Imaging of Aortic Atherosclerosis and Inflammation in the Metabolic Syndrome

代谢综合征中主动脉粥样硬化和炎症的影像学

• 批准号: 7921681
• 负责人: WARREN J MANNING
• 金额: $ 82.3万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-29 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7921681
• 关键词: 21 year old; 3-nitrotyrosine; Acute-Phase Proteins; Adipocytes; Aerobic Exercise; Affect; Age; American; Anti-Inflammatory Agents; Anti-inflammatory; Aorta; Apolipoprotein A-I; Apolipoproteins B; Area; Arterial Fatty Streak; Arteries; Atherosclerosis; Autopsy; Behavior Therapy; Biochemical; Biochemical Markers; Blood Circulation; Blood Vessels; C-Peptide; C-reactive protein; Calcified; Calcium; Cardiovascular Diseases; Cardiovascular system; Cell Adhesion Molecules; Characteristics; Chest; Cholesterol; Clinical; Coronary; Coronary Angiography; Coronary Arteriosclerosis; Coronary Circulation; Coronary artery; Coronary heart disease; Data; Development; Diabetes Mellitus; Diet; Disease Progression; Dose; Dyslipidemias; Environment; Essential Fatty Acids; Evaluation; Family history of; Fasting; Fatty Acids; Fibrinogen; Fibrosis; Funding; Gadolinium DTPA; Gelatinase B; Gender; Glucose; Goals; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Histologic; Homeostasis; Homocysteine; Homocystine; Hyperinsulinism; Hypertension; Image; Imaging Techniques; Inflammation; Inflammation Process; Inflammatory; Insulin; Insulin Resistance; Intercellular adhesion molecule 1; Interleukin-6; Interleukins; Israel; Knowledge; LDL Cholesterol Lipoproteins; Life Style; Lipids; Lipoprotein (a); Lipoproteins; Liver; Low-Density Lipoproteins; Magnetic Resonance; Magnetic Resonance Imaging; Margarine; Matrix Metalloproteinases; Measures; Medial; Medical center; Metabolic; Metabolic syndrome; Methods; Modeling; Monitor; Morbidity - disease rate; NF-kappa B; National Heart, Lung, and Blood Institute; Nonesterified Fatty Acids; Nonionizing Radiation; Obesity; Oxidative Stress; Parents; Participant; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Phospholipase A2; Phytosterols; Placebos; Plasma; Plasminogen Activator Inhibitor 1; Plasminogen Inactivators; Population; Prevalence; Principal Investigator; Process; Protein C; Radiology Specialty; Randomized; Randomized Clinical Trials; Recruitment Activity; Research; Research Project Grants; Research Subjects; Risk Factors; Risk Reduction; Route; Salicylic Acids; Serum amyloid A protein; Smoke; Smoking; Specialized Center; Stress; Supplementation; TNF gene; Testing; Therapeutic; Thick; Trans Fats; Trans Fatty Acids; Tumor Necrosis Factor-alpha; Ultrasonography; United States; Vascular Cell Adhesion Molecule-1; Vascular remodeling; Woman; X-Ray Computed Tomography; abdominal aorta; adiponectin; adverse outcome; arm; cost; cytokine; dimer; follow-up; heart disease risk; hypertensive heart disease; impaired glucose tolerance; indexing; inflammatory marker; injury and repair; insulin sensitivity; lifestyle intervention; lipoprotein-associated phospholipase A(2); macrophage; male; men; mortality; neovascularization; non-smoker; novel; premature; programs; research study; response; salicylsalicylic acid; saturated fat; treatment as usual

Despite advances in both identification and risk reduction, atherosclerotic cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the United States. Atherosclerosis primarily affects large and medium sized vessels with autopsy data demonstrating that the abdominal aorta offers a valuable early window for the study of atherosclerosis. Coronary heart disease (CHD) risk factors include age, male gender, family history of premature CHD, hypertension, smoking, diabetes, elevated LDL-C, and low HDL-C. The Metabolic Syndrome [obesity, insulin resistance, hypertension, impaired glucose tolerance, hyperinsulinemia, and dyslipidemia), highly prevalent in the United States and implicated in CHD and inflammation, is increasingly accepted as a major contributor to the pathogenesis both of atherosclerosis and of insulin resistance. Non-invasive vascular imaging techniques, including cardiovascular magnetic resonance (CMR) and multidetector computed tomography (MDCT) offer the opportunity to identify, quantify, and characterize atherosclerosis. CMR and MDCT are complementary in providing information about plaque volume and characterization, with increased sensitivity of CMR for providing information regarding plaque components, including inflammation in a non-ionizing radiation environment and in the absence of iodinated contrast. Contrast-enhanced CMR (CE-CMR) is a new CMR application that has been shown to be useful for the evaluation of aortic plaque for fibrosis and for identification of focal inflammation in the fibrous cap. A Specialized Center of Clinically Oriented Research (SCCOR) program in Vascular Injury, Repair, and Remodeling with the central theme "Metabolic Syndrome, Inflammation and Vascular Remodeling" was recently funded by the NHLBI at our insitution. This parent SCCOR will randomize 720 subjects with CHD and Metabolic Syndrome to 30 months of 1) usual care 2) novel anti-inflammatory salsalates or 3) intensive lifestyle modification with monitoring inflammatory markers and baseline/30 month coronary MDCT to monitor atherosclerosis. This parent SCCOR offers the timely and cost-effective opportunity to expand our knowledge regarding the atherosclerotic process including the impact of these novel therapies on focal plaque inflammation by applying advanced CMR methods to characterize aortic atherosclerosis and inflammation in the Metabolic Syndrome, its relationship to biochemical inflammatory markers, and the response of the plaque and plaque components (including inflammation) to usual and novel treatment. We will also have the opportunity to compare these findings with coronary MDCT measures of soft and calcified plaque. We propose to recruit a subset of 420 subjects (n=140 in each treatment group) of the 720 parent SCCOR subjects with Metabolic Syndrome. The primary and secondary aims include relating quantitative CMR measures of aortic plaque volume, plaque components, vessel wall area, vessel inflammation with MDCT plaque measures and systemic biochemical measures of systemic inflammation and to characterize the response of these CMR measures to 30 months of conventional and novel antiinflammatory therapies with correlation with changes in systemic biochemical measures of inflammation. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page Principal Investigator/Program Director (Last, First, Middle): Manning, Warren J. Despite advances in both identification and risk reduction, atherosclerotic cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the United States. Atherosclerosis primarily affects large and medium sized vessels with autopsy data demonstrating that the abdominal aorta offers a valuable early window for the study of atherosclerosis. Non-invasive vascular imaging techniques, including cardiovascular magnetic resonance (CMR) and multidetector computed tomography (MDCT) offer the opportunity to identify, quantify, and characterize atherosclerosis. A Specialized Center of Clinically Oriented Research (SCCOR) program in Vascular Injury, Repair, and Remodeling with the central theme "Metabolic Syndrome, Inflammation and Vascular Remodeling" was recently funded by the NHLBI at our insitution. This parent SCCOR will randomize 720 subjects with CHD and Metabolic Syndrome to 30 months of 1) usual care 2) novel anti-inflammatory salsalates or 3) intensive lifestyle modification with monitoring inflammatory markers and baseline/30 month coronary MDCT to monitor atherosclerosis. In this study, the primary and secondary aims include relating CMR measures of aortic plaque volume, vessel wall area, vessel inflammation with MDCT plaque measures and measures of biochemical markers of systemic inflammation and to characterize the response of these CMR measures to 30 months of conventional and novel antiinflammatory therapies with correlation with systemic biochemical markers of inflammation.

尽管在识别和降低风险方面取得了进展，动脉粥样硬化性心血管疾病（CVD）仍然是美国发病和死亡的主要原因。动脉粥样硬化主要影响大中型血管，尸检数据表明腹主动脉为动脉粥样硬化的研究提供了宝贵的早期窗口。冠心病 (CHD) 危险因素包括年龄、男性、早发冠心病家族史、高血压、吸烟、糖尿病、低密度脂蛋白胆固醇 (LDL-C) 升高和高密度脂蛋白胆固醇 (HDL-C) 低。代谢综合征（肥胖、胰岛素抵抗、高血压、糖耐量受损、高胰岛素血症和血脂异常）在美国非常普遍，与冠心病和炎症有关，越来越多地被认为是动脉粥样硬化和胰岛素发病机制的主要因素反抗。非侵入性血管成像技术，包括心血管磁共振 (CMR) 和多排计算机断层扫描 (MDCT)，为识别、量化和表征动脉粥样硬化提供了机会。 CMR 和 MDCT 在提供有关斑块体积和特征的信息方面是互补的，CMR 提高了提供有关斑块成分的信息的灵敏度，包括非电离辐射环境中和没有碘造影剂的情况下的炎症。对比增强 CMR (CE-CMR) 是一种新的 CMR 应用，已被证明可用于评估主动脉斑块的纤维化和识别纤维帽中的局灶性炎症。最近，NHLBI 在我们机构资助了一个以“代谢综合征、炎症和血管重塑”为中心主题的血管损伤、修复和重塑专业临床研究中心 (SCCOR) 项目。该母公司 SCCOR 将随机分配 720 名患有 CHD 和代谢综合征的受试者，接受 30 个月的 1) 常规护理 2) 新型抗炎双水杨酸盐或 3) 强化生活方式改变，监测炎症标志物和基线/30 个月冠状动脉 MDCT，以监测动脉粥样硬化。该母公司 SCCOR 提供了及时且经济高效的机会，以扩展我们对动脉粥样硬化过程的了解，包括通过应用先进的 CMR 方法来表征代谢综合征中的主动脉粥样硬化和炎症及其与生化的关系，这些新疗法对局灶性斑块炎症的影响炎症标志物，以及斑块和斑块成分（包括炎症）对常规和新治疗的反应。我们还将有机会将这些发现与软斑块和钙化斑块的冠状动脉 MDCT 测量结果进行比较。我们建议从 720 名患有代谢综合征的父母 SCCOR 受试者中招募 420 名受试者（每个治疗组中 n=140）的子集。主要和次要目标包括将主动脉斑块体积、斑块成分、血管壁面积、血管炎症的定量 CMR 测量与 MDCT 斑块测量和全身炎症的全身生化测量联系起来，并表征这些 CMR 测量对 30 个月常规和治疗的反应。与全身炎症生化指标变化相关的新型抗炎疗法。 PHS 398/2590（修订版。 09/04，重新发布 4/2006） 页继续格式 页 首席研究员/项目主任（最后、第一、中间）：Manning, Warren J. 尽管在识别和降低风险方面取得了进展，但动脉粥样硬化性心血管疾病（CVD）仍然是美国发病率和死亡率的主要原因。动脉粥样硬化主要影响大中型血管，尸检数据表明腹主动脉为动脉粥样硬化的研究提供了宝贵的早期窗口。非侵入性血管成像技术，包括心血管磁共振 (CMR) 和多排计算机断层扫描 (MDCT)，为识别、量化和表征动脉粥样硬化提供了机会。最近，NHLBI 在我们机构资助了一个以“代谢综合征、炎症和血管重塑”为中心主题的血管损伤、修复和重塑专业临床研究中心 (SCCOR) 项目。该母公司 SCCOR 将随机分配 720 名患有 CHD 和代谢综合征的受试者，接受 30 个月的 1) 常规护理 2) 新型抗炎双水杨酸盐或 3) 强化生活方式改变，监测炎症标志物和基线/30 个月冠状动脉 MDCT，以监测动脉粥样硬化。在这项研究中，主要和次要目标包括将主动脉斑块体积、血管壁面积、血管炎症的 CMR 测量与 MDCT 斑块测量和全身炎症生化标志物测量联系起来，并表征这些 CMR 测量对 30 个月常规治疗的反应。以及与全身炎症生化标志物相关的新型抗炎疗法。