PLASMA ENDOTHELIN-1 LEVELS, PULMONARY-HYPERTENSION, AND LUNG FIBROSISIN PATIENTS WITH SYSTEMIC-SCLEROSIS

PURPOSE: TO investigate the behavior of circulating endothelin (ET)-1 concentrations in patients affected by systemic sclerosis, and to eluc idate the possible relationships existing in this disease among plasma peptide levels, pulmonary hypertension, and lung fibrosis. PATIENTS A ND METHODS: Circulating ET-1 levels were determined by reverse-phase, high-pressure liquid chromatography followed by sensitive radioimmunoa ssay in 20 patients affected by systemic sclerosis (18 women and 2 men , mean age 48.1 +/- 13.7 years) with or without pulmonary hypertension as evaluated by Doppler echocardiography, or lung fibrosis as measure d by a score method based on lung examination by high-resolution compu ted tomography (HRCT). A group of 18 normal volunteers served as contr ols (15 women and 3 men, mean age 45.0 +/- 10.1 years). RESULTS: Plasm a ET-1 levels were significantly higher (P <0.001) in patients with sy stemic sclerosis (1.72 +/- 0.28 pg/mL) than in control subjects (0.63 +/- 0.06 pg/mL). Pulmonary artery systolic hypertension was detected i n 10 patients (50%) with systemic sclerosis (56.2 +/- 18.0 mm Hg, rang e 37 to 97) versus none of the control subjects (30.2 +/- 2.2 mm Hg, P <0.0001). Lung fibrosis was present in 12 patients (60%), with an HRC T overall score of 9.0 +/- 4.6. There were no significant differences in plasma ET-1 levels between patients with pulmonary hypertension (1. 58 +/- 0.20 pg/mL) or without it (1.76 +/- 0.39 pg/mL, P = 0.188, not significant [NS]); or between patients with lung fibrosis (1.65 +/- 0. 14 pg/mL) or without fibrosis (1.78 +/- 0.37 pg/mL, P = 0.290, NS). In particular, 6 patients had neither pulmonary hypertension nor lung fi brosis. In these patients, plasma ET-1 levels were similar compared wi th the others (1.85 +/- 0.49 versus 1.66 +/- 0.13, respectively; P = 0 .180, NS). No correlations were observed between ET-1 levels and eithe r pulmonary pressure levels or HRCT overall scores. CONCLUSIONS: The u se of a sensitive assay, highly selective for ET-1, showed higher leve ls of circulating peptide in patients affected by systemic sclerosis t han in control subjects. Neither pulmonary hypertension nor lung fibro sis was accompanied by a further rise in plasma ET-1 concentrations.