title: Effects of atorvastatin on human C-reactive protein metabolism.
abstract: OBJECTIVE
  Statins are known to reduce plasma C-reactive protein (CRP) concentrations. Our goal was to define the mechanisms by which CRP was reduced by maximal dose atorvastatin.
  
  
  METHODS
  Eight subjects with combined hyperlipidemia (5 men and 3 postmenopausal women) were enrolled in a randomized, placebo-controlled double-blind, cross over study. Subjects underwent a 15-h primed-constant infusion with deuterated leucine after 8 weeks of placebo and 80 mg/day of atorvastatin. CRP was isolated from lipoprotein deficient plasma, (density > 1.21 g/ml) by affinity chromatography. Isotopic enrichment was determined by gas chromatography/mass spectrometry. Kinetic parameters were determined using compartmental modeling. Paired t test and Wilcoxon signed ranks test were used to compare differences between placebo and atorvastatin.
  
  
  RESULTS
  Compared with placebo, atorvastatin decreased median CRP pool size by 28.4% (13.31 ± 3.78 vs 10.26 ± 3.93 mg; p = 0.16), associated with a median CRP fractional catabolic rate increase of 39.9% (0.34 ± 0.06 vs 0.50 ± 0.11 pools/day; p = 0.09), with no significant effect on median CRP production rate (0.050 ± 0.01 vs 0.049 ± 0.01 mg/kg/day; p = 0.78).
  
  
  CONCLUSIONS
  Our data indicate that maximal doses of atorvastatin lower plasma CRP levels by substantially decreasing the median CRP plasma residence time from 2.94 days to 2.0 days, with no significant effect on the median CRP production rate.
authors.affiliation: Lipid Metabolism Laboratory, Tufts University, Boston, MA, USA; Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. nuntakorn.thongtang@tufts.edu
authors.forename: Nuntakorn
authors.initials: N
authors.lastname: Thongtang
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Diffenderfer
authors.forename: Esther M M
authors.initials: EM
authors.lastname: Ooi
authors.forename: Bela F
authors.initials: BF
authors.lastname: Asztalos
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Dolnikowski
authors.forename: Stefania
authors.initials: S
authors.lastname: Lamon-Fava
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Schaefer
mesh_terms: D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000187:drug effects* / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000188:drug therapy / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D002097:C-Reactive Protein; D000069059:Atorvastatin