title: ADMA and arginine derivatives in relation to non-invasive vascular function in the general population.
abstract: OBJECTIVE
  Nitric oxide produced from l-arginine is central to vascular homeostasis. Little is known about the relationship between arginine derivatives including asymmetric dimethylarginine (ADMA) and non-invasive vascular function measures in the general population.
  
  
  RESULTS
  In 5000 individuals (median age 56; 25th/75th percentile: 46, 65; 49% women) taking part in the population-based Gutenberg Health Study (Mainz area, Germany), we measured the relationship between the arginine derivatives asymmetric dimethylarginine (ADMA), N-monomethyl l-arginine (NMMA), symmetric dimethylarginine (SDMA) and l-arginine with flow-mediated dilation (FMD) and peripheral arterial tonometry (PAT). Weak bivariate correlations were observed between all measured arginine derivatives and vascular function measures, except of l-arginine and FMD and SDMA and PAT ratio. In multivariate adjusted linear regression analyses we could show statistically significant relationships between arginine derivatives and vascular function measures, which were influenced by age, sex and body mass index (BMI). Thus, a negative relationship between ADMA and FMD in females who were normal (beta: -0.095, P < 0.001) to overweight (beta: -0.071, P < 0.001) and a negative association of SDMA and FMD for middle-aged females was seen. The relationship between ADMA and PAT was negative for males who were normal (beta: -0.089, P < 0.001) to overweight (beta: -0.051, P = 0.007) and positive for obese females (beta: 0.073, P = 0.021).
  
  
  CONCLUSIONS
  We showed small but significant correlations between ADMA and related arginine derivatives and non-invasive vascular function measures representative of different vascular regions. The associations were markedly influenced by age, sex and BMI. These findings support a complex interplay of arginine metabolism and vascular function.
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Baum
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Germany.
authors.forename: Silke S
authors.initials: SS
authors.lastname: Johannsen
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Germany; Radcliffe Department of Medicine, University of Oxford, UK.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Atzler
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Ojeda
authors.affiliation: Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; DZHK (German Center for Cardiovascular Research), Partner Site RhineMain, Mainz, Germany.
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Wild
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.
authors.forename: Christoph R
authors.initials: CR
authors.lastname: Sinning
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; DZHK (German Center for Cardiovascular Research), Partner Site RhineMain, Mainz, Germany.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Lackner
authors.affiliation: Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; DZHK (German Center for Cardiovascular Research), Partner Site RhineMain, Mainz, Germany.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Gori
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Germany.
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Germany.
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.affiliation: Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; DZHK (German Center for Cardiovascular Research), Partner Site RhineMain, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Germany. Electronic address: r.schnabel@uke.de.
authors.forename: Renate B
authors.initials: RB
authors.lastname: Schnabel
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects*; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011159:Population Surveillance / Q000379:methods*; D015995:Prevalence; D012189:Retrospective Studies; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase
keywords: Biomarkers; Cross-sectional; Flow-mediated dilation; Peripheral arterial tonometry; Population-based study