Weight Loss, Inflammation, and Vascular Remodeling

Beth Israel Deaconess Medical Center, Boston MA

Investigators

Linked publications & trials

Abstract

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