title: Lipidomic approach to evaluate rosuvastatin and atorvastatin at various dosages: investigating differential effects among statins.
abstract: OBJECTIVE
  Lipid profiling (lipidomics) may be useful in revealing detailed information with regard to the effects on lipid metabolism, the cardiovascular risk and to differentiate between therapies. The aims of the present study were to: (1) analyze in depth the lipid changes induced by rosuvastatin and atorvastatin at different dosages; (2) compare differences between the two drugs with respect to the lipid profile change; (3) relate the findings with meaningful pathological mechanisms of coronary artery disease.
  
  
  METHODS
  Liquid chromatography-mass spectrometry was applied to obtain the metabolite profiles of plasma samples taken from a prospectively defined subset (n=80) of participants in the RADAR study where a randomly assigned treatment with rosuvastatin or atorvastatin in increasing dosages was administered during an 18-week period.
  
  
  RESULTS
  A number of sphingomyelins (SPMs) and phosphatidylcholines (PCs) correlate with the different effects of the two statins on the LDL-C/HDL-C ratio. Rosuvastatin increased the plasma concentration of PCs after 6 and 18 weeks, while atorvastatin reduced the plasma concentrations of PCs at both timepoints and dosages (p<0.01 for between-treatment comparison). Both atorvastatin and rosuvastatin lowered plasma SPMs concentrations, but atorvastatin demonstrated a more pronounced effect with the highest dose (p=0.03). Rosuvastatin resulted in a significantly more effective lowering of the [SPMs/(SPMs + PCs)] ratio than atorvastatin at any dose/timepoint (p<0.05), a ratio reported to be of clinical importance in coronary artery disease.
  
  
  CONCLUSIONS
  The lipidomic technique has revealed that statins are different with regards to the effect on detailed lipid profile. The observed difference in lipids may be connected with different clinical outcomes as suggested by the [SPMs/(SPMs + PCs)] ratio.
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Sandrin C
authors.initials: SC
authors.lastname: Bergheanu
authors.forename: Theo
authors.initials: T
authors.lastname: Reijmers
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Ivana
authors.initials: I
authors.lastname: Bobeldijk
authors.forename: Raymond
authors.initials: R
authors.lastname: Ramaker
authors.forename: An-Ho
authors.initials: AH
authors.lastname: Liem
authors.forename: Jan
authors.initials: J
authors.lastname: van der Greef
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankemeier
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
mesh_terms: D000069059:Atorvastatin; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000627:therapeutic use*; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood / Q000145:classification*; D013058:Mass Spectrometry; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin