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左心室重构和功能障碍的高血压患者的细胞因子谱

Cytokines profile in hypertensive patients with left ventricular remodeling and dysfunction.

作者信息

Kuznetsova Tatiana, Haddad Francois, Knez Judita, Rosenberg-Hasson Yael, Sung Janine, Cauwenberghs Nicholas, Thijs Lutgarde, Karakikes Ioannis, Maecker Holden, Mahaffey Kenneth W, Wu Joseph C, Staessen Jan A

机构信息

Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.

Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.

出版信息

J Am Soc Hypertens. 2015 Dec;9(12):975-84.e3. doi: 10.1016/j.jash.2015.10.003. Epub 2015 Oct 17.

Abstract

There is strong evidence that inflammatory mediators play a key role in the progression to heart failure in patients with systemic hypertension (HTN). The present study aimed to identify a set of cytokines that are associated with early left ventricular (LV) remodeling and dysfunction as captured by echocardiography in patients with HTN in a cross-sectional case-control study nested within the FLEMish study on ENvironment, Genes and Health Outcome. We identified three groups of participants from the cohort: normotensive subjects (normotension; n = 30), HTN with normal LV structure and function (HTN [LV-]; n = 30), and HTN with evidence of adverse LV remodeling (HTN [LV+]; n = 50). We measured cytokines using a 63-plex Luminex platform. Using partial least squares-discriminant analysis, we constructed three latent variables from the measured cytokines that explained 35%-45% of the variance between groups. We identified five common cytokines (interleukin 18, monokine induced by gamma interferon, hepatocyte growth factor, epithelial neutrophil-activating peptide 78, and vascular endothelial growth factor D) with a stable signal which had a major impact on the construction of the latent variables. Among these cytokines, after adjustment for confounders, interleukin 18 remained significantly different between HTN participants with and without LV involvement (P = .02). Moreover, granulocyte-macrophage colony-stimulating factor and leptin showed a consistent upward trend in all HTN patients compared with normotensive subjects. In conclusion, in HTN patients with LV remodeling or/and dysfunction, we identified a set of cytokines strongly associated with LV maladaptation. We also found a distinct profile of inflammatory biomarkers that characterize HTN.

摘要

有强有力的证据表明,炎症介质在系统性高血压(HTN)患者进展为心力衰竭的过程中起关键作用。本研究旨在确定一组细胞因子,这些细胞因子与高血压患者早期左心室(LV)重构和功能障碍相关,该研究为一项横断面病例对照研究,嵌套于弗拉芒环境、基因与健康结局研究中,通过超声心动图来捕捉这些情况。我们从该队列中确定了三组参与者:血压正常的受试者(正常血压;n = 30)、左心室结构和功能正常的高血压患者(HTN [LV-];n = 30)以及有左心室不良重构证据的高血压患者(HTN [LV+];n = 50)。我们使用63种细胞因子的Luminex平台来测量细胞因子。通过偏最小二乘判别分析,我们从测量的细胞因子中构建了三个潜在变量这些变量解释了组间35%-45%的方差。我们确定了五种信号稳定的常见细胞因子(白细胞介素18、γ干扰素诱导的单核因子、肝细胞生长因子、上皮中性粒细胞激活肽78和血管内皮生长因子D),它们对潜在变量的构建有重大影响。在这些细胞因子中,在对混杂因素进行调整后,有左心室受累和无左心室受累的高血压参与者之间白细胞介素18仍存在显著差异(P = 0.02)。此外,与血压正常的受试者相比,粒细胞巨噬细胞集落刺激因子和瘦素在所有高血压患者中均呈现一致的上升趋势。总之在有左心室重构或/和功能障碍的高血压患者中,我们确定了一组与左心室适应不良密切相关的细胞因子。我们还发现了一组独特的炎症生物标志物特征,可用于表征高血压。

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