背景:代谢环境在心力衰竭(HF)的发展中起着至关重要的作用。我们之前的研究表明,肌醇,由钠肌醇协同转运蛋白1(SMIT-1)运输的代谢物,可以诱导氧化应激,并可能对心脏功能有害。然而,在射血分数降低的心力衰竭(HFrEF)和射血分数保留的心力衰竭(HFpEF)患者的大型队列中,尚未全面评估血浆肌醇浓度.
方法:使用质谱法测量血浆肌醇水平,并与无HF受试者以及比利时HFrEF和HFpEF患者的临床特征相关(男性,没有HF,53%;HFrEF,84%和HFpEF,40%)和加拿大队列(男性,没有HF,51%;HFrEF,92%和HFpEF,62%)。
结果:HF患者肌醇水平显著升高,在两个队列的HFpEF人群中观察到更明显的增加。在调整了年龄之后,性别,身体质量指数,高血压,糖尿病,心房颤动,我们观察到HFpEF状态和肾功能受损均与血浆肌醇升高相关.不像HFrEF,异常高的肌醇(≥69.8μM)与不利的临床结局相关(风险比,1.62;95%置信区间,[1.05-2.5])在HFpEF患者中。这些升高的水平与NTproBNP相关,肌钙蛋白,以及这部分患者的心脏纤维化。
结论:肌醇是心力衰竭患者体内升高的代谢产物,与肾衰竭密切相关。在HFpEF患者中,高肌醇水平预测不良临床结局,并与心脏不良重塑的标志物相关.这表明肌醇及其转运蛋白SMIT1可能在HFpEF的病理生理学中起作用。
背景:BECAME-HF由魁北克-Wallonie-布鲁塞尔联合会合作双边研究计划支持。
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%).
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.
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.
BACKGROUND: BECAME-HF was supported by Collaborative Bilateral Research Program Québec - Wallonie-Brussels Federation.