Wang Huiqing, Wei Haoran, Zhao Mingming, Wu Junfang, Fei Min, Lin Nan, Zhan Rui, Liu Qingyuan, Zhang Qi, Yao Xiaodong, Wu Yufei, Shan Wenxin, Cui Hongtu, Ji Liang, Pan Bing, Fang Lu, Zhu Yujie, Li Xin, Guo Yansong, Wang Dao Wen, Zheng Lemin
The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center, Peking University, Beijing 100191, China.
Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
iScience. 2024 Sep 23;27(10):111018. doi: 10.1016/j.isci.2024.111018. eCollection 2024 Oct 18.
Heart failure (HF) is a global concern, particularly HF with preserved ejection fraction (HFpEF), lacking effective treatments. Understanding the differences of metabolic profiles between HFpEF and HFrEF (heart failure with reduced ejection fraction) patients is crucial for therapeutic advancements. In this study, pseudotargeted metabolomics was employed to analyze for disparities of plasma metabolic profiles between HFpEF and HFrEF in two cohorts: discovery ( = 514) and validation ( = 3368). Plasma-free carnitine levels were significant changed in HF patients. A non-linear and U-shaped (for HFpEF) or J-shaped (for HFrEF) association between circulating free carnitine levels and the composite risk of cardiac events were observed. Interestingly, HFpEF patients with low free carnitine (≤40.18 μmol/L) displayed a poorer survival, contrasting with HFrEF where higher levels (≥35.67 μmol/L) were linked to poorer outcomes, indicating distinct metabolism pathways. In conclusion, these findings offer insights into HFpEF metabolic profiles, suggesting potential therapeutic targets.
心力衰竭（HF）是一个全球性问题，尤其是射血分数保留的心力衰竭（HFpEF），缺乏有效的治疗方法。了解HFpEF和射血分数降低的心力衰竭（HFrEF）患者代谢谱的差异对于治疗进展至关重要。在本研究中，采用伪靶向代谢组学分析了两个队列（发现队列，n = 514；验证队列，n = 3368）中HFpEF和HFrEF患者血浆代谢谱的差异。HF患者的游离肉碱水平发生了显著变化。观察到循环游离肉碱水平与心脏事件复合风险之间呈非线性和U形（对于HFpEF）或J形（对于HFrEF）关联。有趣的是，游离肉碱水平低（≤40.18 μmol/L）的HFpEF患者生存率较差，而HFrEF患者中游离肉碱水平较高（≥35.67 μmol/L）与较差的预后相关，这表明存在不同的代谢途径。总之，这些发现为HFpEF的代谢谱提供了见解，提示了潜在的治疗靶点。
