M. Kalogirou

Differential Effect of Hypolipidemic Drugs on Lipoprotein-Associated Phospholipase A2

Objective— Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a predictor for incident atherosclerotic disease. We investigated the effect of 3 hypolipidemic drugs that exert their action through different mechanisms on plasma and lipoprotein-associated Lp-PLA2 activity and mass. Methods and Results— In 50 patients with Type IIA dyslipidemia were administered rosuvastatin (10 mg daily), whereas in 50 Type IIA dyslipidemic patients exhibiting intolerance to previous statin therapy were administered ezetimibe as monotherapy (10 mg daily). Fifty patients with Type IV dyslipidemia were given micronised fenofibrate (200 mg daily). Low- and high-density lipoprotein (LDL and HDL, respectively) subclass analysis was performed electrophoretically, whereas lipoprotein subfractions were isolated by ultracentrifugation. Ezetimibe reduced plasma Lp-PLA2 activity and mass attributable to the reduction in plasma levels of all LDL subfractions. Rosuvastatin reduced enzyme activity and mass because of the decrease in plasma levels of all LDL subfractions and especially the Lp-PLA2 on dense LDL subfraction (LDL-5). Fenofibrate preferentially reduced the Lp-PLA2 activity and mass associated with the VLDL+IDL and LDL-5 subfractions. Among studied drugs only fenofibrate increased HDL-associated Lp-PLA2 (HDL-Lp-PLA2) activity and mass attributable to a preferential increase in Lp-PLA2 associated with the HDL-3c subfraction. Conclusion— Ezetimibe, rosuvastatin, and fenofibrate reduce Lp-PLA2 activity and mass associated with the atherogenic apoB-lipoproteins. Furthermore, fenofibrate improves the enzyme specific activity on apoB-lipoproteins and induces the HDL-Lp-PLA2. The clinical implications of these effects remain to be established.

Effect of ezetimibe monotherapy on the concentration of lipoprotein subfractions in patients with primary dyslipidaemia

ABSTRACT Background: Recent studies suggest that the distribution of lipoprotein subfractions is an independent predictor of vascular events. Therefore, we evaluated the effect of ezetimibe (a selective cholesterol transport inhibitor) on the concentrations of lipoprotein subfractions in patients with primary dyslipidaemia. Materials and methods: Patients (n = 50) with primary dyslipidaemias were recruited. The concentrations of the individual lipoprotein subfractions were measured using the Lipoprint system at baseline and after 16 weeks of treatment. Results: Ezetimibe reduced total, low-density lipoprotein cholesterol (LDL‑C) and non-high-density lipoprotein cholesterol (HDL‑C) values as well as apolipoprotein B concentrations. Subfractionation of apolipoprotein B-containing lipoproteins showed that the reduction in LDL‑C values was due to a fall in the concentrations of all LDL subfractions. However, a more pronounced trend towards a decrease in the concentrations of dense LDL subfractions was observed. Patients with triglyceride values >1.7 mmol/L had significantly greater reductions in the concentrations of small, dense LDL particles compared with those with normal triglyceride levels (49 vs. 19%, respectively; p < 0.05). Ezetimibe decreased the concentrations of HDL‑C mainly due to a fall in the concentration of dense HDL subfractions. Conclusion: Ezetimibe can favourably affect the distribution of LDL subfractions, especially in patients with elevated triglyceride values. Further studies are needed to clarify the significance of the ezetimibe-induced reduction in the concentrations of dense HDL particles.

Effect of ezetimibe on lipoprotein subfraction concentrations: the role of atorvastatin pretreatment

Introduction: Recently published data indicate that the effect of ezetimibe on lipoprotein subfraction distribution in patients receiving statin therapy may differ substantially from that observed in patients treated with ezetimibe monotherapy. The aim of our study was to directly compare the effects of ezetimibe added to established atorvastatin treatment on lipoprotein subfractions with those obtained by ezetimibe monotherapy. Material and methods: Forty dyslipidaemic patients who failed to reach their assigned LDL-C target while on atorvastatin therapy (20 mg/day) for at least 6 months were included in the study. Ezetimibe (10 mg/day) was added to atorvastatin in all patients. The concentrations of the individual lipoprotein subfractions were determined using the Lipoprint method at baseline (prior to the addition of ezetimibe) as well as after 16 weeks of combination treatment. The changes in lipoprotein subfraction concentrations were compared with those observed in 40 age- and sex-matched statin-naive patients receiving ezetimibe monotherapy for 16 weeks. Results: Ezetimibe administration reduced VLDL concentrations either when used as monotherapy or when added to established atorvastatin treatment. However, in contrast to ezetimibe monotherapy, which reduced the concentrations of all LDL subfractions, the addition of ezetimibe in patients receiving atorvastatin decreased LDL cholesterol values exclusively by reducing the concentrations of large, buoyant LDL subfractions. In addition, while ezetimibe monotherapy reduced mainly the concentrations of small, dense LDL subspecies, the addition of ezetimibe in patients receiving atorvastatin equally reduced the concentration of all HDL particles. Conclusions: The effect of ezetimibe on lipoprotein subfractions is significantly affected by previous atorvastatin treatment.