Asymmetric dimethylarginine predicts survival in the elderly

Francesco Pizzarelli, Renke Maas, Pietro Dattolo, Giovanni Tripepi, Stefano Michelassi, Graziella D'Arrigo, Maren Mieth, Stefania Bandinelli, Luigi Ferrucci, Carmine Zoccali

Research output: Contribution to journalArticle


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 ADMAwas the strongest predictor of all-cause mortality (HR (0.1 μMol/L) 1.26, 95 % CI 1.10-1.44, P60 μMol/L. Notwithstanding the association ofADMA 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.

Original languageEnglish (US)
Pages (from-to)2465-2475
Number of pages11
Issue number6
Publication statusPublished - Dec 2013
Externally publishedYes



  • ADMA
  • Cardiovascular risk factor
  • Elderly
  • Population study
  • Survival

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Pizzarelli, F., Maas, R., Dattolo, P., Tripepi, G., Michelassi, S., D'Arrigo, G., ... Zoccali, C. (2013). Asymmetric dimethylarginine predicts survival in the elderly. Age, 35(6), 2465-2475.