The association of triglyceride-glucose index with acute myocardial infarction and all-cause mortality in patients with coronary artery disease stratified by acute myocardial infarction status: a large-scale retrospective cohort study from South China

Objectives This study aimed to investigate the association of the triglyceride-glucose (TyG) index with the risk of acute myocardial infarction (AMI) and all-cause mortality in patients with coronary artery disease (CAD), and to inspect whether AMI mediates the relationship between TyG index and mortality. Design A large-scale, retrospective cohort study. Setting This single-centre study was conducted at a tertiary academic hospital in South China. The association between the TyG index and AMI was assessed using multivariable logistic regression, with progressive adjustment for demographic and clinical covariates. Cox proportional hazards models were used to estimate the HRs for all-cause mortality associated with TyG index. Restricted cubic splines and mediation analysis were employed to examine non-linear relationships and the mediating role of AMI. Participants A total of 20 125 patients diagnosed with CAD during hospitalisation between January 2020 and February 2025 were initially enrolled. After applying exclusion criteria (insufficient data), 18 245 participants were included in the final analysis. Outcome measures We examined the association of the TyG index with the risk of AMI, as well as its association with all-cause mortality across different CAD subgroups. Results The association between the TyG index and all-cause mortality was significantly modified by AMI status (P for interaction <0.05). In the fully adjusted model, no significant association was observed in the overall CAD cohort. However, subgroup analysis revealed divergent patterns: among patients without AMI, a modest protective effect was observed (Q3 vs Q1: HR 0.77, 95% CI 0.63 to 0.94), whereas in those with AMI, the TyG index exhibited a harmful, dose-response relationship with mortality (per-SD increase: HR 1.18, 95% CI 1.00 to 1.38; Q4 vs Q1: HR 1.60, 95% CI 1.13 to 2.25). Additionally, each SD increment in the TyG index was associated with 12% higher odds of AMI (OR 1.12, 95% CI 1.05 to 1.19). Mediation analysis further demonstrated that AMI mediated 9.51% of the total effect of TyG index on mortality (p<0.001). Conclusions An elevated TyG index independently predicts the risk of AMI in patients with CAD. Its prognostic value for mortality, however, is critically dependent on the presence of AMI: while a higher TyG index is associated with increased mortality in patients with AMI, moderately elevated TyG levels (Q2–Q3) are associated with lower mortality, whereas the highest quartile shows no significant association. Mediation analysis further reveals that AMI significantly mediates the association between TyG index and mortality, highlighting the importance of AMI prevention in mitigating the adverse prognostic impact of insulin resistance in the CAD population. These findings warrant validation in prospective studies.