Jessica L Rohmann1,2, Shufan Huo1,3,4, Pia S Sperber1,4, Sophie K Piper5,6, Frits R Rosendaal7, Peter U Heuschmann8,9, Matthias Endres1,3,4,10,11, Thomas G Liman1,3,4, Bob Siegerink1,7. 1. Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany. 2. Institute of Public Health, Charité - Universitätsmedizin Berlin, Berlin, Germany. 3. Klinik für Neurologie, Charité - Universitätsmedizin Berlin, Berlin, Germany. 4. Deutsches Zentrum für Herz-Kreislauf-Forschung DZHK, Berlin, Germany. 5. Insitute for Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, Berlin, Germany. 6. Berlin Institute of Health (BIH), Berlin, Germany. 7. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. 8. Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany. 9. Clinical Trial Center Würzburg, University Hospital Würzburg, Würzburg, Germany. 10. German Center for Neurodegenerative Disease DZNE, Charité - Universitätsmedizin Berlin, Berlin, Germany. 11. Excellence Cluster Neurocure, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Abstract
BACKGROUND: Though risk for recurrent vascular events is high following ischemic stroke, little knowledge about risk factors for secondary events post-stroke exists. OBJECTIVES: Coagulation factors XII, XI, and VIII (FXII, FXI, and FVIII) have been implicated in first thrombotic events, and our aim was to estimate their effects on vascular outcomes within 3 years after first stroke. PATIENTS/ METHODS: In the Prospective Cohort with Incident Stroke Berlin (PROSCIS-B) study, we followed participants aged 18 and older for 3 years after first mild to moderate ischemic stroke event or until occurrence of recurrent stroke, myocardial infarction, or all-cause mortality. We compared high coagulation factor activity levels to normal and low levels and also analyzed activities as continuous variables. We used Cox proportional hazards models adjusted for age, sex, and cardiovascular risk factors to estimate hazard ratios (HRs) for the combined endpoint. RESULTS: In total, 94 events occurred in 576 included participants, resulting in an absolute rate of 6.6 events per 100 person-years. After confounding adjustment, high FVIII activity showed the strongest relationship with the combined endpoint (HR = 2.05, 95% confidence interval [CI] 1.28-3.29). High FXI activity was also associated with a higher hazard (HR = 1.80, 95% CI 1.09-2.98), though high FXII activity was not (HR = 0.86, 95% CI 0.49-1.51). Continuous analyses yielded similar results. CONCLUSIONS: In our study of mild to moderate ischemic stroke patients, high activity levels of FXI and FVIII but not FXII were associated with worse vascular outcomes in the 3-year period after first ischemic stroke.
BACKGROUND: Though risk for recurrent vascular events is high following ischemic stroke, little knowledge about risk factors for secondary events post-stroke exists. OBJECTIVES: Coagulation factors XII, XI, and VIII (FXII, FXI, and FVIII) have been implicated in first thrombotic events, and our aim was to estimate their effects on vascular outcomes within 3 years after first stroke. PATIENTS/ METHODS: In the Prospective Cohort with Incident Stroke Berlin (PROSCIS-B) study, we followed participants aged 18 and older for 3 years after first mild to moderate ischemic stroke event or until occurrence of recurrent stroke, myocardial infarction, or all-cause mortality. We compared high coagulation factor activity levels to normal and low levels and also analyzed activities as continuous variables. We used Cox proportional hazards models adjusted for age, sex, and cardiovascular risk factors to estimate hazard ratios (HRs) for the combined endpoint. RESULTS: In total, 94 events occurred in 576 included participants, resulting in an absolute rate of 6.6 events per 100 person-years. After confounding adjustment, high FVIII activity showed the strongest relationship with the combined endpoint (HR = 2.05, 95% confidence interval [CI] 1.28-3.29). High FXI activity was also associated with a higher hazard (HR = 1.80, 95% CI 1.09-2.98), though high FXII activity was not (HR = 0.86, 95% CI 0.49-1.51). Continuous analyses yielded similar results. CONCLUSIONS: In our study of mild to moderate ischemic strokepatients, high activity levels of FXI and FVIII but not FXII were associated with worse vascular outcomes in the 3-year period after first ischemic stroke.