Non lipid, dose-dependent effects of pravastatin treatment on hemostatic system and inflammatory response

Objectives: The aim of the present study was to evaluate the effects of pra vastatin treatment on lipid, inflammation, and coagulation parameters in pa tients suffering from myocardial infarction with or without carotid atheros clerotic lesions (groups 1 and 2, respectively). Methods: In the first phase of the study, a cross-sectional comparison of l ipid, inflammation, and coagulation parameters was performed between the pa tients and the control group (group 3). Highly significant differences in t hese parameters were observed, especially in group 1. In the second phase o f the study, we assessed the effects of a persistent reduction in cholester ol synthesis induced by increasing doses of pravastatin (20 mg daily for 8 weeks and 40 mg daily fora further 8 weeks). In addition to the well-establ ished lipid-lowering effect, significant changes in inflammation and coagul ation parameters were observed. In particular, pravastatin at a dosage of 2 0 mg/day significantly reduced only fibrinogen levels, while at a dosage of 40 mg/day significantly reduced factor VII, fibrinogen, prothrombin fragme nts 1 and 2, thrombin-antithrombin complexes, tissue plasminogen activator antigen (tPA:Ag) before venous occlusion (b.o.), inhibitor of plasminogen a ctivator activity (PAI) b.o., PAI activity after occlusion (a.o.), the huma n autoantibodies against oxidized low-density lipoprotein (LDL), and the c fraction of the third component system levels, and significantly increased tPA:Ag a.o. levels. Results: Our results show that in patients suffering from myocardial infarc tion the risk of thrombotic complications can be decreased with pravastatin , especially by larger doses. However, the relationship must be further inv estigated because the observed reductions in the hemostatic system and infl ammatory response seemed to be dose dependent, while the effects of pravast atin treatment were not significantly correlated with total and LDL cholest erol changes.