A pilot observational study of the association between fatigue after stroke and C-reactive protein

Background: The aetiology of fatigue after stroke is unknown. We explored the relationship between fatigue and C-reactive protein (CRP) as a marker of inflammation. Methods: This cross-sectional study recruited inpatients with a stroke (onset within the previous three months) over a five-week period. Those with dysphasia or confusion severe enough to prevent informed consent and those with current infection were excluded. A semi-structured interview determined a) fulfilment of a case definition for fatigue and b) severity of fatigue (fatigue assessment scale, FAS). Venous blood was taken for CRP. A hospital anxiety and depression score (HADS) was used to screen for emotional distress. Results: Of the 28 patients recruited (mean age 72.7 years, proportion men 47%), 15 (53%) fulfilled the case definition for fatigue. C-reactive protein data were logarithmically transformed for analysis. C-reactive protein levels did not differ significantly between those with and without fatigue, according to the case definition (n=28, p=0.35). After exclusion of those with pre-stroke fatigue and those with high scores on the HADS (suggestive of emotional distress), the geometric mean CRP of the fatigued group was 16.04 mg/l (95% CI: 7.12-36.14) compared with 5.16 mg/l (95% CI: 2.7-9.85) in the non-fatigued group (n=21, p=0.025, unpaired t test), but the relationship between FAS and CRP was not statistically significant (r=0.37, p=0.098). Conclusion: This pilot study is the first to demonstrate an association between fatigue after stroke and higher CRP, after excluding patients with pre-stroke fatigue and those with probable mood disorders. If this finding is confirmed in a larger number of patients, it might provide a target for treating fatigue after stroke.