Fatigue is associated with excess mortality in the general population: results from the EPIC-Norfolk study

Neil Basu* (Corresponding Author), Xingzi Yang, Robert N. Luben, Daniel Whibley, Gary J. Macfarlane, Nicolas J. Wareham, Kay-Tee Khaw, Phyo Kyaw Myint

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Background: Significant fatigue is a frequent reason for seeking medical advice in the general population. Patients however commonly feel their complaint is ignored. This situation may be because clinicians perceive fatigue to be benign, unrelated to traditional biomedical outcomes such as premature mortality. The present study aimed to investigate whether an association between significant fatigue and mortality actually exists and if so to identify potential mechanisms of this association.

Methods: A population based cohort of 18,101 men and women aged 40-79 years who completed a measure of fatigue (SF-36-VT) in addition to providing information on possible confounding factors (age, sex, body mass index, marital status, smoking, education level, alcohol consumption, social class, depression, bodily pain, diabetes, use of β blockers, physical activity and diet) and mechanisms (haemoglobin, CRP, thyroid function) were followed up prospectively for up to 20 years. Mortality from all causes, cancer and cardiovascular disease (CVD) was ascertained using death certification linkage with the UK Office of National Statistics.

Results: During 300,322 person years of follow-up (mean 16.6 years), 4397 deaths occurred. After adjusting for confounders, the hazard ratios (HR) for all-cause mortality were 1.40 (1.25-1.56) for those reporting the highest fatigue (bottom SF36-VT quartile) compared with those reporting the lowest fatigue (top SF-36-VT quartile). This significant association was specifically observed for those deaths related to CVD (HR 1.45, 1.18-1.78) but not cancer (HR 1.09, 0.90-1.32). Of the considered mechanisms, thyroid function was most notable for attenuating this association. The risk of all-cause mortality however remained significant even after considering all putative confounders and mechanisms (HR 1.26, 1.10-1.45).

Conclusion: High levels of fatigue are associated with excess mortality in the general population. . This commonly dismissed symptom demands greater evaluation and should not automatically be considered benign.
Original languageEnglish
Article number122
Number of pages8
JournalBMC medicine
Publication statusPublished - 20 Aug 2016

Bibliographical note

We gratefully thank the participants of the EPIC-Norfolk study. We also thank
the collaborating general practices, staff of the EPIC-Norfolk and our funders.

This work was supported by programme grants from the Medical Research
Council G1000143 and the Cancer Research UK 8257. Funders had no role in
study design, analysis or interpretation of the findings.


  • fatigue
  • mortality
  • cardiovascular
  • cancer


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