Correlates of arterial stiffness in an ageing population: Role of asymmetric dimethylarginine

Abstract

A number of previous investigators have demonstrated that arterial augmentation index (AIx), a measure of apparent arterial stiffness, reflects in part vascular endothelial function, and that AIx is modulated by nitric oxide (NO) responses. We evaluated AIx in a population of 253 ageing subjects (mean age 63.4+/-6 (standard deviation, SD) years) and its relationship to (i) plasma levels of asymmetric dimethylarginine (ADMA), a marker and mediator of vascular endothelial dysfunction and (ii) the ratio of ADMA to its non-metabolised enantiomer symmetric dimethylarginine (SDMA), an inverse index of ADMA metabolic clearance. Evaluation was performed by univariate followed by multivariate analyses. On multivariate analyses, both ADMA (beta=0.16, p=0.01) and ADMA:SDMA (beta=0.21, p<0.001) ratio were significant direct correlates of AIx. Other significant correlates of AIx on multivariate analysis were: use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEi/ARB) (beta=-0.24, p=0.004), smoking history (beta=0.15, p=0.007), male gender (beta=-0.38, p<0.001), creatinine clearance (CrCL) (beta=-0.25, p<0.001), and history of hypertension (beta=0.17, p=0.04). We conclude that (1) endothelial dysfunction engendered by impairment of NO synthesis may represent the basis for increased arterial stiffness in ageing individuals and (2) the fundamental biochemical anomaly may be impairment of ADMA clearance. These pathophysiological factors are likely to be relevant to optimize therapy to ameliorate disorders of arterial compliance in the ageing population.