Triglyceride–glucose index and atherogenic index of plasma as predictors of cardiovascular risk in rectal cancer survivors

Background Rectal cancer survivors face elevated cardiovascular disease (CVD) risk, but simple metabolic indices for risk stratification remain underexplored. We investigated associations of triglyceride-glucose index (TyG) and atherogenic index of plasma (AIP) with secondary CVD in rectal cancer patients. Methods We analyzed rectal cancer patient data from the First Affiliated Hospital of Gannan Medical University (January 2010 to December 2023) to evaluate the associations between TyG, AIP and CVD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using UK Biobank proteomics data to identify mediating proteins. Results This study included 1,431 cases, among which 1,240 had no CVD and 191 had CVD. Both TyG (OR 1.102, 95% CI: 1.030–1.179, p = 0.005) and AIP (OR 1.062, 95% CI: 1.010–1.116, p = 0.018) showed independent associations with CVD risk in multivariable models. Age significantly modified these associations (interaction p < 0.05), with stronger effects in patients ≥62 years. Combined TyG + AIP modestly improved prediction (IDI: 1.2%, p = 0.013) compared to clinical variables alone. Proteomic analysis identified 14 mediating proteins enriched in lipid metabolism, complement/coagulation, and tight junction pathways. Conclusions TyG and AIP indices were independently associated with secondary CVD risk in rectal cancer patients, with age-dependent effects. While the predictive improvement was modest, these easily obtainable indices may aid risk stratification when combined with traditional factors. Proteomic findings suggest potential mechanistic pathways warranting further investigation.