Elsevier

Biological Psychiatry

Volume 66, Issue 9, 1 November 2009, Pages 871-878
Biological Psychiatry

Archival Report
Prospective Association Between C-Reactive Protein and Fatigue in the Coronary Artery Risk Development in Young Adults Study

https://doi.org/10.1016/j.biopsych.2009.06.008Get rights and content

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 β = .126, p < .001). After adjustment for potential confounders, this association remained significant (adjusted β = .044, p = .033). Additionally, baseline CRP independently predicted fatigue in the subgroup of participants without medical comorbidity (adjusted β = .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.

Section snippets

Subjects

The CARDIA study is a longitudinal study of cardiovascular risk factors in white and African American men and women aged 18 to 30 years at study inception. Full details of the study design and methods have been published previously (29). Briefly, 5115 individuals were recruited from four US cities (Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California) to take part in the baseline clinical examination (1985–1986). Of the 5115 individuals originally enrolled at

Baseline Characteristics

Overall, mean fatigue score and median CRP concentration at baseline were 1.93 (standard deviation 1.15) and 1.36 mg/L (interquartile range .53–3.72), respectively (Figure 1 in Supplement 1). Fatigue score of 1.93 indicates “a lot of energy during a good bit of the time.” Table 1 describes characteristics of the participants by levels of fatigue at baseline. A higher level of fatigue was associated with lower education level, higher BMI, more severe pain, lower physical activity level, higher

Discussion

In a community sample, higher plasma CRP concentration predicted higher fatigue level 5 years later independent of a series of risk factors, such as BMI, depressive symptoms, sleep quality, pain, and physical activity. To our knowledge, this is the first study to demonstrate a prospective association between a marker of systemic inflammation and fatigue in a general population. In addition, among participants without comorbid medical disorders, the association between CRP and fatigue was

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