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Reference intervals of plasma homoarginine from the German Gutenberg Health Study

  • Dorothee Atzler EMAIL logo , 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
Published/Copyright: November 12, 2015
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 54 Issue 7

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.

Keywords: Gutenberg Health Study; homoarginine; reference intervals
Corresponding author: Dorothee Atzler, PhD, Department of Cardiovascular Medicine, University of Oxford, Wellcome Trust Centre for Human Genetics, Roosevelt Dr, Oxford OX3 7BN, UK, E-mail: ; Department of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; and German Centre for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany
aKarl J. Lackner and Edzard Schwedhelm contributed equally to this work.

Acknowledgments

We gratefully thank Mariola Kastner and Anna Steenpaß for their excellent technical assistance. The contributions to data collection made by field workers, study physicians, ultrasound technicians, interviewers, and computer assistants are gratefully acknowledged. Dr. Atzler acknowledges the support of the European Union under a Marie Curie Intra-European Fellowship for Career Development.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: The Gutenberg Health Study is funded through the government of Rhineland-Palatinate (“Stiftung Rheinland-Pfalz für Innovation”, contract AZ 961-386261/733), the research programs “Wissen schafft Zukunft” and “Center for Translational Vascular Biology (CTVB)” of the Johannes Gutenberg-University of Mainz, and its contract with Boehringer Ingelheim and PHILIPS Medical Systems, including an unrestricted grant for the Gutenberg Health Study. This work was supported by the Stiftung für Pathobiochemie und Molekulare Diagnostik (DGKL). PSW is funded by the Federal Ministry of Education and Research (BMBF 01EO1003).

Employment or leadership: PSW, SB, RHB, TM and TZ are PIs of the German Centre for Cardiovascular Research (DZHK).

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplemental Material:

The online version of this article (DOI: 10.1515/cclm-2015-0785) offers supplementary material, available to authorized users.

Received: 2015-8-14
Accepted: 2015-10-12
Published Online: 2015-11-12
Published in Print: 2016-7-1

©2016 by De Gruyter

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https://doi.org/10.1515/cclm-2015-0785
Keywords for this article
Gutenberg Health Study; homoarginine; reference intervals

Articles in the same Issue

  1. Frontmatter
  2. In Memoriam: Gérard Siest (1936–2016)
  3. Editorials
  4. Improving diagnosis and reducing diagnostic errors: the next frontier of laboratory medicine
  5. The quality indicator paradox
  6. Review
  7. Clinical utility of the (-2)proPSA and evaluation of the evidence: a systematic review
  8. Mini Review
  9. Why are clinical practice guidelines not followed?
  10. EFLM Position Paper
  11. Patient identification and tube labelling – a call for harmonisation
  12. Genetics and Molecular Diagnostics
  13. A fast and simple method for detecting and quantifying donor-derived cell-free DNA in sera of solid organ transplant recipients as a biomarker for graft function
  14. Performance of two commercially available BCR-ABL1 quantification assays that use an international reporting scale
  15. HAND1 loss-of-function mutation associated with familial dilated cardiomyopathy
  16. General Clinical Chemistry and Laboratory Medicine
  17. Performance criteria and quality indicators for the post-analytical phase
  18. Assessing the commutability of reference material formats for the harmonization of amyloid-β measurements
  19. Quantitative determination of four immunosuppressants by high resolution mass spectrometry (HRMS)
  20. Measurement of plasma vitamin K1 (phylloquinone) and K2 (menaquinones-4 and -7) using HPLC-tandem mass spectrometry
  21. Therapeutic drug monitoring of infliximab: performance evaluation of three commercial ELISA kits
  22. High level of oxysterols in neonatal cholestasis: a pitfall in analysis of biochemical markers for Niemann-Pick type C disease
  23. Reference Values and Biological Variations
  24. Reference intervals of plasma homoarginine from the German Gutenberg Health Study
  25. TSH and fT4 during pregnancy: an observational study and a review of the literature
  26. Cancer Diagnostics
  27. Mean corpuscular volume levels and all-cause and liver cancer mortality
  28. Cardiovascular Diseases
  29. Circulating endothelial-derived apoptotic microparticles and insulin resistance in non-diabetic patients with chronic heart failure
  30. Hematology and Coagulation
  31. Platelet aggregation in response to ADP is highly variable in normal donors and patients on anti-platelet medication
  32. Letters to the Editor
  33. EQA-derived metrics to assess overall instrument performance
  34. Misidentification in laboratory medicine and diagnostic process: a neglected problem calling for action
  35. Impact of the routine implementation of automated indirect immunofluorescence antinuclear antibody analysis: 1 year of experience
  36. The importance of angiogenic markers in the differential diagnosis of HELLP syndrome vs. non-HELLP thrombocytopenia
  37. Bisalbuminemia accompanying bisalbuminuria detected in capillary electrophoresis, not in gel electrophoresis
  38. Prognostic value of red blood cell distribution width in acute pancreatitis patients admitted to intensive care units: an analysis of a publicly accessible clinical database MIMIC II
  39. Differences in analytical and biological results between older and newer lots of a widely used irisin immunoassay question the validity of previous studies
  40. A diagnostic algorithm for the detection of inhibitors against coagulation Factor V
  41. Interference of anticoagulants on coagulation testing
  42. Congress Abstracts
  43. Swiss MedLab 2016 and 74th Annual Meeting of the Swiss Society of Microbiology SSM, Bern, 13–16 June 2016
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