Serum Asymmetric Dimethylarginine Negatively Correlates with Intima-Media Thickness in Early-Onset Atherosclerosis

Abstract

Asymmetric dimethylarginine (ADMA) assumes a significant role in atherosclerosis by inhibiting the endothelial nitric oxide synthase (eNOS). Moreover, ADMA inhibits the inducible NOS (iNOS), the isoform that triggers atherosclerosis via peroxynitrite formation. Therefore, we investigated whether ADMA is a risk or protective factor in the atherosclerotic process. Intima-media thickness (IMT) of the common carotid artery, a surrogate for vascular diseases, was chosen as the outcome variable of interest. Sixty patients younger than 55 years having at least 30% stenosis of the internal carotid artery and 30 age- and gender-matched controls were recruited at a community-based neurosonological laboratory. We investigated relatively young patients to circumvent the confounding effect age has in the development of atherosclerosis. The IMT showed a negative correlation with ADMA upon analysis of the pooled data (Spearman correlation coefficient -0.300, p = 0.0041) and the atherosclerotic stratum (Spearman correlation coefficient -0.323, p = 0.012). A multiple linear regression model containing all determinant factors of IMT previously identified by simple regression was used to further quantify the relationship between IMT and ADMA. The negative association between IMT and ADMA remained statistically significant (beta: -0.510, CI: -0.894, -0.127; p = 0.010), furthermore it was even stronger in the atherosclerotic stratum (beta: -0.67, CI: -1.16, -0.18; p = 0.008). A minimal increase in ADMA concentration may be protective by inhibiting iNOS but not eNOS in states where iNOS is induced, e.g. inflammation accompanying atherosclerosis.