title: The additive burden of iron deficiency in the cardiorenal-anaemia axis: scope of a problem and its consequences.
abstract: OBJECTIVE
  Iron deficiency (ID), anaemia, and chronic kidney disease (CKD) are common co-morbidities in chronic heart failure (CHF) and all independent predictors of unfavourable outcome. The combination of anaemia and CKD in CHF has been described as the cardiorenal-anaemia syndrome. However, the role of ID within this complex interplay of co-existing pathologies is unclear.
  
  
  RESULTS
  We studied the clinical correlates of ID (defined as ferritin <100 µg/L or 100-299 µg/L in combination with a transferrin saturation <20%, anaemia) and renal dysfunction (defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2) ) and their prognostic implications in an international pooled cohort, comprising 1506 patients with CHF. Mean age was 64 ± 13 years, 74.2% were male, and 47.3% were in NYHA functional class III. The presence of ID, anaemia, CKD, or a combination of these co-morbidities was observed in 69.3% of the patients. During a median (Q1-Q3) follow-up of 1.92 years (1.18-3.26 years), 440 patients (29.2%) died. Eight-year survival rates decreased significantly from 58.0% for no co-morbidities to 44.6, 33.0, and 18.4%, for one, two, or three co-morbidities, respectively (P < 0.001). Multivariate hazard models revealed ID to be the key determinant of prognosis, either individually (P = 0.04) or in combination with either anaemia (P = 0.006), CKD (P = 0.03), or both (P = 0.02).
  
  
  CONCLUSIONS
  Iron deficiency frequently overlaps with anaemia and/or CKD in CHF. The presence of ID amplifies mortality risk, either alone or in combination with anaemia, CKD, or both, making it a potential viable therapeutic target.
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Ijsbrand T
authors.initials: IT
authors.lastname: Klip
authors.forename: Ewa A
authors.initials: EA
authors.lastname: Jankowska
authors.forename: Cristina
authors.initials: C
authors.lastname: Enjuanes
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.forename: Waldemar
authors.initials: W
authors.lastname: Banasiak
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruguera
authors.forename: Piotr
authors.initials: P
authors.lastname: Rozentryt
authors.forename: Lech
authors.initials: L
authors.lastname: Polonski
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.forename: Josep
authors.initials: J
authors.lastname: Comin-Colet
authors.forename: Peter
authors.initials: P
authors.lastname: van der Meer
mesh_terms: D000368:Aged; D018798:Anemia, Iron-Deficiency / Q000401:mortality / Q000503:physiopathology*; D059347:Cardio-Renal Syndrome / Q000401:mortality / Q000503:physiopathology*; D015897:Comorbidity; D005260:Female; D005293:Ferritins / Q000097:blood; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D016019:Survival Analysis; D015996:Survival Rate; D014168:Transferrin / Q000378:metabolism
chemical_list: D014168:Transferrin; D005293:Ferritins
keywords: Anaemia; Heart failure; Iron deficiency; Kidney disease