title: Relationship between baseline ET-1 plasma levels and outcome in patients with idiopathic pulmonary hypertension treated with bosentan.
abstract: OBJECTIVE
  To address if baseline endothelin-1 (ET-1) plasma levels might predict clinical worsening (CW) in patients with idiopathic pulmonary hypertension (IPAH) treated with bosentan.
  
  
  METHODS
  Forty-four consecutive patients with IPAH (WHO classes II-III) were included in this study. After an initial assessment (clinical status, pulmonary hemodynamics, samples for adrenomedullin (ADM), ET-1 and brain natriuretic peptide (BNP) plasma levels), patients were treated with bosentan and followed-up for CW.
  
  
  RESULTS
  We observed CW in 24 patients. Actuarial rates of freedom from CW were 74% at 1 year, 56% at 2 years, and 43% at 3 years. Patients with CW had a worse WHO functional class (II/III; no-CW 14/6 vs CW 5/19, p=0.002), six-minute walk-test distance (no-CW 439+94 m vs CW 385+82 m, p=0.04), mean pulmonary artery pressure (no-CW 47.4+10.6mm Hg vs CW 56+12.6mm Hg, p=0.02) and pulmonary vascular resistance (PVR no-CW 12.5+4.8 WU vs CW 16.4+6.3 WU, p=0.03) than the no-CW group. Moreover ET-1 (no-CW 14.1+4.2 pg/ml vs CW 21.3+6.3 pg/ml, p=0.0001), ADM (no-CW 14.9+7 pg/ml vs CW 21.5+10.4 pg/ml p=0.002) and BNP (no-CW 82.8+35.3 pg/ml vs CW 115.4+39.6 pg/ml, p=0.007) plasma levels were significantly higher in the CW group than in the no-CW group. The multivariate Cox proportional hazards model identified WHO class III (RR 4.6, 95%CI 14.6-1.45), ET-1 plasma levels (RR 1.1, 95%CI 2.05-1.01) and PVR (RR 1.2, 95%CI 1.3-1.03) as independent risk factors for CW.
  
  
  CONCLUSIONS
  These data confirm the high rate of CW in patients with IPAH treated with bosentan and document the impact of the endothelin system on CW of these patients.
authors.affiliation: Dept Cardiovascular and Respiratory Science, University of Rome, La Sapienza, Italy. dario.vizza@uniroma1.it
authors.forename: Carmine Dario
authors.initials: CD
authors.lastname: Vizza
authors.forename: Claudio
authors.initials: C
authors.lastname: Letizia
authors.forename: Roberto
authors.initials: R
authors.lastname: Badagliacca
authors.forename: Roberto
authors.initials: R
authors.lastname: Poscia
authors.forename: Beatrice
authors.initials: B
authors.lastname: Pezzuto
authors.forename: Cristina
authors.initials: C
authors.lastname: Gambardella
authors.forename: Alfred
authors.initials: A
authors.lastname: Nona
authors.forename: Silvia
authors.initials: S
authors.lastname: Papa
authors.forename: Serena
authors.initials: S
authors.lastname: Marcon
authors.forename: Massimo
authors.initials: M
authors.lastname: Mancone
authors.forename: Carlo
authors.initials: C
authors.lastname: Iacoboni
authors.forename: Valeria
authors.initials: V
authors.lastname: Riccieri
authors.forename: Maurzio
authors.initials: M
authors.lastname: Volterrani
authors.forename: Francesco
authors.initials: F
authors.lastname: Fedele
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D000077300:Bosentan; D019332:Endothelin-1 / Q000097:blood*; D005080:Exercise Test / Q000379:methods; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D019332:Endothelin-1; D013449:Sulfonamides; D000077300:Bosentan