Atherothrombotic and thrombolytic biomarkers in incident stroke and atrial fibrillation-related stroke: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background and aims: Although several biomarkers have been studied in thromboembolic stroke, measuring the balance between thrombus formation and thrombolysis and data on its role in predicting stroke and atrial fibrillation (AF) -related stroke is limited. We sought to assess atherothrombotic biomarkers grouped into composite factors that reflect thrombotic and thrombolytic potential, and the balance between these factors as it relates to incident stroke or transient ischemic attack (TIA) and stroke/TIA in AF. Methods: A Thrombotic Factor, derived from fibrinogen, plasmin-antiplasmin complex, factor VIII, D-dimer, and lipoprotein(a); and a Thrombolytic Factor, derived from plasminogen and oxidized phospholipids on plasminogen, were evaluated at baseline in 5,764 Multi -Ethnic Study of Atherosclerosis (MESA) participants. We evaluated the association between these two factors representative of thrombotic and thrombolytic potential and incident stroke/TIA (n = 402), and AF -related stroke/TIA (n = 82) over a median of 13.9 and 3.7 years, respectively. Cox proportional hazard models adjusted for medication use, cardiovascular risk factors and CHA2DS2-VASc score were utilized. Harrell's C -index was estimated to evaluate model performance. Results: In models including both factors, Thrombotic Factor was positively while Thrombolytic Factor was inversely associated with incident stroke/TIA and AF -related stroke/TIA. Incorporating these factors along with the CHA2DS2-VASc in adjusted models resulted in a small improvement in risk prediction of incident stroke/TIA and AF -related stroke/TIA compared to models without the factors (C -index from 0.697 to 0.704, and from 0.657 to 0.675, respectively). Conclusions: Composite biomarker factors, representative of the balance between thrombotic and thrombolytic propensity, provided an improvement in predicting stroke/TIA beyond CHA2DS2-VASc score.