Abstract 3474: Plasma Concentrations of Asymmetric Dimethylarginine (ADMA) Predict LV Mass Independent of Afterload
Background: In experimental models, left ventricular hypertrophy (LVH) is under the negative control of nitric oxide (NO), largely via paracrine, load-independent mechanisms. However, it remains uncertain to what extent LVH is controlled by NO clinically.
Methods: We evaluated potential correlations between LV mass index (LV mass/height 2.7) and plasma levels of asymmetric dimethylarginine (ADMA), a competitive inhibitor of NO synthase. Subjects (n=74; aged 67.7 +/− 5.8 (SD) years), without known cardiovascular disease or treated hypertension were evaluated. LV volumes were calculated from the short axis stack of cardiac MRI and LV mass was indexed to ht2.7, utilizing Philips Intera 1.5T magnet. Plasma ADMA concentrations were determined by HPLC. All putative correlations with LV mass were examined by univariate and stepwise multiple linear regression analyses.
Results: None of the subjects had definite left ventricular hypertrophy according to standard clinical definitions. On univariate analysis, there was a significant positive correlation (R=0.26; p<0.05) between LV mass index and ADMA concentrations. On multiple linear regressions, significant correlates of LV mass index were: ADMA concentrations (p<0.05), male gender (p<0.001), resting systolic blood pressure (p=0.01), and body mass index (p<0.001). On analysis of covariance (ANCOVA), subjects in the highest ADMA quartile (ADMA ≥0.58 μM) had significantly higher LV mass index for a given blood pressure vs those with ADMA <0.58 μM (F=6.4, p=0.01).
Conclusions: We therefore conclude the following:
increases in LV mass index in an ageing, normotensive population, free of established cardiovascular disease, are directly correlated with ADMA concentrations, suggesting a potential link between impaired NO formation and initiation of left ventricular hypertrophy;
this process is at least partially afterload-independent and therefore potentially paracrine in origin.