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Influence of Atrial Fibrillation on Plasma Von Willebrand Factor, Soluble E-Selectin, and N-Terminal Pro B-type Natriuretic Peptide Levels in Systolic Heart Failure^*

^* From the Haemostasis Thrombosis and Vascular Biology Unit (Dr. Freestone, Chong, and Lip), University Department of Medicine, City Hospital, Birmingham, UK; Department of Cardiology B (Dr. Gustafsson), Rigshospitalet, Denmark; Department of Cardiology and Endocrinology E (Dr. Corell), Frederiksberg University Hospital, Frederiksberg, Denmark; Department of Endocrinology (Dr. Kistorp), Herlev University Hospital, Herlev, Denmark; and Department of Medicine (Dr. Hildebrandt), Roskilde University Hospital, Roskilde, Denmark.

Correspondence to: Gregory Y. H. Lip, MD, City Hospital, Dudley Rd, Birmingham, B18 7QH, UK; e-mail: G.Y.H.LIP{at}bham.ac.uk

Abstract

Background: Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF.

Methods: We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis.

Results: One hundred ninety patients (73% men; mean age, 69.0 ± 10.1 years [± SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels when compared to SR-HF patients. On multivariate analysis, the presence of AF was related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017).

Conclusions: There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.

Key Words: atrial fibrillation • heart failure • N-terminal pro B-type natriuretic peptide • von Willebrand factor