title: Influence of withdrawal of statin treatment on proinflammatory response and fibrinolytic activity in humans: an effect independent on cholesterol elevation.
abstract: BACKGROUND
  In addition to lowering lipid profile, statins have pleiotropic effects on improving vascular function. Changes of these pleiotropic effects and their relationship to lipid profile after withdrawal of statin treatment remained unclear.
  
  
  METHODS
  We investigated the changes of lipid profile and plasma concentrations of human soluble vascular cell adhesion molecule-1 (sVCAM-1) and human tissue type plasminogen activator (tPA) after withdrawal of statin treatment. Twenty-two patients (14 F, 8 M, aged 63+/-13 years) with hypercholesterolemia were treated with atorvastatin (ATOR; 10 mg/day) for 12 weeks. Blood samplings for serum lipid and markers were collected before, after and withdrawal of statin treatment.
  
  
  RESULTS
  The total cholesterol, LDL-cholesterol and sVCAM-1 (from 394.4+/-251.7 to 321.0+/-198.9 ng/ml, p<0.05) all decreased significantly and the tPA (from 9.47+/-3.57 to 11.62+/-3.99 ng/ml, p<0.05) increased significantly after atorvastatin treatment. During the following 3 days after withdrawal of atorvastatin, the total cholesterol and LDL-cholesterol did not show any significant change. However, the plasma sVCAM-1 significantly elevated on day 2 (from 321.0+/-198.9 to 371.2+/-220.4 ng/ml, p<0.05) and the plasma tPA significantly decreased on day 1 (from 11.62+/-3.99 to 10.52+/-3.55 ng/ml, p<0.05) and day 3 (from 11.62+/-3.99 to 10.27+/-3.69 ng/ml, p<0.05). Both the significant elevation of sVCAM-1 and decrease of tPA after withdrawal of atorvastatin treatment occurred within 3 days, while the serum cholesterol and LDL-chol levels did not have any significant change and were still within the therapeutic range.
  
  
  CONCLUSIONS
  After 12 weeks of atorvastatin treatment, the beneficial pleiotropic effects can be demonstrated simultaneously with lowering the lipid profile. However, after withdrawal of atorvastatin, the beneficial pleiotropic effects are abrogated rapidly within days and are independent on elevation of serum cholesterol.
authors.affiliation: Section of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Shih-Chuang 1st Rd., Kaohsiung 80708, Taiwan. wtlai@cc.kmu.edu.tw
authors.forename: Wen-Ter
authors.initials: WT
authors.lastname: Lai
authors.forename: Kun-Tai
authors.initials: KT
authors.lastname: Lee
authors.forename: Chih-Sheng
authors.initials: CS
authors.lastname: Chu
authors.forename: Wen-Choi
authors.initials: WC
authors.lastname: Voon
authors.forename: Hsueh-Wei
authors.initials: HW
authors.lastname: Yen
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Tsai
authors.forename: Sheng-Hsiung
authors.initials: SH
authors.lastname: Sheu
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000097:blood*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
chemical_list: D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D019010:Vascular Cell Adhesion Molecule-1; D002784:Cholesterol; D000069059:Atorvastatin; D010959:Tissue Plasminogen Activator