title: Asymmetric dimethylarginine predicts survival in the elderly.
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.
authors.affiliation: Nephrology Unit, SM Annunziata Hospital, via dell' Antella 58, 50011, Florence, Italy, fpizzarelli@yahoo.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pizzarelli
authors.forename: Renke
authors.initials: R
authors.lastname: Maas
authors.forename: Pietro
authors.initials: P
authors.lastname: Dattolo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tripepi
authors.forename: Stefano
authors.initials: S
authors.lastname: Michelassi
authors.forename: Graziella
authors.initials: G
authors.lastname: D'Arrigo
authors.forename: Maren
authors.initials: M
authors.lastname: Mieth
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Carmine
authors.initials: C
authors.lastname: Zoccali
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality*; D002423:Cause of Death / Q000639:trends; D002853:Chromatography, Liquid; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D011159:Population Surveillance; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D015415:Biomarkers; C018524:N,N-dimethylarginine; D001120:Arginine