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

doi:10.1373/clinchem.2014.229013

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

Institut for Klinisk Medicin

31 Citationer (Scopus)

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 >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.

Originalsprog	Engelsk
Tidsskrift	Clinical Chemistry
Vol/bind	60
Udgave nummer	11
Sider (fra-til)	1419-1428
Antal sider	10
ISSN	0009-9147
DOI	https://doi.org/10.1373/clinchem.2014.229013
Status	Udgivet - 1 nov. 2014

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10.1373/clinchem.2014.229013

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@article{18fbee41ec644041b359ebb1445a8ba5,

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 >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.",

keywords = "Adult, Aged, Aged, 80 and over, Biological Markers, Cohort Studies, Denmark, Female, Ferritins, Humans, Kaplan-Meier Estimate, Longitudinal Studies, Male, Middle Aged, Mortality, Proportional Hazards Models, Young Adult",

author = "Christina Ellervik and Marott, {Jacob Louis} and Anne Tybj{\ae}rg-Hansen and Peter Schnohr and Nordestgaard, {B{\o}rge G}",

note = "{\textcopyright} 2014 American Association for Clinical Chemistry.",

year = "2014",

month = nov,

day = "1",

doi = "10.1373/clinchem.2014.229013",

language = "English",

volume = "60",

pages = "1419--1428",

journal = "Clinical Chemistry",

issn = "0009-9147",

publisher = "American Association for Clinical Chemistry, Inc.",

number = "11",

}

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

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 -

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

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