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

基本信息

批准号：
7690863
负责人：
WARREN J MANNING
金额：
$ 82.39万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
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/7690863
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 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 Modification 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 Upper arm Vascular Cell Adhesion Molecule-1 Vascular remodeling Woman X-Ray Computed Tomography abdominal aorta adiponectin 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

项目摘要

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.

尽管鉴定和降低风险都取得了进步，但在美国，动脉粥样硬化心血管疾病（CVD）仍然是发病率和死亡率的主要原因。动脉粥样硬化主要影响具有尸检数据的大型和中型血管，表明腹主动脉为研究动脉粥样硬化提供了宝贵的早期窗口。冠心病（CHD）危险因素包括年龄，男性性别，早产冠心家族史，高血压，吸烟，糖尿病，LDL-C升高和HDL-C升高。代谢综合征[肥胖，胰岛素抵抗，高血压，葡萄糖耐受性受损，高胰岛素血症和血脂异常）在美国高度普遍，与CHD和炎症有关，被越来越多地接受为对动脉粥样硬化和胰岛素耐药性的病原体的主要因素。非侵入性血管成像技术，包括心血管磁共振（CMR）和多探测器计算机断层扫描（MDCT），提供了识别，量化和表征动脉粥样硬化的机会。 CMR和MDCT是提供有关斑块体积和表征的信息的补充，CMR的灵敏度提高了提供有关斑块成分的信息，包括在非离子化辐射环境中以及没有碘对比度的情况下的炎症。对比增强的CMR（CE-CMR）是一种新的CMR应用，已证明可用于评估主动脉斑块的纤维化和鉴定纤维帽中的局灶性炎症。 NHLBI最近由NHLBI资助了一个中心主题“代谢综合征，炎症和血管重塑”中心主题“代谢综合征，炎症和血管重塑”的专门针对血管损伤，修复和重塑的专业中心。该母子SCCOR将将720名CHD和代谢综合征的受试者随机，至30个月1）通常的护理2）新型的抗炎味或3）3）强化生活方式修饰，并通过监测炎症标记和30个月的冠状动脉MDCT监测动脉粥样硬化。 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 治疗。我们还将有机会将这些发现与冠状动脉MDCT的软牙菌斑进行比较。我们建议在720名患有代谢综合征的父母SCCOR受试者中招募420名受试者（n = 140个）的子集。主要和次要的目的包括将主动脉斑块体积的定量CMR测量，牙菌斑成分，船只壁面积，带有MDCT斑块测量的血管炎症和系统性炎症的全身性生物化测量，以对这些CMR响应的响应以及抗体抗体的30个月响应的响应，以进行抗脉络性和新型抗抗素的响应。炎症。博士398/2590（修订版09/04，重新发布4/2006）页面延续格式页面首席研究员/计划主管（最后，第一，中间）：曼宁·J·沃伦·J·J·沃伦·J。尽管识别和降低风险的进步，但动脉粥样硬化性心血管疾病（CVD）仍然是造成美国丧生和抵押的主要原因。动脉粥样硬化主要影响具有尸检数据的大型和中型血管，表明腹主动脉为研究动脉粥样硬化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）和多探测器计算机断层扫描（MDCT），提供了识别，量化和表征动脉粥样硬化的机会。 NHLBI最近由NHLBI资助了一个中心主题“代谢综合征，炎症和血管重塑”中心主题“代谢综合征，炎症和血管重塑”的专门针对血管损伤，修复和重塑的专业中心。该母子SCCOR将将720名CHD和代谢综合征的受试者随机，至30个月1）通常的护理2）新型的抗炎味或3）3）强化生活方式修饰，并通过监测炎症标记和30个月的冠状动脉MDCT监测动脉粥样硬化。在这项研究中，主要和次要目的包括将CMR的主动脉斑块体积测量，血管壁面积，具有MDCT斑块措施的血管炎症和全身性炎症的生化标志物的测量方法，以表征这些CMR对30个月的CMR测量与使用抗毒素的抗炎性治疗的响应。