Microbially Produced Imidazole Propionate Is Associated With Heart Failure and Mortality

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, Gerard Helft, Michael Stumvoll, Oluf Pedersen, J. Gustav Smith, W. H.Wilson Tang, Karine Clément, Stanley L. Hazen, Fredrik Bäckhed*, Renato AlvesChloe Amouyal, Ehm Astrid Andersson Galijatovic, Fabrizio Andreelli, Olivier Barthelemy, Jean Philippe Bastard, 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 (Medlem af forfattergruppering), Leopold Fezeu, Sofia Forslund, Sebastien Fromentin, Pilar Galan, Philippe Giral, Jens Peter Gøtze (Medlem af forfattergruppering), Tue H. Hansen, Agnes Hartemann, Jens Juul Holst (Medlem af forfattergruppering), Helle Krogh Pedersen (Medlem af forfattergruppering), Henrik Vestergaard (Medlem af forfattergruppering), MetaCardis Consortium

*Corresponding author af dette arbejde
21 Citationer (Scopus)

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.

OriginalsprogEngelsk
TidsskriftJACC: Heart Failure
Vol/bind11
Udgave nummer7
Sider (fra-til)810-821
Antal sider12
ISSN2213-1779
DOI
StatusUdgivet - jul. 2023

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