title: Low homoarginine concentration is a novel risk factor for heart disease.
abstract: 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.
  
  
  OBJECTIVE
  To investigate whether serum homoarginine concentrations are associated with myocardial function, energy metabolism and fatal events.
  
  
  METHODS
  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.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria. stefan.pilz@chello.at
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
authors.forename: Andreas
authors.initials: A
authors.lastname: Tomaschitz
authors.forename: Christiane
authors.initials: C
authors.lastname: Drechsler
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.forename: Vera
authors.initials: V
authors.lastname: Krane
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Boehm
authors.forename: Winfried
authors.initials: W
authors.lastname: März
mesh_terms: D015415:Biomarkers / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D017023:Coronary Angiography; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D004734:Energy Metabolism; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D005998:Glycine / Q000031:analogs & derivatives / Q000097:blood; D006331:Heart Diseases / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D006709:Homoarginine / Q000097:blood*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D015996:Survival Rate / Q000639:trends; D013997:Time Factors
chemical_list: D015415:Biomarkers; D006709:Homoarginine; D003404:Creatinine; C004946:glycocyamine; D005998:Glycine