title: Simvastatin increases clot permeability and susceptibility to lysis in patients with LDL cholesterol below 3.4 mmol/l.
abstract: BACKGROUND
  Statins produce additional beneficial effects, including attenuation of prothrombotic mechanisms. In patients at high cardiovascular risk, who have markedly elevated low-density lipoprotein (LDL) cholesterol levels, simvastatin can reduce thrombin generation. Moreover, we have described simvastatin-induced improvement of fibrin clot properties, the formation of which represents the final step of blood coagulation.
  
  
  OBJECTIVE
  The aim of the present study was to assess the effect of simvastatin on fibrin features observed in subjects with LDL cholesterol <3.4 mmol/l.
  
  
  METHODS
  Thirty subjects (24M, 6F) aged <70 years with LDL cholesterol <3.4 mmol/l with no history of cardiovascular events were enrolled in the study. Patients were excluded if they had diabetes mellitus, chronic inflammatory diseases and renal insufficiency. Prior to and following a 3-month treatment with simvastatin (40 mg/d), ex vivo plasma fibrin clot permeability and efficiency of clot lysis were measured.
  
  
  RESULTS
  Simvastatin led to a significant decrease in total cholesterol, LDL cholesterol, triglycerides and C-reactive protein (CRP), while fibrinogen levels remained unaltered. There were posttreatment increase in clot permeability by 4.4% (p<0.001) and shortening of clot lysis by 11.2% (p<0.001) compared to pretreatment values. These changes were correlated with reduction in CRP following simvastatin. Simvastatin-induced increase in clot permeability was associated only with age and decrease in CRP levels (R2 for the model = 0.61), while shortening of clot lysis time observed following simvastatin use was predicted only by reduction of triglycerides and CRP (R2 for the model = 0.62).
  
  
  CONCLUSIONS
  Simvastatin exerts unique properties involving enhanced fibrin clot lysis and increased clot permeability in subjects with LDL cholesterol <3.4 mmol/l, which is associated with its anti-inflammatory effects. Altered fibrin clot function might contribute to clinical benefits of statins.
authors.affiliation: Institute of Cardiology, Jagiellonian University School of Medicine, Kraków, Poland. mmundas@cyf-kr.edu.pl
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
authors.forename: Roman
authors.initials: R
authors.lastname: Topór-Madry
authors.forename: Wiesława
authors.initials: W
authors.lastname: Tracz
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D002097:C-Reactive Protein / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010539:Permeability; D019821:Simvastatin / Q000008:administration & dosage*; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D014280:Triglycerides; D002097:C-Reactive Protein; D019821:Simvastatin