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.

IF 9.7 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL EBioMedicine Pub Date : 2024-09-01 Epub Date: 2024-08-08 DOI:10.1016/j.ebiom.2024.105264

Anne-Catherine Pouleur, Nassiba Menghoum, Julien Cumps, Alice Marino, Maria Badii, Sibille Lejeune, Julie Thompson Legault, Gabrielle Boucher, Damien Gruson, Clotilde Roy, Sylvain Battault, Louiza Mahrouche, Valérie Pedneault-Gagnon, Daniel Charpentier, Alexandra Furtos, Julie Hussin, David Rhainds, Jean-Claude Tardif, Luc Bertrand, Christine Des Rosiers, Sandrine Horman, Christophe Beauloye

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Abstract

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: 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: 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: 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: BECAME-HF was supported by Collaborative Bilateral Research Program Québec - Wallonie-Brussels Federation.

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心力衰竭患者血浆肌醇升高：临床意义和预后意义。比利时和加拿大高频心衰代谢组学（BECAME-HF）研究项目的结果。

背景：代谢环境在心力衰竭（HF）的发展过程中起着至关重要的作用。我们之前的研究表明，肌醇（一种由钠-肌醇共转运体 1（SMIT-1）转运的代谢产物）可诱发氧化应激，并可能对心脏功能有害。然而，在射血分数降低型心力衰竭（HFrEF）和射血分数保留型心力衰竭（HFpEF）患者中，尚未对血浆肌醇浓度进行全面评估：方法：使用质谱法测量血浆肌醇水平，并将其与来自比利时队列（男性，无心衰，53%；HFrEF，84%；HFpEF，40%）和加拿大队列（男性，无心衰，51%；HFrEF，92%；HFpEF，62%）的无心衰受试者、HFrEF和HFpEF患者的临床特征相关联：研究结果：心房颤动患者肌醇水平明显升高，两个队列中的心房颤动患者肌醇水平升高更为明显。在对年龄、性别、体重指数、高血压、糖尿病和心房颤动等因素进行调整后，我们发现 HFpEF 状态和肾功能受损均与血浆肌醇升高有关。与高频低氧血症不同，肌醇异常升高（≥69.8 μM）与高频低氧血症患者不利的临床结果有关（危险比为 1.62；95% 置信区间为 [1.05-2.5]）。在这部分患者中，肌醇水平的升高与NTproBNP、肌钙蛋白和心脏纤维化相关：肌醇是心房颤动患者体内升高的代谢物，与肾衰竭密切相关。在高频肾衰竭患者中，肌醇水平高预示着较差的临床预后，并与心脏不良重塑的标志物有关。这表明肌醇及其转运体SMIT1可能在高频肾衰竭的病理生理学中发挥作用：BECAME-HF得到了魁北克-瓦隆-布鲁塞尔联邦双边合作研究计划的支持。

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.