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(Circulation. 2004;110:1794-1798.)
© 2004 American Heart Association, Inc.

Heart Failure

Endothelial Dysfunction and Damage in Congestive Heart Failure

Relation of Flow-Mediated Dilation to Circulating Endothelial Cells, Plasma Indexes of Endothelial Damage, and Brain Natriuretic Peptide

Aun Yeong Chong, MRCP; Andrew D. Blann, PhD; Jeetesh Patel, PhD; Bethan Freestone, MRCP; Elizabeth Hughes, MD; Gregory Y.H. Lip, MD

From the Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, England, UK.

Correspondence to Prof G.Y.H. Lip, Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, England, UK. E-mail g.y.h.lip{at}bham.ac.uk

Received December 30, 2003; de novo received April 10, 2004; accepted June 18, 2004.

Background— Congestive heart failure (CHF) is associated with endothelial perturbation (as defined by flow-mediated endothelial-dependent vasodilation [FMD, an index of endothelial dysfunction], circulating endothelial cells [CECs, an index of endothelial damage], or plasma indexes of endothelial damage/dysfunction [eg, von Willebrand factor (vWf) and soluble thrombomodulin (sTM)]) and raised plasma levels of brain natriuretic peptide (BNP, a peptide hormone associated with left ventricular systolic dysfunction and prognosis). However, the relations between these parameters are unclear.

Methods and Results— To test the hypothesis that there is a relation between endothelial perturbation (defined by FMD, CECs, vWf, and sTM) and BNP in CHF, we studied these indexes in 30 patients with CHF who were compared with 20 age-matched control subjects. FMD, CECs, plasma vWf, and BNP levels (but not sTM) were all abnormal in patients with CHF. There were significant inverse correlations between FMD and vWf (P=0.001), CECs (P=0.002) and BNP (P=0.006) as well as a positive correlation between CECs and vWf (P=0.032). In multivariate analysis, BNP (P<0.001) and FMD (P<0.001) were both independently associated with CHF.

Conclusions— Ample evidence of endothelial cell damage/dysfunction in CHF cannot be fully explained by the variance in plasma BNP per se. Therefore, the routes by which these indexes influence the pathophysiology of CHF as well as predict adverse outcomes may be independent.

Key Words: heart failure • endothelium • von Willebrand factor • endothelium-derived factors • natriuretic peptides

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