Marchesi S, Lupattelli G, Siepi D, Schillaci G, Vaudo G, Roscini A R, Sinzinger H, Mannarino E
Department of Clinical and Experimental Medicine, University of Perugia, Italy.
J Cardiovasc Pharmacol. 2000 Nov;36(5):617-21. doi: 10.1097/00005344-200011000-00011.
Endothelial dysfunction represents the earliest stage of atherosclerosis and is usually present in hypercholesterolemia. Treatment with statins has been shown to normalize endothelial function in middle-aged men with hypercholesterolemia. We evaluated the effect over time of atorvastatin on the endothelial reactivity in postmenopausal hypercholesterolemic women (mean age, 58 +/- 6 years), receiving atorvastatin, 10 mg daily (n = 20) or American Heart Association step 1 diet (n = 10) for 8 weeks. Lipid profile and brachial artery flow-mediated vasodilation (FMV) were determined at baseline and after 1, 2, 4, and 8 weeks. FMV increased progressively in subjects treated with atorvastatin, and the difference was significant (p < 0.05 vs. baseline) after the second week (baseline 3.8 +/- 3%; first week, 4.8 +/- 3%; second week, 9.2 +/- 3%; fourth week, 11.0 +/- 3%; eighth week, 11.7 +/- 3%). No significant changes were observed in subjects receiving diet (baseline, 3.1 +/- 4%; first week, 2.4 +/- 2%; second week, 2.9 +/- 2%; fourth week, 3.1 +/- 2%; eighth week, 3.3 +/- 2%; p = NS). In the atorvastatin group, low-density lipoprotein (LDL) cholesterol showed a significant decrease since the first week (baseline, 228 +/- 37 mg/dl; first week, 171 +/- 32; second week, 147 +/- 27; fourth week, 139 +/- 29; eighth week, 135 +/- 27; all p < 0.05). In the control group, LDL cholesterol showed a smaller but significant (p < 0.05) reduction after the second week (baseline, 226 +/- 17 mg/dl; first week, 225 +/- 16; second week, 220 +/- 17; fourth week, 203 +/- 27; eighth week, 198 +/- 27). In conclusion, hypercholesterolemic women treated with atorvastatin show a significant improvement in endothelial reactivity after as early as 2 weeks of therapy. The extent to which these beneficial effects are attributable to cholesterol reduction or to a direct effect of the drug remains to be established.
内皮功能障碍是动脉粥样硬化的最早阶段，通常存在于高胆固醇血症中。已证明，他汀类药物治疗可使中年高胆固醇血症男性的内皮功能恢复正常。我们评估了阿托伐他汀对绝经后高胆固醇血症女性（平均年龄58±6岁）内皮反应性的长期影响，这些女性接受阿托伐他汀每日10毫克（n = 20）或美国心脏协会一级饮食（n = 10）治疗8周。在基线以及第1、2、4和8周后测定血脂谱和肱动脉血流介导的血管舒张（FMV）。接受阿托伐他汀治疗的受试者的FMV逐渐增加，第二周后差异显著（与基线相比，p < 0.05）（基线3.8±3%；第一周，4.8±3%；第二周，9.2±3%；第四周，11.0±3%；第八周，11.7±3%）。接受饮食治疗的受试者未观察到显著变化（基线，3.1±4%；第一周，2.4±2%；第二周，2.9±2%；第四周，3.1±2%；第八周，3.3±2%；p = 无显著性差异）。在阿托伐他汀组中，自第一周起低密度脂蛋白（LDL）胆固醇显著降低（基线，228±37毫克/分升；第一周，171±32；第二周，147±27；第四周，139±29；第八周，135±27；所有p < 0.05）。在对照组中，第二周后LDL胆固醇有较小但显著的降低（p < 0.05）（基线，226±17毫克/分升；第一周，225±16；第二周，220±17；第四周，203±27；第八周，198±27）。总之，接受阿托伐他汀治疗的高胆固醇血症女性在治疗仅2周后内皮反应性就有显著改善。这些有益作用在多大程度上归因于胆固醇降低或药物的直接作用仍有待确定。
