Linking the triglyceride-glucose index to major adverse cardiocerebrovascular events in individuals with cardiovascular-kidney-metabolic syndrome: insights from an aggregate-data systematic review and dose–response meta-analysis

Background Epidemiological research has indicated a potential association between the triglyceride-glucose (TyG) index and the risk of major adverse cardiocerebrovascular events (MACCE). Nevertheless, the precise nature and magnitude of this relationship remain to be fully elucidated. Objectives This study aims to assess the dose–response relationship between the TyG index and MACCE among individuals with cardiovascular-kidney-metabolic (CKM) syndrome. Methods A comprehensive literature search was conducted using the PubMed and Web of Science databases to identify relevant studies on the TyG-MACCE relationship up to 16 June 2026. Data were synthesized using both random- and fixed-effects models, and nonlinear dose–response meta-analyses were performed using restricted cubic spline models. Results The analysis incorporated eight cohort studies, encompassing over two million participants and 179 thousand MACCE cases. The aggregated risk estimate for MACCE, comparing the highest to the lowest categories of TyG index exposure, was 1.20 (95% confidence interval [CI] = 1.11–1.30, I 2 = 77.2%, p heterogeneity < 0.001). The dose–response analysis revealed a nonlinear positive association between the TyG index and MACCE risk ( p nonlinear < 0.001), with summary risk estimates calculated for each 1-unit increment in the TyG index being 1.05 (95% CI = 1.02–1.08, I 2 = 81.1%, p heterogeneity < 0.001). Subgroup and sensitivity analyses yielded similar results. Conclusions This suggests that the TyG index may contribute to adverse MACCE in individuals with CKM syndrome. Further studies are needed to confirm causality and the predictive power of the TyG index. The research was prospectively registered in the Prospective Register for Systematic Reviews (registration number: CRD420261278535). Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261278535 , identifier CRD420261278535.