title: Homoarginine, kidney function and cardiovascular mortality risk.
abstract: BACKGROUND
  Homoarginine is a novel biomarker for cardiovascular diseases. In the present large cohort study, we evaluate how homoarginine is linked to kidney function and examine the potential interaction of homoarginine and kidney function as predictors of cardiovascular outcomes.
  
  
  METHODS
  Serum homoarginine (mean: 2.41 ± 1.05 µmol/L), cystatin C and creatinine-based estimated GFR (eGFR, mean: 86.2 ± 23.0 mL/min per 1.73 m(2)) were measured in 3037 patients (mean age: 62.8 ± 10.6 years; 31.5% women) who were referred to coronary angiography.
  
  
  RESULTS
  Homoarginine was positively associated with eGFR (age- and gender-adjusted partial correlation coefficient: 0.20, P < 0.001); using multiple regression analysis, eGFR emerged as an independent predictor of serum homoarginine (β = 0.10, SE 0.01, P < 0.001). Overall cardiovascular mortality was 18.5% (563 cardiovascular deaths) after 9.9 years. Multivariate Cox proportional hazard analysis revealed that compared with participants in the highest gender-specific homoarginine tertile, those in the lowest tertile were at increased risk of cardiovascular death [multivariate-adjusted HR 1.47; 95% confidence interval (95% CI) 1.15-1.87, P = 0.002]. After adjustment for confounders, both homoarginine and eGFR were associated independently with cardiovascular mortality, with a strong synergistic interaction (P for interaction 0.005). After stratifying the cohort into persons with eGFRs <60 and ≥60 mL/min per 1.73 m(2), there was a stronger association between homoarginine and cardiovascular mortality in patients within eGFR below 60 (mean: 46.5 ± 12.0 mL/min per 1.73 m(2); HR per log SD increment of homoarginine 0.78; 95% CI 0.65-0.95, P = 0.013) compared to those with eGFR values ≥60 mL/min per 1.73 m(2). Subgroup analysis revealed that homoarginine is exclusively associated with death due to heart failure in subjects with eGFR values <60 mL/min per 1.73 m(2) (HR per log SD 0.56; 95% CI 0.37-0.85; P = 0.006).
  
  
  CONCLUSIONS
  Low homoarginine is strongly related to decreased kidney function, adverse cardiovascular events and death due to heart failure. The relationship between low homoarginine and adverse cardiovascular outcomes is most obvious when kidney function is impaired.
authors.affiliation: Department of Cardiology, Medical University of Graz, Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Tomaschitz
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.forename: Jutta
authors.initials: J
authors.lastname: Rus-Machan
authors.forename: Bernd
authors.initials: B
authors.lastname: Genser
authors.forename: Christiane
authors.initials: C
authors.lastname: Drechsler
authors.forename: Tanja
authors.initials: T
authors.lastname: Grammer
authors.forename: Vera
authors.initials: V
authors.lastname: Krane
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.forename: Burkert
authors.initials: B
authors.lastname: Pieske
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kraigher-Krainer
authors.forename: Astrid
authors.initials: A
authors.lastname: Fahrleitner-Pammer
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: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000097:blood* / Q000209:etiology / Q000401:mortality; D006709:Homoarginine / Q000097:blood*; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000150:complications / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009026:Mortality; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D006709:Homoarginine
keywords: cardiovascular mortality; homoarginine; kidney function