Activated factor XI is associated with increased factor VIIa – Antithrombin complexes in stable coronary artery disease: Impact on cardiovascular outcomes

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 FXI...

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Published in:European journal of clinical investigation 2022-12, Vol.52 (12), p.e13857-n/a
Main Authors: Paszek, Elżbieta, Pociask, Elżbieta, Ząbczyk, Michał, Butenas, Saulius, Undas, Anetta
Format: Article
Language:English
Subjects:
Antithrombin
C-reactive protein
Cardiovascular disease
Cerebral infarction
Chemical compounds
Coagulation factor VIIa
Coagulation factors
Coronary artery disease
Coronary vessels
factor VII–antithrombin complex
factor XIa
Health risks
Heart diseases
Inflammation
Interleukin 6
Ischemia
Isoprostanes
Myocardial infarction
Oxidative stress
Patients
Prostaglandin F2a
Prothrombin
Stroke
Thrombin
Thromboembolism
Tissue factor
Vein & artery diseases
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Summary: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. In 120 patients with advanced coronary artery disease elevated levels of factor VIIa‐antithrombin complexes were positively associated with detectable factor XIa and isoprostanes, markers of oxidative stress. In long‐term observation (median 106 months) high baseline levels of factor VIIa‐antithrombin complexes were associated with a 4.6× higher risk of stroke and/or systemic thromboembolism and a 7.5× higher risk of a composite endpoint defined as myocardial infarction + stroke + systemic thromboembolism + cardiovascular death.
ISSN:0014-2972
1365-2362
DOI:10.1111/eci.13857