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Published on: September 9, 2012
Activated factor XI is associated with increased factor VIIa - Antithrombin complexes in stable coronary artery
Elżbieta Paszek1,2, Elżbieta Pociask3, Michał Ząbczyk2,4
1Clinical Department of Interventional Cardiology, John Paul II Hospital, Krakow, Poland.
Insights
High factor VIIa-antithrombin complexes in coronary artery disease patients indicate increased tissue factor exposure and predict stroke risk. These findings suggest a need for targeted antithrombotic therapies in advanced CAD.
Area of Science:
- Cardiovascular Medicine
- Hemostasis and Thrombosis
- Biomarkers in Disease
Background:
- Coronary artery disease (CAD) is linked to a prothrombotic state, evidenced by elevated factor VIIa-antithrombin (FVIIa-AT) complexes, a marker of tissue factor (TF) exposure, and activated factor XI (FXIa).
- Understanding the interplay between these factors and clinical outcomes is crucial for managing CAD patients.
Purpose of the Study:
- To investigate the association between elevated FVIIa-AT complexes, FXIa, and active TF in CAD patients.
- To determine if FVIIa-AT complexes predict major adverse clinical outcomes in this population.
Main Methods:
- Assessed FVIIa-AT complex concentrations, circulating FXIa, and active TF in 120 CAD patients.
- Measured oxidative stress markers (8-iso-PGF2α), inflammatory markers, and thrombin generation markers.
- Recorded incidence of myocardial infarction, ischemic stroke, systemic thromboembolism, and cardiovascular death during long-term follow-up.
Main Results:
- FVIIa-AT complexes correlated with smoking and multivessel CAD, and were associated with FXIa/active TF and increased isoprostanes.
- High baseline FVIIa-AT complexes significantly predicted ischemic stroke/systemic thromboembolism (HR 4.61) and a composite endpoint of major adverse cardiovascular events (HR 7.47).
- No association was found between FVIIa-AT complexes and thrombin generation or inflammatory markers.
Conclusions:
- Elevated FVIIa-AT complexes identify advanced CAD patients with FXIa and active TF, partly due to oxidative stress.
- High FVIIa-AT complexes are a significant predictor of ischemic stroke/systemic thromboembolism in long-term follow-up.
- These findings underscore the importance of developing effective antithrombotic strategies for CAD management.
Background:
Coronary artery disease (CAD) is associated with a prothrombotic tendency including increased factor (F) VIIa-antithrombin (FVIIa-AT) complexes, a measure of tissue factor (TF) exposure, and activated FXI (FXIa). We investigated whether increased FVIIa-AT complexes are associated with FXIa and active TF and if major adverse clinical outcomes are predicted by the complexes in CAD.
Methods:
In 120 CAD patients, we assessed FVIIa-AT complex concentrations and the presence of circulating FXIa and active TF. Levels of 8-iso-prostaglandin F2α (8-iso-PGF2α), interleukin-6, high-sensitivity C reactive protein, prothrombin fragment 1 + 2, and free Tissue Factor Pathway Inhibitor were determined. Myocardial infarction (MI), ischemic stroke, systemic thromboembolism (SE), and cardiovascular (CV) death were recorded separately and as a composite endpoint, during follow-up.
Results:
FVIIa-AT complexes were positively associated with current smoking and multivessel CAD. Elevated FVIIa-AT complexes characterized patients with circulating FXIa and/or active TF in association with increased plasma isoprostanes but not with thrombin generation or inflammatory markers. During a median follow-up of 106 months (interquartile range 95-119), high baseline levels of FVIIa-AT complexes predicted ischemic stroke/SE (HR 4.61 [95% CI 1.48-18.42]) and a composite endpoint of MI, stroke/SE, and CV death (HR 7.47 [95% CI 2.81-19.87]).
Conclusions:
This study is the first to show that high FVIIa-AT complexes characterize advanced CAD patients with detectable FXIa and active TF, which is, in part, driven by oxidative stress. High FVIIa-AT complexes were associated with the risk of ischemic stroke/SE during long-term follow-up, highlighting the need for effective antithrombotic agents in CAD.
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