Microbially Produced Imidazole Propionate Is Associated With Heart Failure and Mortality

BACKGROUND Over the past years, it has become clear that the microbial ecosystem in the gut has a profound capacity to interact with the host through the production of a wide range of bioactive metabolites. The microbially produced metabolite imidazole propionate (ImP) is clinically and mechanistically linked with insulin resistance and type 2 diabetes, but it is unclear how ImP is associated with heart failure. OBJECTIVES The authors aimed to explore whether ImP is associated with heart failure and mortality. METHODS ImP serum measurements in 2 large and independent clinical cohorts of patients (European [n =1,985] and North American [n = 2,155]) with a range of severity of cardiovascular disease including heart failure. Univariate and multivariate Cox regression analyses were performed to delineate the impact of ImP on 5-year mortality in the North American cohort, independent of other covariates. RESULTS ImP is independently associated with reduced ejection fraction and heart failure in both cohorts, even after adjusting for traditional risk factors. Elevated ImP was a significant independent predictor of 5-year mortality (for the highest quartile, adjusted HR: 1.85 [95% CI: 1.20-2.88]; P < 0.01). CONCLUSIONS The gut microbial metabolite ImP is increased in individuals with heart failure and is a predictor of overall survival. (J Am Coll Cardiol HF 2023;11:810-821 ) <(c)> 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

The gut microbial metabolite ImP is associated with heart failure and predicts overall survival. This study sheds light on the relationship between ImP and heart failure.