title: Hepcidin-25 is related to cardiovascular events in chronic haemodialysis patients.
abstract: BACKGROUND
  The development of atherosclerosis may be enhanced by iron accumulation in macrophages. Hepcidin-25 is a key regulator of iron homeostasis, which downregulates the cellular iron exporter ferroportin. In haemodialysis (HD) patients, hepcidin-25 levels are increased. Therefore, it is conceivable that hepcidin-25 is associated with all-cause mortality and/or fatal and non-fatal cardiovascular (CV) events in this patient group. The aim of the current analysis was to study the relationship between hepcidin-25 and all-cause mortality and both fatal and non-fatal CV events in chronic HD patients.
  
  
  METHODS
  Data from 405 chronic HD patients included in the CONvective TRAnsport STudy (NCT00205556) were studied (62% men, age 63.7 ± 13.9 years [mean ± SD]). The median (range) follow-up was 3.0 (0.8-6.6) years. Hepcidin-25 was measured with mass spectrometry. The relationship between hepcidin-25 and all-cause mortality or fatal and non-fatal CV events was investigated with multivariate Cox proportional hazard models.
  
  
  RESULTS
  Median (interquartile range) hepcidin-25 level was 13.8 (6.6-22.5) nmol/L. During follow-up, 158 (39%) patients died from any cause and 131 (32%) had a CV event. Hepcidin-25 was associated with all-cause mortality in an unadjusted model [hazard ratio (HR) 1.14 per 10 nmol/L, 95% CI 1.03-1.26; P = 0.01], but not after adjustment for all confounders including high-sensitive C-reactive protein (HR 1.02 per 10 nmol/L, 95% CI 0.87-1.20; P = 0.80). At the same time, hepcidin-25 was significantly related to fatal and non-fatal CV events in a fully adjusted model (HR 1.24 per 10 nmol/L, 95% CI 1.05-1.46, P = 0.01).
  
  
  CONCLUSIONS
  Hepcidin-25 was associated with fatal and non-fatal CV events, even after adjustment for inflammation. Furthermore, inflammation appears to be a significant confounder in the relation between hepcidin-25 and all-cause mortality. These findings suggest that hepcidin-25 might be a novel determinant of CV disease in chronic HD patients.
authors.affiliation: Department of Nephrology, VU Medical Centre, Amsterdam, The Netherlands.
authors.forename: Neelke C
authors.initials: NC
authors.lastname: van der Weerd
authors.forename: Muriel P C
authors.initials: MP
authors.lastname: Grooteman
authors.forename: Michiel L
authors.initials: ML
authors.lastname: Bots
authors.forename: Marinus A
authors.initials: MA
authors.lastname: van den Dorpel
authors.forename: Claire H
authors.initials: CH
authors.lastname: den Hoedt
authors.forename: Albert H A
authors.initials: AH
authors.lastname: Mazairac
authors.forename: Menso J
authors.initials: MJ
authors.lastname: Nubé
authors.forename: E Lars
authors.initials: EL
authors.lastname: Penne
authors.forename: Jack F M
authors.initials: JF
authors.lastname: Wetzels
authors.forename: Erwin T
authors.initials: ET
authors.lastname: Wiegerinck
authors.forename: Dorine W
authors.initials: DW
authors.lastname: Swinkels
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Blankestijn
authors.forename: Piet M
authors.initials: PM
authors.lastname: Ter Wee
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism* / Q000401:mortality; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D064451:Hepcidins / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000401:mortality; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000009:adverse effects*; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D064451:Hepcidins; C545475:hepcidin 25, human; D002097:C-Reactive Protein
keywords: cardiovascular events; haemodialysis; hepcidin-25; inflammation; mortality