S428 Impact of Cardiovascular and Metabolic Comorbidities on Immune-Mediated Diarrhea and Colitis Severity and Outcomes

Introduction: Chronic low-grade inflammation, insulin resistance, and atherosclerosis are known to alter gut microbiome composition by disrupting the intestinal barrier, impairing glucose metabolism, and reducing gut perfusion. Additionally, long-term use of medications for coronary artery disease (CAD), type 2 diabetes mellitus, heart failure (HF), and hypertension may also influence gut microbial balance. Given the established association between dysbiosis and immune-mediated diarrhea and colitis (IMDC) in patients receiving immune checkpoint inhibitors, this study investigates the impact of pre-existing cardiovascular and metabolic conditions on the clinical presentation and severity of IMDC. Methods: This retrospective, single-center study included patients diagnosed with IMDC between 2015 to 2025. Statistical analyses were performed using chi-square and binary logistic regression models with SPSS 24 (IBD Corp, Armonk, NY). Results: Among 1,128 patients, 58.6% were men and 89.8% White. Serum lipid profile, average plasma glucose, and blood pressure were not significantly associated with IMDC outcomes. However, diagnosis of HF (9.5% vs 5.7%, P = 0.025) and CAD (20.6% vs 14.9%, P= 0.017) were more common in patients with colitis Common Terminology Criteria for Adverse Events grade <2. Patients with CAD were less frequently treated with corticosteroids (66.8% vs 74.4%, P= 0.027) or selective immunosuppressive therapy (SIT) (37.1% vs 44.6%, P= 0.050). No significant associations were observed between cardiovascular risk factors and diarrhea severity. Univariate analysis revealed that HF (OR: 0.6, CI: 0.3–0.9, P= 0.026) and CAD (OR: 0.6, CI: 0.5–0.9, P= 0.017) were associated with milder colitis. Despite this, all-cause mortality was significantly higher in patients with HF (72.5% vs 52.2%, P < 0.0001) and CAD (60% vs 52.4%, P= 0.049). Conclusion: This is the first study to evaluate the influence of cardiovascular and metabolic conditions on IMDC severity and outcomes. While HF and CAD were associated with milder colitis, these patients had higher all-cause mortality. Findings suggest chronic disease or its treatment may modulate immune-related toxicity, potentially through gut microbiome or systemic pathways. Lower use of corticosteroids/SIT may reflect therapeutic caution due to cardiovascular risk. Despite less severe gastrointestinal disease, this population remains clinically vulnerable. Further studies are needed to validate these associations and to elucidate the mechanisms by which chronic comorbidities and their management may influence IMDC outcomes.