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

ABSTRACT

OBJECTIVES: The aim of the present study was to evaluate the effects of pravastatin treatment on lipid, inflammation, and coagulation parameters in patients suffering from myocardial infarction with or without carotid atherosclerotic lesions (groups 1 and 2, respectively). METHODS: In the first phase of the study, a cross-sectional comparison of lipid, inflammation, and coagulation parameters was performed between the patients and the control group (group 3). Highly significant differences in these parameters were observed, especially in group 1. In the second phase of the study, we assessed the effects of a persistent reduction in cholesterol synthesis induced by increasing doses of pravastatin (20 mg daily for 8 weeks and 40 mg daily for a further 8 weeks). In addition to the well-established lipid-lowering effect, significant changes in inflammation and coagulation parameters were observed. In particular, pravastatin at a dosage of 20 mg/ day significantly reduced only fibrinogen levels, while at a dosage of 40 mg/day significantly reduced factor VII, fibrinogen, prothrombin fragments 1 and 2, thrombin-antithrombin complexes, tissue plasminogen activator antigen (tPAAg) before venous occlusion (b.o.), inhibitor of plasminogen activator activity (PAI) b.o., PAI activity after occlusion (a.o.), the human autoantibodies against oxidized low-density lipoprotein (LDL), and the c fraction of the third component system levels, and significantly increased tPAAg a.o. levels. RESULTS: Our results show that in patients suffering from myocardial infarction the risk of thrombotic complications can be decreased with pravastatin, especially by larger doses. However, the relationship must be further investigated because the observed reductions in the hemostatic system and inflammatory response seemed to be dose dependent, while the effects of pravastatin treatment were not significantly correlated with total and LDL cholesterol changes.