鉴别射血分数降低型心力衰竭与射血分数保留型心力衰竭的病理生理学机制。
Identifying Pathophysiological Mechanisms in Heart Failure With Reduced Versus Preserved Ejection Fraction.
机构信息
Department of Cardiology, University of Groningen, Groningen, the Netherlands; National Heart Centre Singapore, Singapore; Duke-NUS Medical School, Singapore, Singapore.
Department of Cardiology, University of Groningen, Groningen, the Netherlands.
出版信息
J Am Coll Cardiol. 2018 Sep 4;72(10):1081-1090. doi: 10.1016/j.jacc.2018.06.050.
BACKGROUND
Information on the pathophysiological differences between heart failure with reduced ejection fraction (HFrEF) versus heart failure with preserved ejection fraction (HFpEF) is needed OBJECTIVES: The purpose of this study was to establish biological pathways specifically related to HFrEF and HFpEF.
METHODS
The authors performed a network analysis to identify unique biomarker correlations in HFrEF and HFpEF using 92 biomarkers from different pathophysiological domains in a cohort of 1,544 heart failure (HF) patients. Data were independently validated in 804 patients with HF. Networks were enriched with existing knowledge on protein-protein interactions and translated into biological pathways uniquely related to HFrEF, HF with a midrange ejection fraction, and HFpEF.
RESULTS
In the index cohort (mean age 74 years; 34% female), 718 (47%) patients had HFrEF (left ventricular ejection fraction [LVEF] <40%) and 431 (27%) patients had HFpEF (LVEF ≥50%). A total of 8 (12%) correlations were unique for HFrEF and 6 (9%) were unique to HFpEF. Central proteins in HFrEF were N-terminal B-type natriuretic peptide, growth differentiation factor-15, interleukin-1 receptor type 1, and activating transcription factor 2, while central proteins in HFpEF were integrin subunit beta-2 and catenin beta-1. Biological pathways in HFrEF were related to DNA binding transcription factor activity, cellular protein metabolism, and regulation of nitric oxide biosynthesis. Unique pathways in patients with HFpEF were related to cytokine response, extracellular matrix organization, and inflammation. Biological pathways of patients with HF with a midrange ejection fraction were in between HFrEF and HFpEF.
CONCLUSIONS
Network analysis showed that biomarker profiles specific for HFrEF are related to cellular proliferation and metabolism, whereas biomarker profiles specific for HFpEF are related to inflammation and extracellular matrix reorganization. (The BIOlogy Study to TAilored Treatment in Chronic Heart Failure [BIOSTAT-CHF]; EudraCT 2010-020808-29).
背景
需要了解射血分数降低型心力衰竭（HFrEF）与射血分数保留型心力衰竭（HFpEF）之间的病理生理学差异信息。
目的
本研究旨在确定与 HFrEF 和 HFpEF 相关的特定生物学途径。
方法
作者使用来自心力衰竭（HF）患者不同病理生理领域的 92 种生物标志物，对 1544 例 HF 患者进行网络分析，以确定 HFrEF 和 HFpEF 中独特的生物标志物相关性。数据在 804 例 HF 患者中进行了独立验证。使用现有蛋白质-蛋白质相互作用知识对网络进行了丰富，并将其转化为与 HFrEF、射血分数中等的心力衰竭和 HFpEF 相关的独特生物学途径。
结果
在指数队列（平均年龄 74 岁，34%为女性）中，718 例（47%）患者为 HFrEF（左心室射血分数[LVEF]＜40%），431 例（27%）患者为 HFpEF（LVEF≥50%）。有 8 个（12%）相关性是 HFrEF 特有的，6 个（9%）是 HFpEF 特有的。HFrEF 的中心蛋白是 N 端 B 型利钠肽、生长分化因子-15、白细胞介素-1 受体 1 和激活转录因子 2，而 HFpEF 的中心蛋白是整合素亚基β-2 和连接蛋白β-1。HFrEF 的生物学途径与 DNA 结合转录因子活性、细胞蛋白质代谢和一氧化氮生物合成的调节有关。HFpEF 患者的独特途径与细胞因子反应、细胞外基质组织和炎症有关。射血分数中等的心力衰竭患者的生物学途径介于 HFrEF 和 HFpEF 之间。
结论
网络分析表明，HFrEF 特有的生物标志物谱与细胞增殖和代谢有关，而 HFpEF 特有的生物标志物谱与炎症和细胞外基质重排有关。（生物学研究以适应慢性心力衰竭的治疗[BIOSTAT-CHF]；EudraCT 2010-020808-29）。
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