Inflammation mediates the association between the triglyceride-glucose index and non-target lesions progression after PCI: a cohort study

The progression of non-target lesions (NTLs) following percutaneous coronary intervention (PCI) is an important clinical issue, yet the role of triglyceride–glucose (TyG) in this process is unclear. This study enrolled patients with coronary artery disease who underwent PCI between 2017 and 2020, and completed follow-up coronary angiography 6–24 months after the procedure. Coronary stenosis was evaluated by visual estimation and verified using quantitative coronary angiography. We used TyG values at baseline and follow-up as the primary exposures, and defined NTLs progression as the study endpoint. Patterns of TyG changes were identified with K-means clustering. Analysis focused on the association between the TyG index and NTLs progression, while mediation analysis evaluated the role of inflammation, and the robustness of the findings was assessed using NTL-related PCI as a secondary outcome. Among the 889 patients included, 246 (27.7%) showed NTLs progression. Higher TyG levels were associated with increased risk: each 1-unit increase corresponded to a 61% higher risk (HR = 1.61, 95% CI 1.26–2.05), and patients in the highest TyG quartile (Q4) had an 86% higher risk of NTLs progression compared with those in the lowest quartile (Q1) (HR = 1.86, 95% CI 1.28–2.70). After clustering, persistently high TyG was linked to a 163% higher risk compared with persistently low levels (HR = 2.63, 95% CI 1.76–3.92). The association appeared linear according to RCS analysis. CRP mediated about 12% of this effect (95% CI 4.21%–28.6%, P = 0.002). Sensitivity analysis further showed a significant association between TyG and NTL-related PCI (HR = 1.91, 95% CI: 1.39–2.63, P < 0.001). Elevated TyG levels independently predicted NTLs progression after PCI. This finding highlights the role of metabolic and inflammatory pathways in residual atherosclerotic activity. Monitoring TyG may help identify patients at risk for future lesion progression despite successful revascularization.