Prognostic Value of Plasma von Willebrand Factor and Soluble P-Selectin as Indices of Endothelial Damage and Platelet Activation in 994 Patients With Nonvalvular Atrial Fibrillation

Abstract

Background-Abnormal plasma markers of a prothrombotic state have been described in atrial fibrillation (AF), but no such marker has yet been shown to reliably predict future stroke or cardiovascular outcome in AF. We hypothesized that raised plasma levels of von Willebrand factor (vWf, an index of endothelial damage/dysfunction) and/or soluble P-selectin (sP-sel, an index of platelet activation) might predict vascular events in AF. Methods and Results-We measured vWf and sP-sel levels by ELISA in 994 participants receiving aspirin in the Stroke Prevention in Atrial Fibrillation III trial, at study entry or after 3 months, and related these indices to the subsequent incidence of stroke and vascular events. Plasma vWf levels were a significant predictor of both stroke (Pϭ0.03) and vascular events (PϽ0.001), with the greatest risk for those with the highest levels of vWf. After adjustment for other clinical predictors, the relationship between vWf and stroke became nonsignificant, but vWf remained an independent predictor of vascular events (relative risk, 1.2 [95% CI, 1.0 -1.4] per 20 IU/dL increase in vWf; Pϭ0.02). No significant relationships were found between sP-sel levels and outcome. Conclusion-Among patients with AF who received aspirin, raised levels of vWf (endothelial damage/dysfunction) were predictive of stroke and vascular events, but raised sP-sel levels (platelet activation) were not associated with increased cardiovascular risk. Endothelial damage/dysfunction (or vWf itself) may play an important role in the mechanisms behind stroke and cardiovascular outcome among aspirin-treated AF patients and might represent a target for novel therapies or an adjunctive aid to risk stratification in AF.

Intracardiac Hemostasis and Fibrinolysis Parameters in Patients with Atrial Fibrillation

“…An elevation of FVIII [18, 34] and VWF [35–38] has been described earlier in the peripheral samples AF patients and it has been proposed to be attributed to endothelial damage. Moreover, elevated levels of VWF have been associated with increased stroke risk and poor prognosis [36, 39, 40]. Only few papers enrolling a limited number of patients have investigated the levels of VWF in AF patients from both intracardiac and peripheral blood samples, but in these studies FVIII levels were not determined [27, 41].…”

Stroke: Morbidity, Risk Factors, and Care in Taiwan

“…However, the event rates were similar between groups with and without atrial fibrillation for males. A possible interpretation for the gender difference in atrial fibrillation-related thromboembolism risk was that a higher von Willebrand factor level was observed in females with atrial fibrillation, but not in males with atrial fibrillation, as compared with that of non- atrial fibrillation patients 30. In a hospital-based study of 947 patients with first-ever ischemic stroke, the prevalence of atrial fibrillation was significantly higher in elderly patients aged 80 years or older (29%) than in those aged less than 80 years (11%) 31…”

Evaluating the Atrial Myopathy Underlying Atrial Fibrillation

“…149 In multivariable Cox models, the hazard ratio for incident AF associated with a 1-standard deviation increase in VWF was 1.17 (95% CI 1.11–1.23). Conway et al 150 and Krishnamoorthy et al 151 reported that raised VWF levels in patients with AF predicted stroke and vascular events, and Roldan et al 152 found that high VWF levels are an independent risk factor for adverse events in AF patients on anticoagulant therapy. The concentrations of VWF in LA blood are increased in patients with persistent AF and are higher than in the LA of those with paroxysmal AF or controls.…”