TY - JOUR
T1 - Platelet hyperaggregability in patients with atrial fibrillation
T2 - Evidence of a background proinflammatory milieu
AU - Procter, Nathan E.K.
AU - Ball, Jocasta
AU - Ngo, Doan T.M.
AU - Chirkov, Yuliy Y.
AU - Isenberg, Jeffrey S.
AU - Hylek, Elaine M.
AU - Stewart, Simon
AU - Horowitz, John D.
N1 - Funding Information:
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.
Publisher Copyright:
© 2015, Urban & Vogel.
PY - 2016/2
Y1 - 2016/2
N2 - 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.
AB - 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.
KW - Asymmetric dimethylarginine
KW - Atrial fibrillation
KW - Myeloperoxidase
KW - Platelet aggregation
KW - Thrombospondin-1
UR - http://www.scopus.com/inward/record.url?scp=84958156477&partnerID=8YFLogxK
U2 - 10.1007/s00059-015-4335-y
DO - 10.1007/s00059-015-4335-y
M3 - Article
C2 - 26135468
AN - SCOPUS:84958156477
SN - 0340-9937
VL - 41
SP - 57
EP - 62
JO - Herz
JF - Herz
IS - 1
ER -