Koh K K, Cardillo C, Bui M N, Hathaway L, Csako G, Waclawiw M A, Panza J A, Cannon R O
Cardiology Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1650, USA.
Circulation. 1999 Jan 26;99(3):354-60. doi: 10.1161/01.cir.99.3.354.
Lipoproteins affect endothelium-dependent vasomotor responsiveness. Because lipoprotein effects of estrogen and cholesterol-lowering therapies differ, we studied the vascular responses to these therapies in hypercholesterolemic postmenopausal women.
We randomly assigned 28 women to conjugated equine estrogen (CE) 0.625 mg, simvastatin 10 mg, and their combination daily for 6 weeks. Compared with respective baseline values, simvastatin alone and combined with CE reduced LDL cholesterol to a greater extent than CE alone (both P<0.05). CE alone and combined with simvastatin raised HDL cholesterol and lowered lipoprotein(a) to a greater extent than simvastatin alone (all P<0.05). Flow-mediated dilation of the brachial artery (by ultrasonography) improved (all P<0.001 versus baseline values) on CE (4.0+/-2.6% to 10.2+/-3.9%), simvastatin (4.3+/-2.4% to 10.0+/-3.9%), and CE combined with simvastatin (4.6+/-2.0% to 9.8+/-2.6%), but similarly among therapies (P=0.507 by ANOVA). None of the therapies improved the dilator response to nitroglycerin (all P>/=0.184). Only therapies including CE lowered levels of plasminogen activator inhibitor type 1 and the cell adhesion molecule E-selectin (all P<0. 05 versus simvastatin).
Although estrogen and statin therapies have differing effects on lipoprotein levels, specific improvement in endothelium-dependent vasodilator responsiveness is similar. However, only therapies including estrogen improved markers of fibrinolysis and vascular inflammation. Thus, estrogen therapy appears to have unique properties that may benefit the vasculature of hypercholesterolemic postmenopausal women, even if they are already on cholesterol-lowering therapy.
脂蛋白会影响内皮依赖性血管舒缩反应性。由于雌激素和降胆固醇疗法对脂蛋白的影响不同，我们研究了高胆固醇血症绝经后女性对这些疗法的血管反应。
我们将28名女性随机分为三组，分别每日服用0.625毫克结合马雌激素（CE）、10毫克辛伐他汀以及二者的组合，为期6周。与各自的基线值相比，单独使用辛伐他汀以及与CE联合使用时，降低低密度脂蛋白胆固醇的程度均大于单独使用CE（均P<0.05）。单独使用CE以及与辛伐他汀联合使用时，升高高密度脂蛋白胆固醇和降低脂蛋白(a)的程度均大于单独使用辛伐他汀（均P<0.05）。肱动脉的血流介导的扩张（通过超声检查）在使用CE（从4.0±2.6%至10.2±3.9%）、辛伐他汀（从4.3±2.4%至10.0±3.9%）以及CE与辛伐他汀联合使用（从4.6±2.0%至9.8±2.6%）时均有改善（与基线值相比均P<0.001），但各疗法之间相似（方差分析P=0.507）。所有疗法均未改善对硝酸甘油的舒张反应（均P≥0.184）。只有包含CE的疗法降低了纤溶酶原激活物抑制剂1型和细胞黏附分子E选择素的水平（与辛伐他汀相比均P<0.05）。
尽管雌激素和他汀类疗法对脂蛋白水平有不同影响，但内皮依赖性血管舒张反应性的特定改善是相似的。然而，只有包含雌激素的疗法改善了纤溶和血管炎症的标志物。因此，雌激素疗法似乎具有独特的特性，可能使高胆固醇血症绝经后女性的血管受益，即使她们已经在接受降胆固醇治疗。
