Circulating collagen biomarkers as indicators of disease severity in pulmonary arterial hypertension.
Circulating collagen biomarkers as indicators of disease severity in pulmonary arterial hypertension.
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DOI：
10.1016/j.jchf.2014.03.013
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Entman M
中科院分区：
文献类型：
--
作者：
Safdar Z;Tamez E;Chan W;Arya B;Ge Y;Deswal A;Bozkurt B;Frost A;Entman M
本研究的目的是确定肺动脉高压（PAH）中胶原代谢的生物标志物是否可以识别疾病更严重和死亡风险更高的患者。胶原代谢标志物、疾病程度和PAH结局之间的关系尚不清楚。前瞻性入组了稳定的特发性、多西他赛相关性和遗传性PAH患者。测量胶原蛋白生物标志物水平：III型前胶原的N-末端前肽（PIIINP）、I型胶原的C-末端端肽（CITP）、基质金属蛋白酶9（MMP-9）和金属蛋白酶组织抑制剂1（TIMP-1）。患者分为轻度、中度和重度PAH组。在每种生物标志物的三分位数之间比较数据。进行Pearson相关和斯皮尔曼等级系数分析。通过Kaplan-Meier生存曲线检查至死亡或移植时间的数据。PAH组（N=68）中PIIINP、CITP、MMP 9和TIMP 1的循环水平高于年龄和性别匹配的健康对照组（N=37）（均为p<0.001）。PIIINP水平随着疾病严重程度的增加而增加（p=0.004）。PIIINP三分位数据表明，随着水平的增加，6分钟步行距离（6 MWD）和心脏指数（CI）下降，WHO FC恶化，静息心率增加。PIIINP与WHO FC恶化存在显著相关性（rs=0.319，p=0.008），与CI和6 MWD呈负相关（r分别为-0.304和-0.361; p<0.05）。PIIINP三分位数显示在具有较高三分位数（肺移植或死亡）的患者中有更差结果的趋势（p=0.07，对数秩检验）。胶原代谢标志物与PAH患者病情恶化相关。
The goal of this study was to determine if biomarkers of collagen metabolism in pulmonary arterial hypertension (PAH) identify patients with worse disease and higher risk of death. The relationship between markers of collagen metabolism, degree of disease, and outcome in PAH is unknown. Stable idiopathic, anorexigen-associated and hereditary PAH patients were prospectively enrolled. Collagen biomarkers levels were measured: N-terminal propeptide of type III procollagen (PIIINP), C-terminal telopeptide of collagen type I (CITP), matrix metalloproteinsase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1). Patients were divided into mild, moderate, and severe PAH groups. Data was compared between tertiles of each biomarker. Pearson correlation and Spearman rank coefficient analyses were performed. Data on time to death or transplantation was examined by Kaplan-Meier survival curves. Circulating levels of PIIINP, CITP, MMP9 and TIMP1 were higher in the PAH group (N=68) as compared to age- and gender-matched healthy controls (N=37) (p<0.001 for each). PIIINP levels increased with the severity of disease (p=0.004). PIIINP tertile data indicated that with increasing levels, six-minute walk distance (6MWD) and cardiac index (CI) decreased and WHO FC worsened, and resting heart rate increased. A significant correlation existed between PIIINP with worsening WHO FC (rs=0.319, p=0.008) and a negative correlation with CI and 6MWD (r=-0.304 and -0.361 respectively; p<0.05). PIIINP tertiles showed a trend towards worse outcome in patients with higher tertile (lung transplant or death) (p=0.07, log rank test). Markers of collagen metabolism were associated with worse disease in PAH patients.
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DOI：
10.1164/ajrccm/146.3.701
发表时间：
1992-09-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
LOW, RB;GIANCOLA, MS;DAVIS, GS
通讯作者：
DAVIS, GS
影响因子：
24.3
作者：
Barst, R. J.;Galie, N.;Rubin, L. J.
通讯作者：
Rubin, L. J.
影响因子：
3.1
作者：
Deng, Wei;Chen, Qing-Wei;Wu, Zhi-Qin
通讯作者：
Wu, Zhi-Qin
影响因子：
37.8
作者：
Izawa, H;Murohara, T;Yokota, M
通讯作者：
Yokota, M
影响因子：
10.8
作者：
BISHOP, JE;RHODES, S;STIREWALT, WS
通讯作者：
STIREWALT, WS