Laboratory measures of systemic inflammation, particularly C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR), are routinely used in the diagnosis and assessment of disease activity in patients with rheumatoid arthritis (RA). Prior research has associated higher levels of CRP with greater body mass index (BMI) and adiposity in the general population, especially among women. This association may indicate that these inflammatory markers may perform as a biomarker of disease activity among obese patients with RA.
To assess this possibility, Michael D. George, MD, MSCE, from the University of Pennsylvania, Philadelphia, and colleagues designed a study to evaluate the connection between BMI and inflammatory markers in people with RA, determine if these associations are similar to patients without RA and examine the potential effect of obesity on disease activity. Their findings were published in December 2017 Arthritis Care & Research.
Using data that from two RA cohorts, the cross-sectional Body Composition (BC) cohort and the longitudinal Veterans Affairs Rheumatoid Arthritis (VARA) registry, researchers identified 2,103 patients with RA. For comparison, researchers used data from the National Health and Nutrition Examination Survey to evaluate the general population.
“Obesity was associated with higher CRP levels in women with RA,” write the authors in their discussion. “A similar association was observed in a non-RA sample, suggesting that elevated CRP level values among obese women with RA are not reflective of greater RA disease activity, but rather are an expected phenomenon related to adiposity. In contrast …, low BMI and not obesity was associated with higher CRP levels in men with RA.”
In women, both with and without RA, BMI was positively associated with CRP levels. Women with RA in higher BMI categories had higher predicted CRP levels—particularly for severely obese women. Additionally, DXA-measured fat mass was strongly associated with CRP levels, and adjustment for fat mass completely attenuated the association between BMI and CRP level, suggesting that higher CRP levels among women with RA and elevated BMI are due to increased adiposity. When examining ESR, researchers also observed higher ESRs in higher BMI categories in women with and without RA. However, only severely obese women in one RA cohort had significantly higher ESRs compared with normal-weight women.
Researchers note, “A higher BMI was not associated with greater swollen joint count, tender joint count or patient global health score in women with RA in similar analyses, and the positive association between BMI and CRP level among women with RA was not attenuated with adjustment for swollen joint count, tender joint count and patient global health scores.”
In men with RA, BMI was not associated with CRP level. This finding differed from the general population in which BMI as a continuous variable was positively associated with CRP level in men. Men with RA and high BMIs did not have significantly higher CRP levels compared with normal-weight men. However in both RA cohorts, underweight men had significantly higher CRP levels than normal-weight men. “This inverse association between BMI and CRP level in men is an RA-specific phenomenon and not a direct causal effect of adiposity,” note the authors.
Additionally, ESR was only modestly associated with BMI in men in the general population, while ESR was not associated with BMI among men with RA in the BC cohort and was negatively associated with BMI in the VARA registry.
“The current study is the largest to address this issue and illustrates the effect of inflammatory markers in specific BMI categories,” write the authors. “The inclusion of a non-RA control population demonstrates the normal relationship between BMI and inflammatory markers as a reference. … The effect of obesity on the CRP level may alter its performance as a biomarker of disease activity in clinical trials and in practice. … Furthermore, because obesity may be expected to impact the reliability of other component measures of disease activity, clinicians may tend to rely more on objective measures, such as CRP, for diagnosis or to make treatment decisions.”
George MD, Giles JT, Katz PP, et al. Impact of obesity and adiposity on inflammatory markers in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2017 Dec;69(12): . doi: 10.1002/acr.23229.