Association of metabolic indices with in-stent restenosis and its angiographic severity after drug-eluting stent implantation: a case-control study.

Background: Metabolic abnormalities may contribute to in-stent restenosis (ISR) after percutaneous coronary intervention, but the comparative associations of commonly used metabolic indices with ISR within the same patient population remain incompletely characterized. Objective: To compare the associations of the triglyceride-glucose (TyG) index, atherogenic index of plasma (AIP), and metabolic score for insulin resistance (METS-IR) with angiographically detected ISR and its severity, and to explore potential heterogeneity according to sex and clinical presentation. Design: Retrospective, propensity-score-matched case-control study of patients undergoing follow-up coronary angiography between 2019 and 2024. Participants: The propensity-score-matched cohort comprised 774 patients, including 387 patients with ISR and 387 matched controls without ISR. Angiographic severity analyses were performed among the 387 matched patients with ISR. Main measures: TyG, AIP, and METS-IR were assessed separately in multivariable models. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC), paired DeLong testing, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Sex- and clinical-presentation analyses were considered exploratory. Key results: The baseline clinical and procedural model yielded an AUC of 0.716 (95% CI 0.672-0.763) for ISR occurrence. Addition of TyG increased the AUC to 0.756 (95% CI 0.708-0.803; ΔAUC +0.040; paired DeLong p=0.003), while addition of AIP increased the AUC to 0.772 (95% CI 0.726-0.806; ΔAUC +0.056; p<0.001). Addition of METS-IR did not improve discrimination (AUC 0.716, 95% CI 0.671-0.748; p=0.642). Bootstrap analyses supported the incremental discrimination associated with TyG and AIP but not METS-IR. For ISR severity, addition of TyG or AIP produced only modest increases in AUC, neither of which was significant by paired DeLong testing. Formal interaction analyses did not demonstrate significant effect modification by sex, and analyses according to clinical presentation were limited by small subgroup sizes. Conclusions: In this retrospective matched cohort, TyG and AIP provided incremental discriminatory information for angiographically detected ISR beyond conventional clinical and procedural factors, whereas METS-IR provided little additional value. Evidence regarding angiographic severity was less robust, and findings across sex and clinical-presentation subgroups should be considered exploratory. Prospective external validation is required before these indices can be considered for clinical risk stratification.