title: 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: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece.
authors.forename: Christos V
authors.initials: CV
authors.lastname: Rizos
authors.forename: Evangelos N
authors.initials: EN
authors.lastname: Liberopoulos
authors.forename: Constantinos C
authors.initials: CC
authors.lastname: Tellis
authors.forename: Matilda
authors.initials: M
authors.lastname: Florentin
authors.forename: Moses S
authors.initials: MS
authors.lastname: Elisaf
authors.forename: Alexandros D
authors.initials: AD
authors.lastname: Tselepis
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000494:pharmacology; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology; D004338:Drug Combinations; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage* / Q000494:pharmacology; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage* / Q000494:pharmacology; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D004338:Drug Combinations; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D047495:PPAR gamma; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000077333:Telmisartan