PB0038 - Low thrombin inactivation capacity is associated with an increased risk of recurrent cardiovascular events in young patients with ischemic stroke

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

JS

Janneke Spiegelenberg, MD

PhD student
Department of Internal Medicine, Radboud University Medical Center (Radboudumc)
Arnhem, Gelderland, Netherlands

Co-Author(s)

Mark Roest

PhD, Clinical Director
Synapse Research Institute
Maastricht, Limburg, Netherlands
Bd

Bas de Laat

General Director
Synapse Research Institute
Maastricht, Limburg, Netherlands
Rd

Romy de Laat-Kremers

Research Project Leader
Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
Mv

Marleen van Gelder

Assistant Professor in Pharmacoepidemiology
Department for Health Evidence, Radboud university medical center, Nijmegen, the Netherlands.
Nijmegen, Gelderland, Netherlands
Saskia Middeldorp, MD, PhD

Internist, Professor
Radboud university medical center
Nijmegen, Gelderland, Netherlands
AT

Anil Tuladhar

Neurologist
Department of Neurology, Center for Neuroscience, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands
Nijmegen, Gelderland, Netherlands
FD

Frank-Erik De Leeuw

Neurologist
Department of Neurology, Center for Neuroscience, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands
Nijmegen, Gelderland, Netherlands
Jenneke Leentjens

Internist and Junior Principal Clinician
Department of Internal Medicine, Radboud Institute for Health Sciences, Radboud University Medical Centre
Nijmegen, Gelderland, Netherlands

Background: Patients with ischemic stroke at young age (18-50 years) have a long-term increased risk of recurrent ischemic events. Hypercoagulability may be of greater etiologic significance in young patients.

Aims: To investigate associations between in/ex vivo coagulation parameters and the risk of recurrent ischemic events after a first ischemic stroke or TIA in young patients.

Methods: We included patients with first-ever TIA or ischemic stroke between 1980 and 2010 from the prospective FUTURE cohort. Blood samples were collected in 2010 and patients were followed for recurrent ischemic events between 2010 and 2023. Pro- and anticoagulation biomarkers and thrombin generation (TG) were measured. Prothrombin conversion and thrombin inactivation were calculated. We applied Fine and Gray regression analysis to estimate hazard ratios per one standard deviation increase. The linearity of these associations were explored using restricted cubic spline regression.

Results: During a mean follow-up of 6.4 years, 70 of 332 included patients experienced recurrence. We found a higher risk for recurrent ischemic events in patients with lower antithrombin activity (adjusted HR=0.76 [95% CI 0.58-0.99]) and in patients with higher fibrinogen levels (adjusted HR=1.31 [1.00-1.72]; table 1). Plasma thrombin generation was not associated with recurrence. The pro- and anticoagulant processes underlying thrombin generation were studied separately through computational analysis (table 2). This revealed negative associations between recurrence and the capacity to form thrombin-antithrombin complexes and the overall capacity to inhibit thrombin (TDC) (HR=0.86 [95% CI 0.74-0.99] and 0.63 [0.46-0.87]).

Conclusion(s): Low thrombin inactivation capacity, attributable to low antithrombin levels and high fibrinogen levels, is associated with higher risk of recurrent ischemic events after an acute ischemic stroke or TIA at young age, even in the long term.