维生素E补充剂联合辛伐他汀治疗对高胆固醇血症男性肱动脉血管反应性的额外益处。

Additional benefit of vitamin E supplementation to simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men.

作者信息

Neunteufl T, Kostner K, Katzenschlager R, Zehetgruber M, Maurer G, Weidinger F

机构信息

Department of Cardiology, University of Vienna, Austria.

出版信息

J Am Coll Cardiol. 1998 Sep;32(3):711-6. doi: 10.1016/s0735-1097(98)00295-2.

DOI:10.1016/s0735-1097(98)00295-2

PMID:9741516

Abstract

OBJECTIVES

The aim of this study was to determine whether the combination of lipid-lowering therapy and vitamin E supplementation improves peripheral endothelial function and whether it is more effective than lipid-lowering therapy alone.

BACKGROUND

Endothelium-dependent vasodilation is impaired in coronary and peripheral arteries of patients with hypercholesterolemia. Coronary endothelial function has been shown to improve under lipid-lowering and antioxidant therapy, but the effect of additive vitamin E supplementation in the brachial artery is unknown.

METHODS

Seven patients with hypercholesterolemia (mean+/-SD; age 51+/-10 yr) were studied. Endothelium-dependent, flow-mediated dilation (FMD) and endothelium-independent nitroglycerin-induced dilation (NMD) were assessed in the brachial artery using high resolution ultrasound 1) at baseline (BL I), 2) after 8 weeks of simvastatin (20 mg) and vitamin E (300 IU) therapy (Comb I), 3) after withdrawal of vitamin E for 4 weeks (Statin), 4) after therapy as in #2 for 4 weeks (Comb II) and 5) after withdrawal of both drugs for 4 weeks (BL II).

RESULTS

Combined simvastatin and vitamin E therapy reduced total cholesterol (Comb I vs. BL I: 276+/-22 vs. 190+/-14 mg/dl, p < 0.0001) and low-density lipoprotein (LDL)-C (197+/-22 vs. 106+/-22 mg/dl, p < 0.00001), augmented alpha tocopherol levels normalized to LDL (12.2+/-4.1 vs. 4.9+/-0.9 microg alpha-T/100 mg% LDL-C, p < 0.01) and resulted in significant improvements in FMD (16.4+/-4.7 vs. 4.9+/-2.5%, p < 0.001) as well as NMD (17.9+/-4.3 vs. 11.2+/-2.8%, p < 0.01). The ratio of FMD to NMD (0.92+/-0.17 vs. 0.46+/-0.24%, p < 0.05) also increased under combination therapy, indicating a greater improvement of FMD than that of NMD. After withdrawal of vitamin E, both FMD (Comb I vs. Statin: 16.4+/-4.7 vs. 7.9+/-4.7%, p < 0.01) and NMD (17.9+/-4.3 vs. 10.9+/-4.5%, p < 0.05) decreased significantly such that simvastatin alone only tended to improve FMD and did not change NMD. Results under combination therapy (Comb II vs. BL II) were reproducible.

CONCLUSIONS

Combined vitamin E and simvastatin therapy leads to an improvement of FMD and NMD in the brachial artery of patients with hypercholesterolemia. The improvement of FMD is more pronounced after combination therapy than after lipid-lowering therapy alone, similar to previous findings in the coronary circulation.

摘要

目的

本研究旨在确定降脂治疗与补充维生素E联合应用是否能改善外周血管内皮功能，以及是否比单纯降脂治疗更有效。

背景

高胆固醇血症患者的冠状动脉和外周动脉中，内皮依赖性血管舒张功能受损。降脂和抗氧化治疗已显示可改善冠状动脉内皮功能，但补充维生素E对肱动脉的影响尚不清楚。

方法

对7例高胆固醇血症患者（平均±标准差；年龄51±10岁）进行研究。使用高分辨率超声在肱动脉评估内皮依赖性血流介导的舒张功能（FMD）和内皮非依赖性硝酸甘油诱导的舒张功能（NMD）：1）在基线时（BL I）；2）辛伐他汀（20 mg）和维生素E（300 IU）治疗8周后（联合治疗I）；3）停用维生素E 4周后（他汀治疗）；4）按2）治疗4周后（联合治疗II）；5）两种药物都停用4周后（BL II）。

结果

辛伐他汀与维生素E联合治疗降低了总胆固醇（联合治疗I与BL I：276±22与190±14 mg/dl，p<0.0001）和低密度脂蛋白（LDL）-C（197±22与106±22 mg/dl，p<0.00001），使按LDL标准化的α-生育酚水平升高（12.2±4.1与4.9±0.9 μg α-T/100 mg% LDL-C，p<0.01），并导致FMD（16.4±4.7与4.9±2.5%，p<0.001）以及NMD（17.9±4.3与11.2±2.8%，p<0.01）显著改善。联合治疗下FMD与NMD的比值（0.92±0.17与0.46±0.24%，p<0.05）也升高，表明FMD的改善比NMD更显著。停用维生素E后，FMD（联合治疗I与他汀治疗：16.4±4.7与7.9±4.7%，p<0.01）和NMD（17.9±4.3与10.9±4.5%，p<0.05）均显著下降，使得仅辛伐他汀治疗仅倾向于改善FMD且未改变NMD。联合治疗（联合治疗II与BL II）的结果具有可重复性。