Asymmetric dimethylarginine predicts survival in the elderly

Age (Dordr). 2013 Dec;35(6):2465-75. doi: 10.1007/s11357-013-9523-1. Epub 2013 Apr 13.

Abstract

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase implicated in several age-related biological mechanisms such as telomere shortening and cell senescence. We tested the hypothesis that ADMA blood level is an independent predictor of mortality in elderly. This is a longitudinal population-based cohort study. Participants are a representative cohort of 1,025 men and women (age range 65-102 years) living in Chianti area, Tuscany, Italy. The plasma ADMA was measured by liquid chromatography-tandem mass spectrometry. During the follow-up (95 ± 32 months), 384 individuals died, of whom 141 (37 %) died of cardiovascular (CV) causes. In adjusted analyses, the plasma ADMA was the strongest predictor of all-cause mortality (HR (0.1 μMol/L) 1.26, 95 % CI 1.10-1.44, P < 0.001) with a non-significant trend for CV mortality (HR 1.22, P = 0.07). The predictive effect of the ADMA level on mortality was statistically significant among participants with low to low-normal L-arginine levels (≤ 60 μMol/L), but not in those with L-arginine >60 μMol/L. Notwithstanding the association of ADMA with all-cause mortality was robust, this biomarker failed to add predictive power to a simple model based on the risk factors in the elderly (area under the ROC curve 0.85 ± 0.01 vs. 0.84 ± 0.01). ADMA is a strong independent predictor of mortality in the older population, and L-arginine modifies the effect of ADMA on survival. The mechanisms for this association should be targeted by future studies.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Biomarkers / blood
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / mortality*
  • Cause of Death / trends
  • Chromatography, Liquid
  • Female
  • Follow-Up Studies
  • Humans
  • Italy / epidemiology
  • Male
  • Population Surveillance*
  • Predictive Value of Tests
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Tandem Mass Spectrometry
  • Time Factors

Substances

  • Biomarkers
  • N,N-dimethylarginine
  • Arginine