Abstract 6284: Asymmetric Dimethylarginine (ADMA) Plasma Levels and Total Mortality in the Community: The Framingham Offspring Study
Introduction. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), induces endothelial dysfunction. Although elevated plasma ADMA levels have been associated with increased risk of cardiovascular disease (CVD) events and mortality in referral samples, the prognostic significance of ADMA in the community has not been evaluated adequately. Hypothesis. We hypothesized that ADMA is related to all-cause mortality and incident CVD events in a large community-based cohort.
Methods. We related plasma ADMA, L-arginine (Arg, the precursor of NO), and the Arg/ADMA ratio measured at a routine Framingham Offspring examination to the incidence of CVD and all-cause mortality, considered separately.
Results. On follow-up (median 2.9 years) of 2956 CVD-freeparticipants (55.5% women, mean age 58.4 years) 281 individuals (119 women) developed incident CVD. On follow-up(median 3.0 years) of 3320 participants (53.3% women, mean age 59.2 years), 285 participants (102 women) died. In multivariable Cox models adjusting for established risk factors, ADMA, L-arginine and the Arg/ADMA ratio were not associated with CVD incidence (p > 0.10 for all). However, ADMA, and the Arg/ADMA ratio were significantly associated with all-cause mortality risk (adjusted-hazard ratio [HR] per SD increment 1.21, 95% CI 1.07–1.37, p = 0.003, and 0.80, 95% CI 0.69 – 0.93, p = 0.004, respectively), whereas L-arginine was not (0.89, 95% CI 0.77–1.02). We noted effect modification by diabetes status: ADMA was associated with mortality risk in individuals without diabetes (adjusted HR per SD increment 1.30, 95% CI 1.13–1.50, p = 0.0002), but not in individuals with diabetes (adjusted HR per SD increment 0.85, 95% CI 0.62–1.16).
Conclusions. We conclude that in our large community-based sample, ADMA was not associated with CVD incidence, but was associated with all-cause mortality, especially so in individuals without diabetes.