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：（根据调查员的摘要改编），尽管 识别可修改的发展和发展风险因素 动脉粥样硬化，冠状动脉疾病（CHD）仍然是最单一的 美国重要的慢性病（美国）。 早期干预 动脉粥样硬化疾病可能需要完成民族 降低冠心病死亡率的目标。 来自动物和的大量数据 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。 补充维生素E已显示与 无症状男性和女性中冠心病风险的降低。 最近的序列 定量冠状动脉造影（QCA）和B模式 超声学普通颈动脉（CCA）内膜培养基厚度（IMT） 降低动脉粥样硬化研究（CLAS）的胆固醇测量 受监测的动脉粥样硬化回归研究（MARS）证明 补充维生素E摄入量减少了 在两年期间，动脉粥样硬化增加了50％至80％。 维生素E。 补充提供了一种有前途的主要预防方法 CHD由于天然，安全，高度可容忍且价格便宜。 因此， 提供直接证据的公共卫生影响 补充维生素E在减少动脉粥样硬化进展的过程中将 对基于人群的介入策略具有巨大影响 用于主要预防冠心病。 使用CHD的初级预防试验 事件成果通常需要5到10万个人 在5到10年中检测治疗差异。 连续选修课 冠状动脉造影在原发性预防中不能在道德上进行 试验是由于无症状并发症的不可接受风险 个人。 但是，自动计算机边缘检测图像 CCA远墙IMT的B模式超声图像的分析减少 超声测量误差，使其可行 侵入性测试补充维生素E早期的功效 动脉粥样硬化的进展大幅降低了样本量（200 受试者）和研究持续时间（2年）需要进行主要 预防干预试验对没有CHD的个人没有风险。 因此，研究人员提出了一个单中心2年，随机分组 安慰剂对照，双盲，非侵入性动脉成像主要 健康男性和女性补充维生素E的预防试验 35至75岁，LDL-C水平在100 mg/dl至200 mg/dl之间。 治疗臂将是DL-A-生育酚400 IU/DAY与安慰剂；两个都 手臂将获得低脂胆固醇饮食（NCEP第一步）。 基本的 试验结果度量将是远端CCA远处墙IMT的变化率 在计算机图像处理的B模式超声图中。 调查人员 指出这种非侵入性血管终点测量已显示出治疗 受益于他们的两个冠状动脉血管造影/颈动脉 超声学临床轨迹，与颈动脉和冠状动脉相关 通过血管造影确定的动脉动脉粥样硬化。

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