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Elevated inflammatory markers linked to severe obesity in women with, without RA
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Severe obesity was linked to higher C-reactive protein level and erythrocyte sedimentation rate in both women with and without rheumatoid arthritis, elevations that are related to fat mass rather than RA disease activity, according to findings published in Arthritis Care and Research.
The researchers, led by Michael D. George, MD, MSCE, of the University of Pennsylvania in Philadelphia, also concluded that low BMI is associated with higher C-reactive protein (CRP) levels in men with RA — an unexpected finding that is likely not a direct effect of adiposity, they said.
“A fascinating and rapidly increasing body of literature has begun to explore the complicated relationship between obesity and RA,” George told Healio Rheumatology. “Some studies have identified obesity as a possible risk factor for the development of RA or for having more treatment resistant disease, but at the same time obesity is known to be associated with pain and fatigue that may make it more difficult to accurately assess RA disease activity.”
He noted, “Our study evaluates the impact of obesity on the CRP and erythrocyte sedimentation rate — blood tests that are markers of inflammation and which are used to help diagnosis, and especially to monitor treatment, in patients with rheumatoid arthritis.”
To determine to what extent obesity biases CRP and erythrocyte sedimentation rate (ESR), the researchers studied BMI associations with these biomarkers in two RA cohorts. The cross-sectional Body Composition cohort contained 451 patients and included whole-body dual X-ray absorptiometry measures of fat mass index. The other cohort, the longitudinal Veterans Affairs Rheumatoid Arthritis (VARA) registry, included 1,652 patients.
The researchers used multivariable models stratified by sex and evaluated associations in the general population using the National Health and Nutrition Examination Survey.
According to the researchers, higher BMI was associated with higher CRP levels among women with RA in the general population, especially in those with severe obesity (P < 0.001 for BMI 35 kg/m2 vs. 20–25 kg/m2). This association remained after the researchers adjusted for joint counts and patient global health scores (P < 0.001 in the Body Composition cohort and P < 0.01 in VARA cohort), they wrote. However, this association was weakened after adjusting for fat mass index (P = 0.17). Positive associations between BMI and ESR in women were more modest, the researchers said.
Among men with RA, lower BMI was associated with higher CRP levels and ESR, contrasting positive associations among men in the general population.
“These findings suggest that the same connection between obesity and inflammatory markers that has been described in the general population is also present in women with RA, and has the potential to bias assessment of disease activity,” George said. “In other words, patients with obesity may appear to have more severe disease activity because of higher CRP and ESR, when in reality the CRP and ESR are elevated because of increased weight. This could explain in part why patients with obesity are sometimes described as having more severe or treatment-resistant rheumatoid arthritis.”
According to George, the researchers were surprised that men with RA showed a different pattern.
“Men who were underweight, rather than overweight, had the highest levels of inflammatory markers,” he said. “We suspect that this connection is related to RA disease activity — severe inflammatory disease may have led to weight loss in some of these men.”
George added that, when assessing patients with possible inflammatory disease, physicians should be aware that patients with obesity — especially severe obesity — may have modest elevations of CRP or ESR due to their obesity.
“Both clinicians and researchers should be aware that obesity can lead to increases in common disease activity measures used to track disease,” George said. “These lab tests need to be interpreted cautiously in patients with obesity.” – by Jason Laday
Disclosure: George reports funding form the NIH and a Rheumatology Research Foundation Scientist Development Award.
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