Microbially Produced Imidazole Propionate Is Associated With Heart Failure and Mortality

JACC Heart Fail. 2023 Jul;11(7):810-821. doi: 10.1016/j.jchf.2023.03.008. Epub 2023 Apr 26.

Abstract

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.

Keywords: heart failure; histidine; imidazole propionate; microbiota.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2*
  • Ecosystem
  • Heart Failure*
  • Humans
  • Imidazoles / therapeutic use
  • Stroke Volume

Substances

  • 5-imidazolepropionic acid
  • Imidazoles