Endogenous t-PA-antigen is an independent predictor of adverse cardiovascular events and all-cause death in patients with atrial fibrillation

J Thromb Haemost. 2013 Jun;11(6):1069-77. doi: 10.1111/jth.12213.


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).

Conclusion: 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.

Keywords: P-Selectin; atrial fibrillation; tissue plasminogen activator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atrial Fibrillation / blood*
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / mortality*
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / diagnosis
  • Electrocardiography
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • P-Selectin / metabolism
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prospective Studies
  • Risk
  • Stroke / complications
  • Stroke / diagnosis
  • Thrombosis
  • Tissue Plasminogen Activator / blood*


  • P-Selectin
  • Tissue Plasminogen Activator