Association of triglyceride-glucose muscle loss index with major adverse cardiovascular events in angina patients: the potential mediating role of inflammation

Background This study aims to explore the association between triglyceride-glucose muscle loss index (TyG-MLI) and the risk of major adverse cardiovascular events (MACE), as well as the potential mediating role of inflammation. Methods The association between TyG-MLI and MACE was analyzed using Cox proportional hazards models, Kaplan–Meier curves, restricted cubic splines (RCS), receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI). A sensitivity analysis comparing multiplicative and additive formulations was performed, and subgroup analysis was conducted. Mediation analysis was conducted to explore the potential contribution of neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) to this association. Results A total of 858 patients with angina who underwent their first percutaneous coronary intervention (PCI) were enrolled in this study. During the 2-year follow-up, 144 cases of MACE were identified. After adjusting for potential confounders, a significant positive association was found between TyG-MLI and MACE (HR 1.203, 95% CI 1.146–1.262). Kaplan–Meier survival analysis revealed that patients in the highest TyG-MLI tertile had the highest risk. RCS analysis showed a linear relationship between TyG-MLI and MACE ( p -overall < 0.017; p -non-linear = 0.219). ROC curve analysis demonstrated that TyG-MLI outperformed both TyG and MLI in diagnostic ability. NRI and IDI analyses confirmed that TyG-MLI significantly improved risk reclassification compared with the TyG alone (IDI = 0.347, NRI = 0.263, both p < 0.001). Sensitivity analysis showed that the multiplicative formulation had superior model fit (AIC = 1799.58) and discrimination (C-index = 0.747) compared with the additive index (AIC = 1826.88, C-index = 0.720). Similar results were observed in subgroup analyses. Mediation analysis indicated that NLR and SII partially accounted for the association between TyG-MLI and MACE, although the proportions mediated were modest (approximately 2.4–2.8%). Conclusion TyG-MLI is independently associated with the occurrence of MACE in patients with angina undergoing their first PCI. Inflammatory markers accounted for a small proportion of this association, suggesting that other unmeasured pathways may also be involved.