Interactions between inflammatory activation and endothelial dysfunction selectively modulate valve disease progression in patients with bicuspid aortic valve

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.