title: Atorvastatin has antithrombotic effects in patients with type 1 diabetes and dyslipidemia.
abstract: BACKGROUND
  Diabetes is a prothrombotic state involving a more thrombogenic fibrin network. In the present study we investigated the effects of lipid-lowering therapy with atorvastatin on fibrin network structure and platelet-derived microparticles in patients with type 1 diabetes and dyslipidemia.
  
  
  METHODS
  Twenty patients were treated with atorvastatin (80 mg daily) or placebo during 2 months in a randomized, double-blind, cross-over study. Fibrin network permeability, expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles, plasma endogenous thrombin potential, plasminogen activator inhibitor-1 and tissue plasminogen activator antigen levels were assessed. Additionally, levels of plasma fibrinogen, high-sensitivity C-reactive protein and glycated haemoglobin were measured.
  
  
  RESULTS
  During treatment with atorvastatin, fibrin network permeability increased (p=0.01), while endogenous thrombin potential and expression of glycoprotein IIIa, P-selectin and tissue factor decreased (p<0.01). In vitro experiments indicated that platelet-derived microparticles influence the fibrin network formation as fibrin network permeability decreased significantly when platelet-derived microparticles were added to normal plasma. Baseline levels of plasminogen activator inhibitor-1 and tissue plasminogen activator antigen as well as plasma fibrinogen and high-sensitivity C-reactive protein were within reference values and not significantly changed during atorvastatin treatment, while glycated haemoglobin increased 0.3% (p<0.001).
  
  
  CONCLUSIONS
  Novel treatment effects were found in patients with type 1 diabetes and dyslipidemia during atorvastatin therapy, i.e. a more porous fibrin network, to which reduced expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles may contribute. The observed impairment of glycemic control during long-term statin treatment deserves attention.
authors.affiliation: Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Division of Internal Medicine, Stockholm, Sweden. sara.tehrani@ds.se
authors.forename: Sara
authors.initials: S
authors.lastname: Tehrani
authors.forename: Fariborz
authors.initials: F
authors.lastname: Mobarrez
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Antovic
authors.forename: Pia
authors.initials: P
authors.lastname: Santesson
authors.forename: Per-Eric
authors.initials: PE
authors.lastname: Lins
authors.forename: Ulf
authors.initials: U
authors.lastname: Adamson
authors.forename: Peter
authors.initials: P
authors.lastname: Henriksson
authors.forename: N Håkan
authors.initials: NH
authors.lastname: Wallén
authors.forename: Gun
authors.initials: G
authors.lastname: Jörneskog
mesh_terms: D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications*; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005337:Fibrin / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D039661:Integrin beta3 / Q000097:blood; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011758:Pyrroles / Q000627:therapeutic use*; D013548:Sweden; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000069059:Atorvastatin; D015415:Biomarkers; D002097:C-Reactive Protein; D005337:Fibrin; D005343:Fibrinolytic Agents; D006442:Glycated Hemoglobin; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D039661:Integrin beta3; D019007:P-Selectin; D017395:Plasminogen Activator Inhibitor 1; D011758:Pyrroles; D013917:Thrombin; D013925:Thromboplastin; C051321:SERPINE1 protein, human; C517652:hemoglobin A1c protein, human