Abstract
Background: The physiological bases for differential thromboembolic risk in patients with atrial fibrillation (AF) remain uncertain. In particular, the associations between documented increased and (1) female gender, (2) recent onset AF remain unexplained. We tested the hypotheses that gender and heart rate during AF each adversely impact platelet homeostasis, as assessed via ADP: nitric oxide (NO) response balance. Methods: Patients presenting with AF were evaluated at hospital admission. ADP-induced aggregation and its inhibition by the NO donor sodium nitroprusside were evaluated using whole blood impedance aggregometry. Determinants of ADP and NO response were sought via univariate followed by multivariate analyses. Results: Among 87 patients (72.0± 11.6 [SD] yrs, 48.3% female, 25.3% new onset AF), HR was elevated in new onset AF (129± 31 [SD] bpm vs 91± 33 [SD] bpm, p< 0.01) compared to pre-existing AF. Females exhibited greater ADP response (9.4± 3.5 [SD] vs 7.5± 3.8 [SD] , p< 0.05) and smaller NO response (13± 27 [SD]% inhibition vs 27± 28 [SD]% inhibition, p< 0.05) than males. Both heart rate and female gender were significant correlates of increased ADP and decreased NO response on ANCOVA (see figure), and of increased ADP response on multivariate analysis (p< 0.05 for both) while new onset AF was a significant multivariate correlate of poor NO response (p< 0.05). Conclusion:ElevatedHR and female sex independently increased ADP response and platelet resistance to NO. These homeostatic disturbances may combine to increase risk of thrombotic events in new onset AF.
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