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Abstract
Background: High-density lipoprotein (HDL) includes discrete subfractions. HDL exhibits anti-atherogenic properties, which have been partly linked to the activity of HDL-associated enzymes, such as the lipoprotein associated phospholipase A2 (HDL-LpPLA2) and paraoxonase-1 (PON1). Objective: We assessed in an open-label randomised study the effect of orlistat and ezetimibe, alone or in combination, on plasma HDL subclasses and HDL-associated enzyme activities in overweight and obese subjects (body mass index > 28 kg/m2) with hypercholesterolemia [total cholesterol > 200 mg/100 ml (5.2 mmol/l)]. Methods: Eighty-six people were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg, three times daily (O group), ezetimibe 10 mg/day (E group) or both (OE group) for 6 months. HDL subfractions were determined using a polyacrylamide gel-tube electrophoresis method. Results: Levels of HDL cholesterol (HDL-C) and apolipoprotein AI did not change significantly in any group. In group O the cholesterol concentration of HDL-2 subclass increased significantly, while the cholesterol of HDL-3 subclass decreased significantly. In groups E and OE HDL-2 subclass did not significantly change, while the cholesterol concentration of HDL-3 subclass decreased significantly. We observed a non-significant decrease in the HDL-LpPLA2 and PON1 activity in all groups. However, the ratios of both enzyme activities to low-density lipoprotein cholesterol (LDL-C) levels (an index of atherogenicity) significantly increased in all groups. Conclusion: Although HDL-C levels did not change after treatment with orlistat and ezetimibe, alone or in combination, there were alterations of the HDL-2 and HDL-3 subclasses. The activity of HDL-LpPLA2 and PON1 per mg LDL-C increased significantly in all groups.