INTIMAL THICKENING & ANTIOXIDANTS IN HISPANICS & ANGLOS

内膜增厚

• 批准号: 2637997
• 负责人: JAMES H DWYER
• 金额: $ 64.41万
• 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 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2637997
• 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 一个新的发现从胆固醇降低动脉粥样硬化 一项临床试验研究（CLAS）表明，颈总动脉内膜- 中膜厚度（IMT）对LDL-C的反应更快，更明显 降低治疗比血管造影冠状动脉狭窄或颈动脉 粗糙. 来自灵长类动物模型的新数据也显示了超声检测 高胆固醇饮食引起的内膜增厚 12个月 这些结果表明颈动脉IMT是一个可靠的， 动脉粥样硬化程度的快速反应标志物。 然而，不到三分之一的观察到的治疗效果对颈动脉 CLAS中发现的IMT可通过LDL-C和HDL-C的变化来解释，提示 相关（或其他）因素与动脉粥样硬化的发生更直接相关， 机制等 此外，芬兰的一项流行病学研究发现，LDL-C是 仅在人群中预测颈动脉IMT（IMT）进展率 血清中铜的含量很高 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/延迟， 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特定的 假设增长率之间的正相关 颈动脉IMT和LDL-C（β-δ IMT/LDL）在患有以下疾病的人中更大[1] 较高水平的血清促氧化剂（相对于较低水平的人） 血清促氧化剂水平），[2]血清抗氧化剂水平较低， [3]低水平的饮食抗氧化剂;和[4]回归 30例患者将检测到与戒烟相关的颈动脉IMT 个月 可行性。 该研究的可行性源于[1]最近 超声颈动脉IMT自动界面检测的开发 可将再现性误差降低70-90%; [2] 饮食测量错误;[3]受试者来自 稳定，合作，良好的描述，和多民族的人口， 来自南加州爱迪生的员工。 设计 假设将通过纵向观察进行检验， 西班牙裔和非西班牙裔白色女性和男性的颈动脉IMT。 的 包括西班牙裔和妇女的动机是他们在 研究人群（18%的西班牙裔，40%的女性），并根据最近的报告， 西班牙裔美国人住院心肌梗死的发病率升高。 来自4个种族性别群体的73人，年龄在40-60岁之间（n-292）， 83名吸烟者和近期戒烟者（n-166）将从 在一项正在进行的研究中。 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个月时颈动脉IMT的变化。