title: Effects of atorvastatin and simvastatin on low-density lipoprotein subfraction profile, low-density lipoprotein oxidizability, and antibodies to oxidized low-density lipoprotein in relation to carotid intima media thickness in familial hypercholesterolemia.
abstract: BACKGROUND
  Little is known about the effects of statins on the quality of circulating low-density lipoprotein (LDL) in relation to atherosclerosis progression.
  
  
  METHODS
  In a double-blind, randomized trial of 325 patients with familial hypercholesterolemia (FH), we assessed the effects of high-dose atorvastatin (80 mg) and conventional-dose simvastatin (40 mg) on LDL subfraction profile (n = 289), LDL oxidizability (n = 121), and circulating autoantibodies to oxidized LDL (n = 220). Progression of atherosclerosis was measured by carotid intima media thickness (IMT) (n = 325).
  
  
  RESULTS
  At baseline, the patients showed an intermediate LDL subfraction profile composed of three LDL subfractions (LDL1, LDL2, LDL3), with LDL2 as the predominant subfraction. A strong negative correlation was found between plasma triglycerides and the LDL subfraction profile (r = -.64, p = .000). Both plasma levels of triglycerides and small dense LDL3 correlated weakly with baseline IMT (r = .11, p = .04 and r = .15, p = .01, respectively; n = 289). No association was found between baseline IMT and oxidation parameters or circulating antibodies to oxidized LDL. Atorvastatin reduced triglycerides, LDL cholesterol, and all LDL subfractions to a greater extent than did simvastatin and led to regression of carotid IMT. However, LDL subfraction pattern and plasma levels of autoantibodies to oxidized LDL remained unchanged in both treatment groups, and LDL oxidizability increased minimally to a similar extent in both groups. Significant treatment differences were found for the rate of in vitro oxidation of LDL and the amount of dienes formed during in vitro oxidation of LDL, which both decreased more following atorvastatin than after simvastatin.
  
  
  CONCLUSIONS
  Change of IMT after statin treatment was associated with baseline IMT (r = .41), LDL cholesterol (r = -.20), and the amount of dienes formed during in vitro oxidation of LOL (r = .28) but not with plasma levels of antibodies to oxidized LDL, in vitro LDL oxidizability, and LDL subfraction profile.
authors.affiliation: Department of Medicine, Division of General Internal Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands. B.vantits@aig.umcn.nl
authors.forename: Lambertus J H
authors.initials: LJ
authors.lastname: van Tits
authors.forename: Tineke J
authors.initials: TJ
authors.lastname: Smilde
authors.forename: Sanne
authors.initials: S
authors.lastname: van Wissen
authors.forename: Jacqueline
authors.initials: J
authors.lastname: de Graaf
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Anton F H
authors.initials: AF
authors.lastname: Stalenhoef
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000187:drug effects; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000276:immunology; D008077:Lipoproteins, LDL / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000187:drug effects; D014463:Ultrasonography
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D008077:Lipoproteins, LDL; D011758:Pyrroles; C099252:oxidized low density lipoprotein; D000069059:Atorvastatin; D019821:Simvastatin