TY - JOUR
T1 - Platelet hyperaggregability in patients with atrial fibrillation: 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.
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.
U2 - 10.1007/s00059-015-4335-y
DO - 10.1007/s00059-015-4335-y
M3 - Article
VL - 41
SP - 57
EP - 62
JO - Herz
JF - Herz
SN - 0340-9937
IS - 1
ER -