title: Total and cause-specific mortality by moderately and markedly increased ferritin concentrations: general population study and metaanalysis.
abstract: BACKGROUND
  Previous population-based studies of plasma ferritin concentration have not revealed a relationship with total mortality. We tested the possible association of increased ferritin concentrations with increased risk of total and cause-specific mortality in the general population.
  
  
  METHODS
  We examined total and cause-specific mortality according to baseline plasma ferritin concentrations in a Danish population-based study (the Copenhagen City Heart Study) of 8988 individuals, 6364 of whom died (median follow-up 23 years). We also included a metaanalysis of total mortality comprising population-based studies according to ferritin quartiles or tertiles.
  
  
  RESULTS
  Multifactorially adjusted hazard ratios (HRs) for total mortality for individuals with ferritin ≥200 vs <200 μg/L were 1.1 (95% CI 1.1-1.2; P = 0.0008) overall, 1.1 (1.0-1.2; P = 0.02) in men, and 1.2 (1.0-1.3; P = 0.03) in women. Stepwise increasing concentrations of ferritin were associated with a stepwise increased risk of premature death overall (log rank, P = 2 × 10(-22)), with median survival of 55 years at ferritin concentrations ≥600 μg/L, 72 years at 400-599 μg/L, 76 years at 200-399 μg/L, and 79 years at ferritin <200 μg/L. The corresponding HR for total overall mortality for ferritin ≥600 vs <200 μg/L was 1.5 (1.2-1.8; P = 0.00008). Corresponding adjusted HRs for ferritin ≥600 vs <200 μg/L were 1.6 (1.1-2.3; P = 0.01) for cancer mortality, 2.9 (1.7-5.0; P = 0.0001) for endocrinological mortality, and 1.5 (1.1-2.0; P = 0.01) for cardiovascular mortality. The metaanalysis random effects odds ratio for total mortality for ferritin upper vs reference quartile or tertile was 1.0 (0.9-1.1; P = 0.3) (P heterogeneity = 0.5).
  
  
  CONCLUSIONS
  Moderately to markedly increased ferritin concentrations represent a biological biomarker predictive of early death in a dose-dependent linear manner in the general population.
authors.affiliation: Department of Research, Nykøbing Falster Hospital, Nykøbing Falster, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; christina@ellervik.dk.
authors.forename: Christina
authors.initials: C
authors.lastname: Ellervik
authors.affiliation: The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark;
authors.forename: Jacob Louis
authors.initials: JL
authors.lastname: Marott
authors.affiliation: Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjærg-Hansen
authors.affiliation: The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark;
authors.forename: Peter
authors.initials: P
authors.lastname: Schnohr
authors.affiliation: Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark; Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005293:Ferritins / Q000097:blood*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009026:Mortality; D016016:Proportional Hazards Models; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005293:Ferritins