Grodzińska Lilia, Starzyk Dorota, Bieroń Krzysztof, Goszcz Aleksandra, Korbut Ryszard
Department of Pharmacology, Department of Clinical Pharmacology, Jagiellonian University School of Medicine, 31-531 Cracow, 16 Grzegorzecka, Poland.
Basic Clin Pharmacol Toxicol. 2005 Jun;96(6):413-9. doi: 10.1111/j.1742-7843.2005.pto_03.x.
Improvement of endothelial function caused by statin treatment is not related to lowering of the cholesterol levels but results primarily from statin pleiotropic effects. Accordingly, we designed a pilot study in 10 normocholesterolaemic and 10 hypercholesterolaemic patients with peripheral arterial occlusive disease to investigate potential biological effects of statins in relation to their effects on endothelial function. The patients were treated with simvastatin 40 mg/daily for 3 months. Simvastatin led to significant reduction in total cholesterol and trigliceride levels in normocholesterolaemic and hypercholesterolaemic patients. Elongation of pain-free and total walking distance was observed in both groups studied. Inconsiderable changes in rest ankle brachial index were seen. Flow-mediated dilation increased in normocholesterolaemic group by 153% and in the hypercholesterolaemic group by 180% after 3 months of treatment. Euglobulin clot lysis time was shortened significantly in both groups each time after drug intake. Platelet aggregates ratio was increased in normocholesterolaemic patients by 8.9% and in hypercholesterolaemic patients by 17.6% each time after intake and remained significantly increased during the observation after 1 and 3 months. Simvastatin inhibited platelet aggregation induced by collagen and ADP in both study groups 3 hr after intake, but the platelets of hypercholesterolaemic patients were less sensitive to these aggregatory agents after 3 months of treatment. Simvastatin therapy caused clinical improvement in normocholesterolaemic and hypercholesterolaemic patients with peripheral occlusive disease. It is suggested that this effect is due to the restoration of endothelial function.
他汀类药物治疗引起的内皮功能改善与胆固醇水平降低无关，而主要来源于他汀类药物的多效性作用。因此，我们设计了一项初步研究，纳入10例正常胆固醇血症和10例高胆固醇血症的外周动脉闭塞性疾病患者，以研究他汀类药物对内皮功能的影响及其潜在的生物学效应。患者接受辛伐他汀40mg/日治疗3个月。辛伐他汀使正常胆固醇血症和高胆固醇血症患者的总胆固醇和甘油三酯水平显著降低。在两个研究组中均观察到无痛行走距离和总行走距离延长。静息踝肱指数变化不大。治疗3个月后，正常胆固醇血症组的血流介导的血管舒张增加了153%，高胆固醇血症组增加了180%。每次服药后两组的优球蛋白凝块溶解时间均显著缩短。每次服药后，正常胆固醇血症患者的血小板聚集率增加8.9%，高胆固醇血症患者增加17.6%，并在1个月和3个月的观察期内持续显著升高。服药3小时后，辛伐他汀在两个研究组中均抑制了胶原和ADP诱导的血小板聚集，但治疗3个月后，高胆固醇血症患者的血小板对这些聚集剂的敏感性较低。辛伐他汀治疗使正常胆固醇血症和高胆固醇血症的外周闭塞性疾病患者的临床症状得到改善。提示这种效应是由于内皮功能的恢复。
