ADMA, subclinical changes and atrial fibrillation in the general population

BackgroundPathways of oxidative stress, nitric oxide bioavailability and l-arginine derivatives are hypothesized to be related to atrial fibrillation (AF). Circulating methylated l-arginine metabolites can be assessed in the general population and may show an association with AF.MethodsWe determined l-arginine and its metabolites asymmetric dimethylarginine (ADMA), l-Nω-monomethylarginine (NMMA) and symmetric dimethylarginine (SDMA) in the population-based Gutenberg Health Study (n = 5000), mean age 55 ± 11 years, 51% men, in association with clinical variables of AF such as electrocardiographic and echocardiographic measures and manifest AF.ResultsIndividuals with AF (N = 161), 71% men, were older, mean age 64.9 ± 8.3 years. In Bonferroni-corrected multivariable-adjusted regression analyses we observed moderate inverse associations for l-arginine, SDMA, and l-arginine/ADMA ratio with ventricular heart rate, and for l-arginine and l-arginine/ADMA ratio with QTc interval. l-arginine was correlated with QRS duration. In echocardiographic analyses, SDMA was related to left atrial diameter and deceleration time, ADMA and NMMA were correlated with left ventricular mass.ADMA (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.11-1-32; p = 0.013) and NMMA (OR 1.17, 95% CI 1.09-1.26, p = 0.014) were related to prevalent AF. l-arginine/ADMA ratio was inversely associated (OR 0.8, 95% CI 0.71-0.90, p = 0.0082). Results were similar after adjustment for creatinine.ConclusionsIn our large, population-based cohort, we observed moderate associations of l-arginine metabolites and intermediate electrocardiographic and echocardiographic variables and AF. Our findings support further investigations to define the role of l-arginine derivatives in AF and their clinical utility.