title: Comparison of the effects of low-dose rosuvastatin on plasma levels of cholesterol and oxidized low-density lipoprotein in 3 ultracentrifugally separated low-density lipoprotein subfractions.
abstract: BACKGROUND
  Plasma-oxidized (ox) low-density lipoprotein (LDL) is an atherogenic lipoprotein. The distribution of ox-LDL in plasma LDL subfractions and the effect of statins on this distribution have not been investigated in detail.
  
  
  OBJECTIVE
  We examined the distribution of cholesterol and ox-LDL in 3 ultracentrifugally separated plasma LDL subfractions and investigated the effects of a statin, rosuvastatin, on the levels of these lipoproteins.
  
  
  METHODS
  Thirty-one polygenic hypercholesterolemic subjects were included in this study. Levels of cholesterol and ox-LDL in 3 plasma LDL subfractions and plasma levels of remnant-like particle cholesterol, ox-LDL, and adiponectin were measured after 0, 3, 6, and 12 months of treatment with rosuvastatin. Sequential ultracentrifugation was performed to subfractionate plasma lipoproteins.
  
  
  RESULTS
  The mean daily dose of rosuvastatin over the 12 months of treatment was 2.9 ± 1.0 mg (mean ± standard deviation). The cholesterol subfraction distribution was 43 ± 10% as low-density LDL, 46 ± 8% as medium-density LDL, and 13 ± 5% as high-density LDL. Similarly, the distribution of ox-LDL was 31 ± 10% as low-density LDL, 48 ± 7% as medium-density LDL, and 22 ± 8% as high-density LDL. After 12 months of treatment with rosuvastatin, the level of cholesterol was significantly reduced in all 3 subfractions (P < .0001), as was the level of ox-LDL (P < .0001). Furthermore, the plasma cholesterol level in high-density lipoprotein2 increased significantly.
  
  
  CONCLUSIONS
  The distribution of ox-LDL in plasma LDL subfractions was more skewed toward the denser subfractions, compared with cholesterol. Rosuvastatin treatment significantly reduced plasma levels of cholesterol and ox-LDL in all LDL subfractions.
authors.affiliation: Department of Emergency and Critical Care Medicine, School of Medicine, Keio University, Tokyo, Japan; Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. Electronic address: homma@keio.jp.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Homma
authors.affiliation: Department of Internal Medicine, Hiratsuka Lifestyle-Related Diseases and Hemodialysis Clinic, Kanagawa, Japan; Department of Clinical Health Science, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Homma
authors.affiliation: Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ozawa
authors.affiliation: Department of Clinical Health Science, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shiina
authors.affiliation: Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Shibata
authors.affiliation: Apheresis and Dialysis Center, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanda
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Tokuyama
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Wakino
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.affiliation: Department of Emergency and Critical Care Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Hori
mesh_terms: D052242:Adiponectin / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D059168:Carotid Intima-Media Thickness; D002784:Cholesterol / Q000097:blood* / Q000302:isolation & purification*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D008077:Lipoproteins, LDL / Q000097:blood* / Q000302:isolation & purification*; D008297:Male; D008875:Middle Aged; D000068718:Rosuvastatin Calcium / Q000494:pharmacology* / Q000627:therapeutic use; D014461:Ultracentrifugation
chemical_list: D052242:Adiponectin; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D000068718:Rosuvastatin Calcium; D002097:C-Reactive Protein; D002784:Cholesterol
keywords: Adiponectin; Carotid atherosclerosis; Cholesterol; LDL subfractions; Oxidized LDL; Rosuvastatin; hs-CRP