title: Short-term impact of low-dose atorvastatin on serum proprotein convertase subtilisin/kexin type 9.
abstract: OBJECTIVE
  Several small studies have found that moderate- to high-dose statins (HMG-CoA reductase inhibitors) could increase the serum proprotein convertase subtilisin/kexin type 9 (PCSK9) level. However, little is known regarding the short-term, dose-dependent effects of low-dose atorvastatin and the rapid effects of a single dose of atorvastatin on PCSK9. The objective of this study was to investigate the short-term impact of low-dose atorvastatin on PCSK9 in humans.
  
  
  METHODS
  In this randomized study, data from 66 subjects were analyzed. In protocol I, 32 patients were randomized to atorvastatin 10 mg/day (n = 19) or 20 mg/day (n = 13) and eight healthy subjects without therapy were controls for 8 weeks. Serum PCSK9 and lipid profile were determined at day 0, week 4, and week 8. In protocol II, 26 patients were randomized to a single dose of atorvastatin 10 mg (n = 11) or 80 mg (n = 15), and serum levels of PCSK9 were measured at 24 h after treatment.
  
  
  RESULTS
  Atorvastatin 10 mg/day decreased low-density lipoprotein cholesterol (LDL-C) by 32 % at 4 weeks and by 33 % at 8 weeks, and atorvastatin 20 mg/day resulted in reduction of LDL-C by 41 % at 4 weeks and by 38 % at 8 weeks. Atorvastatin 10 mg/day slightly increased serum PCSK9 by 5-7 % but without a significant difference, while atorvastatin 20 mg/day significantly increased serum PCSK9 by 30 % at 4 weeks and by 35 % at 8 weeks (p = 0.009 and p = 0.002, respectively). In addition, 24 h after a single dose, atorvastatin 10 mg significantly increased serum PCSK9 by 13 % and atorvastatin 80 mg by 27 % (p = 0.042 and p = 0.001, respectively).
  
  
  CONCLUSIONS
  The short-term impact of low-dose atorvastatin on PCSK9 was time and dose dependent, with a rapid increase in PCSK9 levels being observed within 24 h of dosing.
authors.affiliation: Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beilishi Road 167, Beijing, 100037, China.
authors.forename: Yuan-Lin
authors.initials: YL
authors.lastname: Guo
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Rui-Xia
authors.initials: RX
authors.lastname: Xu
authors.forename: Cheng-Gang
authors.initials: CG
authors.lastname: Zhu
authors.forename: Na-Qiong
authors.initials: NQ
authors.lastname: Wu
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Jiang
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Li
mesh_terms: D000328:Adult; D000069059:Atorvastatin; D004305:Dose-Response Relationship, Drug; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000097:blood*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases