Increased expression of P-selectin in patients with chronic atrial fibrillation

Abstract

Previous studies have shown that platelets are activated during atrial fibrillation (AF). However, prophylactic therapy with aspirin is not associated with a reduction of thromboembolic complications in patients with AF. Stimulation of platelet thrombin and ADP receptors causes a release of P-selectin, which is not affected by aspirin. The purpose of this study was to assess the influence of AF on platelet P-selectin expression. Blood samples from 30 patients were studied ex vivo. Nineteen patients had chronic AF (> 3 months), 11 patients were in sinus rhythm (SR). P-selectin expression was determined by flow cytometry (antibody binding capacity [BC]) at baseline and after platelet stimulation with adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP). To determine the effect of heart rate and atrial pressure (RAP), measurements were repeated after 10 minutes of ventricular pacing (120 beats/min) in patients with SR. P-selectin expression was increased in patients with AF at baseline (AF: 1329 +/- 81 BC vs SR: 968 +/- 108 BC; P < 0.05) and after stimulation with ADP (AF: 1445 +/- 101 BC vs SR: 1061 +/- 109 BC; P < 0.05) and TRAP (AF: 13,783 +/- 2442 BC vs SR: 5977 +/- 800 BC; P < 0.05). RAP (2.0 +/- 0.5 vs 6.0 +/- 0.8 mmHg; P < 0.01) and atrial rate (75 +/- 5 vs 114 +/- 5 beats/min; P < 0.001) increased during ventricular pacing. However, P-selectin levels remained stable. AF was accompanied by increased P-selectin expression. In contrast, increased ventricular rate and elevated atrial pressure alone had no effect on platelet activity. Further studies are needed to determine if platelet ADP receptor inhibitors offer a therapeutic benefit in patients with AF.