The function of the imaging core will be to optimize the methodology for reproducibly assessing both soft and calcified plaque in coronary arteries, as well as the assessment of abdominal and liver fat deposition using MDCT. This technology is currently being assessed as part of multi-center studies to compare MDCTA coronary arteriography to standard quantitative coronary angiography. These techniques will be applied to the clinical study population who are obese and have established CHD and meet criteria for the metabolic syndrome. The Imaging Core will be responsible for providing the clinical investigators with measurements of soft and calcified plaque and change in character or volume in the coronary tree as assessed by high resolution computed tomography using IV contrast, the amount of visceral fat and liver lipid as assessed by non contrast CT at baseline and after 30 months of treatment. The most important measure will be to assess the degree of vascular and plaque remodeling with this new technology over a 30 month period in the usual care group versus the other treatment groups. The primary endpoint in the clinical projects will be assessment of coronary soft plaque remodeling as determined by MDCTA at baseline and at 30 months. A secondary endpoint will be to assess change in the amount and location of calcification in plaque as it relates to progression, regression or stabilization. This CT modality without contrast material will also be used to assess total body (subcutaneous and visceral) and liver fat reduction or deposition. Estimated coefficients of variation for soft plaque (mean and SD volume 39 and 12 mm3) are 6%. We estimate progression of 5% in the usual care group and regression of up to 5% in the treatment groups, requiring a sample size of at least 202 subjects per intervention to attain a p<0.05. """"""""Metabolic syndrome, inflammation and vascular remodeling"""""""", will evaluate the effect of three interventions: 1) life style (diet, exercise, weight loss);2) HDL raising with niacin and fenofibrate;and 3) disalsid on progression, regression and stabilization of coronary artery plaque and inflammatory markers in patients with CHD and metabolic syndrome. An integral part of this SCCOR proposal is the Imaging Core which will enable the measurement of coronary artery calcified and non-calcified plaque burden, the accumulation or reduction of hepatic and total body fat using established quantifiable imaging techniques by the most advanced computed tomographic scanner . The spatial resolution of the scanner is 0.4mm and therefore creates pixels of 0.4mm2 and isotropic 0.4 mm voxels. The information gained from MDCT imaging could allow us to determine which risk factors are the most important for developing cardiovascular disease and would help direct future intervention strategies for prevention. The data from coronary artery calcium combined with CT coronary arteriographic studies could tell us whether the calcification that has increased in volume represents progression of calcification into new areas of non calcified plaque, indicating progression, or if the calcium increase is in a positively remodeled artery, suggesting that plaque burden is not increasing, therefore atherosclerosis is not progressing. The change in character and volume of non- calcified plaque over time is especially important to evaluate regression or stability, i.e., change from fatty to fibrous plaque or regression of fatty plaque on clinical projects by Shoelson and Welty may indicate the most appropriate dietary interventions and treatments to promote regression and/or stabilization. This type of information can also be obtained from total body and hepatic fat since the subjects will be followed longitudinally with repeat MDCTA scanning for calcified and noncalcified plaque, total body and hepatic fat content at 30 months.
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