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Type: Journal article
Title: Interactions between inflammatory activation and endothelial dysfunction selectively modulate valve disease progression in patients with bicuspid aortic valve
Author: Ali, O.
Chapman, M.
Thanh, H.
Chirkov, Y.
Heresztyn, T.
Mundisugih, J.
Horowitz, J.
Citation: Heart, 2014; 100(10):800-805
Publisher: BMJ Publishing Group
Issue Date: 2014
ISSN: 1355-6037
Statement of
Onn Akbar Ali, Matthew Chapman, Thanh Ha Nguyen, Yuliy Y Chirkov, Tamila Heresztyn, Juan Mundisugih, John D Horowitz
Abstract: OBJECTIVES: Bicuspid aortic valve (BAV) is associated with increased risk of valvular degeneration and ascending aortic aneurysm formation and rupture. We sought to evaluate the roles of endothelial dysfunction and inflammatory activation in modulating these processes. METHODS: We performed a case-control study of patients with BAV together with a multivariate analysis within the BAV group to identify factors associated with: development of significant valvular disease; dilatation of the ascending aorta; differential valve relative to aortic disease. Endothelial function of patients and controls was evaluated via flow-mediated dilatation (FMD) and plasma concentrations of asymmetric dimethylarginine (ADMA). Correlations with inflammatory markers and endothelial progenitor cell counts were also examined. Morphological and physiological assessment of the valve and ascending aorta was performed with transthoracic echocardiography and MRI. RESULTS: Patients with BAV (n=43) and controls (n=25) were matched for age and gender. FMD was significantly lower in patients than controls (7.85±3.48% vs 11.58±3.98%, p=0.001), and these differences were age-independent. Within the BAV cohort, multivariate correlates of peak aortic valve velocity were plasma concentrations of ADMA and myeloperoxidase (MPO) (both p<0.01), while increasing age was an independent correlate of ascending aortic diameter (p<0.05). Furthermore, both low FMD and inflammatory activation were multivariate correlates of selectivity for valvular disease. CONCLUSIONS: BAV is associated with endothelial dysfunction. The extent of inflammatory activation (specifically MPO release) and that of endothelial dysfunction impact primarily on integrity of the valve rather than aortic structure.
Keywords: Aorta
Endothelium, Vascular
Aortic Valve
Heart Valve Diseases
Disease Progression
Magnetic Resonance Imaging, Cine
Severity of Illness Index
Retrospective Studies
Follow-Up Studies
Middle Aged
Nitric Oxide Synthase
Bicuspid Aortic Valve Disease
Rights: © 2014 BMJ Publishing Group Ltd & British Cardiovascular Society All rights reserved.
DOI: 10.1136/heartjnl-2014-305509
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