Rosuvastatin and vascular dysfunction markers in pulmonary arterial hypertension: a placebo-controlled study

• Published in: Brazilian journal of medical and biological research Vol. 41; no. 8; pp. 657 - 663
• Main Authors: Barreto, A C, Maeda, N Y, Soares, R P S, Cícero, C, Lopes, A A
• Format: Journal Article
• Language: English; Portuguese
• Published: Brazil Associação Brasileira de Divulgação Científica 01.08.2008
• Subjects: Adolescent; Adult; BIOLOGY; Biomarkers - blood; Case-Control Studies; Endothelial dysfunction; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Enzyme-Linked Immunosorbent Assay; Female; Fluorobenzenes - therapeutic use; Heart Defects, Congenital - complications; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypertension, Pulmonary - blood; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - physiopathology; Male; MEDICINE, RESEARCH & EXPERIMENTAL; Middle Aged; P-selectin; P-Selectin - blood; Pulmonary hypertension; Pyrimidines - therapeutic use; Rosuvastatin Calcium; Severity of Illness Index; Statins; Sulfonamides - therapeutic use; Tissue Plasminogen Activator - antagonists & inhibitors; Tissue Plasminogen Activator - blood; Tissue-plasminogen activator and inhibitor; von Willebrand factor; von Willebrand Factor - analysis; von Willebrand Factor - immunology; Young Adult; Endothelial dysfunction; von Willebrand factor; Pulmonary hypertension; Statins; P-selectin; Tissue-plasminogen activator and inhibitor
• ISSN: 0100-879X; 1414-431X; 1414-431X; 0100-879X
• DOI: 10.1590/S0100-879X2008000800003

We investigated whether chronic rosuvastatin administration could improve the abnormalities of the circulating levels of vascular dysfunction markers in pulmonary arterial hypertension (PAH). Sixty patients, aged 13 to 60 years, with idiopathic (N = 14) or congenital heart disease-associated PAH (N = 46) were equally but randomly assigned to rosuvastatin treatment (10 mg a day, orally) or placebo for 6 months in a blind fashion. Plasma levels of P-selectin, tissue-plasminogen activator and its inhibitor as well as von Willebrand factor antigen were measured by enzyme-linked immunoassay before and after 1, 3, and 6 months of treatment. Baseline levels of biomarkers were elevated (68, 16, 45 and 46% increase relative to controls, for P-selectin, von Willebrand factor antigen, tissue-plasminogen activator and its inhibitor, respectively; P < 0.001). P-selectin values at baseline, 1, 3, and 6 months were 39.9 +/- 18.5, 37.6 +/- 14.6, 34.8 +/- 14.6, and 35.4 +/- 13.9 ng/mL, respectively, for the rosuvastatin group and 45.7 +/- 26.8, 48.0 +/- 26.9, 48.1 +/- 25.7, and 45.7 +/- 25.6 ng/mL for the placebo group. The P-selectin level was lower in the rosuvastatin group compared with placebo throughout treatment (P = 0.037, general linear model). A trend was observed towards a decrease in tissue-plasminogen activator in the statin group (16% reduction, P = 0.094), with no significant changes in the other markers. Since P-selectin is crucial in inflammation and thrombosis, its reduction by rosuvastatin is potentially relevant in the pathophysiological scenario of PAH.