The effect of orlistat and fenofibrate, alone or in combination, on small dense LDL and lipoprotein-associated phospholipase A(2) in obese patients with metabolic syndrome

Department of Chemistry, University of Ioannina, Yannina, Epirus, Greece
Atherosclerosis (Impact Factor: 3.99). 08/2007; 193(2):428-37. DOI: 10.1016/j.atherosclerosis.2006.07.010
Source: PubMed


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).
The primary endpoint of this study was the effect of orlistat and fenofibrate, alone or in combination, on Lp-PLA(2) activity and LDL phenotype in overweight and obese patients (body mass index>28 kg/m(2)) with MetS.
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 200mg/day (F group) or both (OF group) for 6 months.
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-PLA(2) was more pronounced with OF administration compared with each monotherapy (p<0.05).
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.

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    • "Since growing evidence supports a pro-atherogenic role for Lp-PLA2, ongoing research is investigating its utility as a therapeutic target. Since Lp-PLA2 circulates primarily bound to LDL cholesterol, drugs that influence lipoprotein concentration have been shown to influence Lp-PLA2 levels, including statins [20, 21], niacin [22], fenofibrate [23], and gemfibrozil [24]. The cholesteryl ester transfer protein (CETP) inhibitor dalcetrapib (no longer in development) was shown in phase II testing to increase Lp-PLA2 mass by approximately 17% as compared with placebo [25]. "
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