Elevated plasma factor XI predicts cardiovascular events in patients with type 2 diabetes: a long-term observational study.
Factor XI
Myocardial Infarction, Stroke, Cardiovascular Mortality
Type 2 Diabetes Mellitus
Journal
Cardiovascular diabetology
ISSN: 1475-2840
Titre abrégé: Cardiovasc Diabetol
Pays: England
ID NLM: 101147637
Informations de publication
Date de publication:
17 07 2023
17 07 2023
Historique:
received:
12
05
2023
accepted:
27
06
2023
medline:
19
7
2023
pubmed:
18
7
2023
entrez:
17
7
2023
Statut:
epublish
Résumé
Type 2 diabetes mellitus (T2DM) patients are at high risk of cardiovascular (CV) events. Factor XI (FXI) is associated with arterial thromboembolism, including myocardial infarction (MI), stroke, and CV mortality. The role of FXI in T2DM is unknown. We investigated whether plasma FXI is associated with CV events in T2DM patients in long-term observation. In 133 T2DM patients (aged 66 ± 8 years, 40.6% women, median T2DM duration 5 [2-10] years) we assessed plasma FXI levels, along with fibrin clot properties, thrombin generation, and fibrinolysis proteins. A composite endpoint of MI, stroke, or CV death, as well as CV mortality alone were assessed during a median follow-up of 72 months. Plasma FXI above the 120% upper normal limit was detected in 25 (18.8%) patients and showed positive association with LDL cholesterol and thrombin activatable fibrinolysis inhibitor, but not glycated hemoglobin, inflammatory markers or thrombin generation. The composite endpoint (n = 21, 15.8%) and CV death alone (n = 16, 12%) were more common in patients with elevated FXI (hazard ratio [HR] 10.94, 95% confidence interval [CI] 4.46-26.87, p < 0.001 and HR 7.11, 95% CI 2.61-19.31, p < 0.001, respectively). On multivariable analysis, FXI remained an independent predictor of the composite endpoint and CV death, regardless of concomitant coronary artery disease. To our knowledge, this study is the first to show that in T2DM patients, elevated FXI could predict major CV events, including mortality, which suggest that anti-FXI agents might be a potential novel antithrombotic option in this disease.
Sections du résumé
BACKGROUND
Type 2 diabetes mellitus (T2DM) patients are at high risk of cardiovascular (CV) events. Factor XI (FXI) is associated with arterial thromboembolism, including myocardial infarction (MI), stroke, and CV mortality. The role of FXI in T2DM is unknown. We investigated whether plasma FXI is associated with CV events in T2DM patients in long-term observation.
METHODS
In 133 T2DM patients (aged 66 ± 8 years, 40.6% women, median T2DM duration 5 [2-10] years) we assessed plasma FXI levels, along with fibrin clot properties, thrombin generation, and fibrinolysis proteins. A composite endpoint of MI, stroke, or CV death, as well as CV mortality alone were assessed during a median follow-up of 72 months.
RESULTS
Plasma FXI above the 120% upper normal limit was detected in 25 (18.8%) patients and showed positive association with LDL cholesterol and thrombin activatable fibrinolysis inhibitor, but not glycated hemoglobin, inflammatory markers or thrombin generation. The composite endpoint (n = 21, 15.8%) and CV death alone (n = 16, 12%) were more common in patients with elevated FXI (hazard ratio [HR] 10.94, 95% confidence interval [CI] 4.46-26.87, p < 0.001 and HR 7.11, 95% CI 2.61-19.31, p < 0.001, respectively). On multivariable analysis, FXI remained an independent predictor of the composite endpoint and CV death, regardless of concomitant coronary artery disease.
CONCLUSIONS
To our knowledge, this study is the first to show that in T2DM patients, elevated FXI could predict major CV events, including mortality, which suggest that anti-FXI agents might be a potential novel antithrombotic option in this disease.
Identifiants
pubmed: 37460982
doi: 10.1186/s12933-023-01905-5
pii: 10.1186/s12933-023-01905-5
pmc: PMC10353137
doi:
Substances chimiques
Factor XI
9013-55-2
Thrombin
EC 3.4.21.5
Types de publication
Observational Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
182Informations de copyright
© 2023. The Author(s).
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