title: Plasma von Willebrand factor levels are an independent risk factor for adverse events including mortality and major bleeding in anticoagulated atrial fibrillation patients.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the prognostic value of plasma von Willebrand factor (vWF) levels and fibrin d-dimer in a large cohort of anticoagulated permanent atrial fibrillation (AF) patients.
  
  
  BACKGROUND
  In nonanticoagulated AF patients, plasma vWF levels have been related to stroke and vascular events. There are limited data on the prognostic role of biomarkers in anticoagulated AF patients in relation to adverse events (including thromboembolism), mortality, and major bleeding.
  
  
  METHODS
  We studied 829 patients (50% male; median age 76 years) with permanent AF who were stabilized (for at least 6 months) on oral anticoagulation therapy (international normalized ratio: 2.0 to 3.0). Plasma d-dimer and vWF levels were quantified by enzyme-linked immunosorbent assay. Patients were followed for 2 years, and adverse events (thrombotic and vascular events, mortality, and major bleeding) were recorded.
  
  
  RESULTS
  Patients were followed for a median of 828 days (range 18 to 1,085 days). 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, 95% confidence interval: 1.86 to 10.75; p < 0.001). High plasma vWF levels were able to refine clinical risk stratification schema for stroke (CHADS₂ [Congestive heart failure, Hypertension, Age ≥ 75, Diabetes mellitus, and prior Stroke or transient ischemic attack (doubled)], CHA₂DS₂-VASc [Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes mellitus, Stroke, Vascular disease, Age 65 to 74 years, Sex category]) and bleeding (HAS-BLED [Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile International Normalized Ratio, Elderly, Drugs/alcohol concomitantly]). d-dimer did not show any significant impact on adverse events.
  
  
  CONCLUSIONS
  High plasma vWF levels (≥221 IU/dl) are an independent risk factor for adverse events in anticoagulated permanent AF patients. This biomarker may potentially be used to refine stroke and bleeding clinical risk stratification in AF.
authors.affiliation: Hematology and Medical Oncology Unit, Hospital Universitario Morales Meseguer, University of Murcia, Murcia, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Roldán
authors.forename: Francisco
authors.initials: F
authors.lastname: Marín
authors.forename: Begoña
authors.initials: B
authors.lastname: Muiña
authors.forename: Jose Miguel
authors.initials: JM
authors.lastname: Torregrosa
authors.forename: Diana
authors.initials: D
authors.lastname: Hernández-Romero
authors.forename: Mariano
authors.initials: M
authors.lastname: Valdés
authors.forename: Vicente
authors.initials: V
authors.lastname: Vicente
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D015415:Biomarkers / Q000097:blood; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006470:Hemorrhage / Q000097:blood* / Q000209:etiology; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D014841:von Willebrand Factor