Atorvastatin has antithrombotic effects in patients with type 1 diabetes and dyslipidemia☆

Abstract 

Introduction

Diabetes is a prothrombotic state involving a more thrombogenic fibrin network. In the present study we investigated the effects of lipid-lowering therapy with atorvastatin on fibrin network structure and platelet-derived microparticles in patients with type 1 diabetes and dyslipidemia.

Materials and Methods

Twenty patients were treated with atorvastatin (80mg daily) or placebo during 2months in a randomized, double-blind, cross-over study. Fibrin network permeability, expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles, plasma endogenous thrombin potential, plasminogen activator inhibitor-1 and tissue plasminogen activator antigen levels were assessed. Additionally, levels of plasma fibrinogen, high-sensitivity C-reactive protein and glycated haemoglobin were measured.

Results

During treatment with atorvastatin, fibrin network permeability increased (p=0.01), while endogenous thrombin potential and expression of glycoprotein IIIa, P-selectin and tissue factor decreased (p<0.01). In vitro experiments indicated that platelet-derived microparticles influence the fibrin network formation as fibrin network permeability decreased significantly when platelet-derived microparticles were added to normal plasma. Baseline levels of plasminogen activator inhibitor-1 and tissue plasminogen activator antigen as well as plasma fibrinogen and high-sensitivity C-reactive protein were within reference values and not significantly changed during atorvastatin treatment, while glycated haemoglobin increased 0.3% (p<0.001).

Conclusions

Novel treatment effects were found in patients with type 1 diabetes and dyslipidemia during atorvastatin therapy, i.e. a more porous fibrin network, to which reduced expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles may contribute. The observed impairment of glycemic control during long-term statin treatment deserves attention.

Abbreviations: PDMPs, Platelet-derived microparticles, Ks, fibrin network permeability coefficient, GP, glycoprotein, TF, tissue factor, ETP, endogenous thrombin potential, hsCRP, high-sensitivity C-reactive protein, HbA_1C, glycated haemoglobin, CVD, cardiovascular disease, MESF, molecules of equivalent soluble fluorochrome, TRAP, thrombin receptor activator peptide, C, cholesterol, HDL-C, high-density lipoprotein cholesterol, TG, triglyceride, LDL-C, low-density lipoprotein cholesterol, ALT, alanine aminotransferase, F1+2, prothrombin fragment 1+2, PAI-1, plasminogen activator inhibitor-1, tPA, tissue plasminogen activator

Keywords: Atorvastatin, Fibrin network, Microparticles, Diabetes