title: Elevated levels of plasma transforming growth factor-β1 in idiopathic and heritable pulmonary arterial hypertension.
abstract: BACKGROUND
  Aberrant transforming growth factor (TGF)-β signaling is involved in the pathogenesis of pulmonary arterial hypertension (PAH). We aimed to investigate the predictive value of the upstream ligand of TGF-β signaling (TGF-β1) on long-term mortality and the clinical characteristics of patients with idiopathic pulmonary arterial hypertension (IPAH) and heritable PAH (HPAH).
  
  
  RESULTS
  Plasma TGF-β1 levels were measured in 151 IPAH and 65 HPAH patients retrospectively enrolled between January 2008 and March 2013, and compared to 61 healthy subjects. Data for mortality over time were obtained from hospital databases and from telephone follow-ups. The main outcome was all-cause death. Plasma TGF-β1 was significantly higher in IPAH/HPAH patients compared to control subjects (4.74 vs. 2.61ng/mL, respectively; P<0.001). Mean follow-up time was 3.4±1.8years, during which 86 patients died. ROC curves were utilized to determine TGF-β1 cutoff values. Compared to patients with TGF-β1 of <3.74ng/mL, heart function was significantly impaired (percentage of patients with WHO functional class III/IV, 51.4% vs. 65.5%, P=0.043) and mortality risk was elevated (P=0.009) for patients with TGF-β1>3.74ng/mL. However, the difference in mortality rate between patients with higher and lower TGF-β1 levels was only statistically significant for female patients (P=0.004), despite a similar trend for male patients. Multivariate analyses revealed that TGF-β1 (HR after log transformation base of 10: 2.623; 95%CI: 1.228-5.603; P=0.013) emerged as the independent predictor for all-cause mortality.
  
  
  CONCLUSIONS
  High circulating levels of TGF-β1 were an independent predictor of a poor outcome for IPAH/HPAH patients.
authors: Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China.
authors: Yi
authors: Y
authors: Yan
authors: State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Xiao-Jian
authors: XJ
authors: Wang
authors: State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Su-Qi
authors: SQ
authors: Li
authors: State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Shu-Hui
authors: SH
authors: Yang
authors: State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Zi-Chao
authors: ZC
authors: Lv
authors: State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Li-Ting
authors: LT
authors: Wang
authors: State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Yang-Yang
authors: YY
authors: He
authors: State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Xin
authors: X
authors: Jiang
authors: Department of Gerontology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
authors: Yong
authors: Y
authors: Wang
authors: Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China; State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: jingzhicheng@vip.163.com.
authors: Zhi-Cheng
authors: ZC
authors: Jing
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D065627:Familial Primary Pulmonary Hypertension / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D053773:Transforming Growth Factor beta1 / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053773:Transforming Growth Factor beta1
keywords: Pulmonary arterial hypertension; Survival; Transforming growth factor-β1