Combined Prognostic Value of Triglyceride-Glucose Index and Bilirubin in Drug-Eluting Stent Restenosis: From Clinical Risk Stratification to Exploratory Vascular-Cell Findings

Background Drug-eluting stent in-stent restenosis (DES-ISR) remains a clinically relevant complication after percutaneous coronary intervention for acute coronary syndrome (ACS). We assessed the combined predictive value of the triglyceride-glucose (TyG) index and total bilirubin (TB), alongside exploratory vascular-cell findings.Methods This retrospective cohort included 1,160 ACS patients undergoing drug-eluting stent implantation and angiographic follow-up. Associations with DES-ISR, discrimination, calibration, and incremental prediction were evaluated using multivariable models and split-sample internal validation. HUVECs and VSMCs were exposed to high-glucose/high-triglyceride or bilirubin-related conditions; network pharmacology, reverse docking, and selected pathway experiments were used to generate and evaluate hypotheses.Results Higher TyG was associated with increased DES-ISR risk (adjusted OR = 1.487, 95% CI 1.067-2.073), whereas higher TB was associated with lower risk (OR = 0.875, 95% CI 0.838-0.914). The TyG-TB model had AUCs of 0.702 (training) and 0.676 (validation), with Brier score 0.134, calibration slope 0.858, and Hosmer-Lemeshow P = 0.868. Adding TyG and TB improved prediction (ΔAUC = 0.078; continuous NRI = 0.714; IDI = 0.060; all P Conclusion TyG and TB showed opposite associations with DES-ISR and jointly provided moderate incremental predictive information. The cell findings support RAGE-related vascular responses under the tested conditions but require external and mechanistic validation before clinical application.