Association of ferritin and transferrin saturation with all-cause mortality, and the effect of concurrent inflammation: a danish cohort study

Abstract

The association between ferritin and transferrin saturation (TS), respectively, and all-cause mortality is unclear. Furthermore, the influence of concurrent inflammation has not been sufficiently elucidated. We investigated these associations and the effect of concurrently elevated C-reactive protein (CRP), and accordingly report the levels associated with lowest all-cause mortality for females and males with and without inflammation.

Blood test results from 161,921 individuals were included. Statistical analyses were performed in sex-stratified subpopulations, with ferritin or TS level as continuous exposure variables, and were adjusted for age, co-morbidity and inflammation status using CRP. An interaction was used to investigate whether the effect of ferritin or TS on all-cause mortality was modified by inflammation status (CRP ≥ 10 mg/L or CRP < 10 mg/L). Low and high ferritin and TS levels were respectively associated with increased all-cause mortality in females and in males. These associations persisted with concurrent CRP ≥ 10 mg/L. The ferritin level associated with lowest mortality was 60 µg/L for females and 125 µg/L for males with CRP < 10 mg/L. It was 52 µg/L for females and 118 µg/L for males with CRP ≥ 10 mg/L. The TS level associated with lowest mortality was 33.9% for females and 32.3% for males with CRP < 10 mg/L. It was 28.7% for females and 30.6% for males with CRP ≥ 10 mg/L.

Our findings can nuance clinical interpretation and further aid in defining recommended ranges for ferritin and TS.

Keywords:

• Ferritins
• transferrin
• iron
• iron metabolism disorders
• iron deficiencies
• iron overload
• C-reactive protein
• acute-phase proteins
• acute-phase reaction
• inflammation
• mortality
• public health
• primary health care

Acknowledgements

The authors thank the Department of Clinical Biochemistry, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. Funder. Did not influence: study design; collection, analysis and interpretation of data; the writing of the report; the decision to submit the article for publication.

The authors thank the Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

Author contributions

NHM, BSL, HLJ, CLA, MKG and MK were involved in designing the study. MK, MKG and CWB were responsible for the data requisition and analyses. BSL contributed with information on CopLab methods and materials. All authors contributed to the interpretation of the data. NHM drafted the manuscript and all additional authors were involved in the revision.

All authors approved the final version of the manuscript.

NHM is the corresponding author. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data providing the grounds of this study is located at server housed by Statistics Denmark. Access to the data is restricted, and data is thus not available to the public.