Patients with metabolic syndrome, who are invariably obese, exhibit a cluster of risk factors for cardiovascular disease including diabetes mellitus, hypertension, and abnormalities in cholesterol metabolism. The major morbidity in such patients is myocardial infarction and stroke caused by accelerated atherosclerosis. The complex pathophysiological disturbances that promote atherogenesis also include chronic inflammation, adipocyte endocrine dysfunction, and abnormalities in vascular compliance. The development of insulin resistance is a critical underlying feature of metabolic syndrome, which results in abnormal levels of insulin and other hormones. We hypothesize that in addition to the enhanced deposition of lipid in large, well-characterized subcutaneous and visceral fat stores, another unifying feature of metabolic syndrome is innapropriate deposition of lipid in smaller depots. These inappropriate stores include hepatocellular triglyceride, perivascular and pericardial triglyceride, and atherosclerotic cholesterol, which may serve as localized markers of disease. We further hypothesize that decection of these lipid stores noninvasively in a site-specific manner will provide new insights into mechanisms by which they exert systemic effects and illuminate specific risk factors for determining adverse outcomes. Magnetic resonance imaging (MRI) is a non-invasive tool that can detect the pathological lipid deposition and identify early atherosclerotic vascular changes. We will use MR-based techniques to identify site-specific abnormalities in obese patients with metabolic syndrome but without known atherosclerosis who are undergoing medically supervised weight loss and/or gastric bypass (bariatric) surgery. We will apply MRI to identify changes in vascular stiffness and correlate these changes to the concentration of lipid in the vessel (atherosclerotic plaque) and surrounding the blood vessel (triglyceride). We will quantify triglyceride stores in the liver and surrounding the heart and blood vessels (perivascular/pericardial fat), and associate these findings with hormone levels and the presence of early atherosclerotic disease. We will monitor regression of these parameters in patients with metabolic sydnrome following successful weight loss. In patients with metabolic syndrome but advanced atherosclerosis who are undergoing carotid endarterectomy, we will use molecular MR techniques to determine evidence of inflammation and plaque vulnerability and perform in vivo and ex vivo studies to quantify lipid. This work will elucidate the complex interplay between risk factors and clinical phenotype, through the demonstration of which lipid deposits are most detrimental to future health. An important outcome our work will be a non-invasive MR-based protocol that will further stratify cardiovascular risk in this increasingly prevalent cohort of patients, and provide a means to evaluate the efficacy of specific therapies.
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