Weight Loss, Inflammation, and Vascular Remodeling

减肥、炎症和血管重塑

基本信息

批准号：
8379443
负责人：
FRANCINE K WELTY
金额：
$ 53.42万
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：
资助国家：
美国
起止时间：
至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8379443
关键词：
3-nitrotyrosine Abdomen Adipocytes Adult Aerobic Exercise Age Albumins Angiography Apolipoproteins A Apolipoproteins B Behavior Therapy Biochemical Biochemical Markers Body Weight Body Weight decreased C-Peptide C-reactive protein Calcified Calories Cause of Death Cell Adhesion Molecules Central obesity Characteristics Cholesterol Coronary Coronary Arteriosclerosis Coronary artery Coronary heart disease Creatinine Deposition Diabetes Mellitus Diet Dietary Supplementation Docosahexaenoic Acids Eicosapentaenoic Acid 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)Lipoproteins Liver Margarine Matrix Metalloproteinases Measures Metabolic syndrome Modality Nonesterified Fatty Acids Obesity Oxidative Stress Patients Phospholipase A2 Physical activity Phytosterols Placebos Plasma Plasminogen Activator Inhibitor 1 Plasminogen Inactivators Process Randomized Recording of previous events Risk Risk Factors Scanning Serum amyloid A protein Slice Smoking Societies Supplementation TNF gene Testing Trans Fats Trans Fatty Acids Tumor Necrosis Factor-alpha Urine Vascular Cell Adhesion Molecule-1 Vascular remodeling Visceral Vitamin B 12 Vitamin B Complex Vitamin B6 abdominal fat adiponectin arm capsule cytokine detector dietary supplements disability follow-up heart disease risk human TNF protein inflammatory marker intravenous injection lipoprotein-associated phospholipase A(2)macrophage new technology programs saturated fat treatment as usual vessel regression waist circumference

项目摘要

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（CHD）的风险，冠心病（CHD）是我们社会中死亡和残疾的主要原因。西方饮食富含卡路里，饱和脂肪，反式脂肪，胆固醇和血糖负荷以及中枢肥胖，通过激活NF-KB级联反应并增加血浆促炎细胞因子的血浆水平，TNF-Alpha和IL-6，以及炎症标记的水平，以及CRAMEAM的水平（SAA）和SAA蛋白质（CRP）（CRP）（CRP）（CRP）（CRP）纤维蛋白原。 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，代谢综合征的第一线治疗是旨在通过饮食和增加体育锻炼来减轻体重（尤其是中央肥胖）的生活方式改变。在这个项目中，“体重减轻，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）将被随机化为生活方式修改计划（30分钟的日常运动，每天1500-2000卡路里，<7％饱和脂肪，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脂肪酸，叶酸和维生素B 6和B12的营养补充剂或通常的护理。冠状斑块将通过基线和30个月的随访中的多探测器计算机层析成绩（MDCTA）评估。肝脏和腹部脂肪也将通过MDCT评估。由于西方饮食和肥胖会激活NF-KB级联反应并导致炎症，因此我们假设通过饮食和运动干预实现的体重减轻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）与通常的护理臂的进展（约5％）相比，生活方式臂中的那些人将具有柔软斑块的回归（约5％），并且肝脂肪和腹部脂肪的降低以及CRP的降低以及CRP的水平明显较低，TNF-Alpha，TNF-Alpha，TNF-Alpha，MMP 9，MMP 9，MMP 9，纤维纤维，PAI，PAI，PAI，PAI，PAI，PAI，a-1，iil-a和a，pai-1，pai，pai，ai，a和a，pai-1，iil-iil，iil-i il iil，iil，iil-il iil，ic，ic，ic，ic，ic，ic，ic，ic，ic，ic，ic，ic，ic，i。硝基酪氨酸； 2）回归量将与肝脂肪，体重和腹部脂肪的降低百分比直接相关； 3）炎症标记的降低％将与软斑块变化的％变化以及肝脂肪和体重的降低相关。这些研究将使我们能够检验以下假设：体重减轻和营养补充剂的积极生活方式改变将对CHD风险的血管重塑和炎症标志物产生有利的影响，而单独的毒品疾病患者的代谢综合症患者仅对平常的护理产生了有利的影响。