Postprandial Lipemia and Endothelial Function In ACCORD

ACCORD 中的餐后脂血症和内皮功能

• 批准号: 6527993
• 负责人: HENRY N GINSBERG
• 金额: $ 35.84万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6527993
• 关键词: antihyperlipoproteinemic agent; atherosclerosis; blood chemistry; blood lipoprotein; cardiovascular disorder chemotherapy; cardiovascular disorder epidemiology; cardiovascular function; cell adhesion molecules; cholesterol; clinical research; coagulation factor VII; diet; dietary lipid; disease /disorder proneness /risk; fibrinogen; human subject; hyperlipidemia; nutrition related tag; oxidative stress; plasminogen activator inhibitors; simvastatin; vascular endothelium

DESCRIPTION (provided by applicant): The ACCORD trial will use two connected 2x2 designs to test the efficacy of (a) optimal glucose control (HbA1c = 6.0%) versus standard control (HbA1c + 7.5%) in 10,000 patients with type 2 diabetes mellitus, (b) more intense systolic blood pressure control (120 mm Hg) versus less intense control (140 mm Hg) in 4,200 of those patients, and (c) combined low density lipoprotein cholesterol lowering, triglyceride lowering, and high density lipoprotein cholesterol raising versus only low density lipoprotein cholesterol lowering in 5,800 of those patients. The primary outcome for the overall ACCORD trial is a combination of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. The comparison of lipid-altering therapies will be carried out in the Lipid Arm of ACCORD, in which the 5,800 subjects will all be treated with simvastatin and, in addition, be randomly assigned to receive either fenofibrate or placebo. The main ACCORD trial will measure only fasting blood samples for lipids, lipoprotein fractions, and apolipoproteins. In the proposed ancillary study, we will compare the effects of simvastatin plus fenofibrate with the effects of simvastatin alone on postprandial lipemia in 250 ACCORD patients at 4 sites in the Northeast Network. In addition, we will compare the effects of the two treatment strategies on baseline and postprandial endothelial function, and on markers of coagulation, endothelial function, and oxidative stress. The propose ancillary study will provide a unique opportunity to determine possible mechanisms whereby simvastatin plus fenofibrate therapy will be associated with reduced cardiovascular events in the overall ACCORD trail. The study is divided into three specific aims. Specific Aim A: To carry out high fat load studies of postprandial lipemia in patients who are participating in the Lipid Arm of the ACCORD trial and compare postprandial excursions of triglycerides, triglyceride-rich lipoproteins, retinyl palmitate, and remnant lipoprotein cholesterol in patients receiving fenofibrate plus simvastatin with those postprandial excursions in patients receiving only simvastatin. Specific Aim B: To determine brachial artery dilatation in response to increased blood flow post- forearm ischemia just prior to, and five hours after, ingestion of a high fat load in the two patient groups. Specific Aim C: To determine baseline levels of PAI-1, fibrinogen and factor VII, and postprandial excursions of factor VII, sVCAM-1, sICAM-1, and sE-selectin in the two patient groups. ACCORD provides a unique opportunity to compare, in detail, the effects of statin therapy alone with statin plus fibrate therapy on several emerging risk factors for atherosclerotic cardiovascular disease in a representative subgroup of the ACCORD cohort that is being followed for cardiovascular endpoints.

描述（由申请人提供）： 协议试验将使用两种连接的2x2设计来测试 （a）最佳葡萄糖控制（HBA1C = 6.0％）与标准对照（HBA1C + 在10,000例2型糖尿病患者中，有7.5％），（b）更激烈 收缩压控制（120毫米Hg）与较少强烈的控制（140 其中4,200名患者和（c）低密度脂蛋白合并 胆固醇降低，甘油三酸酯降低和高密度脂蛋白 胆固醇饲养与仅低密度脂蛋白胆固醇降低 在5,800名患者中。 整体协议试验的主要结果 是非致命性心肌梗塞，非致命性中风和 心血管死亡。 脂质改变疗法的比较将是 在协议的脂质臂中进行，其中5,800名受试者将全部 用辛伐他汀治疗，此外，被随机分配给接收 fenobibrate或安慰剂。 主协议审判只会衡量 脂质，脂蛋白部分和载脂蛋白的空腹血液样本。 在拟议的辅助研究中，我们将比较辛伐他汀的影响 再加上单独使用辛伐他汀对餐后脂肪血症的影响 在东北网络的4个地点的250名雅阁患者中。 另外，我们 将比较两种治疗策略对基线和 餐后内皮功能，以及凝结的标记，内皮的标记 功能和氧化应激。 建议的辅助研究将提供 确定辛伐他汀加的可能机制的独特机会 非诺贝特治疗将与减少的心血管事件有关 整体雅致跟踪。 该研究分为三个特定目标。 特定目的A：在 参加协议试验的脂质臂的患者 比较甘油三酸酯，甘油三酸酯富含甘油三酸酯的餐后游览 脂蛋白，视黄棕榈酸酯和残留的脂蛋白胆固醇 餐后接受非诺贝特和辛伐他汀的患者 仅接受辛伐他汀的患者中的游览。特定目标B： 确定臂动脉扩张，以响应于血流的增加 - 摄入高脂之前的前臂缺血，五个小时后五个小时 加载两个患者组。 特定目标C：确定基线水平 PAI-1，纤维蛋白原和因子VII以及因子的餐后游览 在两个患者组中，VII，SVCAM-1，SICAM-1和SE-选择蛋白。 符合 提供了一个独特的机会来详细比较他汀类药物的影响 单独使用他汀类药物加上纤维化疗法的治疗 代表性动脉粥样硬化心血管疾病的因素 心血管符合协议队列的子组 端点。