ANTIOXIDANTS AND PREVENTION OF EARLY ATHEROSCLEROSIS

抗氧化剂和预防早期动脉粥样硬化

• 批准号: 2430737
• 负责人: JAMES H DWYER
• 金额: $ 22.96万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-06-01 至 1999-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2430737
• 关键词: African American; angiocardioultrasonography; antioxidants; atherosclerosis; cardiovascular disorder prevention; carotid artery; dietary supplements; human middle age (35-64); human subject; longitudinal human study; nutrition related tag; pathologic process; questionnaires; statistics /biometry; tocopherols; vitamin therapy; young adult human (21-34)

BACKGROUND. There is evidence from epidemiologic studies, and one unpublished trial, that greater intake of antioxidant vitamins (AV) is associated with reduced risk of CHD and stroke. Findings from an animal model indicate that increased intake of AV prevents progression of aortic fatty streaks induced by an atherogenic diet but not advanced injury- induced lesions. These observations suggest the hypothesis that increased AV intake may prevent further progression of early atherosclerosis, possible via reduced susceptibility of LDL to oxidative modification and consequent cytotoxic, chemotactic, chemostatic and unregulated uptake effects. A new automated method for determining intima-media thickness (IMT) of the common carotid artery (CCA) makes it feasible to test the primary prevention impact of AV on early atherosclerosis. Results of two trials at our institute demonstrate the LDL lowering effects on CCA IMT can be detected rapidly (within 12 to 24 months) in small samples (less than 30 per group) with automated IMT. Retardation of IMT progression was achieved in both studies without significant changes in average vessel diameter -- suggesting effects on early lesions. Furthermore, a Finish study found an inverse association between 12 month change in plasma alpha-tocopherol levels and change in carotid IMT. These findings imply that if there is an effect of alpha-tocopherol supplement on early atherosclerosis then it may be detectible with automated IMT in a small study within 12 to 24 months. HYPOTHESIS. Epidemiologic studies indicate cardiac protection after two years of vitamin E supplementation. It is thus hypothesized that, relative to placebo, vitamin E supplements (800 USP units/day) can retard the progression rate of CCA IMT over a period of 24 months. The hypothesis will be tested among African Americans since, relative to whites, cardiovascular mortality is sharply elevated in blacks under age 65, and they have been found to have increased CCA IMT in cross-sectional surveys. FEASIBILITY. The feasibility of the study stems from [1] recent development of an automated ultrasound IMT measure that reduces reproducibility error and required sample size; [2] portability and low- cost of the ultrasound system so that imaging can be conducted in a mobile van; [3] safety of both vitamin E supplementation at 573 mg/day and ultrasound exposure; [4] availability of subjects from a demonstrably cooperative community/school district that is participating in ongoing studies; and [15] increased compliance relative to longer term studies among persons at risk for cardiac events. DESIGN. Volunteering female and male African Americans aged 35-59 will be screened for carotid IMT at a school or at home (Screen 1). After 12 months, those subjects above the age and sex adjusted 66th percentile at Screen I will be rescreened (Screen II); those showing the greatest progression will be invited to participate in a run-in. Those subjects found to be cooperative and compliant (by plasma alpha-tocopherol level) will be randomized to vitamin E (573 mg/day) and placebo conditions. CCA IMT will be observed at 12 and 24 months follow ups. The primary outcome will be 24 month rate of change in average CCA IMT.

背景资料。有来自流行病学研究的证据，还有一项 未发表的试验表明，更多的抗氧化剂维生素(AV)的摄入量 与降低冠心病和中风的风险有关。一只动物的发现 模型表明，增加AV摄入量可防止主动脉病变进展 脂肪条纹是由致动脉粥样硬化的饮食引起的，但不是晚期损伤- 诱导性损伤。这些观察表明，假设增加了 摄取AV可能会阻止早期动脉粥样硬化的进一步发展， 可能通过降低低密度脂蛋白对氧化修饰的敏感性和 随之而来的细胞毒性、趋化性、趋化性和无调节摄取 效果。 颈动脉内膜-中层厚度(IMT)自动测定的新方法 颈总动脉(CCA)使检测原发性 血管紧张素转换酶对早期动脉粥样硬化的预防作用两项试验的结果位于 我们的研究所证明了降低CCA IMT的低密度脂蛋白的作用可以是 在小样本(少于30个月)中快速检测(12至24个月内) 每组)，具有自动IMT。IMT进展缓慢 在这两项研究中，平均血管直径没有显著变化-- 提示对早期损伤的影响。此外，一项完成的研究发现， 血浆α-生育酚12个月变化之间的负相关性 颈动脉IMT水平及变化。这些发现意味着，如果有一个 补充α-生育酚对早期动脉粥样硬化的影响 在12至24个月的小型研究中，可以通过自动IMT检测到。 假设。流行病学研究表明对心脏有保护作用 多年的维生素E补充剂。因此，可以假设，相对的 对于安慰剂，维生素E补充剂(800 USP/天)可以延缓 24个月内颈总动脉IMT进展率。假说 将在非裔美国人中进行测试，因为相对于白人， 65岁以下黑人的心血管死亡率急剧上升， 在横断面调查中，他们被发现增加了CCA的IMT。 可行性。这项研究的可行性源于[1]最近 一种自动超声IMT测量方法的研制 再现性误差和所需样本量；[2]便携性和低成本。 超声系统的成本，以便可以在移动设备中进行成像 每日补充维生素E 573毫克和补充维生素E的安全性 超声波暴露；[4]受试者是否可从明显的 参与正在进行的合作社区/学区 研究；和[15]与长期研究相比，依从性增加 在有心脏事件风险的人群中。 设计。35-59岁的女性和男性非洲裔美国人将成为志愿者 在学校或家里筛查颈动脉IMT(屏幕1)。12点以后 月，年龄和性别以上的受试者调整为第66个百分位数 屏幕I将被重新放映(屏幕II)；那些显示最伟大的 进步将被邀请参加磨合。那些科目 被发现是合作和顺从的(通过血浆α-生育酚水平) 将随机分为维生素E(每天573毫克)和安慰剂两组。共同国家评估 术后12个月和24个月观察IMT情况。主要结果是 将以24个月的平均颈总动脉IMT变化率。