BACKGROUND: Fatigue is highly prevalent and causes serious disruption in quality of life. Although the underlying biological mechanism is unknown, increases in inflammation have been implicated. This prospective study examined the association between C-reactive protein (CRP), a biomarker of systemic inflammation, and fatigue 5 years later.

METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study is a population-based longitudinal study conducted in four U.S. cities. Highly sensitive CRP concentration and fatigue were measured in 2983 African American and white adults at both year 15 (2000-2001, ages 33-45 years) and year 20 (2005-2006) examinations. Fatigue was assessed using the vitality subscale of the 12-item Short Form Health Survey.

RESULTS: Plasma CRP concentration at baseline (i.e., CARDIA year 15) was a significant predictor of fatigue level 5 years later (unadjusted beta = .126, p < .001). After adjustment for potential confounders, this association remained significant (adjusted beta = .044, p = .033). Additionally, baseline CRP independently predicted fatigue in the subgroup of participants without medical comorbidity (adjusted beta = .051, p = .039). Fatigue was associated with a persistent elevation of CRP at both examinations but not with a transient elevation of CRP at only one of the examinations.

CONCLUSIONS: This is the first study to demonstrate a prospective association between an inflammatory marker and fatigue in a general population. Furthermore, the association between low-grade systemic inflammation and fatigue seems primarily driven by persistent immune activation and not explained by the presence or development of medical comorbidity.