline established in 2015, 46 754 participants meeting CKM stages 0-3 criteria were identified from the Cheeloo Longitudinal Epidemiological Analysis Database (LEAD) during the investigation period (2015-01-01—2017-12-31). Participants were categorized into quartiles based on baseline TYG indices: Q1 (6.79≤TYG<8.19, n=11 979), Q2 (8.19≤TYG<8.55, n=11 493), Q3 (8.55≤TYG<8.93, n=11 647), and Q4 (8.93≤TYG≤11.7, n=11 635). Cox proportional hazards regression models were employed to systematically analyze the association between TYG and CVD risk within this cohort. Survival curves were plotted using the Kaplan-Meier method, and differences in survival rates among different TYG groups were analyzed using the Log-rank test. Dose-response curves were evaluated using restricted cubic splines (RCS) across the total CKM stages 0-3 population. Subgroup analyses by gender (male and female) and CKM stages (<stage 2 and ≥stage 2) were conducted to verify the robustness of the associations. Stratified multivariable Cox models were constructed, incorporating average TYG and cumulative TYG as continuous variables to explore their impact on CVD occurrence.

A total of 46 754 participants were included, comprising 19 884 males (42.5%) and 26 870 females (57.5%), with a median age of 69(65, 73) years. The mean baseline TYG was 8.59±0.60, and 32 837 (70.2%) participants were at CKM stage 2. Cox regression analysis revealed that per unit increase in TYG as a continuous variable was associated with a 19.4% increased risk of CVD incidence (HR=1.194, 95%CI=1.162-1.226, P<0.001). Group analysis indicated that the risk of newly developed CVD in Q4 was 28.0% higher than in Q1 (HR=1.280, 95%CI=1.222-1.341), with a significant dose-response relationship (P<0.05). Cumulative incidences of CVD across Q1-Q4 showed a gradient increase (33.7%, 35.2%, 42.0%, and 43.7%, respectively). Kaplan-Meier curves demonstrated statistically significant differences in CVD incidence rates among Q1-Q4 groups (χ²=328.853, P<0.05). RCS analysis suggested a linear positive correlation between TYG and CVD risk in the overall CKM stages 0-3 population (P<0.001, P_non-lineari=0.282); stratification by CKM stage also showed a linear positive correlation in CKM stages 0-1 (P<0.001, P_non-linear=0.616) and 2-3 (P<0.001, P_non-linear=0.180).

In the 0-3 stage of CKM, TYG is revealed as an early warning of CVD risk in this population, which provides theoretical support for the establishment of a precision prevention strategy based on metabolic-cardiorenal intervention.

美国心脏协会（AHA）于2023年首次定义了心血管-肾脏-代谢综合征（CKM），阐明了代谢危险因素、慢性肾脏病（CKD）和心血管疾病（CVD）之间复杂的联系，并强调在CKM 0~3期进行早期干预，可降低终末期心血管事件发生风险。三酰甘油-葡萄糖指数（TYG）作为新型脂质代谢标志物，在一般人群中已证实与CVD相关，但其在CKM 0~3期人群中与CVD的相关性仍有待循证医学的证据支持。

本研究旨在探索CKM 0~3期人群中TYG水平与CVD风险的关联。

以2015年为基线，纳入齐鲁全生命周期电子健康研究型数据库（Cheeloo LEAD）中调查期间（2015-01-01—2017-12-31）46 754例符合CKM 0~3期标准的研究对象，依据基线TYG四分位数将研究对象分为Q1（6.79≤TYG<8.19，n=11 979）、Q2（8.19≤TYG<8.55，n=11 493）、Q3（8.55≤TYG<8.93，n=11 647）、Q4组（8.93≤TYG≤11.7，n=11 635）。采用Cox比例风险回归模型系统分析CKM 0~3期人群中TYG与CVD风险的关联。采用Kaplan-Meier法绘制生存曲线，采用Log-rank检验分析不同TYG组的生存率差异。采用限制性立方样条（RCS）在CKM 0~3期总人群中绘制剂量-反应曲线。并通过性别（男性和女性）和CKM分期（<2期和≥2期）进行亚组分析验证关联稳健性。构建分层调整多因素Cox模型，将平均TYG和累积TYG作为连续性变量分别纳入模型，探讨TYG对CVD发生的影响。

共纳入46 754名研究对象，男19 884名（42.5%），女26 870名（57.5%），中位年龄69（65，73）岁，平均基线TYG为（8.59±0.60），32 837名（70.2%）研究对象处于CKM 2期。Cox比例风险回归模型结果显示，TYG作为连续变量时水平每升高1个单位，CVD发病风险增加19.4%（HR=1.194，95%CI=1.162~1.226，P<0.001）。分组分析显示，Q4组新发CVD风险较Q1组增加28.0%（HR=1.280，95%CI=1.222~1.341），趋势检验显示剂量-反应关系显著（P<0.05）。Q1、Q2、Q3、Q4组CVD累积发病率呈梯度升高趋势（33.7%、35.2%、42.0%、43.7%）。Kaplan-Meier生存曲线显示，Q1~Q4组的CVD发病率比较，差异有统计学意义（χ²=328.853，P<0.05）。RCS曲线显示CKM 0~3期的总人群中，TYG与CVD发病风险呈线性正相关（P<0.001，P_非线性=0.282）；按CKM分期分层后，在CKM 0~1期（P<0.001，P_非线性=0.616）和2~3期（P<0.001，P_非线性=0.180）的人群中，TYG与CVD发病风险呈线性正相关。

在CKM 0~3期人群中，TYG对CVD具有风险预警作用，为建立基于代谢-心肾干预的精准预防策略提供理论支撑。