The prognostic value of combined TyG and SIRI categories for cardiovascular disease and all-cause mortality among adults: Evidence from the NHANES 1999–2010
Background The triglyceride-glucose (TyG) index and Systemic Inflammatory Response Index (SIRI) are markers of insulin resistance and inflammation, respectively, and are each independently associated with mortality. Their combined prognostic value is not well established. This study aimed to investigate the association between combined categories of TyG and SIRI and cardiovascular (CVD) and all-cause mortality. Methods We included 11,010 participants from the NHANES 1999–2010. All analyses accounted for the complex survey design. We employed Cox models, restricted cubic splines, and time-dependent ROC analyses. The incremental predictive value of the combined categories was assessed using the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results A TyG threshold of 8.64 (linear association) and an SIRI threshold of 0.63 (L-shaped association) were identified. Compared to the low-risk group (TyG ≤ 8.64 and SIRI≤0.63), participants with both TyG > 8.64 and SIRI>0.63 had a 68% higher risk of CVD mortality (HR = 1.68, 95% CI: 1.08–2.61, P = 0.021) and a 52% higher risk of all-cause mortality (HR = 1.52, 95% CI: 1.21–1.91, P < 0.0001). Adding the combined categories to a model of traditional risk factors significantly improved reclassification for CVD mortality (NRI = 0.15, P < 0.05). Subgroup and sensitivity analyses supported the robustness of the findings. Conclusions Concurrently high TyG and SIRI identifies individuals at significantly increased mortality risk. This simple, threshold-based stratification may serve as a practical tool for cardiovascular risk assessment.