The effect of orlistat and fenofibrate, alone or in combination, on small dense LDL and lipoprotein-associated phospholipase A2 in obese patients with metabolic syndrome

Background: Increased concentration of small dense LDL cholesterol (sdLDL-C) and activity of lipoprotein-associated phospholipase A2 (Lp-PLA(2)) are considered as emerging cardiovascular risk factors and are commonly encountered in subjects with metabolic syndrome (MetS). Objective: The primary endpoint of this study was the effect of orlistat and fenofibrate, alone or in combination, on Lp-PLA2 activity and LDL phenotype in overweight and obese patients (body mass index > 28 kg/m(2)) with MetS. Methods: Patients (n = 89) were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg three times daily (O group), micronized fenofibrate 200 mg/day (F group) or both (OF group) for 6 months. Results: Significant reductions of sdLDL-C levels were observed in all treatment groups. Groups F and OF experienced a greater reduction in sdLDL-C levels (p < 0.05) together with a greater increase in LDL particle diameter (p < 0.05) compared with group O. Total plasma Lp-PLA(2) activity significantly decreased in all treatment groups. The reduction of Lp-PLA2 was more pronounced with OF administration compared with each monotherapy (p < 0.05). Conclusion: Orlistat and fenofibrate exhibited favorable effects on Lp-PLA(2) activity and LDL phenotype in overweight and obese patients with MetS. Importantly, combination treatment had a more favorable effect on these risk factors. (c) 2006 Elsevier Ireland Ltd. All rights reserved.