Abstract
BACKGROUND: The Triglyceride-Glucose (TyG) index has been recognized as an independent predictor of cardiovascular disease (CVD) risk. However, the combined effect of TyG index with obesity indices, such as body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), conicity index (CI), weight-adjusted waist index (WWI), and body roundness index (BRI), on CVD risk remains inconsistent across different studies. This study aims to evaluate the relationship between TyG index and its related indices with the risk of coronary artery disease (CAD) and explore the mediating role of glycated hemoglobin (HbA1c) in this association. METHODS: This study included patients who underwent coronary angiography for the first time. Logistic regression models, restricted cubic spline (RCS) regression, and threshold effect analysis were used to assess the relationship between the TyG index and its related indices with the risk of CAD. The area under the curve (AUC) for each index was calculated using receiver operating characteristic (ROC) curves, and AUC differences were compared using DeLong's test. Stratified analysis was performed to validate the robustness of the results, and mediation analysis was conducted to evaluate the mediating role of HbA1c in the relationship between TyG index, its related indices, and CAD risk. RESULTS: This retrospective observational study included a total of 3, 641 participants. After adjusting for covariates, the TyG index and its related indices were significantly positively associated with CAD (TyG: OR = 1.642, 95% CI = 1.447, 1.866; TyG-BMI: OR = 1.010, 95% CI = 1.007, 1.012; TyG-WC: OR = 1.392, 95% CI = 1.289, 1.504; TyG-WHtR: OR = 1.839, 95% CI = 1.621, 2.087; TyG-CI: OR = 1.233, 95% CI = 1.168, 1.301; TyG-WWI: OR = 1.027, 95% CI = 1.020, 1.033; TyG-BRI: OR = 1.029, 95% CI = 1.022, 1.037). A linear relationship was observed between TyG index and CAD risk (P-nonlinear = 0.053). A nonlinear relationship was found between TyG-related indices in relation to CAD risk (P-nonlinear ≤ 0.001). Threshold effect analysis showed that after surpassing a certain threshold, the association between TyG-related indices and CAD risk became more significant. ROC analysis revealed that TyG-WHtR had similar predictive ability to the TyG index, while other combinations had lower predictive efficacy than the TyG index alone. Subgroup analyses across different strata consistently demonstrated significant associations between TyG index and its related indices and CAD risk. Mediation analysis showed that HbA1c partially mediated the relationship between TyG index and its related indices with CAD risk, with the highest contribution rate being 27.86%. CONCLUSION: The TyG index and its related indices are significantly associated with the risk of CAD, and HbA1c partially mediates this relationship. Furthermore, the clinical applicability of TyG-related indices need further validation to avoid over-interpretation.