INTIMAL THICKENING & ANTIOXIDANTS IN HISPANICS & ANGLOS

内膜增厚

• 批准号: 2225950
• 负责人: JAMES H DWYER
• 金额: $ 58.61万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-01-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2225950
• 关键词: Hispanic Americans; antihypercholesterolemic agent; antioxidants; artery occlusion; atherosclerosis; biomarker; cardiovascular disorder epidemiology; carotid artery; caucasian American; cholesterol; coronary disorder; dietary constituent; disease /disorder proneness /risk; female; gender difference; human subject; longitudinal human study; male; nutrition related tag; oxidizing agents; racial /ethnic difference; remission /regression; smoking cessation

BACKGROUND. A new finding from the Cholesterol Lowering Atherosclerosis Study (CLAS), a clinical trial, indicates that common carotid intima- media thickness (IMT) responds more rapidly and more markedly to LDL-C lowering treatment than angiographic coronary stenosis or carotid roughness. New data from a primate model also show ultrasound detection of intimal thickening in response to a hypercholesterolemic diet within 12 months. These findings suggest that carotid IMT is a reliable and rapidly responding marker of extent of atherosclerosis. However, less than a third of the observed therapeutic benefit on carotid IMT found in CLAS was explained by change in LDL-C and HDL-C, suggesting that related (or other) factors are more directly linked to atherogenic mechanisms. In addition, a Finnish epidemiologic study found that LDL-C was predicative of rate of progression in carotid IMT (IMT) only in persons with high serum levels of (pro-oxidant) copper. HYPOTHESES. These and other data support a model of atherosclerosis in which intracellular accumulation of modified LDL is promoted/retarded by serum pro-oxidants/antioxidants. The proposed epidemiologic study is thus designed to test the specific hypotheses that the positive association between rate of increase in carotid IMT and LDL-C (beta deltaIMT/LDL) is greater in persons with [1] higher levels of serum pro-oxidants (relative to persons with lower levels of serum pro-oxidants), [2] lower levels of serum antioxidants, [3] lower levels of dietary antioxidants; and [4] that regression of carotid IMT associated with smoking cessation will be detected in 30 months. FEASIBILITY. The feasibility of the study stems from [1] recent development of automated interface detection for ultrasound carotid IMT that reduces reproducibility error by 70-90%; [2] models to adjust for error in dietary measures; and [3] availability of subjects from a stable, cooperative, well described, and multi-ethnic population of employees from Southern California Edison. DESIGN. Hypothesis will be tested with longitudinal observation of carotid IMT in Hispanic and non-Hispanic white women and men. The inclusion of Hispanics and women is motivated by their prevalence in the study population (18% Hispanic, 40% women), and by the recent report that incidence of hospitalized myocardial infarction is elevated in Hispanics. 73 persons from each of 4 ethnicity-sex groups aged 40-60 years (n-292), and 83 smokers and recent quitters (n-166) will be recruited from employees in an ongoing study. Baseline blood, diet and potential confounder variables will be related to 18 and 36 month (6, 12, 18, 24 and 30 month in smoker(s) changes in carotid IMT.

背景。 降低胆固醇动脉粥样硬化的新发现 研究（CLAS）是一项临床试验，表明颈总动脉内膜 中层厚度 (IMT) 对 LDL-C 的反应更快、更显着 治疗费用低于冠状动脉狭窄或颈动脉血管造影 粗糙度。 来自灵长类动物模型的新数据也显示了超声波检测 高胆固醇血症饮食引起的内膜增厚 12个月。 这些发现表明颈动脉 IMT 是一种可靠且可靠的方法。 动脉粥样硬化程度的快速反应标志物。 然而，所观察到的颈动脉治疗益处还不到三分之一 CLAS 中发现的 IMT 可以通过 LDL-C 和 HDL-C 的变化来解释，表明 相关（或其他）因素与动脉粥样硬化更直接相关 机制。 此外，芬兰的一项流行病学研究发现，LDL-C 仅预测个人颈动脉 IMT (IMT) 的进展率 血清中铜（促氧化）水平较高。 假设。 这些和其他数据支持动脉粥样硬化模型 修饰的 LDL 的细胞内积累被促进/延缓 血清促氧化剂/抗氧化剂。 因此，拟议的流行病学研究旨在测试具体的 假设增长率之间存在正相关关系 患有以下疾病的人颈动脉 IMT 和 LDL-C (beta deltaIMT/LDL) 较高 [1] 血清促氧化剂水平较高（相对于健康水平较低的人而言） 血清促氧化剂水平），[2] 血清抗氧化剂水平较低， [3]膳食抗氧化剂水平较低；和 [4] 的回归 与戒烟相关的颈动脉 IMT 将在 30 年内检测到 几个月。 可行性。 该研究的可行性源于[1]最近 超声颈动脉 IMT 自动接口检测的开发 再现性误差减少 70-90%； [2] 调整的模型 饮食措施错误； [3] 科目的可用性 稳定、合作、描述清楚、多种族的人口 南加州爱迪生公司的员工。 设计。 假设将通过纵向观察来检验 西班牙裔和非西班牙裔白人女性和男性的颈动脉 IMT。 这 西班牙裔和女性的包容性是因为她们在社会中的普遍存在 研究人群（18% 西班牙裔，40% 女性），最近的报告显示 西班牙裔住院心肌梗塞的发生率较高。 来自 4 个种族-性别群体各 73 名年龄在 40-60 岁之间的人 (n-292)， 83 名吸烟者和最近戒烟者 (n-166) 将从 员工正在进行一项持续的研究。 基线血液、饮食和潜力 混杂变量将与 18 和 36 个月（6、12、18、24 吸烟者 30 个月颈动脉 IMT 变化。