title: Endogenous t-PA-antigen is an independent predictor of adverse cardiovascular events and all-cause death in patients with atrial fibrillation.
abstract: BACKGROUND
  Atrial fibrillation (AF) is associated with raised levels of P-selectin and an apparent prothrombotic state. However, levels of tissue plasminogen activator (t-PA)-antigen are increased also. We investigated whether high levels of endogenous t-PA-antigen or soluble P-Selectin (sP-Selectin), independently of CHADS(2-) or CHA(2) DS(2) VASc-scores, predict major adverse cardiovascular events (MACE) in patients with AF when treated according to current guidelines.
  
  
  METHODS
  This prospective, longitudinal single-center study included 269 patients with AF. Blood samples were analyzed for sP-Selectin and t-PA-antigen concentration by means of commercially available enzyme-linked immunoassays.
  
  
  RESULTS
  Patients were followed for a median duration of 1933 (1517-2277) days, during which 78 MACE and 82 deaths occurred. In multivariable analyses t-PA-antigen above the median of 4.22 ng mL(-1) was associated with MACE and all-cause death (HR 2.55 [1.43-4.57]; P = 0.002) and (HR 2.54 [1.38-4.68]; P = 0.003), respectively. There was no association of sP-Selectin with MACE or all-cause death. Furthermore, t-PA-antigen above the median independently of the CHADS(2-) or CHA(2) DS(2) VASc-scores predicted MACE and all-cause death. In patients with low and intermediate-risk for cardiovascular events according to the CHADS(2)-score the addition of high t-PA-antigen levels (> 4.22 ng mL(-1) ) had a significant impact on the patients' outcome (low-risk group, HR 3.25 [1.13-9.38]; P = 0.029 and intermediate-risk group, HR 2.33 [1.27-4.26]; P = 0.006, respectively).
  
  
  CONCLUSIONS
  High endogenous t-PA-antigen independently predicts MACE and all-cause death in patients with AF. Accordingly, t-PA-antigen as an indicator of a prothrombotic state represents a novel biomarker, which might add to risk stratification in patients with AF.
authors.affiliation: 3rd Medical Department, Cardiology and Emergency Medicine, Wilhelminen Hospital, Vienna, Austria. matthias.freynhofer@meduniwien.ac.at
authors.forename: M K
authors.initials: MK
authors.lastname: Freynhofer
authors.forename: D F
authors.initials: DF
authors.lastname: Draxler
authors.forename: S C
authors.initials: SC
authors.lastname: Gruber
authors.forename: V
authors.initials: V
authors.lastname: Bruno
authors.forename: T
authors.initials: T
authors.lastname: Höchtl
authors.forename: B
authors.initials: B
authors.lastname: Fellner
authors.forename: G
authors.initials: G
authors.lastname: Jakl-Kotauschek
authors.forename: J
authors.initials: J
authors.lastname: Wojta
authors.forename: I
authors.initials: I
authors.lastname: Pabinger-Fasching
authors.forename: K
authors.initials: K
authors.lastname: Huber
authors.forename: C
authors.initials: C
authors.lastname: Ay
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood* / Q000150:complications / Q000401:mortality*; D002318:Cardiovascular Diseases / Q000150:complications / Q000175:diagnosis; D004562:Electrocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D020521:Stroke / Q000150:complications / Q000175:diagnosis; D013927:Thrombosis; D010959:Tissue Plasminogen Activator / Q000097:blood*
chemical_list: D019007:P-Selectin; D010959:Tissue Plasminogen Activator
keywords: P-Selectin; atrial fibrillation; tissue plasminogen activator