Association between triglyceride-glucose-related indices and cardiovascular disease risk in population with cardio-kidney-metabolic syndrome stages 0–3: a systematic review and meta-analysis

Abstract Objective This systematic review and meta-analysis aimed to compare the associations of four triglyceride-glucose (TyG)-derived indices (TyG, TyG-BMI, TyG-WC, TyG-WHtR) with incident cardiovascular disease (CVD) risk among individuals with stage 0–3 cardio-kidney-metabolic (CKM) syndrome, and explore potential sources of inter-study heterogeneity using pre-specified subgroup analyses and exploratory meta-regression analyses. Methods We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from database inception to May 1, 2026. Two independent reviewers completed study screening, data extraction, and quality assessment using the Newcastle–Ottawa Scale (NOS). Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were synthesized using fixed- or random-effects models according to between-study heterogeneity, which was quantified by Cochran’s Q test and the I² statistic. Subgroup analyses, exploratory univariable meta-regression analyses, leave-one-out sensitivity analyses, and publication bias assessments were performed to investigate potential sources of heterogeneity and evaluate the robustness of the findings. Results Nine high-quality prospective cohort studies were ultimately included. Participants in the highest versus lowest quantiles of each index had significantly elevated CVD risk: TyG (HR = 1.24, 95% CI 1.16–1.33, I² = 76%), TyG-BMI (HR = 1.44, 95% CI 1.26–1.66, I² = 93%), TyG-WC (HR = 1.42, 95% CI 1.21–1.67, I² = 96%), and TyG-WHtR (HR = 1.45, 95% CI 1.28–1.65, I² = 91%). Exploratory meta-regression suggested that follow-up duration may contribute to heterogeneity in TyG, whereas age may contribute to heterogeneity in TyG-WHtR; substantial residual heterogeneity remained for TyG-WC and TyG-WHtR. Sensitivity analyses supported the robustness of the findings. No significant publication bias was detected, but statistical power was limited by fewer than 10 studies per index. Conclusions This meta-analysis suggests that elevated TyG-derived indices are significantly associated with increased incident CVD risk among individuals with stage 0–3 CKM syndrome. Composite TyG-derived indices showed numerically higher pooled effect estimates than the TyG index; however, overlapping confidence intervals and the absence of direct statistical comparisons prevent conclusions regarding the superiority of any specific index. Given the observational nature of the included studies, limited population diversity, and substantial residual heterogeneity, these findings should be interpreted cautiously. TyG-derived indices may represent potential auxiliary markers for CVD risk stratification, and further large-scale multi-ethnic prospective studies are warranted to evaluate their clinical utility.