Association of the C-reactive protein–triglyceride–glucose index with the risk of incident cardiovascular disease in rectal cancer survivors
Background and objective Rectal cancer survivors face an elevated cardiovascular disease (CVD) burden shaped by tumor- and treatment-related pathophysiology beyond conventional risk factors. We evaluated the association between the C-reactive protein–triglyceride–glucose index (CTI)—a composite inflammatory–metabolic indicator—and incident CVD in this population. Methods This retrospective cohort study enrolled 1,160 rectal cancer survivors from a Chinese tertiary hospital as the discovery cohort and 1,752 from the UK Biobank as an independent validation cohort. Incident CVD was the primary outcome. Multivariable logistic regression, restricted cubic splines, and model performance metrics were used to assess the association, dose–response relationship, and incremental predictive value of CTI. Results After full multivariable adjustment, each one-SD increment in CTI was associated with an 18% higher risk of incident CVD (OR = 1.18, 95% CI: 1.02–1.36, p = 0.025), with an approximately linear dose–response relationship (p for non-linearity = 0.448) and excess risk concentrated in the highest quartile (Q4 vs. Q1: OR = 1.60, 95% CI: 1.07–2.42, p = 0.024). Adding CTI improved discrimination (AUC = 0.718) beyond the CRP-based model (AUC = 0.713, p = 0.050) and the TyG-based model (AUC = 0.715, p = 0.042), and significantly improved risk reclassification (categorical NRI = 0.052, 95% CI: 0.018–0.086, p = 0.005). The association was stronger in patients aged <65 years (OR = 1.63; p for interaction = 0.007) and those without baseline hypertension (OR = 1.33; p for interaction = 0.034). In the UK Biobank cohort, the CTI–CVD association attenuated progressively and became non-significant after full adjustment (OR = 1.08, 95% CI: 0.95–1.22, p = 0.261; AUC = 0.649). Conclusion CTI was independently associated with incident CVD in rectal cancer survivors and improved risk reclassification beyond CRP or TyG alone, with effects concentrated in younger and non-hypertensive patients. Its incremental value attenuated in a community-based population, suggesting that CTI is most informative in oncology settings with high inflammatory–metabolic burden.