Coagulation factor XII, XI, and VIII activity levels and secondary events after first ischemic stroke

Background and Purpose: Though risk for recurrent vascular events is high following ischemic stroke, little is known about risk factors for secondary events post-stroke. The coagulation factors XII, XI, and VII (FXII, FXI, and FVIII) have already been implicated in first thrombotic events, and our aim was to estimate their effects on vascular outcomes within 3 years after first stroke. Methods: In the PROSpective Cohort with Incident Stroke Berlin (PROSCIS-B) study, we followed participants aged 18 and older for three years after first mild to moderate ischemic stroke event or until occurrence of recurrent stroke, myocardial infarction or all-cause mortality (combined endpoint). High coagulation factor activity levels were compared to normal and low levels, and activities were also analyzed 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, 92 events occurred in 570 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%CI 1.28-3.29). High FXI activity was also associated with an increased risk (HR=1.80, 95%CI 1.09-2.98). Contrarily, high FXII activity was not associated with the combined endpoint (HR=0.86, 95%CI 0.49-1.51). Continuous analyses per standard deviation of each biomarker 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 three-year period after first ischemic stroke. This is of special interest in light of the ongoing trials of antithrombotic treatments targeting FXI.