Plasma myo-inositol elevation in heart failure: clinical implications and prognostic significance. Results from the BElgian and CAnadian MEtabolomics in HFpEF (BECAME-HF) research project.

HFpEF Heart failure Kidney Metabolites Myo-inositol Prognosis

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
08 Aug 2024
Historique:
received: 29 11 2023
revised: 14 07 2024
accepted: 20 07 2024
medline: 10 8 2024
pubmed: 10 8 2024
entrez: 9 8 2024
Statut: aheadofprint

Résumé

The metabolic environment plays a crucial role in the development of heart failure (HF). Our prior research demonstrated that myo-inositol, a metabolite transported by the sodium-myo-inositol co-transporter 1 (SMIT-1), can induce oxidative stress and may be detrimental to heart function. However, plasmatic myo-inositol concentration has not been comprehensively assessed in large cohorts of patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Plasmatic myo-inositol levels were measured using mass spectrometry and correlated with clinical characteristics in no HF subjects and patients with HFrEF and HFpEF from Belgian (male, no HF, 53%; HFrEF, 84% and HFpEF, 40%) and Canadian cohorts (male, no HF, 51%; HFrEF, 92% and HFpEF, 62%). Myo-inositol levels were significantly elevated in patients with HF, with a more pronounced increase observed in the HFpEF population of both cohorts. After adjusting for age, sex, body mass index, hypertension, diabetes, and atrial fibrillation, we observed that both HFpEF status and impaired kidney function were associated with elevated plasma myo-inositol. Unlike HFrEF, abnormally high myo-inositol (≥69.8 μM) was linked to unfavourable clinical outcomes (hazard ratio, 1.62; 95% confidence interval, [1.05-2.5]) in patients with HFpEF. These elevated levels were correlated with NTproBNP, troponin, and cardiac fibrosis in this subset of patients. Myo-inositol is a metabolite elevated in patients with HF and strongly correlated to kidney failure. In patients with HFpEF, high myo-inositol levels predict poor clinical outcomes and are linked to markers of cardiac adverse remodelling. This suggests that myo-inositol and its transporter SMIT1 may have a role in the pathophysiology of HFpEF. BECAME-HF was supported by Collaborative Bilateral Research Program Québec - Wallonie-Brussels Federation.

Sections du résumé

BACKGROUND BACKGROUND
The metabolic environment plays a crucial role in the development of heart failure (HF). Our prior research demonstrated that myo-inositol, a metabolite transported by the sodium-myo-inositol co-transporter 1 (SMIT-1), can induce oxidative stress and may be detrimental to heart function. However, plasmatic myo-inositol concentration has not been comprehensively assessed in large cohorts of patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).
METHODS METHODS
Plasmatic myo-inositol levels were measured using mass spectrometry and correlated with clinical characteristics in no HF subjects and patients with HFrEF and HFpEF from Belgian (male, no HF, 53%; HFrEF, 84% and HFpEF, 40%) and Canadian cohorts (male, no HF, 51%; HFrEF, 92% and HFpEF, 62%).
FINDINGS RESULTS
Myo-inositol levels were significantly elevated in patients with HF, with a more pronounced increase observed in the HFpEF population of both cohorts. After adjusting for age, sex, body mass index, hypertension, diabetes, and atrial fibrillation, we observed that both HFpEF status and impaired kidney function were associated with elevated plasma myo-inositol. Unlike HFrEF, abnormally high myo-inositol (≥69.8 μM) was linked to unfavourable clinical outcomes (hazard ratio, 1.62; 95% confidence interval, [1.05-2.5]) in patients with HFpEF. These elevated levels were correlated with NTproBNP, troponin, and cardiac fibrosis in this subset of patients.
INTERPRETATION CONCLUSIONS
Myo-inositol is a metabolite elevated in patients with HF and strongly correlated to kidney failure. In patients with HFpEF, high myo-inositol levels predict poor clinical outcomes and are linked to markers of cardiac adverse remodelling. This suggests that myo-inositol and its transporter SMIT1 may have a role in the pathophysiology of HFpEF.
FUNDING BACKGROUND
BECAME-HF was supported by Collaborative Bilateral Research Program Québec - Wallonie-Brussels Federation.

Identifiants

DOI: 10.1016/j.ebiom.2024.105264 PMID: 39121579
pubmed: 39121579
pii: S2352-3964(24)00300-1
doi: 10.1016/j.ebiom.2024.105264
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

105264

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests Jean-Claude Tardif reports grants from Amarin, AstraZeneca, Ceapro, DalCor Pharmaceuticals, Esperion, Ionis, Merck, Novartis, Pfizer and RegenXBio; honoraria from AstraZeneca, DalCor Pharmaceuticals, HLS Pharmaceuticals, Pendopharm and Pfizer; minor equity interest in DalCor Pharmaceuticals; and authorship of patents on pharmacogenomics-guided CETP inhibition and use of colchicine after myocardial infarction. No other conflict of interest was declared for the present study.

Auteurs

Anne-Catherine Pouleur (AC)

Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium; Department of Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

Nassiba Menghoum (N)

Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium.

Julien Cumps (J)

Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium.

Alice Marino (A)

Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium.

Maria Badii (M)

Department of Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

Sibille Lejeune (S)

Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium.

Julie Thompson Legault (JT)

Research Centre, Montreal Heart Institute, Montréal, QC H1T 1C8, Canada.

Gabrielle Boucher (G)

Research Centre, Montreal Heart Institute, Montréal, QC H1T 1C8, Canada.

Damien Gruson (D)

Department of Clinical Biology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

Clotilde Roy (C)

Department of Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

Sylvain Battault (S)

Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium.

Louiza Mahrouche (L)

Department of Chemistry, Université de Montréal, Montréal, QC H3T IJ4, Canada.

Valérie Pedneault-Gagnon (V)

Research Centre, Montreal Heart Institute, Montréal, QC H1T 1C8, Canada.

Daniel Charpentier (D)

Research Centre, Montreal Heart Institute, Montréal, QC H1T 1C8, Canada.

Alexandra Furtos (A)

Department of Chemistry, Université de Montréal, Montréal, QC H3T IJ4, Canada.

Julie Hussin (J)

Research Centre, Montreal Heart Institute, Montréal, QC H1T 1C8, Canada.

David Rhainds (D)

Research Centre, Montreal Heart Institute, Montréal, QC H1T 1C8, Canada.

Jean-Claude Tardif (JC)

Research Centre, Montreal Heart Institute, Montréal, QC H1T 1C8, Canada; Department of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada.

Luc Bertrand (L)

Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium.

Christine Des Rosiers (CD)

Research Centre, Montreal Heart Institute, Montréal, QC H1T 1C8, Canada; Department of Nutrition, Université de Montréal, Montréal, QC H3T 1J4, Canada.

Sandrine Horman (S)

Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium.

Christophe Beauloye (C)

Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium; Department of Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Department of Cardiovascular Intensive Care, Cliniques Universitaires Saint-Luc, Brussels, Belgium. Electronic address: christophe.beauloye@saintluc.uclouvain.be.

Classifications MeSH