Malnutrition as an independent risk factor for fluoropyrimidine- and oxaliplatin-based chemotherapy-induced cardiovascular toxicity in colorectal cancer: a single-center retrospective cohort study

Background Fluoropyrimidine- and oxaliplatin-based regimens (FOLFOX/XELOX) are the standard of care for colorectal cancer (CRC) but carry significant cardiovascular toxicity. Malnutrition, present in up to 60% of post-surgical CRC patients, may amplify this toxicity through systemic inflammation and pharmacokinetic alterations; however, this relationship has not been specifically investigated. Methods We conducted a retrospective cohort study of 320 CRC patients receiving FOLFOX or XELOX at the Shanghai songjiang sijing hospital (January 2020—December 2023). Nutritional status was assessed by the Nutritional Risk Screening 2002 (NRS-2002) and serum albumin. The primary endpoint was chemotherapy-induced cardiovascular toxicity events (CICVT), defined per 2022 ESC Cardio-Oncology Guidelines. Multivariable logistic regression, 1:1 propensity score matching (PSM), and receiver operating characteristic (ROC) analysis were performed. An intestinal fistula subgroup compared outcomes between total parenteral nutrition (TPN) and early enteral nutrition (EEN). Results Nutritional risk (NRS-2002 ≥ 3) was identified in 112 patients (35.0%). CICVT occurred in 31.3% of patients at nutritional risk vs. 11.5% of well-nourished patients ( p < 0.001). After PSM (89 matched pairs), malnutrition remained an independent risk factor (OR 2.93, 95% CI 1.41–6.07; p < 0.001). Multivariable analysis confirmed NRS-2002 ≥ 3 (adjusted OR 3.18, 95% CI 1.69–5.98; p < 0.001) and serum albumin < 35 g/L (adjusted OR 2.43, 95% CI 1.34–4.40; p = 0.003) as independent predictors. ROC AUC improved from 0.718 (NRS-2002 alone) to 0.764 when combined with albumin. Among 49 fistula patients, the TPN group had significantly higher CICVT rates than the EEN group (38.7% vs. 16.7%; p = 0.043). Conclusion Malnutrition is an independent and modifiable risk factor for chemotherapy-induced cardiovascular toxicity in CRC. Integrating nutritional assessment into pre-chemotherapy cardiovascular risk stratification and prioritizing early enteral nutrition in fistula patients may mitigate cardiovascular morbidity.