Elevated postprandial lipemia (PL), a high level of triglyceride-rich lipoproteins and their remnants after eating, is independently associated with increased atherosclerosis and a higher cardiovascular risk. An important mechanism by which elevated PL presumably results in cardiovascular disease is via the induction of endothelial dysfunction, an early factor in atherogenesis. Recent reports demonstrate a positive correlation between the peak level of PL to the degree of impairment in endothelial function following a high fat meal in normal patients. Obese patients manifest a significantly larger increment in PL following a meal than do non-obese patients. The primary purpose of this study is to determine if higher peak PL levels in overweight patients relative to non-obese controls is associated with greater impairment in postprandial endothelial function. Secondly, the effect of Orlistat, a pancreatic lipase inhibitor, on both PL and postprandial endothelial dysfunction will be determined in overweight patients. Flow-mediated dilatation (FMD) of the brachial artery, a process that is nitric oxide (NO) and endothelial dependent, will be studied 4 hours after a high fat meal in 10 normal patients and in 10 obese patients before and after treatment with Orlistat. In addition to furthering our understanding of the pathophysiology linking PL to cardiovascular disease, the finding that Orlistat improves both PL as well as the resultant endothelial dysfunction may have significant clinical implications, particularly for patients with concomitant obesity and/ or atherosclerotic cardiovascular disease.
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