Abstract
Objective
Atrial fibrillation (AF) is a condition where platelet hyperaggregability is commonly present. We examined potential physiological bases for platelet hyperaggregability in a cohort of patients with acute and chronic AF. In particular, we sought to identify the impact of inflammation [myeloperoxidase (MPO) and C-reactive protein (CRP)] and impaired nitric oxide (NO) signaling.
Methods
Clinical and biochemical determinants of adenosine diphosphate (ADP)-induced platelet aggregation were sought in patients (n = 106) hospitalized with AF via univariate and multivariate analysis.
Results
Hyper-responsiveness of platelets to ADP was directly (r = 0.254, p < 0.01) correlated with plasma concentrations of thrombospondin-1 (TSP-1), a matricellular protein that impairs NO responses and contributes to development of oxidative stress. In turn, plasma TSP-1 concentrations were directly correlated with MPO concentrations (r = 0.221, p < 0.05), while MPO concentrations correlated with those of asymmetric dimethylarginine (ADMA, r = 0.220, p < 0.05), and its structural isomer symmetric dimethylarginine (SDMA, r = 0.192, p = 0.05). Multivariate analysis identified TSP-1 (β = 0.276, p < 0.05) concentrations, as well as female sex (β = 0.199, p < 0.05), as direct correlates of platelet aggregability, and SDMA concentrations (β = − 0.292, p < 0.05) as an inverse correlate.
Conclusion
We conclude that platelet hyperaggregability, where present in the context of AF, may be engendered by impaired availability of NO, as well as via MPO-related inflammatory activation.
Zusammenfassung
Ziel
Bei Vorhofflimmern ist oft eine Hyperaggregabilität der Thrombozyten vorhanden. Mögliche physiologische Gründe dafür wurden in einer Kohorte von Patienten mit akutem oder chronischem Vorhofflimmern untersucht. Insbesondere wurde die Rolle von Entzündungsparametern evaluiert, namentlich Myeloperoxidase, C-reaktives Protein und eventuelle Störungen im Stickstoffmonoxid(NO)-Signalweg.
Methoden
Bei 106 wegen Vorhofflimmerns stationär aufgenommenen Patienten wurden klinische und biochemische Ursachen der adenosindiphosphatinduzierten Thrombozytenaggregation mittels univariater und multivariater statistischer Analysen untersucht.
Ergebnisse
Die Hyperreaktivität von Thrombozyten auf ADP war direkt (r = 0,254; p < 0,01) mit der Plasmakonzentration von Thrombospondin-1 (TSP-1) korreliert, einem Matrixprotein, das die Funktion von NO inhibiert und damit zum oxidativen Stress beiträgt. Plasmathrombospondin-1 korrelierte dagegen mit der Plasma-MPO-Konzentration (r = 0,221; p < 0,05). MPO wiederum korrelierte signifikant mit asymmetrischem Dimethylarginin (ADMA, r = 0,220; p < 0,05) und auch dessen strukturellem Isomer, dem symmetrischen Dimethylarginin (SDMA, r = 0,192; p = 0,05). Die multivariate Analyse ergab, dass eine direkte Korrelation der Thrombozytenhyperreaktivität mit dem Plasma-TSP-1 (β = 0,276; p < 0,05) und weiblichem Geschlecht bestand, während die Plasma-SDMA-Konzentration eine negative Korrelation aufwies (β = − 0,292, p < 0,05).
Schlussfolgerung
Die Hypothese der Autoren lautet, dass die bei Vorhofflimmern auftretende Thromozytenhyperaggregabilität durch eine geringere Verfügbarkeit von NO und auch durch einen MPO-induzierten Entzündungszustand bedingt sein könnte.
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Acknowledgments
This investigation was supported by an NHMRC Program Grant and the NHMRC Centre of Research Excellence to Reduce Inequality in Heart Disease. Nathan Procter is supported by The University of Adelaide and the Basil Hetzel Institute for Translational Research. Jocasta Ball and Simon Stewart are supported by the National Health and Medical Research Council. Jeffrey Isenberg is supported by NIH grants P01 HL103455, R01 HL-108945, R01 HL112914-01A1, and also by the Institute for Transfusion Medicine, the Hemophilia Center of Western Pennsylvania, as well as the Vascular Medicine Institute.
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J.S. Isenberg is Chair of the Scientific Advisory Boards of Vasculox, Inc. (St. Louis, MO) and Radiation Control Technologies, Inc. (RCT1; New York, NY) and holds equity in the same.
N.E.K. Procter, J. Ball, D.T.M. Ngo, Y.Y. Chirkov, E.M. Hylek, S. Stewart, and J.D. Horowitz state that there are no conflicts of interest. All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.
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Procter, N., Ball, J., Ngo, D. et al. Platelet hyperaggregability in patients with atrial fibrillation. Herz 41, 57–62 (2016). https://doi.org/10.1007/s00059-015-4335-y
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DOI: https://doi.org/10.1007/s00059-015-4335-y