Inflammation, Procoagulation, and Plaque Vulnerability

炎症、促凝血和斑块脆弱性

• 批准号: 6640484
• 负责人: BURTON E SOBEL
• 金额: $ 30.3万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6640484
• 关键词: acute phase protein; atherosclerosis; blood chemistry; blood coagulation; cardiovascular disorder risk; clinical research; coronary disorder; diabetes mellitus therapy; diabetic angiopathy; fibrinogen; human subject; inflammation; insulin sensitivity /resistance; noninsulin dependent diabetes mellitus; patient oriented research

DESCRIPTION (provided by applicant): Type 2 diabetes is associated with enormous morbidity and mortality attributable to heart disease caused by atherosclerosis in coronary arteries that supply blood to the heart muscle itself. Two processes associated with diabetes, inflammation and heightened coagulability of blood, have been implicated in accelerating the coronary disease. The NIH-sponsored BARI 2D trial, which involves more than 40 clinical sites studying 2800 patients with both type 2 diabetes and coronary artery disease being followed for 5 years, is comparing two types of therapy for diabetes one that results in increased concentrations of insulin in blood and the other in reduction of resistance to insulin in tissues. This project is designed to characterize effects of each of the two types of therapy on inflammation and procoagulation and to determine whether amelioration of either or both leads to retardation of progression of coronary disease and its sequelae. Markers of both inflammation and procoagulation (C-reactive protein, fibrinogen, D-dimer, and fibrinopeptide A) will be assayed in serially obtained blood samples. Results will be analyzed with respect to all the end points in BARI 2D including morbidity and mortality attributable to coronary artery disease. The BARI 2D trial, sponsored by the National Institutes of Health, was initiated to address two questions: 1) is invasive compared with noninvasive management advantageous or disadvantageous compared with aggressive medical management alone in patients with type 2 diabetes and overt coronary artery disease; and 2) does the mode of achieving metabolic control (insulin sensitizing compared with insulin providing regimens) influence morbidity, mortality, and the progression of coronary disease in patients with type 2 diabetes and overt coronary artery disease? The Principal Investigator (PI) of this proposal is the PI of the BARI 2D Fibrinolytic System Core Laboratory funded by the NIH through an R01 grant. We propose to study all 2800 patients in the BARI 2D trial to determine the extent to which inflammation, procoagulation, neither, or both are modified by each of the therapeutic approaches to be implemented in BARI 2D. In addition, we seek to determine whether attenuation of either or both results from treatment with an insulin sensitizing regimen and, if so, whether attenuation presages improved clinical outcomes and, therefore, implicates inflammation, procoagulation or both as a determinant of progression of coronary artery disease in type 2 diabetes.

描述（由申请人提供）： 2型糖尿病与巨大的发病率和巨大的发病率和死亡率有关，归因于冠状动脉动脉动脉粥样硬化引起的心脏病，这些动脉为心脏肌肉本身供应血液。与糖尿病有关的两个过程，炎症和血液凝结性的增强与加速冠状动脉疾病有关。 NIH赞助的BARI 2D试验涉及40多个临床部位，研究了2800例2型糖尿病和冠状动脉疾病的患者5年，正在比较两种类型的糖尿病治疗方法，一种治疗一种导致血液中胰岛素浓度的增加，另一种是对组织中胰岛素的抗性减少。该项目旨在表征两种治疗中每种治疗对炎症和突发性的影响，并确定对冠状动脉疾病及其后遗症进展的缓解是否会减轻。将在串行获得的血液样本中测定炎症和突发性的标记（C反应蛋白，纤维蛋白原，D-二二聚体和纤维蛋白肽A）。将根据BARI 2D的所有终点进行分析，包括归因于冠状动脉疾病的发病率和死亡率。由美国国立卫生研究院赞助的BARI 2D试验被启动以解决两个问题：1）与单独的2型糖尿病患者和明显的冠状动脉疾病的患者相比，与非侵入性管理有利或不利的医疗管理相比，与非侵入性管理有利或不利之处相比具有侵入性； 2）在2型糖尿病和明显的冠状动脉疾病的患者中，实现代谢控制的模式（与提供方案的胰岛素相比，胰岛素敏化与提供方案的敏感性）会影响发病率，死亡率和冠状动脉疾病进展吗？该提案的主要研究员（PI）是由NIH通过R01赠款资助的Bari 2d纤维蛋白水解系统的PI。我们建议在BARI 2D试验中研究所有2800名患者，以确定炎症，突发性，或两者均未通过在Bari 2d中实施的每种治疗方法来修饰的程度。此外，我们试图确定胰岛素敏化方案的治疗导致的衰减是否会导致衰减，如果是这样，衰减是否会改善临床结局的改善，因此涉及炎症，促进，促进，还是作为2型糖尿病中冠状动脉疾病进展的决定性。