title: Total mortality by transferrin saturation levels: two general population studies and a metaanalysis.
abstract: BACKGROUND
  There is evidence for increased mortality in patients with clinically overt hereditary hemochromatosis. Whether increased transferrin saturation (TS), as a proxy for iron overload is associated with increased mortality in the general population is largely unknown.
  
  
  METHODS
  We examined mortality according to baseline TS in 2 Danish population-based follow-up studies (the Copenhagen General Population Study and the Copenhagen City Heart Study) comprising a total of 45 159 individuals, of whom 4568 died during up to 18 years of follow-up, and in a metaanalysis comprising the present studies and an additional general population study.
  
  
  RESULTS
  In combined studies, the cumulative survival was reduced in individuals with TS≥50% vs <50% (log-rank P<0.0001). Multifactorially adjusted hazard ratios for total mortality for TS≥50% vs <50% were 1.4 (95% CI 1.2-1.6; P<0.001) overall, 1.3 (1.1-1.6; P=0.003) in men, and 1.5 (1.1-2.0; P=0.005) in women. Results were similar if the 2 studies were considered separately. A stepwise increased risk of total mortality was observed for stepwise increasing levels of TS (log-rank P<0.0001), with the highest risk conferred by TS≥80% vs TS<20% with a hazard ratio of 2.2 (1.4-3.3; P<0.001). The population-attributable risk for total mortality in the combined studies in individuals with TS≥50% vs <50% was 0.8%. In metaanalysis, the odds ratio for total mortality for TS≥50% vs <50% was 1.3 (1.2-1.5; P<0.001) under the fixed-effects model.
  
  
  CONCLUSIONS
  Individuals in the general population with TS≥50% vs <50% have an increased risk of premature death.
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Herlev, Denmark.
authors.forename: Christina
authors.initials: C
authors.lastname: Ellervik
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjærg-Hansen
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006432:Hemochromatosis / Q000097:blood / Q000235:genetics / Q000401:mortality*; D006801:Humans; D019190:Iron Overload / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011159:Population Surveillance; D014168:Transferrin / Q000032:analysis / Q000378:metabolism*
chemical_list: D014168:Transferrin