Abstract
Systemic inflammation may play a role in the development of idiopathic fatigue, that is, fatigue not explained by infections or diagnosed chronic illness, but this relationship has never been investigated in community studies including the entire adult age span. We examine the association of the inflammatory marker C-reactive protein (CRP) and fatigue assessed annually in a 3-year outcome period for UK adults aged 16-98. Multilevel models were used to track fatigue 7, 19, and 31 months after CRP measurement, in 10 606 UK individuals. Models accounted for baseline fatigue, demographics, health conditions diagnosed at baseline and during follow-up, adiposity, and psychological distress. Sensitivity analyses considered factors including smoking, sub-clinical disease (blood pressure, anaemia, glycated haemoglobin), medications, ethnicity, and alcohol consumption. Fatigue and CRP increased with age, and women had higher values than men. CRP was associated with future self-reported fatigue, but only for the oldest participants. Thus, in those aged 61-98 years, high CRP (>3 mg/L) independently predicted greater fatigue 7, 19, and 31 months after CRP measurement [odds ratio for new-onset fatigue after 7 months: 1.88, 95% confidence interval (CI) 1.21-2.92; 19 months: 2.25, CI 1.46-3.49; 31 months: 1.65, CI 1.07-2.54]. No significant longitudinal associations were seen for younger participants. Our findings support previously described CRP-fatigue associations in older individuals. However, there are clear age modifications in these associations, which may reflect a contribution of unmeasured sub-clinical disease of limited relevance to younger individuals. Further work is necessary to clarify intervening processes linking CRP and fatigue in older individuals.
Highlights
Idiopathic fatigue and possible causesIn healthy individuals, fatigue is usually experienced as a transient response to physical exertion or prolonged activity, which reduces with rest and does not normally interfere with daily tasks (Kluger et al 2013)
It has been suggested that low-grade inflammatory activity may play a role in otherwise unexplained fatigue (Cho et al 2009; Alexander et al 2010; Cho et al 2013), based on experiments showing that exogenous inflammatory agents can induce fatigue in healthy humans (Spath-Schwalbe et al 1998), and the fact that fatigue is a key component of the ‘sickness behaviour’ triggered by the acute inflammatory response to infection or injury (Dantzer et al 2008; Miller et al 2009)
We find the association of fatigue and C-reactive protein (CRP) levels indicative of systemic inflammation to be substantially modified by age
Summary
Fatigue is usually experienced as a transient response to physical exertion or prolonged activity, which reduces with rest and does not normally interfere with daily tasks (Kluger et al 2013). It can be persistent, and not clearly attributable to exertion: this kind of ongoing fatigue can disrupt quality of life, as well as social or occupational functioning (Finsterer & Mahjoub, 2014). Systemic inflammation may play a role in the development of idiopathic fatigue, that is, fatigue not explained by infections or diagnosed chronic illness, but this relationship has never been investigated in community studies including the entire adult age span. Further work is necessary to clarify intervening processes linking CRP and fatigue in older individuals
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