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: 8307891
• 负责人: WARREN J MANNING
• 金额: $ 79.92万
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8307891
• 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; Carotid Arteries; Cell Adhesion Molecules; Characteristics; Chest; Cholesterol; Clinical; Clinical Markers; 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; 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; 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 effective; 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，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一个有价值的早期窗口。冠心病（CHD）的危险因素包括年龄、男性、早发CHD家族史、高血压、吸烟、糖尿病、高LDL-C和低HDL-C。代谢综合征[肥胖、胰岛素抵抗、高血压、葡萄糖耐量受损、高胰岛素血症和血脂异常]在美国高度流行，与CHD和炎症有关，越来越多地被认为是动脉粥样硬化和胰岛素抵抗发病机制的主要因素。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在提供有关斑块体积和表征的信息方面具有互补性，CMR在提供有关斑块成分的信息方面具有更高的灵敏度，包括在非电离辐射环境和不存在碘化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，已被证明可用于评价主动脉斑块的纤维化和识别纤维帽中的局灶性炎症。一个临床导向研究的专业中心（SCCOR）计划在血管损伤，修复和重塑的中心主题是“代谢综合征，炎症和血管重塑”最近由NHLBI在我们的insiution资助。该母SCCOR将720例CHD和代谢综合征受试者随机分配至30个月的1）常规护理2）新型抗炎双水杨酸酯或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提供了及时和具有成本效益的机会，以扩大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，其与生化炎症标志物的关系，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结果与冠状动脉MDCT测量的软斑块和钙化斑块进行比较。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n=140）。主要和次要目的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相关联，并表征这些CMR测量对30个月常规和新型血管内治疗的反应，并与炎症的全身生化测量的变化相关联。PHS 398/2590（09/04修订版，2006年4月重新发布）第续页格式第页主要研究者/项目负责人（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一个有价值的早期窗口。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。一个临床导向研究的专业中心（SCCOR）计划在血管损伤，修复和重塑的中心主题是“代谢综合征，炎症和血管重塑”最近由NHLBI在我们的insiution资助。该母SCCOR将720例CHD和代谢综合征受试者随机分配至30个月的1）常规护理2）新型抗炎双水杨酸酯或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。在本研究中，主要和次要目的包括将主动脉斑块体积、血管壁面积、血管炎症的CMR测量值与MDCT斑块测量值和全身炎症生化标志物测量值相关联，并表征这些CMR测量值对30个月常规和新型血管内治疗的反应，并与全身炎症生化标志物相关联。