Total and cause-specific mortality by moderately and markedly increased ferritin concentrations: General population study and metaanalysis

Christina Ellervik, Jacob Louis Marott, Anne Tybjærg-Hansen, Peter Schnohr, Børge G. Nordestgaard

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Abstrakt

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 >200μg/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.

OriginalsprogEngelsk
Sider (fra-til)1419-1428
Antal sider10
TidsskriftClinical Chemistry
Vol/bind60
Udgave nummer11
DOI
StatusUdgivet - 1 nov. 2014

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