title: Impact of simvastatin on hemostatic and fibrinolytic regulators in Type 2 diabetes mellitus.
abstract: Simvastatin, a widely used 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, effectively reduced cardiac death and ischemic events in patients with coronary heart disease (CHD) and diabetes mellitus (DM). The mechanism of cardiovascular benefits of statins in DM remains unclear. We examined how simvastatin influences the levels of several in vivo markers for coagulation and fibrinolysis in 26 Type 2 DM patients. The diabetic patients received 20 mg/day of simvastatin up to 12 months. The levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-c) and triglycerides in peripheral circulation of patients were significantly reduced after > or =6 weeks of simvastatin treatment. Levels of prothrombin fragment 1+2 (F1+2), factor VII, plasminogen activator inhibitor-1 (PAI-1) and tissue factor pathway inhibitor (TFPI) antigens, but not tissue plasminogen activator (tPA) antigen, in the pre-simvastatin plasmas of the diabetic patients were significantly higher than the levels found in plasmas of healthy subjects. Significant reductions in F1+2 and PAI-1 levels were evident > or =6 weeks after the diabetic patients received simvastatin. Levels of total tPA, TFPI, FVII, hemoglobin A1c, fasting blood glucose, and insulin in the diabetic patients' plasma were not significantly altered by simvastatin treatment. Positive correlations were found between PAI-1 versus TC, PAI-1 versus LDL-c, and FVII versus triglycerides in the plasmas of simvastatin-treated patients. The results suggest that simvastatin reduces in vivo prothrombinase activity and PAI-1 levels in type 2 DM patients. These actions may contribute to the protective properties of simvastatin against ischemic events in diabetic patients.
authors.affiliation: Diabetes Research Group, Department of Internal Medicine, University of Manitoba, 835-715 McDermot Ave., Winnipeg, Man., Canada.
authors.forename: Sora
authors.initials: S
authors.lastname: Ludwig
authors.forename: Sudharshan
authors.initials: S
authors.lastname: Dharmalingam
authors.forename: Sharon
authors.initials: S
authors.lastname: Erickson-Nesmith
authors.forename: Song
authors.initials: S
authors.lastname: Ren
authors.forename: Fuqin
authors.initials: F
authors.lastname: Zhu
authors.forename: Guoping M
authors.initials: GM
authors.lastname: Ma
authors.forename: Ruozhi
authors.initials: R
authors.lastname: Zhao
authors.forename: John W
authors.initials: JW
authors.lastname: Fenton
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Ofosu
authors.forename: Henk Te
authors.initials: HT
authors.lastname: Velthuis
authors.forename: Gerald
authors.initials: G
authors.lastname: van          Mierlo
authors.forename: Garry X
authors.initials: GX
authors.lastname: Shen
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000378:metabolism*; D005167:Factor VII / Q000378:metabolism; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology; D006487:Hemostasis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011516:Prothrombin / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D008055:Lipids; D008074:Lipoproteins; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; C051928:lipoprotein-associated coagulation inhibitor; C045879:prothrombin fragment 1.2; D005167:Factor VII; D011516:Prothrombin; D019821:Simvastatin; D010959:Tissue Plasminogen Activator