Gombos T, Förhécz Z, Pozsonyi Z, Wallentin S, Papassotiriou J, Kunde J, Morgenthaler N G, Jánoskuti L, Prohászka Z
IIIrd Department of Internal Medicine, and Szentágothai Knowledge Center, Semmelweis University, Budapest, Hungary.
Inflamm Res. 2009 Jun;58(6):298-305. doi: 10.1007/s00011-008-8184-5.
Adrenomedullin (ADM) and endothelin-1 (ET-1) are novel promising peptide biomarkers in chronic heart failure (CHF). According to recent studies among their pleiotropic effect they play roles in the regulation of inflammation. The aim of the study was to measure the above mentioned two vasoactive peptides in parallel in a well characterized population of patients with CHF, and study their associations with inflammatory markers.
A total of 186 patients (138 male, 48 female) with <45% left ventricular ejection fraction (LVEF), and without acute inflammatory disease, were enrolled. Plasma midregional-proADM (MR-proADM) and C-terminal-proET-1 (CT-proET-1) were determined by a novel sandwich immunoluminometric assay.
Increased MR-proADM and CT-proET-1 plasma levels were measured in patients with severe CHF (NYHA III-IV) as compared to the group of NYHA I-II (p<0.0001). MR-proADM and CT-proET-1 levels showed significant negative correlation with serum albumin and prealbumin levels (p<or=0.0001), while positive correlations were found with levels of CRP, TNF-alpha, soluble TNF receptors and IL-6 (p<or=0.0001). In multiple linear regression models after adjustments for several potential confounders (disease severity [LV-EF, NYHA classes, NT-proBNP], ion and water homeostasis [sodium and presence of peripheral oedema], renal function [serum creatine]) the relationship between ADM and albumin, CRP, soluble TNF receptors and between ET-1 and CRP, TNF receptors and IL-6 remained significant.
Vasoregulation and inflammation may be connected in heart failure patients independently of the disease severity. The observed link may contribute to the understanding of the complex pathomechanism in CHF.
肾上腺髓质素(ADM)和内皮素-1(ET-1)是慢性心力衰竭(CHF)中有前景的新型肽类生物标志物。根据最近的研究,在它们的多效性作用中,它们在炎症调节中发挥作用。本研究的目的是在一组特征明确的CHF患者中同时测量上述两种血管活性肽,并研究它们与炎症标志物的关联。
共纳入186例左心室射血分数(LVEF)<45%且无急性炎症性疾病的患者(男性138例,女性48例)。采用新型夹心免疫发光分析法测定血浆中段前肾上腺髓质素(MR-proADM)和C末端前内皮素-1(CT-proET-1)。
与纽约心脏协会(NYHA)I-II级组相比,重度CHF(NYHA III-IV级)患者血浆MR-proADM和CT-proET-1水平升高(p<0.0001)。MR-proADM和CT-proET-1水平与血清白蛋白和前白蛋白水平呈显著负相关(p≤0.0001),而与CRP、TNF-α、可溶性TNF受体和IL-6水平呈正相关(p≤0.0001)。在对几个潜在混杂因素(疾病严重程度[左室射血分数、NYHA分级、N末端脑钠肽前体]、离子和水稳态[钠和外周水肿的存在]、肾功能[血清肌酐])进行调整后的多元线性回归模型中,ADM与白蛋白、CRP、可溶性TNF受体之间以及ET-1与CRP、TNF受体和IL-6之间的关系仍然显著。
心力衰竭患者的血管调节和炎症可能相互关联,且与疾病严重程度无关。观察到的这种联系可能有助于理解CHF复杂的发病机制。