Association of the C-Reactive Protein-Triglyceride Glucose Index with Coronary Severity and Incident Heart Failure in Newly Diagnosed Coronary Artery Disease

Abstract Background Chronic inflammation and metabolic dysregulation are key contributors to coronary artery disease (CAD) progression. The C-reactive protein–triglyceride glucose (CTI) index integrates these pathways, but its association with coronary lesion severity and incident heart failure (HF) in patients with newly diagnosed CAD remains unclear. Methods This single-center retrospective cohort included 813 consecutive patients with angiography-confirmed, newly diagnosed CAD between January 2020 and June 2025; patients with pre-existing HF or prior HF hospitalization were excluded. Coronary lesion severity was quantified by the Gensini score. CTI was calculated as 0.412 × ln(CRP [mg/L]) + ln(TG [mg/dL] × FPG [mg/dL]/2). The primary outcome was new-onset clinical HF during follow-up. Restricted cubic spline (RCS) analysis with four knots examined the CTI–Gensini association. Multivariable Cox models with sequential adjustment estimated HRs and 95% CIs. Sensitivity analyses excluded STEMI and HF events within 12 months, used complete-case analysis, and applied LASSO-Cox and Firth penalized regression. Time-dependent ROC, subgroup, and exploratory mediation analyses were also performed. Results Over a median follow-up of 37 months, 64 patients (7.9%) developed HF. HF-free survival decreased across CTI tertiles (log-rank P < 0.001). RCS analysis revealed a non-linear CTI–Gensini association (P for non-linearity < 0.05). After adjustment, each one-unit increase in CTI was associated with a higher HF risk (HR = 2.117, 95% CI 1.498–2.991, P < 0.001), and the association persisted after further adjustment for ejection fraction (HR = 2.057, 95% CI 1.334–3.173). CTI showed good discrimination at 12, 24, and 36 months (AUC 0.791, 0.802, and 0.796), comparable to CRP and superior to the TyG index at 24 and 36 months. Subgroup analyses showed no significant effect modification. Exploratory mediation analysis suggested partial mediation by the Gensini score (30.4%) and E/e′ ratio (17.7%). Sensitivity analyses confirmed the robustness of the association. Conclusion In patients with newly diagnosed CAD, CTI was associated with coronary lesion severity and incident HF after adjustment for confounders. Because CTI is derived from routine laboratory measurements at negligible additional cost, further prospective evaluation of its role in risk stratification is warranted. Trial registration ChiCTR2100044802 (registered on 27 March 2021).