Gender and tachycardia: independent modulation of platelet reactivity in patients with atrial fibrillation.
BACKGROUND
Female patients with atrial fibrillation (AF) experience increased risk of thromboembolism compared to males, an observation that is reflected by its inclusion in the CHA2DS2VASc score. New onset AF (often associated with tachycardia) also confers upon patients increased thromboembolic risk. The mechanisms underlying this risk are uncertain, but new onset AF is associated with profound impairment of platelet nitric oxide (NO) signalling. Given that cardiovascular responses to catecholamines are gender-dependent, and that the presence of tachycardia in new onset AF may represent a response to catecholaminergic stimulation, we explored the potential impact of gender and tachycardia on platelet aggregation and NO signalling.


METHODS
Interactions were sought in 87 AF patients between the extent of adenosine diphosphate (ADP)-induced platelet aggregation, the anti-aggregatory effects of the NO donor, sodium nitroprusside, gender, and admission heart rate. The potential impact of platelet expression of thioredoxin-interacting protein (Txnip) was also evaluated.


RESULTS
Analysis of covariance confirmed the presence of physiological antagonism between platelet ADP and NO responses [F (1, 74) = 12.212, P < 0.01], while female sex correlated with impaired NO responses independent of platelet aggregability [F (2, 74) = 8.313, P < 0.01]. Admission heart rate correlated directly with platelet aggregation (r = 0.235, P < 0.05), and inversely with NO response (r = -0.331, P < 0.01). Txnip expression varied neither with gender nor with heart rate.


CONCLUSIONS
These results indicate that gender and heart rate are independent determinants of platelet function. Prospective studies of the putative benefit of reversal of tachycardia on restoration of normal platelet function are therefore a priority.
Basil Hetzel Institute for Translational Research, Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia.
Nathan Ek
NE
Procter
National Health and Medical Research Council (NHMRC), Centre of Research Excellence to Reduce Inequality in Heart Disease, Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
Jocasta
J
Ball
Basil Hetzel Institute for Translational Research, Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia.
Doan Tm
DT
Ngo
Heart, Lung, Blood and Vascular Medicine Institute, Division of Pulmonary, Allergy and Critical Care Medicine Department, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Jeffrey S
JS
Isenberg
Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
Elaine M
EM
Hylek
Basil Hetzel Institute for Translational Research, Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia.
Yuliy Y
YY
Chirkov
National Health and Medical Research Council (NHMRC), Centre of Research Excellence to Reduce Inequality in Heart Disease, Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
Simon
S
Stewart
Basil Hetzel Institute for Translational Research, Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia.
John D
JD
Horowitz
Atrial fibrillation; Gender; Heart rate; Nitric oxide; Platelet aggregation