Dietary Antioxidents and Markers of Atherosclerosis

描述（由申请人提供）：背景：许多观察和实验研究表明，动脉粥样硬化的公认危险因素促进了血管系统中的炎症氧化环境，这有助于内皮的病理变化。现在有相当多的证据表明，内皮功能障碍既先于动脉粥样硬化，又加速动脉粥样硬化。抗氧化营养素，包括维生素C，类胡萝卜素，生育酚和硒，因此可能被推测可能有助于减少内皮功能障碍，并减少心血管事件的发生率。然而，以前在临床试验中使用抗氧化剂补充剂产生了令人失望和有争议的结果。尽管无效的试验结果，膳食抗氧化维生素的使用在美国继续增长目的：在这个修订后的申请中，我们的目标是确定天然富含抗氧化剂的食物与补充药丸抗氧化剂对炎症和内皮功能标志物的短期疗效在一般健康的受试者中动脉粥样硬化的风险。设计：随机、单盲（饮食）/双盲（补充剂）、平行、可行性研究。90名动脉粥样硬化和心脏病风险因素升高的成年人将被随机分配到：1）继续他们的日常饮食，并接受安慰剂药片（n = 30例患者/Plac），2）继续他们的日常饮食，并接受抗氧化剂补充丸（n = 30例患者/补充剂），或3）增加他们的消费量的抗氧化剂丰富的食物密切匹配的抗氧化剂含量的补充丸（n = 30抗氧化剂食品）八周。将在基线、第4周和第8周收集数据。主要研究结果是炎症标志物，包括c-反应蛋白、纤维蛋白原、IL-6、TNF-α和可溶性ICAM-1。次要结局包括肱动脉血流介导的血管舒张和尿异前列腺素。本研究旨在评估动脉粥样硬化新标志物对抗氧化干预的反应性。炎症标志物和内皮功能的测试可以提供一种快速可靠的方法，以低成本评估抗氧化剂干预的临床结果，并允许微调选择的最佳组合，来源和剂量的抗氧化剂为未来的长期和更大规模的研究。

DESCRIPTION (provided by applicant): BACKGROUND: A number of observational and experimental studies have shown that the recognized risk factors for atherosclerosis promote an inflammatory oxidative environment in the vasculature that is conducive to pathologic changes in the endothelium. Considerable evidence now exists that endothelial dysfunction both precedes and accelerates atherosclerosis. Antioxidant nutrients, including vitamin C, carotenoids, tocopherols and selenium, may therefore be presumed likely to contribute to a decrease of endothelial dysfunction and to diminish the incidence of cardiovascular events. However, the previous use of antioxidant supplements in clinical trials has yielded disappointing and controversial results. Despite the null trial findings, the use of dietary antioxidant vitamins continues to grow in the U.S. OBJECTIVE: In this revised application, our objective is to determine the short-term efficacy of foods naturally rich in antioxidants vs. supplemental pill antioxidants on markers of inflammation and endothelial function in generally healthy subjects at risk of atherosclerosis. DESIGN: This is a randomized, single-blind (diets)/double blind (supplements), parallel, feasibility study. Ninety adults with elevated risk factors for atherosclerosis and heart disease will be randomly assigned to either: 1) continue their usual diet and receive placebo pills (n=30 Usual/Plac), 2) continue their usual diet and receive antioxidant supplement pills (n=30 Usual/Supp), or 3) increase their consumption of antioxidant rich foods closely matched to antioxidant content of the supplement pills (n=30 Antiox-Food) for eight weeks. Data will be collected at baseline, four, and eight weeks. Primary study outcomes are markers of inflammation including c-reactive protein, fibrinogen, IL-6, TNF-alpha and soluble ICAM-1. Secondary outcomes include flow mediated vasodilation of the brachial artery and urinary isoprostanes. IMPLICATIONS: This study is designed to evaluate the responsiveness of novel markers of atherosclerosis to antioxidant interventions. Tests of inflammatory markers and endothelial function may provide a rapid and reliable methodology to assess the clinical outcome of antioxidant interventions at low cost and allow for fine tuning the choice of optimal combinations, sources and doses of antioxidants for future longer term and larger scale studies.