International journal of cardiology · 2012
Relationship between baseline ET-1 plasma levels and outcome in patients with idiopathic pulmonary hypertension treated with bosentan.
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Vizza Carmine Dario, Letizia Claudio, Badagliacca Roberto, Poscia Roberto, Pezzuto Beatrice, Gambardella Cristina, Nona Alfred, Papa Silvia, Marcon Serena, Mancone Massimo, Iacoboni Carlo, Riccieri Valeria, Volterrani Maurzio, Fedele Francesco
Аннотация
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+10.6mm 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.
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.