Barreto A C, Maeda N Y, Soares R P S, Cícero C, Lopes A A
Departamento de Cardiologia Pediátrica e Cardiopatias Congênitas do Adulto, Instituto do Coração, Universidade de São Paulo.
Braz J Med Biol Res. 2008 Aug;41(8):657-63. 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.
我们研究了长期服用瑞舒伐他汀是否能改善肺动脉高压（PAH）患者循环中血管功能障碍标志物水平的异常。60例年龄在13至60岁之间的特发性PAH患者（n = 14）或先天性心脏病相关性PAH患者（n = 46）被平均且随机分为瑞舒伐他汀治疗组（口服10mg/天）或安慰剂组，采用盲法治疗6个月。在治疗1、3和6个月前后，通过酶联免疫吸附测定法测量血浆P-选择素、组织纤溶酶原激活剂及其抑制剂以及血管性血友病因子抗原的水平。生物标志物的基线水平升高（相对于对照组，P-选择素、血管性血友病因子抗原、组织纤溶酶原激活剂及其抑制剂分别增加68%、16%、45%和46%；P < 0.001）。瑞舒伐他汀组在基线、1、3和6个月时的P-选择素值分别为39.9±18.5、37.6±14.6、34.8±14.6和35.4±13.9 ng/mL，安慰剂组分别为45.7±26.8、48.0±26.9、48.1±25.7和45.7±25.6 ng/mL。在整个治疗过程中，瑞舒伐他汀组的P-选择素水平低于安慰剂组（P = 0.037，一般线性模型）。他汀类药物组的组织纤溶酶原激活剂有下降趋势（降低16%，P = 0.094），其他标志物无显著变化。由于P-选择素在炎症和血栓形成中起关键作用，瑞舒伐他汀使其降低可能与PAH的病理生理情况相关。
