Exploratory Analysis of Circulating GLP-1, GIP, and TMAO in Relation to Coronary Artery Disease Severity in Patients with Exertional Angina

<b>Background/Objectives:</b> The gut-heart axis has garnered increasing attention. Incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), along with trimethylamine N-oxide (TMAO), have been implicated in the pathogenesis of coronary artery disease (CAD). This study aimed to investigate associations between plasma levels of GLP-1, GIP, and TMAO and the severity of CAD, alongside their correlations with serum biochemical parameters and fatty acid composition. <b>Methods:</b> Sixty-one patients undergoing coronary angiography were evaluated and stratified by Gensini scores into normal-coronary-artery, moderate-CAD, or severe-CAD groups. Biochemical parameters in serum and plasma GLP-1, GIP, and TMAO levels were measured. Plasma fatty acid composition was analyzed. <b>Results:</b> Fasting plasma GLP-1 and TMAO levels were not associated with CAD severity. Although GIP showed associations with CAD severity, these were not retained after adjustment for age and sex. Plasma myristic acid levels were positively associated with Gensini score. GLP-1 correlated positively with saturated fatty acids and negatively with monounsaturated fatty acids. TMAO levels inversely correlated with n-3 polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid, and positively with the n-6/n-3 PUFA ratio, supporting its potential role in pro-atherogenic lipid profiles. <b>Conclusions:</b> These findings suggest complex associations between gut-derived metabolites, lipid metabolism, and CAD severity.