title: Associations of methylarginines and homoarginine with diastolic dysfunction and cardiovascular risk factors in patients with preserved left ventricular ejection fraction.
abstract: BACKGROUND
  Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and homoarginine are considered to modulate nitric oxide synthesis. We evaluated whether ADMA, SDMA, and homoarginine are associated with diastolic dysfunction.
  
  
  RESULTS
  We investigated primary care patients at cardiovascular risk with preserved left ventricular ejection fraction from the multicenter DIAST-CHF study. We measured serum concentrations of ADMA, SDMA, and homoarginine and performed standardized echocardiographic examinations. Among 1,396 patients (mean age 65.3 ± 8.3 y, 54.6% women), diastolic dysfunction was ruled out in 261 patients (18.7%). Mild and moderate/severe grades of diastolic dysfunction were present in 900 (64.5%) and 235 (16.8%) study participants, respectively. After adjustments for cardiovascular risk factors, ADMA and SDMA were positively and homoarginine negatively associated with N-terminal pro-B-type natriuretic peptide and midregional pro-adrenomedullin (P < .05 for all). Lower homoarginine levels were associated with diastolic dysfunction, and higher ADMA and SDMA levels were associated with the severity of diastolic dysfunction (P < .05 for all).
  
  
  CONCLUSIONS
  Higher levels of ADMA and SDMA and lower levels of homoarginine are associated with an adverse cardiovascular risk profile and diastolic dysfunction. Further studies should clarify the potential of these amino acid derivatives for the therapy of cardiovascular diseases.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria; Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands. Electronic address: stefan.pilz@medunigraz.at.
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.affiliation: Department of Cardiology and Pneumology, University of Goettingen, Goettingen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Edelmann
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
authors.affiliation: Coordination Center for Clinical Trials, University of Leipzig, Leipzig, Germany.
authors.forename: Götz
authors.initials: G
authors.lastname: Gelbrich
authors.affiliation: Department of Cardiology and Pneumology, University of Goettingen, Goettingen, Germany.
authors.forename: Ufuk
authors.initials: U
authors.lastname: Döner
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Hans-Dirk
authors.initials: HD
authors.lastname: Düngen
authors.affiliation: Department of Cardiology, Medical University of Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Tomaschitz
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kienreich
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Gaksch
authors.affiliation: Department of Cardiology and Pneumology, University of Goettingen, Goettingen, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Duvinage
authors.affiliation: Department of Cardiology and Pneumology, University of Goettingen, Goettingen, Germany.
authors.forename: Raoul
authors.initials: R
authors.lastname: Stahrenberg
authors.affiliation: Brahms, Hennigsdorf, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Kunde
authors.affiliation: Department of Cardiology, Medical University of Graz, Austria.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria; Synlab Center of Laboratory Diagnostics, Heidelberg, Germany; Mannheim Institute of Public Health, Medical Faculty Mannheim, Ruperto Carola University Heidelberg, Mannheim, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Department of Cardiology and Pneumology, University of Goettingen, Goettingen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Wachter
authors.affiliation: Department of Cardiology, Medical University of Graz, Austria.
authors.forename: Burkert
authors.initials: B
authors.lastname: Pieske
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000000981:diagnostic imaging; D015150:Echocardiography, Doppler; D005260:Female; D054144:Heart Failure, Diastolic / Q000097:blood* / Q000000981:diagnostic imaging; D006709:Homoarginine / Q000097:blood*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000502:physiology*
chemical_list: D015415:Biomarkers; D006709:Homoarginine; D009569:Nitric Oxide; C024917:symmetric dimethylarginine; D001120:Arginine
keywords: Homoarginine; cardiovascular risk; diastolic dysfunction; methylarginines