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

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 CHADS₂- or CHA₂DS₂VASc-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 CHADS₂- or CHA₂DS₂VASc-scores predicted MACE and all-cause death. In patients with low and intermediate-risk for cardiovascular events according to the CHADS₂-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.