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OBJECTIVE: Adrenomedullin (ADM), a vasodilating peptide that possesses antiinflammatory properties, may have a regulatory role in the vascular manifestations of scleroderma (systemic sclerosis, SSc). We examined associations between ADM concentrations and vascular manifestations in a cohort of patients with SSc. METHODS: Patients were examined for manifestations of severe Raynaud's phenomenon (RP), defined as digital resorption, previous iloprost infusion, and sympathectomy. Doppler echocardiography and lung function tests were performed to detect elevation in pulmonary arterial pressure (PAP; > 35 mm Hg) and interstitial lung disease (ILD). Plasma ADM was measured by radioimmunoassay. RESULTS: Plasma ADM was measured in 62 SSc patients and 21 healthy controls. Elevated PAP was found in 15 (24.2%) SSc patients (mean PAP 46.5 +/- 11.2 mm Hg, range 37-74). ADM was not found to be related to age, sex, disease duration, or clinical subset. ADM level was significantly higher (median 13.9 pmol/l) in SSc patients with elevated PAP compared to those with lower PAP (median 7.2 pmol/l) (p = 0.01) and controls (median 7.9 pmol/l) (p = 0.04). ADM level was not different among patients who had elevated PAP with (n = 10) and without concomitant ILD (n = 5) (p = 0.21). SSc patients with severe RP (38.7%; median ADM 11.9 pmol/l) were found not to have different ADM levels compared to controls (p = 0.75). Patients who had both severe RP and elevated PAP were found to have significantly higher ADM levels (median 22.3 pmol/l) than patients who had neither manifestation (median 8.0 pmol/l) (p = 0.006) and those with severe RP alone (median 4.2 pmol/l) (p = 0.006). CONCLUSION: Elevated ADM was found in SSc patients with increased PAP regardless of concomitant ILD.