VITAMIN E ATHEROSCLEROSIS PREVENTION STUDY

维生素 E 预防动脉粥样硬化研究

• 批准号: 2899784
• 负责人: Howard Neil Hodis
• 金额: $ 65.12万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2899784
• 关键词: angiocardioultrasonography; antihypercholesterolemic agent; atherosclerosis; body physical activity; cardiovascular disorder prevention; clinical research; clinical trial phase I; diet therapy; dietary supplements; disease /disorder proneness /risk; human middle age (35-64); human old age (65+); human subject; human therapy evaluation; image processing; longitudinal human study; low density lipoprotein; noninvasive diagnosis; nutrition related tag; pathologic process; statistics /biometry; tocopherols; vitamin therapy; young adult human (21-34)

DESCRIPTION: (Adapted from Investigator's Abstract) Despite identification of modifiable risk factors for development and progression of atherosclerosis, coronary heart disease (CHD) remains the single most important chronic disease in the United States (US). Early intervention of atherosclerotic disease may be necessary to accomplish the national goal of reducing CHD mortality. A large body of data from animal and epidemiological studies provide convincing evidence that antioxidant vitamins can reduce formation and progression of atherosclerosis. Vitamin E supplementation has shown the most consistent association with reduction in CHD risk in asymptomatic men and women. Recent serial quantitative coronary angiographic (QCA) as well as B-mode ultrasonographic common carotid artery (CCA) intima media thickness (IMT) measurements from the Cholesterol Lowering Atherosclerosis Study (CLAS) and the Monitored Atherosclerosis Regression Study (MARS) demonstrate that supplementary vitamin E intake reduces progression of atherosclerosis by 50% to 80% over a 2 year period. Vitamin E supplementation provides a promising approach for primary prevention of CHD since it is natural, safe, highly tolerable, and inexpensive. Thus, the public health impact of providing direct evidence of the efficacy of vitamin E supplementation in reducing progression of atherosclerosis will have immense implications for population based interventional strategies for primary prevention of CHD. Primary prevention trials which use CHD event outcomes typically require 5 to 10 thousand individuals followed for 5 to 10 years to detect treatment differences. Serial elective coronary angiography cannot be ethically performed in primary prevention trials because of unacceptable risk of complications to asymptomatic individuals. However, automated computerized edge detection image analysis of B-mode ultrasound images of CCA far wall IMT reduces ultrasonographic measurement error and makes it feasible to non- invasively test the efficacy of vitamin E supplementation on early atherosclerosis progression in a substantially reduced sample size (200 subjects) and study duration (2 years) required to conduct a primary prevention intervention trial at no risk to individuals free of CHD. Therefore, the investigators propose a SINGLE-CENTER, 2-year, randomized, placebo-controlled, double-blind, non-invasive arterial imaging primary prevention trial with vitamin E supplementation in healthy men and women 35 to 75 years old with LDL-C levels between 100 mg/dL and 200 mg/dL. Treatment arms will be DL-a-tocopherol 400 IU/day versus placebo; both arms will receive a low fat-low cholesterol diet (NCEP Step I). Primary trial outcome measure will be rate of change of distal CCA far wall IMT in computer image processed B-mode ultrasonograms. The investigators state that this non-invasive vascular end point measure has shown therapy benefit in their two previous coronary angiographic/carotid ultrasonographic clinical trails and correlates with carotid and coronary artery atherosclerosis as determined by angiography.

描述：（改编自研究者的摘要）尽管 识别发育和进展的可改变风险因素 动脉粥样硬化中，冠心病（CHD）仍然是最严重的疾病 美国 (US) 的重要慢性疾病。 早期干预 动脉粥样硬化疾病可能是实现国家目标所必需的 降低冠心病死亡率的目标。 来自动物和动物的大量数据 流行病学研究提供了令人信服的证据表明抗氧化剂 维生素可以减少动脉粥样硬化的形成和进展。 维生素 E 补充剂显示出与以下因素最一致的关联： 降低无症状男性和女性的冠心病风险。 最近连载 定量冠状动脉造影 (QCA) 以及 B 模式 超声检查颈总动脉 (CCA) 内膜中层厚度 (IMT) 降低胆固醇动脉粥样硬化研究 (CLAS) 的测量结果 动脉粥样硬化回归监测研究 (MARS) 表明 补充维生素 E 的摄入可以减缓疾病的进展 2年内动脉粥样硬化减少50%至80%。 维生素E 补充剂为一级预防提供了一种有前景的方法 CHD 是因为它天然、安全、耐受性高且廉价。 因此， 提供功效的直接证据对公共卫生的影响 补充维生素 E 可以减缓动脉粥样硬化的进展 对基于人群的干预策略具有巨大影响 用于冠心病的一级预防。 使用 CHD 的一级预防试验 事件结果通常需要 5 到 1 万名个人跟踪 5到10年以检测治疗差异。 系列选修课 在一级预防中进行冠状动脉造影不符合伦理 由于无症状患者出现并发症的风险不可接受而进行试验 个人。 然而，自动计算机边缘检测图像 CCA 远壁 IMT 的 B 型超声图像分析减少 超声测量误差，使得非 侵入性测试维生素 E 补充剂对早期患者的功效 动脉粥样硬化进展的样本量大幅减少（200 进行初级课程所需的科目）和学习期限（2年） 预防干预试验对无冠心病的个体没有风险。 因此，研究人员提出了一项单中心、为期 2 年、随机、 安慰剂对照、双盲、非侵入性动脉成像 在健康男性和女性中补充维生素 E 的预防试验 35 至 75 岁，LDL-C 水平在 100 mg/dL 至 200 mg/dL 之间。 治疗组为 DL-a-生育酚 400 IU/天，对比安慰剂；两个都 手臂将接受低脂肪、低胆固醇饮食（NCEP 步骤 I）。 基本的 试验结果衡量标准为远端 CCA 远壁 IMT 的变化率 在计算机图像处理的 B 型超声图中。 调查人员 声明这种非侵入性血管终点测量已显示出治疗效果 之前两次冠状动脉造影/颈动脉检查的获益 超声临床试验以及与颈动脉和冠状动脉的相关性 通过血管造影确定动脉粥样硬化。

项目成果

Platelet FcgammaRIIA receptor surface expression is increased in patients with ESRD and is associated with atherosclerotic cardiovascular events.

ESRD 患者中血小板 FcgammaRIIA 受体表面表达增加，并且与动脉粥样硬化性心血管事件相关。

• DOI: 10.1053/j.ajkd.2006.09.022
• 发表时间: 2007
• 期刊: American journal of kidney diseases : the official journal of the National Kidney Foundation
• 作者: El-Shahawy,Mohamed;Noureddin,Mazen;Abdullah,Hesham;Mack,WendyJ;Calverley,DavidC
• 通讯作者: Calverley,DavidC