Plasma endothelin-1 levels, pulmonary hypertension, and lung fibrosis in patients with systemic sclerosis

PURPOSE : To investigate the behavior of circulating endothelin (ET)-1 concentrations in patients affected by systemic sclerosis, and to elucidate the possible relationships existing in this disease among plasma peptide levels, pulmonary hypertension, and lung fibrosis. PATIENTS AND METHODS : Circulating ET-1 levels were determined by reverse-phase, high-pressure liquid chromatography followed by sensitive radioimmunoassay 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 measured by a score method based on lung examination by high-resolution computed tomography (HRCT). A group of 18 normal volunteers served as controls (15 women and 3 men, mean age 45.0 ± 10.1 years). RESULTS : Plasma ET-1 levels were significantly higher (P <0.001) in patients with systemic sclerosis (1.72 ± 0.28 pg/mL) than in control subjects (0.63 ± 0.06 pg/mL). Pulmonary artery systolic hypertension was detected in 10 patients (50%) with systemic sclerosis (56.2 ± 18.0 mm Hg, range 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 HRCT 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 fibrosis. In these patients, plasma ET-1 levels were similar compared with 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 either pulmonary pressure levels or HRCT overall scores. CONCLUSIONS : The use of a sensitive assay, highly selective for ET-1, showed higher levels of circulating peptide in patients affected by systemic sclerosis than in control subjects. Neither pulmonary hypertension nor lung fibrosis was accompanied by a further rise in plasma ET-1 concentrations.