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Low homoarginine concentration is a novel risk factor for heart disease
  1. Stefan Pilz1,2,
  2. Andreas Meinitzer3,
  3. Andreas Tomaschitz1,
  4. Christiane Drechsler4,
  5. Eberhard Ritz5,
  6. Vera Krane4,
  7. Christoph Wanner4,
  8. Bernhard O Boehm6,
  9. Winfried März3,7,8
  1. 1Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria
  2. 2Department of Epidemiology and Biostatistics and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands
  3. 3Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
  4. 4Department of Medicine, Division of Nephrology, University of Würzburg, Würzburg, Germany
  5. 5Department of Nephrology, University of Heidelberg, Germany
  6. 6Graduate School Molecular Endocrinology and Diabetes, Ulm University, Ulm, Germany
  7. 7Synlab Center of Laboratory Diagnostics, Heidelberg, Germany
  8. 8Mannheim Institute of Public Health, Ruperto Carola University Heidelberg, Medical Faculty Mannheim, Mannheim, Germany
  1. Correspondence to Stefan Pilz, Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; stefan.pilz{at}


Background Homoarginine is an amino acid which may play a role in nitric oxide and energy metabolism. Low homoarginine concentrations have previously been linked to increased mortality, but the underlying mechanisms remain unknown.

Objectives To investigate whether serum homoarginine concentrations are associated with myocardial function, energy metabolism and fatal events.

Design and patients Serum homoarginine concentrations were measured in 3305 Caucasian patients who were referred for coronary angiography at a tertiary care centre in Germany. After baseline examinations (1997–2000), patients were followed-up with respect to specific causes of death.

Results Homoarginine concentration correlated positively with angiographic ejection fraction and was inversely associated with N-terminal pro-B-type natriuretic peptide (p<0.001 for both). Variables of energy metabolism (guanidinoacetate and creatine) were significantly associated with homoarginine concentration (p<0.001 for both). Over a median follow-up time of 9.9 years, 991 patients died, including 258 sudden cardiac deaths, 148 heart failure deaths and 105 fatal myocardial infarctions. Multivariable adjusted Cox proportional HRs (with 95% CI) for the first versus the fourth homoarginine quartile were 2.44 (1.60 to 3.73) for sudden cardiac deaths, 3.44 (1.89 to 6.24) for heart failure deaths, and 3.78 (1.77 to 8.06) for fatal myocardial infarctions.

Conclusions Homoarginine deficiency is associated with myocardial dysfunction and significantly increased risk of fatal cardiovascular events and may be related to poor energy metabolism. Further studies are warranted to explore the significance of homoarginine metabolism in risk stratification and treatment of heart diseases.

  • Homoarginine
  • cardiovascular
  • mortality
  • amino acids
  • prospective
  • heart failure

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  • This work is dedicated to the whole staff at the Division of Neonatology, Department of Pediatrics, Medical University of Graz, Austria who took care of my brave son Alexander Pilz.

  • Funding LURIC has received funding through the 6th Framework Program (integrated project Bloodomics, grant LSHM-CT-2004-503485) and the 7th Framework Program (integrated project Atheroremo, Grant Agreement number 201668) of the European Union.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Ärztekammer Rheinland-Pfalz, Germany.

  • Provenance and peer review Not commissioned; externally peer reviewed.