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

TY - JOUR

T1 - Total and cause-specific mortality by moderately and markedly increased ferritin concentrations

T2 - general population study and metaanalysis

AU - Ellervik, Christina

AU - Marott, Jacob Louis

AU - Tybjærg-Hansen, Anne

AU - Schnohr, Peter

AU - Nordestgaard, Børge G

N1 - © 2014 American Association for Clinical Chemistry.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Biological Markers

KW - Cohort Studies

KW - Denmark

KW - Female

KW - Ferritins

KW - Humans

KW - Kaplan-Meier Estimate

KW - Longitudinal Studies

KW - Male

KW - Middle Aged

KW - Mortality

KW - Proportional Hazards Models

KW - Young Adult

U2 - 10.1373/clinchem.2014.229013

DO - 10.1373/clinchem.2014.229013

M3 - Journal article

C2 - 25156997

SN - 0009-9147

VL - 60

SP - 1419

EP - 1428

JO - Clinical Chemistry

JF - Clinical Chemistry

IS - 11

ER -