Asymmetric dimethylarginine and all-cause mortality: a systematic review and meta-analysis

Sci Rep. 2017 Mar 15:7:44692. doi: 10.1038/srep44692.

Abstract

Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), impairs the beneficial effect of NO. The predictive value of ADMA for all-cause mortality remains controversial, though it is important in the development of cardiovascular disease (CVD) and progression to dialysis in renal disease. This systematic review and meta-analysis was conducted to investigate the association between circulating ADMA and all-cause mortality. Studies with data pertinent to the association between circulating ADMA and all-cause mortality were reviewed and OR, HR or RR with 95% CI derived from multivariate Cox's proportional-hazards analysis were extracted. A total of 34 studies reporting 39137 participants were included in final analysis. The results demonstrated that circulating ADMA was independently associated with all-cause mortality (RR = 1.27, 95% CI: 1.20-1.34). The association was still statistically significant in patients with pre-existing renal disease (RR = 1.30, 95% CI: 1.19-1.43) and pre-existing CVD (RR = 1.26, 95% CI: 1.16-1.37). In those without pre-existing renal or CVD, ADMA also predicted all-cause mortality (RR = 1.31, 95% CI: 1.13-1.53). The present study suggests a positive association of circulating ADMA with all-cause mortality. Further studies are needed to investigate the effects of interventions on ADMA, and the value of ADMA as a biomarker.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Biomarkers / blood*
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / mortality*
  • Cardiovascular Diseases / physiopathology
  • Humans
  • Nitric Oxide / blood
  • Nitric Oxide Synthase / blood
  • Proportional Hazards Models
  • Renal Dialysis / mortality
  • Risk Factors

Substances

  • Biomarkers
  • dimethylarginine
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase