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Original Research: Pulmonary Vascular Disease |

Elevated Levels of Circulating Bone Morphogenetic Protein 7 Predict Mortality in Pulmonary Arterial Hypertension

Dong Liu, MD; Bing-Xiang Wu, MD; Na Sun, MD; Yi Yan, MD; Ping Yuan, MD; Jie-Ming Qu, MD; Zhi-Cheng Jing, MD
Author and Funding Information

Drs Liu, Wu, and Sun contributed equally to this manuscript as co-first authors; and Drs Qu and Jing contributed equally to this manuscript.

FUNDING/SUPPORT: This study was supported by the National Natural Science Foundation (81200033, 81470243, and 81570041).

aDepartment of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China

bDepartment of Cardiovascular Medicine, the Second Affiliated Hospital of Harbin Medical University, Harbin, China

cDepartment of Pulmonary Medicine, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai, China

dRuijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China

eState Key Laboratory of Cardiovascular Disease, FuWai Hospital, Peking Union Medical College and Chinese Academy Medical Science, Beijing, China

CORRESPONDENCE TO: Zhi-Cheng Jing, MD, Shanghai Pulmonary Hospital, Tongji Univeristy School of Medicine, Shanghai, and State Key Laboratory of Cardiovascular Disease, FuWai Hospital, Peking Union Medical College and Chinese Academy Medical Science, No. 167 Beilishi Rd, Beijing 100037, China


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(2):367-373. doi:10.1016/j.chest.2016.03.007
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Background  This study aimed to show whether circulating bone morphogenetic proteins (BMPs) levels are associated with increased risk of mortality in patients with pulmonary arterial hypertension (PAH).

Methods  A total of 156 patients with PAH including 43 with heritable PAH (HPAH) and 113 with idiopathic PAH (IPAH) diagnosed by gene screening were enrolled in the study. Circulating BMPs were measured by ELISA in plasma samples from patients with HPAH (n = 43) and IPAH (n = 113) and from control subjects (n = 51). Clinical characteristics at baseline and long-term survival were compared according to the different BMP levels.

Results  Patients with HPAH had significantly higher BMP7 concentrations than patients with IPAH and control subjects (20.1 [interquartile range (IQR), 9.4, 55.2] vs 6.5 [IQR, 3.5, 11.7] and 2.5 [IQR, 0.9, 6.6] pg/mL, respectively; P < .001). Elevated plasma BMP7 were associated with a higher risk of mortality after adjustment for sex, 6-minute walk distance, mean right atrial pressure, mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output (HR, 1.904; 95% CI, 1.021-3.551; P = .043). Patients with IPAH with a BMP7 level > 7.85 pg/mL had a higher risk of mortality than those with a low BMP7 concentration (P = .042, log-rank test).

Conclusions  Levels of circulating BMP7 correlate with mortality in PAH, and may be a predictor of disease in patients with HPAH and IPAH.

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