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Microbially Produced Imidazole Propionate Is Associated With Heart Failure and Mortality

2023; Elsevier BV; Volume: 11; Issue: 7 Linguagem: Inglês

10.1016/j.jchf.2023.03.008

2213-1787

Antonio Molinaro, Ina Nemet, Pierre Bel Lassen, Rima Chakaroun, Trine Nielsen, Judith Aron‐Wisnewsky, Per-Olof Bergh, Lin Li, Marcus Henricsson, Lars Køber, Richard Isnard, Gérard Helft, Michael Stümvoll, Oluf Pedersen, J. G. Smith, W.H. Wilson Tang, Karine Clément, Stanley L. Hazen, Fredrik Bäckhed, Renato Alves, Chloé Amouyal, Ehm Astrid Andersson Galijatovic, Fabrizio Andreelli, Olivier Barthélemy, Jean‐Philippe Bastard, Jean-Paul Batisse, Magali Berland, Randa Bittar, Matthias Blüher, Peer Bork, Olivier Bourron, Mickaël Camus, Dominique Adèle Cassuto, Cécile Ciangura, Luís Pedro Coelho, Jean‐Philippe Collet, Marc‐Emmanuel Dumas, S. Dusko Ehrlich, Line Engelbrechtsen, Léopold Fezeu, Sofia K. Forslund, Sébastien Fromentin, Pilar Galán, Philippe Giral, Jens Peter Gøtze, Torben Hansen, Tue H. Hansen, Agnès Hartemann, Bolette Hartmann, Serge Herçberg, Bridget Holmes, Jens J. Holst, Malene Hornbak, Lesley Hoyles, Jean‐Sébastien Hulot, Sophie Jaqueminet, Mathieu Kerneïs, Jean Khémis, Ruby Kozlowski, Helle K. Pedersen, Michael W.M. Kühn, Louise Mannerås-Holm, Lajos Markó, Laura Martinez-Gili Robin Massey, Nicolas Maziers, Jonathan Medina-Stamminger, Lucas Moitinho‐Silva, Gilles Montalescot, Sandrine Moutel, Ana Luísa Neves, Michael Olanipekun, Jean‐Michel Oppert, Christine Poitou, Françoise Pousset, Laurence Pouzoulet, Christine Rouault, Johanne Silvain, Henrik Vestergaard,

Pharmacogenetics and Drug Metabolism

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.