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血浆 YKL-40 水平升高可作为特发性肺动脉高压患者的预后指标。

Elevated plasma YKL-40 as a prognostic indicator in patients with idiopathic pulmonary arterial hypertension.

机构信息

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Respirology. 2014 May;19(4):608-15. doi: 10.1111/resp.12283. Epub 2014 Apr 1.

DOI:10.1111/resp.12283
PMID:24689969
Abstract

BACKGROUND AND OBJECTIVE

Pulmonary vascular remodelling and inflammation have been implicated in pulmonary arterial hypertension (PAH). YKL-40, a marker of tissue remodelling and inflammation, has recently been recognized as a risk predictor of cardiovascular and inflammatory diseases. The study aimed to investigate a potential role of YKL-40 in predicting prognosis in idiopathic PAH (IPAH).

METHODS

Plasma YKL-40 levels were measured in 82 IPAH patients without current or previous PAH-specific treatment during right heart catheterization and in 54 healthy volunteers. Concurrent data included clinical, haemodynamic and biochemical variables.

RESULTS

Plasma YKL-40 levels were increased in IPAH patients compared with control subjects (median, interquartile range: IPAH: 24.90, 17.68-39.78 ng/mL; controls: 16.58, 14.20-19.64 ng/mL; P < 0.001). YKL-40 levels correlated with cardiac index (r = -0.244, P = 0.027) and N-terminal pro-brain natriuretic peptide (NT-proBNP, r = 0.263, P = 0.017). After a median follow-up of 578 days, YKL-40 outperformed NT-proBNP, uric acid, and 6-min walk distance in receiver operating characteristic (ROC) analyses in predicting both clinical worsening (area under the curve (AUC) 0.681) and death (AUC 0.717). Compared with patients with YKL-40 below the ROC-derived cut-off point (24.5 ng/mL), the high YKL-40 group showed higher pulmonary vascular resistance and serum uric acid levels, and showed more clinical worsening events and deaths in Kaplan-Meier analyses. Plasma YKL-40 was independently associated with clinical worsening in univariate and multivariate Cox analyses (all P < 0.05).

CONCLUSIONS

Plasma YKL-40 might serve as a promising indicator of disease severity and prognosis in patients with IPAH.

摘要

背景与目的

肺血管重构和炎症与肺动脉高压(PAH)有关。YKL-40 是组织重构和炎症的标志物,最近被认为是心血管和炎症性疾病的风险预测因子。本研究旨在探讨 YKL-40 在预测特发性 PAH(IPAH)预后中的潜在作用。

方法

在右心导管检查期间,测量了 82 例未经当前或既往 PAH 特异性治疗的 IPAH 患者和 54 名健康志愿者的血浆 YKL-40 水平。同时记录了临床、血流动力学和生化变量。

结果

与对照组相比,IPAH 患者的血浆 YKL-40 水平升高(中位数,四分位距:IPAH:24.90,17.68-39.78ng/ml;对照组:16.58,14.20-19.64ng/ml;P<0.001)。YKL-40 水平与心指数(r=-0.244,P=0.027)和 N 端脑利钠肽前体(NT-proBNP,r=0.263,P=0.017)呈负相关。中位随访 578 天后,YKL-40 在预测临床恶化(ROC 分析的曲线下面积(AUC)0.681)和死亡(AUC 0.717)方面均优于 NT-proBNP、尿酸和 6 分钟步行距离。与 YKL-40 低于 ROC 衍生的截断点(24.5ng/ml)的患者相比,高 YKL-40 组的肺血管阻力和血清尿酸水平更高,Kaplan-Meier 分析显示更多的临床恶化事件和死亡。在单变量和多变量 Cox 分析中,血浆 YKL-40 与临床恶化均相关(均 P<0.05)。

结论

血浆 YKL-40 可能是 IPAH 患者疾病严重程度和预后的一个有前途的指标。

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