Lipid-modulating treatments for mixed dyslipidemia increase HDL-associated phospholipase A2 activity with differential effects on HDL subfractions.

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 40 mg 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 3 months 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.