Chida Ayako, Sato Hiroki, Shintani Masaki, Nakayama Tomotaka, Kawamura Yoichi, Furutani Yoshiyuki, Inai Kei, Saji Tsutomu, Matsuoka Rumiko, Nonoyama Shigeaki, Nakanishi Toshio
Departments of Pediatrics, National Defense Medical College.
Circ J. 2014;78(2):436-42. doi: 10.1253/circj.cj-13-1033. Epub 2013 Dec 4.
Some potential biomarkers have been reported recently in patients with pulmonary arterial hypertension (PAH), but the most clinically useful among these potential biomarkers, especially in childhood PAH, has not been identified. Therefore, this study investigated which biomarker is useful in assessing severity of and patient prognosis in childhood idiopathic PAH (IPAH)/heritable PAH (HPAH).
Fifty-nine patients who were younger than 16 years at onset of IPAH/HPAH were selected. The following 10 biomarker candidates were quantified: high-sensitivity troponin T, human heart fatty acid-binding protein, N-terminal pro-brain natriuretic peptide (NT-proBNP), pentraxin-3, soluble ST2 (sST2), angiopoietin-2 (Ang-2), matrix metalloproteinase 2, tenascin C, endostatin (ES), and thymidine kinase. Functional characteristics and clinical outcomes were analyzed retrospectively. NT-proBNP, sST2, Ang-2, and ES correlated well with New York Heart Association class. On area under the receiver operating characteristic curve analysis, sST2 had a significantly good relationship with prognosis. On Kaplan-Meier curve and univariate Cox regression analyses, elevated sST2 and NT-proBNP level predicted poor outcome of the present patients with childhood IPAH/HPAH. Furthermore, patients with elevated sST2 had significantly worse prognosis among those with high NT-proBNP.
The sST2 and NT-proBNP combination is a useful biomarker to predict clinical condition and outcome in patients with childhood IPAH/HPAH.
最近已报道了一些肺动脉高压(PAH)患者的潜在生物标志物,但这些潜在生物标志物中对临床最有用的,尤其是在儿童PAH中,尚未确定。因此,本研究调查了哪种生物标志物可用于评估儿童特发性PAH(IPAH)/遗传性PAH(HPAH)的严重程度和患者预后。
选择了59例IPAH/HPAH发病时年龄小于16岁的患者。对以下10种候选生物标志物进行了定量分析:高敏肌钙蛋白T、人心脂肪酸结合蛋白、N末端脑钠肽前体(NT-proBNP)、五聚素-3、可溶性ST2(sST2)、血管生成素-2(Ang-2)、基质金属蛋白酶2、腱生蛋白C、内皮抑素(ES)和胸苷激酶。对功能特征和临床结果进行了回顾性分析。NT-proBNP、sST2、Ang-2和ES与纽约心脏协会分级密切相关。在受试者工作特征曲线下面积分析中,sST2与预后有显著的良好关系。在Kaplan-Meier曲线和单变量Cox回归分析中,sST2和NT-proBNP水平升高预示着本研究中儿童IPAH/HPAH患者预后不良。此外,在NT-proBNP水平高的患者中,sST2升高的患者预后明显更差。
sST2和NT-proBNP联合检测是预测儿童IPAH/HPAH患者临床状况和预后的有用生物标志物。