Microbially produced imidazole propionate is associated with heart failure and mortality

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Molinaro, A, Nemet, I, Bel Lassen, P, Chakaroun, R, Nielsen, T, Aron-Wisnewsky, J, Bergh, P-O, Li, L, Henricsson, M, Køber, L, Isnard, R, Helft, G, Stumvoll, M, Pedersen, O, Smith, JG, Tang, WHW, Clément, K, Hazen, SL, Bäckhed, F, Alves, R, Amouyal, C, Andersson Galijatovic, EA, Andreelli, F, Barthelemy, O, Bastard, J-P, Batisse, J-P, Berland, M, Bittar, R, Blüher, M, Bork, P, Bourron, O, Camus, M, Cassuto, D, Ciangura, C, Coelho, LP, Collet, J-P, Dumas, M-E, Ehrlich, SD, Engelbrechtsen, L, Fezeu, L, Forslund, S, Fromentin, S, Galan, P, Giral, P, Gøtze, JP, Hansen, T, Hansen, TH, Hartemann, A, Hartmann, B, Hercberg, S, Holmes, B, Holst, JJ, Hornbak, M, Hoyles, L ORCID: https://orcid.org/0000-0002-6418-342X, Hulot, J-S, Jaqueminet, S, Kerneis, M, Khemis, J, Kozlowski, R, Pedersen, HK, Kuhn, M, Mannerås-Holm, L, Marko, L, Martinez-Gili Robin Massey, L, Maziers, N, Medina-Stamminger, J, Moitinho-Silva, L, Montalescot, G, Moutel, S, Neves, AL, Olanipekun, M, Oppert, J-M, Poitou, C, Pousset, F, Pouzoulet, L, Rouault, C, Silvain, J and Vestergaard, H, 2023. Microbially produced imidazole propionate is associated with heart failure and mortality. JACC: Heart Failure, 11 (7), pp. 810-821. ISSN 2213-1779

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Official URL: https://doi.org/10.1016/j.jchf.2023.03.008

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.

Item Type:	Journal article
Publication Title:	JACC: Heart Failure
Creators:	Molinaro, A., Nemet, I., Bel Lassen, P., Chakaroun, R., Nielsen, T., Aron-Wisnewsky, J., Bergh, P.-O., Li, L., Henricsson, M., Køber, L., Isnard, R., Helft, G., Stumvoll, M., Pedersen, O., Smith, J.G., Tang, W.H.W., Clément, K., Hazen, S.L., Bäckhed, F., Alves, R., Amouyal, C., Andersson Galijatovic, E.A., Andreelli, F., Barthelemy, O., Bastard, J.-P., Batisse, J.-P., Berland, M., Bittar, R., Blüher, M., Bork, P., Bourron, O., Camus, M., Cassuto, D., Ciangura, C., Coelho, L.P., Collet, J.-P., Dumas, M.-E., Ehrlich, S.D., Engelbrechtsen, L., Fezeu, L., Forslund, S., Fromentin, S., Galan, P., Giral, P., Gøtze, J.P., Hansen, T., Hansen, T.H., Hartemann, A., Hartmann, B., Hercberg, S., Holmes, B., Holst, J.J., Hornbak, M., Hoyles, L., Hulot, J.-S., Jaqueminet, S., Kerneis, M., Khemis, J., Kozlowski, R., Pedersen, H.K., Kuhn, M., Mannerås-Holm, L., Marko, L., Martinez-Gili Robin Massey, L., Maziers, N., Medina-Stamminger, J., Moitinho-Silva, L., Montalescot, G., Moutel, S., Neves, A.L., Olanipekun, M., Oppert, J.-M., Poitou, C., Pousset, F., Pouzoulet, L., Rouault, C., Silvain, J. and Vestergaard, H.
Publisher:	Elsevier
Date:	3 July 2023
Volume:	11
Number:	7
ISSN:	2213-1779
Identifiers:	Number Type 10.1016/j.jchf.2023.03.008 DOI 1780429 Other
Rights:	Open Access article under the license: Attribution 4.0 International (CC BY 4.0).
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	17 Jul 2023 13:10
Last Modified:	17 Jul 2023 13:10
URI:	https://irep.ntu.ac.uk/id/eprint/49376