Lipid‐Modulating Treatments for Mixed Dyslipidemia Increase HDL‐Associated Phospholipase A2 Activity with Differential Effects on HDL Subfractions

Abstract

The effect of lipid-modulating treatments on modification of high density lipoprotein (HDL) subfractions remains unknown. In this study, mixed dyslipidemia patients (n=100) inadequately controlled with a standard statin dose were randomized to switch to 40mg of rosuvastatin or add-on extended release nicotinic acid/laropiprant (ER-NA/LRPT) or add-on fenofibrate. The cholesterol concentrations of HDL (HDL-C) subfractions and HDL-associated lipoprotein-associated phospholipase A2 (HDL-Lp-PLA2) activity were assessed at baseline and 3months later. We observed that large HDL-C increased by 50 and 6% in the add-on-ER-NA/LRPT and rosuvastatin groups, respectively, while it decreased by 20% in the add-on-fenofibrate group (p<0.01 vs baseline for all groups and p<0.01 for all comparisons among groups). On the other hand, small HDL-C decreased by 17% in the add-on-ER-NA/LRPT group (p<0.01 vs baseline), while it increased by 25% in the add-on-fenofibrate group (p<0.01 vs baseline) without any change in the rosuvastatin group (p<0.01 for all comparisons among groups). HDL-Lp-PLA2 activity increased by 55, 33 and 18% in add-on-ER-NA/LRPT, add-on-fenofibrate and rosuvastatin groups, respectively (p<0.01 for all comparisons vs baseline and for all comparisons among groups). In conclusion, add-on-ER-NA/LRPT was associated with an increase in large HDL-C and a decrease in small HDL-C, while opposite effects were noticed in the add-on-fenofibrate group. Add-on-ER-NA/LRPT was associated with the most pronounced increase in HDL-Lp-PLA2 activity.