Triglyceride-Rich Lipoproteins and Vascular Function
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The epidemic of obesity in the developed and developing world has resulted in a considerable increase in the number of patients with high plasma triglyceride concentrations. There has been considerable debate about the role of triglyceride-rich lipoproteins (TRLs) in atherosclerosis. These lipoproteins include chylomicrons, VLDL, IDL, and various remnant particles. Although elevated triglyceride levels are common in patients with atherosclerotic disease, establishing a clear link has been made difficult by a number of factors.
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First, elevated triglycerides are usually found in lipoprotein particles that also contain cholesterol. A role for cholesterol in these particles is supported by the fact that non-HDL cholesterol appears to be a more powerful marker of cardiovascular risk than even LDL cholesterol.1 Second, elevated TRLs are strongly associated with low HDL cholesterol concentrations. This association is so powerful that it is very difficult to dissect out the relative contributions of HDL and TRLs, although low HDL is commonly believed to have a greater impact on the atherosclerotic process. Third, triglyceride concentrations have high biological variability, which obscures the statistical strength of any association with cardiovascular disease, particularly when compared with the less variable HDL. Fourth, patients with high TRL levels often possess other risk factors that may explain their predisposition to atherosclerosis, especially those that comprise the metabolic syndrome.2 Finally, the lack of an established pathophysiological mechanism linking TRLs to atherosclerosis has hindered consideration of triglycerides as a cause of atherosclerosis, as opposed to being a marker for other risk factors (ie, insulin resistance, visceral obesity, or hypertension). Identification of a plausible mechanism would help resolve this debate.
Meta-analyses of observational studies have suggested that a 1-mmol/L (89 mg/dL) elevation in triglycerides is …