Abstract 687: Increased Fibrin Clot Permeability and Susceptibility to Lysis as a Novel Antithrombotic Effect of Statins
Dense fibrin clot structure is associated with increased risk of advanced coronary artery disease (CAD). It has been suggested that lipid profile and C-reactive protein (CRP) may alter fibrin clot architecture. The aim of the study was to evaluate the effect of statins on fibrin clot structure and resistance to fibrinolysis. We studied men with stable CAD, aged 40 to 65 (mean, 53) years, with LDL cholesterol > 115 mg/dL and triglycerides < 300 mg/dL. Patients with diabetes mellitus, acute infections, heart failure, recent acute coronary syndromes, or taking anticoagulants were excluded. All participants were treated with low-dose aspirin. Before and after a 3-month treatment with simvastatin at a dose of 20 mg/d (n = 36) or 40 mg/d (n = 34), we determined plasma fibrin clot permeability (expressed as Darcy constant, a measure of the pore size) in a pressure-driven system and susceptibility to fibrinolysis (expressed as lysis time) in a turbidimetric assay. Both groups receiving dosages of simvastatin did not differ with regard to demographic and laboratory characteristics, including lipid profile , both before and after the statin therapy. At baseline, clot permeability was negatively associated with age (r = 0.39; p < 0.03), fibrinogen (r = 0.62; p < 0.001), CRP (r = 0.47; p = 0.01), LDL cholesterol (r = 0.52; p < 0.001), and triglycerides (r = 0.41; p = 0.04). Treatment with simvastatin in both doses resulted in a significant increase in clot permeability (by 24.2 %, p < 0.001 for 40 mg/d and by 22.2%, p < 0.001 for 20 mg/d, respectively) and reduction in lysis time (by 22.8%, p = 0.01 and by 20.5%, p = 0.02, respectively) compared with baseline values. Drug-induced changes in permeability and susceptibility to lysis in all subjects studied were positively correlated with decreases in serum CRP levels (r = 0.62; p < 0.001 and r = 0.58; p = 0.02, respectively), but not with reductions in lipids. Following simvastatin administration, clot variables were not associated only with fibrinogen (r = 0.44; p = 0.02). Our results suggest that statins at doses commonly used in clinical practice improve fibrin clot permeability and susceptibility to fibrinolysis, which represent a novel antithrombotic mechanism that might contribute to clinical benefits of statins.