Combining Rosuvastatin with Sartans of Different Peroxisome Proliferator-Activated Receptor-γ Activating Capacity Is Not Associated with Different Changes in Low-Density Lipoprotein Subfractions and Plasma Lipoprotein-Associated Phospholipase A2

Abstract

Rosuvastatin reduces low-density lipoprotein cholesterol (LDL-C) and plasma lipoprotein-associated phospholipase A₂ (Lp-PLA₂) Some sartans partially activate peroxisome proliferator-activated receptor-γ (PPARγ), possibly having a favorable effect on metabolic parameters. Telmisartan is the most potent partial PPARγ activator, followed by irbesartan, whereas olmesartan does not hold such capacity. In an open-label randomized study, we assessed the effects of combining sartans of different PPARγ- activating capacity with rosuvastatin on LDL subfractions and plasma Lp-PLA₂ in patients with mixed dyslipidemia, hypertension, and prediabetes. Following dietary intervention, patients were allocated randomly to rosuvastatin (10 mg/day) plus telmisartan 80 mg/day (RT group, n = 52) or irbesartan 300 mg/day (RI group, n = 48) or olmesartan 20 mg/day (RO group, n = 51). After 6 months of treatment, changes in LDL subfraction cholesterol and plasma Lp-PLA(2) activity and mass were evaluated blindly. A total of 151 patients (73 male; mean age 60 years) were included. Large LDL-C decreased in the RT (-36%), RI (-39%), and RO (-41%) groups (P < 0.001 for all vs. baseline). Small dense LDL-C decreased in the RT (-67%), RI (-58%), and RO (-61%) groups (P < 0.001 for all vs. baseline). All regimens increased LDL particle size versus baseline (RT + 1.4%, P = 0.002; RI + 1.0%, P = 0.04; and RO + 1.4%, P = 0.001). No difference for the change of LDL subfractions and LDL size was noticed among groups. Plasma Lp-PLA₂ activity decreased equally in all groups (RT -38%, RI -38%, RO -43%) (P < 0.001 for all vs. baseline). Plasma Lp-PLA₂ mass decreased similarly in all groups versus baseline (RT -28%, P = 0.001; RI -32%, P = 0.01; and RO -27%, P = 0.001). No difference for the change of Lp-PLA₂ mass or activity was noticed among groups. The combination of rosuvastatin with sartans of different PPARγ-activating capacity did not differentiate alterations of LDL subfraction cholesterol and plasma Lp-PLA(2) activity and mass.