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

Neil Basu; Xingzi Yang; Robert N. Luben; Daniel Whibley; Gary J. Macfarlane; Nicolas J. Wareham; Kay-Tee Khaw; Phyo Kyaw Myint

doi:10.1186/s12916-016-0662-y

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 journal › Article › peer-review

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Abstract

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 language	English
Article number	122
Number of pages	8
Journal	BMC medicine
Volume	14
DOIs	https://doi.org/10.1186/s12916-016-0662-y
Publication status	Published - 20 Aug 2016

Bibliographical note

Acknowledgements
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.

Funding
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.

Keywords

fatigue
mortality
cardiovascular
cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12916-016-0662-yLicence: CC BY

Fatigue is associated with excess mortality in the general population
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Final published version, 401 KBLicence: CC BY

Gary Macfarlane
Person: Clinical Academic
Phyo Myint, Clinical Chair in Medicine of Old Age
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Cardiovascular and Diabetes Centre
- School of Medicine, Medical Sciences & Nutrition, Applied Health Sciences - Chair in Old Age Medicine (Clinical)
- Institute of Applied Health Sciences
Person: Clinical Academic

Cite this

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

abstract = "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. ",

keywords = "fatigue, mortality, cardiovascular, cancer",

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note = "Acknowledgements 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. Funding 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.",

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doi = "10.1186/s12916-016-0662-y",

language = "English",

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T1 - Fatigue is associated with excess mortality in the general population

T2 - results from the EPIC-Norfolk study

AU - Basu, Neil

AU - Yang, Xingzi

AU - Luben, Robert N.

AU - Whibley, Daniel

AU - Macfarlane, Gary J.

AU - Wareham, Nicolas J.

AU - Khaw, Kay-Tee

AU - Myint, Phyo Kyaw

N1 - Acknowledgements 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. Funding 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.

PY - 2016/8/20

Y1 - 2016/8/20

N2 - 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.

AB - 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.

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KW - mortality

KW - cardiovascular

KW - cancer

U2 - 10.1186/s12916-016-0662-y

DO - 10.1186/s12916-016-0662-y

M3 - Article

SN - 1741-7015

VL - 14

JO - BMC medicine

JF - BMC medicine

M1 - 122

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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Gary Macfarlane

Phyo Myint, Clinical Chair in Medicine of Old Age

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