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Association of C-reactive protein and interleukin-6 with new-onset fatigue in the Whitehall II prospective cohort study.

ABSTRACT: BACKGROUND:Although basic research on neuroimmune interactions suggests that inflammatory processes may play a role in the development of fatigue, population-based evidence on this association is limited. This study examined whether plasma C-reactive protein (CRP) and interleukin-6 (IL-6), biomarkers of systemic inflammation, predict fatigue onset. METHOD:The Whitehall II study is a large-scale cohort study conducted in 20 civil service departments in London. Plasma CRP and IL-6 were measured in 4847 non-fatigued participants at phase 3 (1991-1993, aged 39-63 years). Fatigue was assessed using the Vitality subscale of the 36-item Short Form Health Survey (SF-36) at phase 3 and phase 4 (1995-1996). RESULTS:During a mean follow-up of 3.1 years, 957 new fatigue cases (19.7%) were identified using the pre-established cut-off score of ? 50 on the Vitality subscale. CRP values were dichotomized as low (<1.0 mg/l ) or high (? 1.0 mg/l) using the Centers for Disease Control/American Heart Association recommendations. Similarly, IL-6 values were also dichotomized as low (<1.5 pg/ml) or high (? 1.5 pg/ml). After full adjustment for sociodemographic and biobehavioral covariates, the odds ratios for new-onset fatigue were 1.28 [95% confidence interval (CI) 1.09-1.49, p = 0.003] for high CRP and 1.24 (95% CI 1.06-1.45, p = 0.008) for high IL-6. Similar results were found when CRP and IL-6 were treated as continuous variables. CONCLUSIONS:Plasma CRP and IL-6 were prospectively associated with new-onset fatigue, supporting the hypothesis that low-grade inflammation has a role in the development of fatigue.

SUBMITTER: Cho HJ

PROVIDER: S-EPMC3819455 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Association of C-reactive protein and interleukin-6 with new-onset fatigue in the Whitehall II prospective cohort study.

Cho H J HJ Kivimäki M M Bower J E JE Irwin M R MR

Psychological medicine 20121114 8

<h4>Background</h4>Although basic research on neuroimmune interactions suggests that inflammatory processes may play a role in the development of fatigue, population-based evidence on this association is limited. This study examined whether plasma C-reactive protein (CRP) and interleukin-6 (IL-6), biomarkers of systemic inflammation, predict fatigue onset.<h4>Method</h4>The Whitehall II study is a large-scale cohort study conducted in 20 civil service departments in London. Plasma CRP and IL-6 w ...[more]

PMID: 23151405

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Project description:ObjectiveTo examine the association of midlife and late life multimorbidity, including severity of multimorbidity, with incident dementia.DesignProspective cohort study.SettingCivil service departments in London (Whitehall II study, study inception in 1985-88).Participants10 095 participants, aged 35 to 55 at baseline.Main outcome measureIncident dementia at follow-up between 1985 and 2019. Cause specific Cox proportional hazards regression was used to examine the association of multimorbidity overall and at age 55, 60, 65, and 70 with subsequent dementia, taking into account the competing risk of death.ResultsThe prevalence of multimorbidity (≥2 chronic diseases) was 6.6% (655/9937) at age 55 and 31.7% (2464/7783) at age 70; 639 cases of incident dementia occurred over a median follow-up of 31.7 years. After adjustment for sociodemographic factors and health behaviours, multimorbidity at age 55 was associated with subsequent risk of dementia (difference in incidence rate per 1000 person years 1.56, 95% confidence interval 0.62 to 2.77; hazard ratio 2.44, 95% confidence interval 1.82 to 3.26). The association weakened progressively with older age at onset of multimorbidity. At age 65, onset of multimorbidity before age 55 was associated with 3.86 (1.80 to 6.52) per 1000 person years higher incidence of dementia (hazard ratio 2.46, 1.80 to 2.26) and onset between 60 and 65 was associated with 1.85 (0.64 to 3.39) per 1000 person years higher incidence (1.51, 1.16 to 1.97). Severity of multimorbidity (≥3 chronic diseases) at age 55 was associated with a 5.22 (1.14 to 11.95) per 1000 person years higher incidence of dementia (hazard ratio 4.96, 2.54 to 9.67); the same analyses at age 70 showed 4.49 (2.33 to 7.19) per 1000 person years higher incidence (1.65, 1.25 to 2.18).ConclusionMultimorbidity, particularly when onset is in midlife rather than late life, has a robust association with subsequent dementia. The increasingly younger age at onset of multimorbidity makes prevention of multimorbidity in people with a first chronic disease important.

Project description:Background & aimsLow-grade inflammation appears to play an etiological role in cognitive decline. However the association between an inflammatory dietary pattern and cognitive decline has not been investigated. We aimed to investigate dietary patterns associated with inflammation and whether such diet is associated with cognitive decline.MethodsWe analyzed 5083 participants (28.7% women) from the Whitehall II cohort study. Diet and serum interleukin-6 (IL-6) were assessed in 1991-1993 and 1997-1999. We used reduced rank regression methods to determine a dietary pattern associated with elevated IL-6. Cognitive tests were performed in 1997-1999 and repeated in 2002-2004 and 2007-2009. The association between dietary pattern and cognitive decline between ages 45 and 79 was assessed using linear mixed models.ResultsWe identified an inflammatory dietary pattern characterized by higher intake of red meat, processed meat, peas and legumes, and fried food, and lower intake of whole grains which correlated with elevated IL-6 both in 1991-1993 and 1997-1999. A greater decline in reasoning was seen in participants in the highest tertile of adherence to the inflammatory dietary pattern (-0.37 SD; 95% confidence interval [CI] -0.40, -0.34) compared to those in the lowest tertile (-0.31; 95% CI -0.34, -0.28) after adjustment for age, sex, ethnicity, occupational status, education, and total energy intake (p for interaction across tertiles = 0.01). This association remained significant after multivariable adjustment. Similarly for global cognition, the inflammatory dietary pattern was associated with faster cognitive decline after multivariable adjustment (p for interaction across tertiles = 0.04). Associations were stronger in younger participants (<56 years), reducing the possibility of reverse causation.ConclusionsOur study found that a dietary pattern characterized as higher intake of red and processed meat, peas, legumes and fried food, and lower intake of whole grains was associated with higher inflammatory markers and accelerated cognitive decline at older ages. This supports the case for further research.

Dataset Information

Association of C-reactive protein and interleukin-6 with new-onset fatigue in the Whitehall II prospective cohort study.

Publications

Association of C-reactive protein and interleukin-6 with new-onset fatigue in the Whitehall II prospective cohort study.

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