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

• Published in: Journal of the American College of Cardiology Vol. 55; no. 7; pp. 660 - 668
• Main Authors: Tzemos, Nikolaos, Lyseggen, Erik, Silversides, Candice, Jamorski, Michal, Tong, Jeffrey H., Harvey, Paula, Floras, John, Siu, Samuel
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 16.02.2010; Elsevier; Elsevier Limited
• Subjects: Adult; Aorta - pathology; Aorta - physiopathology; aortic dilation; Aortic Valve - abnormalities; Aortic Valve - diagnostic imaging; Aortic Valve - physiopathology; bicuspid valve; Biological and medical sciences; Blood Flow Velocity - physiology; Brachial Artery - diagnostic imaging; Brachial Artery - physiology; Cardiology; Cardiology. Vascular system; Cardiovascular; Cardiovascular disease; Carotid Arteries - physiology; Case-Control Studies; Congenital heart diseases. Malformations of the aorta, pulmonary vessels and vena cava; Coronary vessels; Cross-Sectional Studies; Dilatation, Pathologic; Endocardial and cardiac valvular diseases; Endothelium, Vascular - physiopathology; Femoral Artery - physiology; flow-mediated vasodilation; Heart; Heart rate; Humans; Hyperemia - physiopathology; Hypertension; Internal Medicine; Male; Matrix Metalloproteinase 2 - blood; Matrix Metalloproteinase 9 - blood; Medical sciences; MMP-2; Nitroglycerin; Plasma; Pulsatile Flow - physiology; pulse wave velocity; Sinuses; Systole - physiology; Tissue Inhibitor of Metalloproteinase-1 - blood; Tissue Inhibitor of Metalloproteinase-2 - blood; Ultrasonography; Vasodilator Agents; GTN; NO; eNOS; aortic dilation; cf-PWV; CMR; flow-mediated vasodilation; LV; pulse wave velocity; MMP; MMP-2; BAV; RT3DE; FMD; bicuspid valve; TIMP; real-time 3-dimensional imaging; tissue inhibitor of matrix metalloproteinase; carotid–femoral pulse wave velocity; glyceryl nitrate; endothelial nitric oxide synthase; left ventricle/ventricular; nitric oxide; bicuspid aortic valve; matrix metalloproteinase; cardiac magnetic resonance; Human; Biological fluid; Femur; Enzyme; Metalloendopeptidases; Cardiovascular disease; Male; Endothelial function; Congenital disease; Gelatinase A; Blood plasma; Peptidases; Cardiac valvular disease; Carotid; Bicuspid aortic valve; Hydrolases; Aorta; Stiffness; Circulatory system; Cardiology
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2009.08.080

This study sought to examine the relationship between proximal aortic dilation and systemic vascular function in men with bicuspid aortic valve (BAV). Proximal aortic dilation in subjects with BAV is associated with structural and functional abnormalities in the ascending aorta. We 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. Despite 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. Young 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.