Engler Marguerite M, Engler Mary B, Malloy Mary J, Chiu Elisa Y, Schloetter Monique C, Paul Steven M, Stuehlinger Markus, Lin Ken Y, Cooke John P, Morrow Jason D, Ridker Paul M, Rifai Nader, Miller Elizabeth, Witztum Joseph L, Mietus-Snyder Michele
University of California, San Francisco, 2 Koret Way, Rm N631, San Francisco, Calif 94143-0610, USA.
Circulation. 2003 Sep 2;108(9):1059-63. doi: 10.1161/01.CIR.0000086345.09861.A0. Epub 2003 Aug 11.
Hyperlipidemia is associated with endothelial dysfunction, an early event in atherosclerosis and predictor of risk for future coronary artery disease. Epidemiological studies suggest that increased dietary intake of antioxidants reduces the risk of coronary artery disease. The purpose of this study was to determine whether antioxidant vitamin therapy improves endothelial function and affects surrogate biomarkers for oxidative stress and inflammation in hyperlipidemic children.
In a randomized, double-blind, placebo-controlled trial, the effects of antioxidant vitamins C (500 mg/d) and E (400 IU/d) for 6 weeks and the National Cholesterol Education Program Step II (NCEP-II) diet for 6 months on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery were examined in 15 children with familial hypercholesterolemia (FH) or the phenotype of familial combined hyperlipidemia (FCH). Antioxidant vitamin therapy improved FMD of the brachial artery compared with baseline (P<0.001) without an effect on biomarkers for oxidative stress (autoantibodies to epitopes of oxidized LDL, F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine), inflammation (C-reactive protein), or levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide.
Antioxidant therapy with vitamins C and E restores endothelial function in hyperlipidemic children. Early detection and treatment of endothelial dysfunction in high-risk children may retard the progression of atherosclerosis.
高脂血症与内皮功能障碍相关，内皮功能障碍是动脉粥样硬化的早期事件及未来冠心病风险的预测指标。流行病学研究表明，增加抗氧化剂的膳食摄入量可降低冠心病风险。本研究的目的是确定抗氧化维生素疗法是否能改善高脂血症儿童的内皮功能，并影响氧化应激和炎症的替代生物标志物。
在一项随机、双盲、安慰剂对照试验中，对15名家族性高胆固醇血症（FH）或家族性混合性高脂血症（FCH）表型的儿童，研究了抗氧化维生素C（500毫克/天）和E（400国际单位/天）治疗6周以及国家胆固醇教育计划第二步（NCEP-II）饮食治疗6个月对肱动脉内皮依赖性血流介导的舒张功能（FMD）的影响。与基线相比，抗氧化维生素疗法改善了肱动脉的FMD（P<0.001），但对氧化应激生物标志物（氧化型低密度脂蛋白表位的自身抗体、F2-异前列腺素、8-羟基-2'-脱氧鸟苷）、炎症（C反应蛋白）或一氧化氮内源性抑制剂不对称二甲基精氨酸水平无影响。
维生素C和E的抗氧化疗法可恢复高脂血症儿童内皮功能。对高危儿童早期检测和治疗内皮功能障碍可能会延缓动脉粥样硬化的进展。
