Reference intervals of plasma homoarginine from the German Gutenberg Health Study

Dorothee Atzler, Sebastian Appelbaum, Kathrin Cordts, Francisco M. Ojeda 4 , Philipp S. Wild, Thomas Münzel, Stefan Blankenberg, Rainer H. Böger, Maria Blettner 8 , Manfred E. Beutel 9 , Norbert Pfeiffer 10 , Tanja Zeller, Karl J. Lackner, and Edzard Schwedhelm
  • 1 Department of Cardiovascular Medicine, University of Oxford, Wellcome Trust Centre for Human Genetics, Roosevelt Dr, Oxford OX3 7BN, UK
  • 2 Department of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
  • 3 German Centre for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany
  • 4 Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Hamburg, Germany
  • 5 German Centre for Cardiovascular Research (DZHK), partner site Rhein/Main, Germany
  • 6 Preventive Cardiology and Preventive Medicine, Department of Medicine II, University Medical Centre of the Johannes-Gutenberg University Mainz, Mainz, Germany
  • 7 Center of Thrombosis and Hemostasis, University Medical Centre of the Johannes-Gutenberg University Mainz, Mainz, Germany
  • 8 Institute for Medical Biostatistics, Epidemiology and Informatics, Mainz, Germany
  • 9 Department of Psychosomatic Medicine and Psychotherapy, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
  • 10 Department of Ophthalmology, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
  • 11 Institute of Clinical Chemistry and Laboratory Medicine, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
Dorothee Atzler, Sebastian Appelbaum, Kathrin Cordts, Francisco M. Ojeda, Philipp S. Wild, Thomas Münzel, Stefan Blankenberg, Rainer H. Böger, Maria Blettner, Manfred E. Beutel, Norbert Pfeiffer, Tanja Zeller, Karl J. Lackner and Edzard Schwedhelm

Abstract

Background: Low circulating homoarginine has been associated with adverse cardiovascular (CV) outcome and mortality in patients at risk and in the general population. The present study aimed to define plasma homoarginine reference intervals from a representative population sample to improve risk stratification between healthy individuals and individuals at risk.

Methods: We determined age- and sex-specific reference intervals for circulating plasma homoarginine in a subgroup of 786 healthy participants (no CV disease or risk factors) of the Gutenberg Health Study. Homoarginine concentrations were measured using a validated liquid chromatography-tandem mass spectrometry method.

Results: Median EDTA plasma homoarginine concentration was 1.88 [25th; 75th percentile, 1.47; 2.41] μmol/L, with lower concentrations in women (1.77 [1.38; 2.26] μmol/L) than in men (2.01 [1.61; 2.56] μmol/L; p<0.001). Sex-specific 2.5th and 97.5th percentiles of reference intervals were 0.84 and 3.89 μmol/L in women and 0.98 and 4.10 μmol/L in men, respectively. Homoarginine concentrations also depended on age and single nucleotide polymorphisms related to the L-arginine:glycine amidinotransferase gene.

Conclusions: We provide plasma homoarginine reference intervals in men and women of the general population. The determination of homoarginine levels might be favorable for individual risk stratification.

    • Supplementary material
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