Simvastatin increases clot permeability and susceptibility to lysis in patients with LDL cholesterol below 3.4 mmol/l

Abstract

Introduction: 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.

Objectives: 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.

Patients and 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.