Endothelial Function, Carotid–Femoral Stiffness, and Plasma Matrix Metalloproteinase-2 in Men With Bicuspid Aortic Valve and Dilated Aorta

ObjectivesThis study sought to examine the relationship between proximal aortic dilation and systemic vascular function in men with bicuspid aortic valve (BAV).BackgroundProximal aortic dilation in subjects with BAV is associated with structural and functional abnormalities in the ascending aorta.MethodsWe studied 32 men (median age 31 years [range 28 to 32 years]) with nonstenotic BAV categorized into 2 subgroups according to proximal ascending aorta dimensions (nondilated ≤35 mm and dilated ≥40 mm, respectively). Sixteen healthy men were studied as control subjects. Flow-mediated dilation in response to hyperemia (a marker of endothelial dysfunction) and carotid–femoral pulse wave velocity (an index of aortic stiffness) were assessed, and peripheral blood was sampled for matrix metalloproteinases (MMP-2 and -9) and their tissue inhibitors (TIMP-1 and -2), respectively. Cardiac chamber and aortic dimensions were assessed by echocardiography and cardiac magnetic resonance imaging, respectively.ResultsDespite the similar severity of aortic stenosis, left ventricular mass, and function, men with dilated aortas had blunted brachial flow-mediated vasodilation to hyperemia (5% [interquartile range (IQR) 4% to 6%] vs. 8% [IQR 7% to 9%] change, p = 0.001), higher carotid–femoral pulse wave velocity (9.3 cm/s [IQR 9 to 10 cm/s] vs. 7 cm/s [IQR 6.9 to 7.4 cm/s], p = 0.001), and significantly higher plasma levels of MMP-2 (1,523 [IQR 1,460 to 1,674] vs. 1,036 [IQR 962 to 1,167], p = 0.001) compared with men with BAV and nondilated aorta. Values for MMP-9, TIMP-1 and -2 levels, and nitroglycerin-induced (endothelium-independent) vasodilation were similar in all 3 groups.ConclusionsYoung men with BAV and dilated proximal aortas manifest systemic endothelial dysfunction, increased carotid–femoral pulse wave velocity, and higher plasma levels of MMP-2. These observations could introduce new targets for screening and perhaps for therapeutic intervention.