title: Direct bilirubin: A new risk factor of adverse outcome in idiopathic pulmonary arterial hypertension.
abstract: BACKGROUND
  Previous studies have shown that elevated total bilirubin was associated with advanced heart failure, yet no study has ascertained the predictive value of direct serum bilirubin (DBIL) in idiopathic pulmonary arterial hypertension (IPAH). This study aimed to investigate the predictive value of both baseline and follow-up DBIL in patients with IPAH.
  
  
  METHODS
  Serum DBIL was measured in 404 IPAH patients at enrollment. Almost 92% patients received specific drugs after diagnosis confirmed. Serum DBIL was repeated in 237 patients after a mean of 8.3months treatment. Survival rate among normal DBIL group and abnormal DBIL group was compared using the Kaplan-Meier method. The prognostic value of baseline variables was tested by Cox regression models.
  
  
  RESULTS
  During median follow-up period of 40months, 153 patients died. Baseline DBIL levels were significantly higher in non-survivors compared with survivors (p<0.001). DBIL levels in survivors decreased significantly during PAH therapy, whereas there was almost no decrease in non-survivors. Patients with abnormal DBIL at baseline or during therapy had a significantly lower survival rates than those with normal DBIL group, according to Kaplan-Meier survival analysis (p=0.002 and p<0.0001, respectively). According to multivariate analyses, baseline DBIL was an independent risk factor of mortality in IPAH.
  
  
  CONCLUSIONS
  Serum DBIL could predict severity and outcomes of IPAH: in particular, no obvious decrease in DBIL during PAH-specific drug therapy is strongly associated with worse prognosis in IPAH.
authors.affiliation: State Key Lab of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xi-Qi
authors.initials: XQ
authors.lastname: Xu
authors.affiliation: State Key Lab of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Zi-Chao
authors.initials: ZC
authors.lastname: Lv
authors.affiliation: State Key Lab of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Liu
authors.affiliation: Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Qin-Hua
authors.initials: QH
authors.lastname: Zhao
authors.affiliation: State Key Lab of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Lab of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.affiliation: State Key Lab of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Lab of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Fu-Hua
authors.initials: FH
authors.lastname: Peng
authors.affiliation: State Key Lab of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: jingzhicheng@vip.163.com.
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Jing
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001663:Bilirubin / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D006328:Cardiac Catheterization / Q000379:methods; D015331:Cohort Studies; D018450:Disease Progression; D065627:Familial Primary Pulmonary Hypertension / Q000097:blood* / Q000175:diagnosis / Q000401:mortality* / Q000503:physiopathology; D005260:Female; D006333:Heart Failure / Q000517:prevention & control; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D016019:Survival Analysis; D014655:Vascular Resistance / Q000502:physiology*
chemical_list: D015415:Biomarkers; D001663:Bilirubin
keywords: Bilirubin; Hypertension, pulmonary; Prognosis; Right heart failure