title: ADMA, subclinical changes and atrial fibrillation in the general population.
abstract: BACKGROUND
  Pathways 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.
  
  
  METHODS
  We determined L-arginine and its metabolites asymmetric dimethylarginine (ADMA), L-N(ω)-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.
  
  
  RESULTS
  Individuals 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.
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: Department of Cardiology and Electrophysiology, University Heart Center Hamburg-Eppendorf, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Ramuschkat
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Germany; DZHK (Deutsches Zentrum fuer Herz-Kreislauf-Forschung e.V.), partner site Hamburg/Kiel/Luebeck, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Appelbaum
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (Deutsches Zentrum fuer Herz-Kreislauf-Forschung e.V.), partner site Hamburg/Kiel/Luebeck, Germany; Preventive Cardiology and Preventive Medicine, Department of Medicine 2, University Medical Center Mainz, Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Atzler
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Germany; DZHK (Deutsches Zentrum fuer Herz-Kreislauf-Forschung e.V.), partner site Hamburg/Kiel/Luebeck, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bauer
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Germany.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Ojeda
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Germany.
authors.forename: Christoph R
authors.initials: CR
authors.lastname: Sinning
authors.affiliation: Department of Cardiology and Electrophysiology, University Heart Center Hamburg-Eppendorf, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Hoffmann
authors.affiliation: University Medical Center of the Johannes Gutenberg-University Mainz, Germany.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Lackner
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (Deutsches Zentrum fuer Herz-Kreislauf-Forschung e.V.), partner site Hamburg/Kiel/Luebeck, Germany.
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
authors.affiliation: DZHK (Deutsches Zentrum fuer Herz-Kreislauf-Forschung e.V.), partner site Hamburg/Kiel/Luebeck, Germany; Center for Cardiovascular research (DZHK), Partner Site Rhein/Main, Germany; Department of Medicine 2, University Medical Center Mainz, Johannes Gutenberg University Mainz, Germany; Center for Thrombosis and Haemostasis, University Medical Center Mainz, Johannes Gutenberg University Mainz, Germany; Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Germany.
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Wild
authors.affiliation: Center for Cardiovascular research (DZHK), Partner Site Rhein/Main, Germany; Department of Medicine 2, University Medical Center Mainz, Johannes Gutenberg University Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Germany; DZHK (Deutsches Zentrum fuer Herz-Kreislauf-Forschung e.V.), partner site Hamburg/Kiel/Luebeck, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (Deutsches Zentrum fuer Herz-Kreislauf-Forschung e.V.), partner site Hamburg/Kiel/Luebeck, Germany.
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Germany; DZHK (Deutsches Zentrum fuer Herz-Kreislauf-Forschung e.V.), partner site Hamburg/Kiel/Luebeck, Germany. Electronic address: schnabelr@gmx.de.
authors.forename: Renate B
authors.initials: RB
authors.lastname: Schnabel
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001281:Atrial Fibrillation / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D002853:Chromatography, Liquid; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity / Q000639:trends; D018384:Oxidative Stress; D011159:Population Surveillance / Q000379:methods*; D053719:Tandem Mass Spectrometry; D019323:omega-N-Methylarginine / Q000097:blood
chemical_list: D015415:Biomarkers; D019323:omega-N-Methylarginine; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: ADMA; Atrial fibrillation; Population-based cohort; l-arginine derivatives