Association of circulating levels of asymmetric dimethylarginine (ADMA) with carotid intima-media thickness: Evidence from 6168 participants

Background: Epidemiologic investigations have linked the circulating levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), to carotid intima-media thickness (IMT). However, these studies result in various extent of relation between ADMA and IMT, the conclusions were inconsistent, and the precise relationship is therefore under debate. The objective of this systematic review and meta-analysis is to provide an overview of the relevant studies evaluating the association of levels of ADMA with carotid IMT and to gain more robust estimate of the relationship. Methods: Studies were identified through PubMed, Cochrane Library, Embase, reviews, and reference lists of relevant papers. Weighted means of the correlation coefficient (R) and partial correlation coefficient (PR) were calculated for relations by using random-effect models. Results: 22 studies with a total of 6168 subjects were included in our meta-analysis. In an overall pooled estimate of correlation coefficient (R), levels of ADMA were significantly related to carotid IMT (pooled R: 0.29; 95% confidence interval [CI]: 0.20-0.38, P<0.001). Pooled estimate of partial correlation coefficient (PR) also resulted in a significant association of ADMA with carotid IMT (pooled PR: 0.21; 95% CI: 0.14-0.29; P<0.001). Furthermore, subgroup analysis found that the relation between ADMA and IMT was stronger in patients with chronic kidney diseases (CKDs) than that in subject with normal renal function. Conclusions: Circulating levels of ADMA were positively related to carotid IMT, especially in patients with CKDs. The findings need confirmation in longitudinal and interventional studies.