Weight Loss, Inflammation, and Vascular Remodeling

减肥、炎症和血管重塑

• 批准号: 7140950
• 负责人: FRANCINE K WELTY
• 金额: $ 38.63万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140950
• 关键词: angiography; behavioral medicine; body composition; cardiovascular imaging /visualization; cholesterol; comorbidity; computed axial tomography; coronary disorder; dietary carbohydrates; dietary lipid; dietary supplements; exercise; folate; human subject; human therapy evaluation; inflammation; lifestyle; longitudinal human study; metabolic syndrome; nutrition related tag; obesity; omega 3 fatty acid; patient oriented research; reducing diet; vitamin B12; vitamin B6; weight loss

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病的比例，并增加冠心病的风险 冠心病（CHD）是我们社会中死亡和残疾的主要原因。西方饮食，其中富含 热量、饱和脂肪、反式脂肪、胆固醇和血糖负荷以及中心性肥胖通过以下方式增加冠心病的风险： 激活NF-κ B级联并增加促炎细胞因子TNF-α和IL-6的血浆水平， 以及炎症标志物如C反应蛋白（CRP）、血清淀粉样蛋白A（SAA）和纤维蛋白原的水平。 NF-κ B的活化导致胰岛素抵抗、甘油三酯水平升高、HDL-C水平降低和脂肪肝， 代谢综合征的所有特征。第三个成人治疗小组建议， 代谢综合征的一线治疗是改变生活方式，以减轻体重（特别是中枢神经系统）， 肥胖症）通过饮食和增加体力活动。在这个项目中，“减肥，炎症和 血管重塑”，患有代谢综合征和CHD的受试者（均接受他汀类药物治疗）将被随机分配至 生活方式改变计划（每天锻炼30分钟，1500-2000卡路里/天，< 7%的饱和脂肪， <200毫克胆固醇/天，低反式脂肪，低血糖负荷饮食，沿着富含co-3的营养补充剂 脂肪酸、叶酸和维生素B 6和B12）或常规护理。将通过以下方式评估冠状动脉斑块： 基线和30个月随访时的多排螺旋CT血管造影（MDCTA）。肝脏和 还将用MDCT评估腹部脂肪。由于西方饮食和肥胖激活了NF-κ B 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，促进血管重塑和消退 MDCTA评估确诊CHD患者软斑块的发生率。待检验的假设为： 1)与进展相比，生活方式组的患者软斑消退（约5%） （约5%）在常规护理组中，肝脏和腹部脂肪也明显减少 CRP、TNF-α、MMP 9、SAA、纤维蛋白原、派-1、IL-6和氧化应激指标水平较低， 硝基酪氨酸; 2）消退量将与肝脂肪、体脂肪和肝细胞百分比的降低直接相关。 3）炎症标志物的%减少将与体重和腹部脂肪的%变化相关。 软斑块和肝脏和腹部脂肪及体重减少%。这些研究将使我们能够 测试假设，积极的生活方式改变与减肥和营养 补充剂将对冠心病的血管重塑和炎症标志物产生有利的影响 合并代谢综合征的冠心病患者的风险与单独常规治疗的比较