Gut microbiota-derived imidazole propionate predicts cardiometabolic risk in patients with coronary artery disease

Background and aims: The gut microbiota is a modulator of cardiometabolic disease. Circulating imidazole propionate (ImP) is a microbiota-derived proatherogenic amino acid metabolite modulating the inflammatory response of myeloid cells, endothelial function and glucose metabolism. This study examined the prognostic value of ImP in patients with coronary artery disease (CAD). Methods: Circulating ImP levels were measured in independent prospective cohorts of patients with acute coronary syndrome (ACS, Switzerland n=4937, Germany n=1497) and chronic coronary syndrome (CCS, Germany n=701). Major adverse cardiovascular events (MACE), defined as the first occurrence of a composite of death, nonfatal myocardial infarction, or nonfatal stroke after admission, were the primary endpoint. Cox models, accounting for established risk factors including the gut-derived cardiovascular risk factor trimethylamine N-oxide (TMAO), were used to evaluate the predictive value of ImP. Conclusions: Gut microbiota-derived ImP predicted MACE in patients with CAD independently of traditional risk factors and holds promise as a therapeutic target. ImP may refine risk stratification for personalised secondary prevention strategies.