#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

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


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 (Short Form 36 vitality domain, SF36-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, C-reactive protein and thyroid function) were followed up prospectively for up to 20 years. Mortality from all causes, cancer and cardiovascular disease 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 ratio (HR) for all-cause mortality was 1.40 (95 % confidence interval [CI] 1.25–1.56) for those reporting the highest fatigue (bottom SF36-VT quartile) compared with those reporting the lowest fatigue (top SF36-VT quartile). This significant association was specifically observed for those deaths related to cardiovascular disease (HR 1.45, 95 % CI 1.18–1.78) but not cancer (HR 1.09, 95 % CI 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, 95 % CI 1.10–1.45).

Conclusions:
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


Autoři: Neil Basu 1*;  Xingzi Yang 1;  Robert N. Luben 2,4;  Daniel Whibley 1;  Gary J. Macfarlane 1;  Nicholas J. Wareham 3,4;  Kay-Tee Khaw 3,4;  Phyo Kyaw Myint 1
Působiště autorů: Epidemiology Group, Institute of Applied Health Sciences, School of Medicine & Dentistry, University of Aberdeen, Foresterhill, Aberdeen, Scotland AB 5 ZD, UK. 1;  Department of Public Health and Primary Care, Strangeway Research Laboratory, University of Cambridge, Cambridge, UK. 2;  Department of Public Health and Primary Care, Clinical Gerontology Unit, University of Cambridge, Cambridge, UK. 3;  MRC Epidemiology Unit, Cambridge, UK. 4
Vyšlo v časopise: BMC Medicine 2016, 14:122
Kategorie: Research article
prolekare.web.journal.doi_sk: https://doi.org/10.1186/s12916-016-0662-y

© 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.
The electronic version of this article is the complete one and can be found online at: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0662-y

Souhrn

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 (Short Form 36 vitality domain, SF36-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, C-reactive protein and thyroid function) were followed up prospectively for up to 20 years. Mortality from all causes, cancer and cardiovascular disease 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 ratio (HR) for all-cause mortality was 1.40 (95 % confidence interval [CI] 1.25–1.56) for those reporting the highest fatigue (bottom SF36-VT quartile) compared with those reporting the lowest fatigue (top SF36-VT quartile). This significant association was specifically observed for those deaths related to cardiovascular disease (HR 1.45, 95 % CI 1.18–1.78) but not cancer (HR 1.09, 95 % CI 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, 95 % CI 1.10–1.45).

Conclusions:
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


Zdroje

1. Cathebras PJ, Robbins JM, Kirmayer LJ, Hayton BC. Fatigue in primary care: prevalence, psychiatric comorbidity, illness behavior, and outcome. J Gen Intern Med. 1992;7(3):276–86.

2. Cullen W, Kearney Y, Bury G. Prevalence of fatigue in general practice. Ir J Med Sci. 2002;171(1):10–2.

3. Gallagher AM, Thomas JM, Hamilton WT, White PD. Incidence of fatigue symptoms and diagnoses presenting in UK primary care from 1990 to 2001. J R Soc Med. 2004;97(12):571–5.

4. Nelson E, Kirk J, McHugo G, Douglass R, Ohler J, Wasson J, Zubkoff M. Chief complaint fatigue: a longitudinal study from the patient's perspective. Fam Pract Res J. 1987;6(4):175–88.

5. Janssen N, Kant IJ, Swaen GMH, Janssen PPM, Schroer CAP. Fatigue as a predictor of sickness absence: results from the Maastricht cohort study on fatigue at work. Occup Environ Med. 2003;60:71–6.

6. Ricci JA, Chee E, Lorandeau AL, Berger J. Fatigue in the US workforce: prevalence and implications for lost productive work time. J Occup Environ Med. 2007;49(1):1–10.

7. Meeuwesen L, Bensing J, van den Brink-Muinen A. Communicating fatigue in general practice and the role of gender. Patient Educ Couns. 2002;48(3):233–42.

8. Kenter EG, Okkes IM, Oskam SK, Lamberts H. Tiredness in Dutch family practice. Data on patients complaining of and/or diagnosed with “tiredness”. Fam Pract. 2003;20(4):434–40.

9. Moreh E, Jacobs JM, Stessman J. Fatigue, function, and mortality in older adults. J Gerontol A Biol Sci Med Sci. 2010;65(8):887–95.

10. Hardy SE, Studenski SA. Fatigue predicts mortality in older adults. J Am Geriatr Soc. 2008;56(10):1910–4.

11. Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP, Asvold BO, Iervasi G, Imaizumi M, Collet TH, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010;304(12):1365–74.

12. Day N, Oakes S, Luben R, Khaw KT, Bingham S, Welch A, Wareham N. EPICNorfolk: study design and characteristics of the cohort. European Prospective Investigation of Cancer. Br J Cancer. 1999;80(1):95–103.

13. Neuberger GB. Measures of fatigue. Arthritis Care Res. 2003;45(5S):175–83.

14. Ware JE. SF-36 health survey: manual and interpretation guide. Lincoln: QualityMetric Inc; 2000.

15. Donovan KA, Jacobsen PB, Small BJ, Munster PN, Andrykowski MA. Identifying clinically meaningful fatigue with the Fatigue Symptom Inventory. J Pain Symptom Manag. 2008;36(5):480–7.

16. Myint PK, Luben RN, Wareham NJ, Bingham SA, Khaw KT. Combined effect of health behaviours and risk of first ever stroke in 20,040 men and women over 11 years’ follow-up in Norfolk cohort of European Prospective Investigation of Cancer (EPIC Norfolk): prospective population study. BMJ. 2009;338:b349.

17. Myint PK, Luben RN, Wareham NJ, Welch AA, Bingham SA, Day NE, Khaw KT. Combined work and leisure physical activity and risk of stroke in men and women in the European prospective investigation into Cancer-Norfolk Prospective Population Study. Neuroepidemiology. 2006;27(3):122–9.

18. Myint PK, Welch AA, Bingham SA, Surtees PG, Wainwright NW, Luben RN, Wareham NJ, Smith RD, Harvey IM, Day NE, et al. Fruit and vegetable consumption and self-reported functional health in men and women in the European Prospective Investigation into Cancer-Norfolk (EPIC-Norfolk): a population-based cross-sectional study. Public Health Nutr. 2007;10(1):34–41.

19. Global database on body mass index [http://apps.who.int/bmi/index.jsp?introPage=intro_3.html]. Accessed 1 Oct 2015.

20. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity [http://www.who.int/vmnis/indicators/haemoglobin.pdf]. Accessed 1 Oct 2015.

21. Afari N, Buchwald D. Chronic fatigue syndrome: a review. Am J Psychiatry. 2003;160(2):221–36.

22. Roberts E, Wessely S, Chalder T, Chang CK, Hotopf M. Mortality of people with chronic fatigue syndrome: a retrospective cohort study in England and Wales from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) Register. Lancet. 2016;387:1638–43.

23. Prescott E, Holst C, Gronbaek M, Schnohr P, Jensen G, Barefoot J. Vital exhaustion as a risk factor for ischaemic heart disease and all-cause mortality in a community sample. A prospective study of 4084 men and 5479 women in the Copenhagen City Heart Study. Int J Epidemiol. 2003;32(6):990–7.

24. Melamed S, Shirom A, Toker S, Berliner S, Shapira I. Burnout and risk of cardiovascular disease: evidence, possible causal paths, and promising research directions. Psychol Bull. 2006;132(3):327–53.

25. Black PH, Garbutt LD. Stress, inflammation and cardiovascular disease. J Psychosom Res. 2002;52(1):1–23.

26. Kop WJ, Hamulyak K, Pernot C, Appels A. Relationship of blood coagulation and fibrinolysis to vital exhaustion. Psychosom Med. 1998;60(3):352–8.

27. Tracy RP. Inflammation, the metabolic syndrome and cardiovascular risk. Int J Clin Pract Suppl. 2003;134:10–7.

28. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352(16):1685–95.

29. Rosmond R, Wallerius S, Wanger P, Martin L, Holm G, Bjorntorp P. A 5-year follow-up study of disease incidence in men with an abnormal hormone pattern. J Int Med. 2003;254(4):386–90.

30. Kronenberg H, Williams RH. Williams textbook of endocrinology. 11th ed. Henry M. Kronenberg … [et al.] editor. Philadelphia: Elsevier Saunders; 2008.

31. Gomberg-Maitland M, Frishman WH. Thyroid hormone and cardiovascular disease. Am Heart J. 1998;135(2 Pt 1):187–96.

Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#