title: The effects of rosuvastatin alone or in combination with fenofibrate or omega 3 fatty acids on inflammation and oxidative stress in patients with mixed dyslipidemia.
abstract: OBJECTIVE
  Mixed dyslipidemia, oxidative stress and inflammation are related to a high risk for cardiovascular events. The aim of this open-label randomized study was to compare the effects of high-dose rosuvastatin, low-dose rosuvastatin plus fenofibrate and low-dose rosuvastatin plus omega 3 fatty acids on inflammation and oxidative stress indices in patients with mixed dyslipidemia.
  
  
  METHODS
  Ninety patients with mixed dyslipidemia participated in the study. Patients were randomly allocated to receive rosuvastatin 40 mg (n = 30, group R), rosuvastatin 10 mg plus fenofibrate 200 mg (n = 30, group RF) or rosuvastatin 10 mg plus omega 3 fatty acids 2 g daily (n = 30, group RΩ). Plasma and high-density lipoprotein (HDL)-associated lipoprotein-associated phospholipase A2 (LpPLA2) activities, high-sensitivity C reactive protein (hsCRP), plasma isoprostane and paraoxonase (PON1) activities were measured at baseline and after 3 months of treatment.
  
  
  RESULTS
  Serum concentrations of non-HDL cholesterol and low-density lipoprotein cholesterol (LDL-C) were significantly reduced in all study groups. However, these changes were more pronounced in the rosuvastatin monotherapy group. In all treatment groups a significant reduction in total plasma LpPLA2 activity was observed (by 41, 38 and 30% for groups R, RF and RΩ, respectively). This decrease was greater in the R and RF groups compared with the RΩ combination (p < 0.05). HDL-LpPLA2 activity was increased more in the RF group (+43%) compared with the R and RΩ groups (+ 18% and + 35%, respectively; p < 0.05 for both comparisons). In all treatment groups there was a nonsignificant reduction in plasma 8-iso-PGF2α levels. A 53% reduction of hsCRP levels was observed in the R group, while in the RF and RΩ groups the reduction was 28 and 23%, respectively (p < 0.05 and p < 0.01 for the comparisons of group R with groups RF and RΩ, respectively). No significant changes were observed in PON activities in all treatment groups.
  
  
  CONCLUSIONS
  The greater non-HDL-C- and LDL-C-lowering efficiency of rosuvastatin monotherapy along with its more potent effect on LpPLA2 activity and hsCRP levels indicate that this regimen is a better treatment option for patients with mixed dyslipidemia.
authors.affiliation: University of Ioannina Medical School, Department of Internal Medicine, 45110 Ioannina, Greece.
authors.forename: Aris P
authors.initials: AP
authors.lastname: Agouridis
authors.forename: Vasilis
authors.initials: V
authors.lastname: Tsimihodimos
authors.forename: Theodosios D
authors.initials: TD
authors.lastname: Filippatos
authors.forename: Andromachi A
authors.initials: AA
authors.lastname: Dimitriou
authors.forename: Costantinos C
authors.initials: CC
authors.lastname: Tellis
authors.forename: Moses S
authors.initials: MS
authors.lastname: Elisaf
authors.forename: Dimitri P
authors.initials: DP
authors.lastname: Mikhailidis
authors.forename: Alexandros D
authors.initials: AD
authors.lastname: Tselepis
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D000328:Adult; D000368:Aged; D043303:Aryldialkylphosphatase / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004338:Drug Combinations; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D011743:Pyrimidines / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D004338:Drug Combinations; D015525:Fatty Acids, Omega-3; D005464:Fluorobenzenes; D000960:Hypolipidemic Agents; D008055:Lipids; D011743:Pyrimidines; D013449:Sulfonamides; C075750:8-epi-prostaglandin F2alpha; D000068718:Rosuvastatin Calcium; D002097:C-Reactive Protein; D015237:Dinoprost; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D011345:Fenofibrate