Asymmetric dimethylarginine predicts survival in the elderly

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.