Active factor XI is associated with the risk of cardiovascular events in stable coronary artery disease patients.


Journal

Atherosclerosis
ISSN: 1879-1484
Titre abrégé: Atherosclerosis
Pays: Ireland
ID NLM: 0242543

Informations de publication

Date de publication:
04 2022
Historique:
received: 18 11 2021
revised: 20 01 2022
accepted: 09 02 2022
pubmed: 6 3 2022
medline: 6 5 2022
entrez: 5 3 2022
Statut: ppublish

Résumé

Tissue factor (TF) and activated factor XI (FXIa) have been associated with acute coronary syndrome, ischemic stroke and venous thromboembolism. Their predictive value in stable coronary artery disease (CAD) is unclear. We investigated whether active TF and FXIa were associated with clinical outcomes in CAD patients in long-term observation. In 124 stable patients with multivessel CAD, we assessed the presence of circulating, active TF and FXIa by measuring a response of thrombin generation to respective inhibitory antibodies. We recorded the composite endpoint of myocardial infarction (MI), stroke, systemic thromboembolism and cardiovascular death during follow-up (median 106 months, interquartile range 95-119). Circulating FXIa and active TF were detected in 40% and 20.8% of the 120 patients (aged 65.0 [57.0-70.3] years, men, 78.3%), who completed follow-up. The composite endpoint occurred more frequently in patients with detectable active TF and FXIa present at baseline (hazard ratio [HR] 4.02, 95% confidence interval [CI] 2.26-7.17, p < 0.001 and HR 6.21, 95% CI 3.40-11.40, p < 0.001, respectively). On multivariate analysis FXIa, but not active TF, was an independent predictor of the composite endpoint, as well as MI, stroke/systemic thromboembolism, and cardiovascular death, when analyzed separately. To our knowledge, this study is the first to show that circulating FXIa predicts arterial thromboembolic events in advanced CAD, supporting a growing interest in FXIa inhibitors as novel antithrombotic agents.

Sections du résumé

BACKGROUND AND AIMS
Tissue factor (TF) and activated factor XI (FXIa) have been associated with acute coronary syndrome, ischemic stroke and venous thromboembolism. Their predictive value in stable coronary artery disease (CAD) is unclear. We investigated whether active TF and FXIa were associated with clinical outcomes in CAD patients in long-term observation.
METHODS
In 124 stable patients with multivessel CAD, we assessed the presence of circulating, active TF and FXIa by measuring a response of thrombin generation to respective inhibitory antibodies. We recorded the composite endpoint of myocardial infarction (MI), stroke, systemic thromboembolism and cardiovascular death during follow-up (median 106 months, interquartile range 95-119).
RESULTS
Circulating FXIa and active TF were detected in 40% and 20.8% of the 120 patients (aged 65.0 [57.0-70.3] years, men, 78.3%), who completed follow-up. The composite endpoint occurred more frequently in patients with detectable active TF and FXIa present at baseline (hazard ratio [HR] 4.02, 95% confidence interval [CI] 2.26-7.17, p < 0.001 and HR 6.21, 95% CI 3.40-11.40, p < 0.001, respectively). On multivariate analysis FXIa, but not active TF, was an independent predictor of the composite endpoint, as well as MI, stroke/systemic thromboembolism, and cardiovascular death, when analyzed separately.
CONCLUSIONS
To our knowledge, this study is the first to show that circulating FXIa predicts arterial thromboembolic events in advanced CAD, supporting a growing interest in FXIa inhibitors as novel antithrombotic agents.

Identifiants

pubmed: 35246318
pii: S0021-9150(22)00078-8
doi: 10.1016/j.atherosclerosis.2022.02.009
pii:
doi:

Substances chimiques

Factor IX 9001-28-9
Thromboplastin 9035-58-9
Factor XIa EC 3.4.21.27

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

124-132

Informations de copyright

Copyright © 2022. Published by Elsevier B.V.

Auteurs

Elżbieta Paszek (E)

Clinical Department of Interventional Cardiology, John Paul II Hospital, 31-202, Krakow, Poland.

Elżbieta Pociask (E)

Department of Biocybernetics and Biomedical Engineering, AGH University of Science and Technology, 30-059, Krakow, Poland.

Michał Ząbczyk (M)

Institute of Cardiology, Jagiellonian University Medical College, 31-202, Kraków, Poland; John Paul II Hospital, 31-202, Krakow, Poland.

Adam Piórkowski (A)

Department of Biocybernetics and Biomedical Engineering, AGH University of Science and Technology, 30-059, Krakow, Poland.

Saulius Butenas (S)

Department of Biochemistry, University of Vermont, 89 Beaumont Avenue, Burlington, VT, 05405-0068, USA.

Jacek Legutko (J)

Clinical Department of Interventional Cardiology, John Paul II Hospital, 31-202, Krakow, Poland; Department of Interventional Cardiology, Jagiellonian University Medical College, 31-202, Krakow, Poland.

Anetta Undas (A)

Institute of Cardiology, Jagiellonian University Medical College, 31-202, Kraków, Poland; John Paul II Hospital, 31-202, Krakow, Poland. Electronic address: mmundas@cyf-kr.edu.pl.

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