Relationship between baseline ET-1 plasma levels and outcome in patients with idiopathic pulmonary hypertension treated with bosentan

Carmine Dario Vizza, Claudio Letizia, Roberto Badagliacca, Roberto Poscia, Beatrice Pezzuto, Cristina Gambardella, Alfred Nona, Silvia Papa, Serena Marcon, Massimo Mancone, Carlo Iacoboni, Valeria Riccieri, Maurzio Volterrani, Francesco Fedele

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: 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 + 10.6 mm Hg vs CW 56 + 12.6 mm 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.

Original languageEnglish
Pages (from-to)220-224
Number of pages5
JournalInternational Journal of Cardiology
Volume167
Issue number1
DOIs
Publication statusPublished - Jul 15 2013

Keywords

  • Bosentan
  • Clinical worsening
  • Endothelin-1
  • Pulmonary arterial hypertension

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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