Plasma von Willebrand Factor and Soluble P-Selectin as Indices of Endothelial Damage and Platelet Activation in 1321 Patients With Nonvalvular Atrial Fibrillation

Abstract

Background— Epidemiological studies have identified clinical and echocardiographic factors associated with increased stroke risk in atrial fibrillation (AF), but mechanisms linking these factors to stroke in AF are incompletely understood. We hypothesized that stroke risk factors may be associated with increased endothelial damage/dysfunction and platelet activation among patients with AF. Methods and Results— We measured plasma levels of von Willebrand factor (vWF, a marker of endothelial damage/dysfunction) and soluble P-selectin (sP-sel, a marker of platelet activation) by ELISA in 1321 participants in the Stroke Prevention in Atrial Fibrillation (SPAF) III study and related these indices to the presence of stroke risk factors and cardiovascular disease. Age ( P <0.001), prior cerebral ischemia ( P <0.01), recent heart failure ( P <0.001), diabetes ( P <0.001), and body mass index ( P <0.001) were independently associated with increased vWF ( r 2 adjusted=9%). Independent associates of increased sP-sel were diabetes ( P =0.01), peripheral vascular disease ( P <0.001), and current smoking ( P =0.01), whereas prior cerebral ischemia ( P =0.002) and female sex ( P <0.001) were associated with reduced sP-sel ( r 2 adjusted=4%). Using prospectively validated stroke risk stratification criteria, we observed a significant stepwise increase in vWF from low- to moderate- to high-risk groups ( r 2 adjusted=3%, P <0.001), whereas sP-sel remained constant ( P = 0.24). Conclusions— Four recognized risk factors for stroke in AF (advancing age, prior cerebral ischemia, recent heart failure, and diabetes) were independently associated with raised plasma vWF (or endothelial damage/dysfunction), whereas only 1 (diabetes) was associated with increased sP-sel (platelet activation). Further longitudinal studies are now needed to confirm relationships between endothelial damage/dysfunction, platelet activation, and stroke in AF.