Author(s): Freynhofer MK, Draxler DF, Gruber SC, Bruno V, Hchtl T,
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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). 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. Copyright © 2013 International Society on Thrombosis and Haemostasis.
This article was published in J Thromb Haemost
and referenced in Medicinal chemistry