Combined triglyceride-glucose index and systemic inflammation for long-term risk stratification in major adverse cardiovascular events: a 10-year prospective study

BACKGROUND AND AIMS: Insulin resistance and systemic inflammation are key drivers of atherosclerosis but are typically evaluated separately. This study aimed to determine whether integrating the triglyceride-glucose (TyG) index with inflammatory markers improves long-term risk stratification for major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD). METHODS AND RESULTS: In this prospective cohort study, 9316 CAD patients were followed for 10 years. Cox regression models were used to assess associations between the TyG index and inflammatory markers with MACE. Incremental predictive value was evaluated using net reclassification improvement (NRI) and integrated discrimination improvement. The combined TyG-inflammation models were significantly associated with an increased risk of 10-year MACE, corresponding to a 19.1% relative increase in hazard. Among the evaluated models, the TyG + systemic inflammation response index (SIRI) combination demonstrated the most consistent performance, primarily through improving risk reclassification rather than discrimination. The model achieved an NRI of 5.5% for overall MACE and 15.4% for cardiac death, indicating improved identification of high-risk patients who would not be detected by the TyG index alone. CONCLUSION: Integrating systemic inflammation, particularly SIRI, with the TyG index significantly enhances long-term cardiovascular risk reclassification in CAD patients. This simple and cost-effective approach based on routine laboratory parameters may improve risk stratification and support more targeted secondary prevention.