Background Physical fatigability, the level of fatigue experienced while undertaking specified physical tasks, increases with age throughout adulthood. These age-related changes, which reflect reductions in energy availability, precipitate declines in activity participation and function. Higher levels of fatigue are also related to increased risk of disability and premature mortality so it is imperative to identify modifiable risk factors across life associated with physical fatigability. Cross-sectional analyses suggest that obesity and inflammation may be associated with increased risk of high physical fatigability. However, whether these inter-related factors act on the same pathway is unclear and requires further investigation in longitudinal studies. We thus aimed to examine the associations of body mass index (BMI) and inflammatory markers from midlife with subsequent levels of perceived physical fatigability in a nationally representative sample.
Methods Up to 2095 men and women from the MRC National Survey of Health and Development, a British cohort followed-up prospectively since birth in 1946, who had valid physical fatigability scores on the Pittsburgh Fatigability Scale (PFS) at age 68 years were included in analyses. Linear regression models were used to assess associations of BMI from age 43 and inflammatory markers (C-reactive protein (CRP) and interleukin-6 (IL-6)) at age 60–64 with continuous PFS scores at age 68. Adjustments were made for sex (where no evidence of interaction was found), long-term limiting illness, physical activity and symptoms of anxiety and depression. All analyses were performed using STATA v14.2.
Results Women had higher mean PFS scores than men (16.0 (SD=9.3) vs 13.4 (SD=9.0), p<0.01), with higher scores indicating greater perceived physical fatigability. In sex-adjusted analyses, higher BMI and higher levels of CRP and IL-6 were associated with higher PFS scores. For example, participants with BMI ≥30kg/m2 at age 43 had sex-adjusted mean PFS scores 4.7 (95% CI: 3.3–6.1) points higher than those with BMI 20–24.9kg/m2 and, those in the highest fifth of IL-6 at age 60–64 had a mean score 4.9 (95% CI: 3.5–6.3) points higher than those in the bottom fifth. When these associations were mutually adjusted and adjusted for other covariates, higher BMI and IL-6 remained associated with higher PFS scores, whereas associations with CRP were fully attenuated.
Conclusion These findings highlight the potentially important influence of inflammatory and other cardio-metabolic processes on physical fatigability. They suggest that both BMI and inflammation from midlife may be important targets for intervention to reduce the burden of this commonly reported symptom in older populations.
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