Microbially Produced Imidazole Propionate Is Associated With Heart Failure and Mortality

• DOI: 10.1016/j.jchf.2023.03.008
• Publication Date: 2023-04-26T18:37:33Z
• Authors: Antonio Molinaro; Ina Nemet; Pierre Bel Lassen; Rima Chakaroun; Trine Nielsen; Judith Aron-Wisne...; Per-Olof Bergh; Lin Li; Marcus Henricsson; Lars Køber; Richard Isnard; Gerard Helft; Michael Stumvoll; Oluf Pedersen; J. Gustav Smith; W.H. Wilson Tang; Karine Clément; Stanley L. Hazen; Fredrik Bäckhed; Renato Alves; Chloe Amouyal; Ehm Astrid Anders...; Fabrizio Andreelli; Olivier Barthelemy; Jean-Philippe Bas...; Jean-Paul Batisse; Magalie Berland; Randa Bittar; Matthias Blüher; Peer Bork; Olivier Bourron; Mickael Camus; Dominique Cassuto; Cecile Ciangura; Luis Pedro Coelho; Jean-Philippe Collet; Marc-Emmanuel Dumas; S. Dusko Ehrlich; Line Engelbrechtsen; Leopold Fezeu; Sofia Forslund; Sebastien Fromentin; Pilar Galan; Philippe Giral; Jens Peter Gøtze; Torben Hansen; Tue H. Hansen; Agnes Hartemann; Bolette Hartmann; Serge Hercberg; Bridget Holmes; Jens Juul Holst; Malene Hornbak; Lesley Hoyles; Jean-Sebastien Hulot; Sophie Jaqueminet; Mathieu Kerneis; Jean Khemis; Ruby Kozlowski; Helle Krogh Pedersen; Michael Kuhn; Louise Mannerås-Holm; Lajos Marko; Laura Martinez-Gi...; Nicolas Maziers; Jonathan Medina-S...; Lucas Moitinho-Silva; Gilles Montalescot; Sandrine Moutel; Ana Luisa Neves; Michael Olanipekun; Jean-Michel Oppert; Christine Poitou; Francoise Pousset; Laurence Pouzoulet; Christine Rouault; Johanne Silvain; Henrik Vestergaard
• Keywords: 2. Zero hunger; Heart Failure; Diabetes Mellitus, Type 2; imidazole propionate; microbiota; Imidazoles; 610; heart failure; Humans; Stroke Volume; histidine; Ecosystem; 3. Good health

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.The authors aimed to explore whether ImP is associated with heart failure and mortality.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.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).The gut microbial metabolite ImP is increased in individuals with heart failure and is a predictor of overall survival.