ANTIOXIDANTS AND PREVENTION OF EARLY ATHEROSCLEROSIS

背景。 有流行病学研究的证据，其中之一 未发表的试验表明，摄入更多的抗氧化维生素 (AV) 与降低冠心病和中风的风险有关。 来自动物的发现 模型表明增加 AV 的摄入量可以预防主动脉的进展 由致动脉粥样硬化饮食引起的脂肪条纹，但不是晚期损伤- 诱发病变。 这些观察结果表明增加的假设 AV 摄入可以预防早期动脉粥样硬化的进一步进展， 可能是通过降低 LDL 对氧化修饰的敏感性来实现的 随之而来的细胞毒性、趋化性、化学抑制性和不受调节的摄取 影响。 一种新的自动测定内膜中层厚度（IMT）的方法 颈总动脉 (CCA) 使得测试初级动脉成为可能 AV 对早期动脉粥样硬化的预防影响。 两项试验的结果 我们的研究所证明 LDL 对 CCA IMT 的降低作用可以是 在小样本（少于 30 个）中快速检测（12 至 24 个月内） 每组）与自动化 IMT。 实现了 IMT 进展的延缓 在这两项研究中，平均血管直径没有显着变化—— 提示对早期病变的影响。 此外，Finish 的一项研究发现 血浆 α-生育酚 12 个月变化之间呈负相关 颈动脉 IMT 水平和变化。 这些发现意味着，如果存在 α-生育酚补充剂对早期动脉粥样硬化的影响可能 在一项小型研究中，可在 12 至 24 个月内通过自动化 IMT 进行检测。 假设。 流行病学研究表明，两次治疗后对心脏有保护作用 多年补充维生素E。 因此可以假设，相对 与安慰剂相比，维生素 E 补充剂（800 USP 单位/天）可以延缓 24 个月内 CCA IMT 的进展率。 假设 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升高，并且 在横断面调查中发现他们的 CCA IMT 有所增加。 可行性。 该研究的可行性源于[1]最近 开发自动超声 IMT 测量，可减少 再现性误差和所需的样本量； [2] 便携性和低功耗 超声系统的成本，以便可以在移动设备中进行成像 货车； [3] 每天补充 573 毫克维生素 E 的安全性 超声波照射； [4] 主题的可用性明显 正在参与正在进行的合作社区/学区 研究； [15] 相对于长期研究，依从性提高 有心脏事件风险的人群。 设计。 年龄在 35 岁至 59 岁之间的非裔美国人女性和男性志愿者将 在学校或家里进行颈动脉 IMT 筛查（屏幕 1）。 12点之后 月，那些高于年龄和性别的受试者调整了第 66 个百分位 将重新筛选筛选 I（筛选 II）；那些表现出最伟大的 进展将被邀请参加磨合。 那些科目 被发现具有合作性和顺从性（根据血浆 α-生育酚水平） 将被随机分配至维生素 E（573 毫克/天）和安慰剂条件组。 CCA IMT 将在 12 个月和 24 个月的随访中进行观察。 主要结果 将是平均 CCA IMT 的 24 个月变化率。

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 There is evidence from epidemiologic studies, and one unpublished trial, that greater intake of antioxidant vitamins (AV) is associated with reduced risk of CHD and stroke.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.