Abstract
BACKGROUND: The triglyceride-glucose (TyG) index, a surrogate marker for insulin resistance, has been shown to be closely associated with cardiovascular risk. However, it remains unclear whether diabetes status affects the association between the TyG index and the risk of major adverse cardiovascular events (MACEs) in patients with coronary heart disease (CHD). The aim of this study is to systematically evaluate the relationship between the TyG index and MACEs among CHD patients with different diabetes statuses. METHODS: We systematically searched PubMed, the Cochrane Library, Web of Science, and Embase from inception to March 13, 2025, for cohort studies examining the association between TyG and MACEs in patients with CHD with different diabetes statuses. The outcomes included all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, and revascularization. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were extracted for the TyG index as both categorical and continuous variables. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). All the statistical analyses were performed using Stata (version 17.0) and R (version 4.4.1). Depending on heterogeneity, either a fixed-effect or random-effects model was used to pool the data. Subgroup analysis and meta-regression are used to explore the sources of heterogeneity. This study was registered in PROSPERO (CRD: 420251018545). RESULTS: A total of 36 longitudinal cohort studies comprising 173,851 participants (119,232 with diabetes and 54,619 without diabetes) were included, with 9159 MACEs reported during the follow-up period. In diabetic patients, a higher TyG index significantly increased the risk of MACEs (categorical HR = 1.98, 95% CI 1.61-2.43; continuous HR = 1.57, 95% CI 1.38-1.78), all-cause mortality (HR = 1.74, 95% CI 1.45-2.08), nonfatal myocardial infarction (HR = 2.05, 95% CI 1.52-2.77), nonfatal stroke (HR = 1.73, 95% CI 1.12-2.66), and revascularization (HR = 2.52, 95% CI 1.26-5.04). In nondiabetic patients, a higher TyG index also significantly increased the risk of MACEs (categorical HR = 1.65, 95% CI 1.33-2.05; continuous HR = 1.74, 95% CI 1.46-2.06), all-cause mortality (HR = 1.50, 95% CI 1.18-1.90), nonfatal myocardial infarction (HR = 2.46, 95% CI 1.11-5.47), and revascularization (HR = 2.09, 95% CI 1.57-2.76). However, no association was observed between the TyG index and nonfatal stroke (HR = 1.66, 95% CI 0.88-3.12) in nondiabetic patients. CONCLUSION: Higher TyG index values appear to be associated with an increased risk of adverse cardiovascular events, all-cause mortality, nonfatal myocardial infarction, and revascularization in both diabetic and nondiabetic patients with CHD. However, no significant association was found between the TyG index and the risk of nonfatal stroke in nondiabetic patients. These findings suggest that the TyG index may offer potential prognostic value in CHD, but further high-quality prospective studies are warranted to confirm these associations and clarify their clinical implications.