Abstract
BackgroundCardiovascular disease with disturbances in the haemostatic system, might lead to thrombotic complications with clinical manifestations like acute myocardial infarction (AMI) and stroke. Activation of the coagulation cascade with subsequent increased thrombin generation, characterizes a prothrombotic phenotype. In the present study we investigated whether prothrombotic markers were associated with risk factors and clinical subgroups in a cohort of patients with angiographically verified coronary artery disease (CAD). The patients were randomized to long-term treatment with the antiplatelet drugs aspirin or clopidogrel, and we further investigated the effect on hypercoagulability of such treatment for 1 year, of which limited data exists.MethodsVenous blood samples were collected in fasting condition between 08:00 and 10:30 am, at baseline when all patients were on aspirin therapy (n = 1001) and in 276 patients after 1 year follow-up on aspirin or clopidogrel. In vivo thrombin generation was assessed by prothrombin fragment 1 + 2 (F1+2) and D-dimer, and the endogenous thrombin potentiale (ETP) in the calibrated automated thrombogram (CAT) assay, representing ex vivo thrombin generation. In addition soluble tissue factor (sTF) and free- and total tissue factor pathway inhibitor (TFPI) were measured.ResultsWe found age to be significantly associated with F1+2 and D-dimer (β = 0.229 and β =0.417 respectively, p <0.001, both). Otherwise, only weak associations were found. F1+2 and D-dimer were higher in women compared to men (p <0.001 and p = 0.033, respectively). Smokers had elevated levels of ETP compared to non-smokers (p = 0.014). Additionally, patients on renin-angiotensin system (RAS) inhibition showed significantly higher levels of F1+2, compared to non-users (p = 0.013). Both aspirin and clopidogrel reduced levels of ETP after 12 months intervention (p = 0.003 and p <0.001, respectively) and the levels of F1+2 were significantly more reduced on aspirin compared to clopidogrel (p = 0.023).ConclusionsIn the present population of stable CAD, we could demonstrate a more hypercoagulable profile among women, smokers and patients on RAS medication, assessed by the prothrombotic markers F1+2, D-dimer and ETP. Long-term antiplatelet treatment with aspirin alone seems to attenuate thrombin generation to a greater extent than with clopidogrel alone. The study is registered at http://www.clinicaltrials.gov: NCT00222261.
Highlights
Cardiovascular disease with disturbances in the haemostatic system, might lead to thrombotic complications with clinical manifestations like acute myocardial infarction (AMI) and stroke
Laboratory methods Levels of soluble tissue factor (TF) (sTF), tissue factor pathway inhibitor (TFPI), fragment 1+2 (F1+2) and D-dimer were assessed by commercially available enzyme immunoassays; Imubind TF kit recognizing TF-apolipoprotein, sTF and TF-VII complexes (American Diagnostic Inc., Greenwich, Conn., USA), Asserachrom free and total TFPI antigen, recognizing full-length and full-length and truncated TFPI molecules associated to lipoproteins, respectively (Stago Diagnostica, Asniere, France), EnzygnostW F1+2 (Siemens, Marburg, Germany) and AsserachromW D-dimer (Stago Diagnostica)
In the present study on patients with stable coronary artery disease (CAD) we could show that age was significantly associated to in vivo thrombin generation assessed by F1+2 and Ddimer
Summary
Cardiovascular disease with disturbances in the haemostatic system, might lead to thrombotic complications with clinical manifestations like acute myocardial infarction (AMI) and stroke. Activation of the coagulation cascade with subsequent increased thrombin generation, characterizes a prothrombotic phenotype. In the present study we investigated whether prothrombotic markers were associated with risk factors and clinical subgroups in a cohort of patients with angiographically verified coronary artery disease (CAD). Expression of subendothelial tissue factor (TF) with subsequent activation of the coagulation cascade generates thrombin at the surface of activated platelets [2,3]. Increased levels of the haemostatic markers sTF, F1+2 and D-dimer, the latter reflecting ongoing fibrin formation and degradation, have been shown in patients with CVD, whereas the role of TFPI in CVD is less clear [6]
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