Dietary Antioxidents and Markers of Atherosclerosis

背景：许多观察和实验研究表明，动脉粥样硬化的已知危险因素促进血管中的炎症性氧化环境，有利于内皮细胞的病理改变。目前有大量证据表明，内皮功能障碍既先于动脉粥样硬化，也加速了动脉粥样硬化。因此，抗氧化营养素，包括维生素C、类胡萝卜素、生育酚和硒，可能有助于减少内皮功能障碍和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。尽管有无效试验结果，膳食抗氧化维生素在美国的使用仍在继续增长。目的：在这项修订后的申请中，我们的目标是确定天然富含抗氧化剂的食物与补充抗氧化剂的药丸对动脉粥样硬化风险的一般健康受试者的炎症和内皮功能标志物的短期疗效。设计：这是一项随机、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：1)继续他们平常的饮食并服用安慰剂（n=30 usual / place）， 2)继续他们平常的饮食并服用抗氧化补充剂（n=30 usual /Supp），或者3)增加他们摄入的富含抗氧化的食物与补充剂中的抗氧化含量密切相关（n=30 Antiox-Food），持续8周。将在基线、4周和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。次要结果包括血流介导的肱动脉血管舒张和尿异前列腺素。意义：本研究旨在评估新型动脉粥样硬化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，并允许微调选择最佳的抗氧化剂组合、来源和剂量，以用于未来更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.