title: Changes in ultracentrifugally separated plasma lipoprotein subfractions in patients with polygenic hypercholesterolemia, familial combined hyperlipoproteinemia, and familial hypercholesterolemia after treatment with atorvastatin.
abstract: BACKGROUND
  Plasma levels of low-density lipoproteins (LDLs) are decreased through stimulation of their hepatic uptake by statins via an LDL receptor. However, it is unclear whether statins equally stimulate the hepatic uptake of all LDL subfractions.
  
  
  OBJECTIVE
  We compared the effects of atorvastatin on 3 LDL subfractions, and their associations with LDL-receptor activities, in Japanese patients with polygenic hypercholesterolemia (PHC), familial combined hyperlipoproteinemia (FCHL), and familial hypercholesterolemia (FH).
  
  
  METHODS
  Atorvastatin was administered to patients with PHC (n = 11), FCHL (n = 16), and FH (n = 13). We measured plasma levels of lipids, remnant-like particle cholesterol, apoproteins, and cholesterol in lipoprotein fractions. Sequential ultracentrifugation was performed to subfractionate the plasma lipoproteins, and lymphocyte LDL-receptor activities were estimated using flow cytometry.
  
  
  RESULTS
  The average daily dosage of atorvastatin was 10, 27, and 40 mg in patients with PHC, FCHL, and FH, respectively; after 12 months of atorvastatin treatment, LDL cholesterol (LDL-C) plasma levels decreased by 44%, 50%, and 53%, respectively (all, P < .0001). Atorvastatin reduced low-density LDL-C plasma levels in patients with PHC (48% reduction), FCHL (53%), and FH (46%) (all, P < .0001). Plasma levels of medium-density and high-density LDL-C were also significantly reduced in the 3 patient groups (all, P ≤ .0147). LDL-receptor activity was negatively correlated with baseline levels of medium-density LDL-C and with the decreases in plasma md-LDL-C levels.
  
  
  CONCLUSIONS
  Atorvastatin decreased the levels of the 3 LDL fractions. The md-LDL decrease appeared to be mainly because of stimulation of LDL-receptor activity.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan; Department of Emergency Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan. Electronic address: homma@keio.jp.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Homma
authors.affiliation: Department of Clinical Health Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Homma
authors.affiliation: Apheresis and Dialysis Center, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Internal Medicine, Tokai University School of Medicine, Shimokasuya, Isehara, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ozawa
authors.affiliation: Department of Clinical Health Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shiina
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Wakino
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.affiliation: Department of Emergency Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Hori
mesh_terms: D000328:Adult; D000368:Aged; D000069059:Atorvastatin / Q000008:administration & dosage*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011973:Receptors, LDL / Q000096:biosynthesis / Q000097:blood; D014461:Ultracentrifugation
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D011973:Receptors, LDL; D000069059:Atorvastatin
keywords: Atorvastatin; Familial combined hyperlipoproteinemia; Familial hypercholesterolemia; Hypercholesterolemia; LDL-receptor activity; Lipoprotein subfractions; Polygenic hypercholesterolemia