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Plasma von Willebrand Factor Levels Are an Independent Risk Factor for Adverse Events Including Mortality and Major Bleeding in Anticoagulated Atrial Fibrillation Patients
Study Questions:
Are high plasma levels of von Willebrand factor (vWF) in patients with atrial fibrillation (AF) predictive of adverse events?
Methods:
A total of 829 patients with permanent AF stabilized on oral anticoagulation therapy (international normalized ratio 2.0-3.0) were studied. Plasma D-dimer and vWF levels were quantified by enzyme-linked immunosorbent assay (ELISA). Patients were followed for 2 years, and adverse events (thrombotic and vascular events, mortality, and major bleeding) were recorded.
Results:
On multivariate analysis, age 75 years and older, previous stroke, heart failure, and high plasma vWF levels (≥221 IU/dl) were associated with future adverse cardiovascular events (all p values < 0.05). High plasma vWF levels, elderly patients, diabetes, hypercholesterolemia, and current smoking were associated with mortality (all p values < 0.05). High plasma vWF levels were also an independent predictor of major bleeding (hazard ratio, 4.47; p < 0.001). High plasma vWF levels were able to refine clinical risk stratification schema for stroke and bleeding. D-dimer did not show any significant impact on adverse events.
Conclusions:
High plasma vWF levels are an independent risk factor for adverse events in anticoagulated AF patients.
Perspective:
High levels of vWF have previously been shown to be predictive of stroke and vascular events in AF patients not receiving anticoagulation. The current study demonstrates that this association remains strong even when patients are anticoagulated with warfarin. High vWF levels were also predictive of bleeding events. Thus, elevated vWF levels in this high-risk patient population may serve as a biomarker of underlying vascular dysfunction that contributes to both bleeding and thrombosis risk. In addition to potential utility for risk stratification of AF patients, vWF levels might also be used to guide novel therapies targeting vascular dysfunction, which may reduce both bleeding and thrombosis risk.
Keywords: von Willebrand Factor, Biomarkers, Heart Failure, Risk Factors, Hemorrhage, Diabetes Mellitus
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