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.
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.


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 (P=0.03) and vascular events (P<0.001), 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; P=0.02). No significant relationships were found between sP-sel levels and outcome.


CONCLUSIONS
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.
Conway
Dwayne S G
DS
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, England.
Pearce
Lesly A
LA
Chin
Bernard S P
BS
Hart
Robert G
RG
Lip
Gregory Y H
GY
D001241:Aspirin / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D006801:Humans; D019007:P-Selectin / Q000097:blood*; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D016019:Survival Analysis; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000032:analysis*
D015415:Biomarkers; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D014841:von Willebrand Factor; D001241:Aspirin