The Ascending Aortopathy And Subclinical Left Ventricular Dysfunction Are Associated With Endothelial Dysfunction And Elevated Plasma Matrix Metalloproteinase-2 Level In Patients With Bicuspid Aortic Valve

Part 1 The Ascending Aortopathy Are Associated with Endothelial Dysfunction and Elevated Plasma Matrix Metalloproteinase-2 Level in Patients with Bicuspid Aortic ValveObjective The aim of this observational study was to test whether enlarged size and impaired elastic properties of the ascending aorta were associated with impaired endothelial function and increases in plasma matrix metalloproteinase(MMP)-2 concentrations in patients with BAV without significant valvular dysfunction(no greater than mild aortic stenosis or regurgitation).Methods The size and the elasticity(including aortic strain,aortic stiffness index and aortic distensibility)of the ascending aorta,and the flow-mediated vasodilation(FMD)in brachial artery in response of hyperemia were evaluated with 2-dimensional echocardiography and high-frequency linear ultrasound in 42 patients with BAV without significant valvular dysfunction and 30 age-and sex-matched healthy controls.In addition,concentrations of plasma MMP-2,MMP-9 and asymmetric dimethylarginine were determined using commercially available human enzyme-linked immunosorbent assay kits according to the manufacturer's instructions.The above parameters were compared between the BAV group and the healthy control group.In addition,the influencing factors of the size and elasticity of the ascending aorta were evaluated in the BAV group.Results In the BAV group,diastolic ascending aortic diameter(Ao D)(32.1 ± 8.1 mm vs.25.3 ± 3.6 mm,P < 0.001)and aortic stiffness index(8.0 ± 5.3 vs.4.0 ± 1.8,P < 0.001)were significantly higher,and aortic strain(7.4 ± 3.6 % vs.11.1 ± 3.0 %,P < 0.001)and aortic distensibility(7.4 ± 4.1 cm2dyn-110-6 vs.11.1 ± 4.3 cm2dyn-110-6,P < 0.001)were significantly lower than those in the control group.The BAV group also showed lower FMD(6.5 ± 2.2 % vs.11.9 ± 2.7 %,P < 0.001)and higher plasma MMP-2 level(226.7 ± 55.0 ng/ml vs.177.0 ± 45.3 ng/ml,P < 0.001)when compared with the control group.The levels of plasma MMP-9 and asymmetric dimethylarginine showed no significant differences between two groups(all P > 0.05).In the BAV group,Ao D,aortic strain,aortic stiffness index,and aortic distensibility significantly correlated with FMD and MMP-2(all P < 0.05).After controlling for age,systolic blood pressure,left ventricular mass index,FMD,asymmetric dimethylarginine,MMP-2,and MMP-9,the multivariable linear regression analysis further indicated that FMD and MMP-2 were independently associated with Ao D(? =-1.1,P = 0.005;? = 0.09,P < 0.001,respectively).Conclusion These findings suggest that enlarged size and impaired elastic properties of the ascending aorta are associated with endothelial dysfunction and elevated plasma MMP-2 level in patients with BAV without significant valvular dysfunction.Reduced FMD and elevated plasma MMP-2 level are the significant and independent predictors of dilatation of the ascending aorta in patients with BAV.Part 2 Subclinical Left Ventricular Dysfunction Are Associated with Endothelial Dysfunction and Elevated Plasma Matrix Metalloproteinase-2 Level in Patients with Bicuspid Aortic ValveObjective The aim of this observational study was to investigate the relationship between reduced left ventricular systolic strain,and impaired flow-mediated vasodilation(FMD)in response to hyperemia and increases in plasma matrix metalloproteinase(MMP)-2 concentrations in bicuspid aortic valve(BAV)patients without significant valvular dysfunction and dilation of ascending aorta.Methods Thirty BAV patients and 26 age-and sex-matched healthy controls were studied.Left ventricular systolic strain was assessed by using 2-dimensional speckle-tracking echocardiography.FMD was evaluated in the brachial artery by using high-resolution ultrasound.In addition,concentrations of plasma MMP-2,MMP-9 and asymmetric dimethylarginine were determined using commercially available human enzyme-linked immunosorbent assay kits according to the manufacturer's instructions.The above parameters were compared between the BAV group and the healthy control group.In addition,the influencing factors of left ventricular systolic strain were evaluated in the BAV group.Results BAV group showed significantly lower global longitudinal(-19.4 ± 2.0 vs-21.0 ± 1.8%,P = 0.004),circumferential(-20.3 ± 1.8 vs-22.0 ± 2.4%,P = 0.005),and radial(35.5 ± 5.4 vs 40.3 ± 8.0%,P = 0.011)strains when compared with the control group.In addition,BAV patients had lower FMD(7.3 ± 1.9 vs 11.7 ± 2.7%,P < 0.001),but higher plasma MMP-2 level(201.6 ± 36.3 vs 170.9 ± 36.1 ng/ml,P = 0.003)than the controls,while the levels of MMP-9 and plasma asymmetric dimethylarginine showed no significant differences between two groups.In the BAV group,global strain was significantly correlated with FMD and MMP-2,respectively(P < 0.005).After controlling for age,mean blood pressure,left ventricular mass index,FMD,asymmetric dimethylarginine,MMP-2,and MMP-9,the multivariate regression analysis further indicated that FMD and MMP-2 were independently associated with global longitudinal(? = 0.338,P = 0.024;? =-0.541,P = 0.001;respectively),circumferential(? = 0.445,P = 0.005;? =-0.417,P = 0.008),and radial(? = 0.347,P = 0.024;? =-0.514,P = 0.001)strains.Conclusion Reduced FMD and elevated plasma MMP-2 level are independent determinants of subclinical left ventricular dysfunction in BAV patients without significant valvular dysfunction and dilation of ascending aorta.