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HDL function and atherosclerosis
There is a strong inverse relationship between serum levels of high-density lipoprotein (HDL) and the risk of developing atherosclerotic cardiovascular disease. This has fostered the search for pharmacological agents that raise HDL, but while several treatments have shown biochemical benefit—including nicotinic acid, fibrates and CETP inhibitors—there are little convincing data to associate these rises with significant reductions in clinical risk. Indeed, increasing numbers of questions are being asked about the benefit of an increase in HDL itself, with HDL particle composition and biological activity being increasingly recognised as key metrics which static measurements are too blunt to identify.
One of the central atheroprotective properties of HDL is its ability to promote reverse cholesterol transport by accepting cholesterol from lipid-laden macrophages, termed cholesterol efflux capacity. Using a technically complex assay involving the use of radiolabelled cholesterol and scintillation counts, the authors recruited 442 patients with angiographically confirmed coronary artery disease, 351 patients without confirmed disease and 203 age-matched healthy volunteers (who also underwent assessment of carotid artery intima-media thickness), and quantified efflux capacity. In healthy volunteers an inverse relationship was noted between efflux capacity and carotid artery intima-media thickness even after adjustment for the HDL cholesterol level. Furthermore, in the comparison between patients with and without coronary disease, efflux capacity was a strong inverse predictor of coronary disease status (adjusted OR for coronary disease, 0.70; …