Weight Loss, Inflammation, and Vascular Remodeling

减肥、炎症和血管重塑

• 批准号: 7629071
• 负责人: FRANCINE K WELTY
• 金额: $ 49.39万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7629071
• 关键词: 3-nitrotyrosine; Abdomen; Adipocytes; Adult; Aerobic Exercise; Age; Albumins; Angiography; Apolipoproteins A; Apolipoproteins B; Biochemical; Biochemical Markers; Body Weight; Body Weight decreased; C-Peptide; C-reactive protein; Calcified; Calories; Caring; Cause of Death; Cell Adhesion Molecules; Central obesity; Characteristics; Cholesterol; Coronary; Coronary Arteriosclerosis; Coronary artery; Coronary heart disease; Creatinine; Daily; Deposition; Diabetes Mellitus; Diet; Dietary Supplementation; Disease regression; Docosahexaenoic Acids; Eicosapentaenoic Acid; End Point; Endothelial Cells; Enrollment; Epidemic; Essential Fatty Acids; Exercise; Fat Body; Fatty Acids; Fatty Liver; Fatty acid glycerol esters; Fibrinogen; Folate; Gelatinase B; Gender; Glycemic Index; Goals; Hepatic; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Homocysteine; Homocystine; Hypertension; Hypertriglyceridemia; Image; Inflammation; Inflammatory; Insulin; Insulin Resistance; Intercellular adhesion molecule 1; Interleukin-6; Interleukins; Intervention; Intra-abdominal; LDL Cholesterol Lipoproteins; Lead; Life Style; Lipids; Lipoprotein (a); Lipoprotein (a-); Lipoproteins; Liver; Margarine; Matrix Metalloproteinases; Measures; Metabolic syndrome; Modality; Modification; Nonesterified Fatty Acids; Obesity; Oxidative Stress; Patients; Phospholipase A2; Physical activity; Phytosterols; Placebos; Plasma; Plasminogen Activator Inhibitor 1; Plasminogen Inactivators; Process; Protein C; Randomized; Recording of previous events; Research Personnel; Risk; Risk Factors; Scanning; Serum amyloid A protein; Slice; Smoking; Societies; Supplementation; Testing; Trans Fats; Trans Fatty Acids; Tumor Necrosis Factor-alpha; Upper arm; Urine; Vascular Cell Adhesion Molecule-1; Vascular remodeling; Visceral; Vitamin B 12; Vitamin B Complex; Vitamin B6; abdominal fat; adiponectin; capsule; cytokine; day; detector; dietary supplements; disability; follow-up; heart disease risk; human TNF protein; intravenous injection; lipoprotein-associated phospholipase A(2); macrophage; new technology; programs; saturated fat; size; waist circumference

Metabolic syndrome and obesity are reaching epidemic proportions and increase the risk of coronary heart disease (CHD), the leading cause of death and disability in our society. The Western diet, which is rich in calories, saturated fat, trans fat, cholesterol and glycemic load, and central obesity increase risk of CHD by activating the NF-KB cascade and increasing plasma levels of proinflammatory cytokines, TNF-alpha and IL-6, and levels of inflammatory markers as C-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen. Activation of NF-KB leads to insulin resistance, increased triglyceride levels, low HDL-C levels and fatty liver, all characteristics of the metabolic syndrome. The third Adult Treatment Panel has recommended that first line therapy for metabolic syndrome be lifestyle changes geared toward weight reduction (especially central adiposity) through diet and increased physical activity. In this project, "Weight Loss, Inflammation and Vascular Remodeling", subjects with metabolic syndrome and CHD (all on statin) will be randomized to a lifestyle modification program (30 minutes of daily exercise, 1500-2000 calories/day, < 7% saturated fat, <200 mg cholesterol/day, low trans fat, low glycemic load diet, along with a nutritional supplement rich in co-3 fatty acids, folate, and vitamins B 6 and B12) or usual care. Coronary plaque will be assessed by multidetector computed tomographic angiography (MDCTA) at baseline and 30-month follow-up. Liver and abdominal fat will also be assessed with MDCT. Since the Western diet and obesity activate the NF-KB cascade and lead to inflammation, we hypothesize that weight loss achieved through dietary and exercise intervention will suppress the subacute inflammatory process to promote vascular remodeling and regression of soft plaque assessed by MDCTA in patients with established CHD. The hypotheses to be tested are that: 1) those in the lifestyle arm will have regression of soft plaque (approximately 5%) compared to progression (approximately 5%) in the usual care arm and also reduction in hepatic and abdominal fat and significantly lower levels of CRP, TNF-alpha, MMP 9, SAA, fibrinogen, PAI-1, IL-6 and a measure of oxidative stress, nitrotyrosine; 2) the amount of regression will be directly correlated with the % decrease in hepatic fat, body weight and abdominal fat; 3) the % reduction in inflammatory markers will be correlated with the % change in soft plaque and % reduction in hepatic and abdominal fat and body weight. These studies will allow us to test the hypothesis that aggressive lifestyle modification with weight loss and nutritional supplements will have favorable effects on vascular remodeling and inflammatory markers of CHD risk versus usual care alone in CHD patients with the metabolic syndrome.

代谢综合征和肥胖症正在达到流行比例，并增加了冠心病的风险 疾病（CHD），我们社会的死亡和残疾的主要原因。西方饮食，丰富 卡路里，饱和脂肪，反式脂肪，胆固醇和血糖负荷以及中枢肥胖使CHD风险增加 激活NF-KB级联反应，并增加血浆促炎细胞因子的水平，TNF-Alpha和IL-6， 作为C反应蛋白（CRP），血清淀粉样蛋白A（SAA）和纤维蛋白原的炎症标记水平。 NF-KB的激活导致胰岛素抵抗，甘油三酸酯水平升高，HDL-C水平低和脂肪肝， 代谢综合征的所有特征。第三个成人治疗面板建议首先 新陈代谢综合征的线路治疗是旨在减轻体重的生活方式变化（尤其是中央 肥胖）通过饮食和增加的体育锻炼。在这个项目中，“减肥，炎症和 血管重塑”，具有代谢综合征和CHD的受试者（全部在他汀类药物上）将被随机分为 生活方式修改计划（每天30分钟，1500-2000卡路里/天，饱和脂肪<7％， <200 mg胆固醇/天，低反式脂肪，低血糖负荷饮食，以及富含CO-3的营养补充剂 脂肪酸，叶酸和维生素B 6和B12或通常的护理。冠状斑块将通过 基线和30个月的随访时多探测器计算机层析成绩（MDCTA）。肝和 还将用MDCT评估腹部脂肪。由于西方饮食和肥胖激活了NF-KB 级联并导致炎症，我们假设通过饮食和运动实现的体重减轻 干预将抑制亚急性炎症过程以促进血管重塑和回归 由MDCTA评估的软斑块已在已建立的CHD患者中进行。要测试的假设是： 1）与进度相比 （约5％）在通常的护理臂中，肝脂肪和腹部脂肪也减少 较低水平的CRP，TNF-Alpha，MMP 9，SAA，纤维蛋白原，PAI-1，IL-6以及氧化应激的度量， 硝基酪氨酸； 2）回归量将直接与肝脂肪的降低百分比直接相关 体重和腹部脂肪； 3）炎症标记的降低％将与％变化相关 肝和腹部脂肪和体重的软斑块和％减少。这些研究将使我们能够 检验以体重减轻和营养的积极生活方式修饰的假设 补品将对冠心病的血管重塑和炎症标记有利 仅在代谢综合征患者中，仅风险与通常的护理。