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Physicians should be careful when using biomarkers for assessment in obese patients, especially women.
C-reactive protein (CRP) levels and erythrocyte sedimentation rates (ESRs) are high in obese women regardless of whether they have rheumatoid arthritis.
Elevated CRP levels and ESRs in obese women with rheumatoid arthritis do not correlate with higher disease activity.
Contrary to what was expected, men with rheumatoid arthritis and a low body mass index (BMI) had higher than normal inflammatory markers.
Both CRP level and ESR are employed in several RA disease activity tools and may be used to direct treatment and derive outcomes.
Michael George at University of Pennsylvania Hospital Rheumatology and colleagues noted that higher CRP levels are found in young women with higher BMIs even in the absence of rheumatoid arthritis. In addition, studies show that belly fat is associated with elevated CRP levels in women but not in men.
The authors sought to find any association between BMI and inflammatory markers in patients who have rheumatoid arthritis and to compare the results with those in patients who do not. They presented their findings in a recent Arthritis Care & Research article.
This cross-sectional cohort study looked at 2 rheumatoid arthritis cohorts that totaled 2103 subjects from the Veterans Affairs Rheumatoid Arthritis Registry (N=1652) and the “Body Composition” cohort (N=451), which represented data from 3 independent studies. The experimental cohorts were compared with a control group.
• BMI was positively and significantly associated with CRP levels in both rheumatoid arthritis cohorts as well as in the control group (0.057, 95% confidence interval, 0.035-0.080; 0.030, 95% CI, 0.014-0.045; and 0.097, 95% CI, 0.092-0.101 respectively; P<0.001).
• The higher the BMI was in women, regardless of group, the higher the predicted CRP levels were.
• These results were unchanged when adjustment for glucocorticoid and disease-modifying antirheumatic drug treatment were factored in.
• A weaker positive association was found between BMI and CRP level was found in control group men (0.085, 95% CI, 0.078-0.091; P<0.001).
• In men with rheumatoid arthritis, BMI was not associated with elevated CRP level in either experimental cohort (0.004, 95% CI, -0.025-0.034; p=0.78 and -0.008, 95% CI, -0.017-0.001; P=0.09).
• In the Veterans Administration experimental group, CRP levels were significantly higher in underweight men than in normal weight men (P<0.01).
• In both experimental cohorts, CRP levels were significantly higher in normal weight men than in men with high BMI.
• BMI in control group women was associated with ESR (0.020, 95% CI, 0.016-0.024; P<0.001).
• There was a positive association between ESR and BMI in women in the experimental groups (0.033, 95% CI, 0.010-0.057; P=0.006 and 0.016, 95% CI, 0.001-0.032; P=0.051).
• ESR was associated with BMI in male controls (0.014, 95% CI, 0.005-0.022; P=0.002).
• ESR was not associated with BMI in men with rheumatoid arthritis (p=0.81) and was negatively associated in the veterans group (-0.026, 95% CI, -0.034-0.018; P<0.001).
• ESRs were significantly higher in normal and underweight men in the veterans group than in higher BMI men (P<0.001).
• Obesity was not associated with higher disease activity measures in men or women with rheumatoid arthritis.
Implications for physicians
• Higher CRP levels in obese women with rheumatoid arthritis are not indicative of increased disease activity.
• Higher CRP levels in persons with higher BMI and rheumatoid arthritis are the result of increased adipose tissue.
• Physicians should be careful when using biomarkers for disease activity in rheumatoid arthritis for treatment and outcomes assessment in obese patients, especially obese women.
• Lower biomarker levels in normal and underweight men are confounding, so care should be taken when interpreting their results in men and women with rheumatoid arthritis.
The NIH, the Rheumatology Research Foundation Scientist Development Award, and the Veterans Affairs Administration provided funding for this project.
George MD, Giles JT, Katz PP, et al. “The impact of obesity and adiposity on inflammatory markers in patients with rheumatoid arthritis.” Arthritis Care Res (Hoboken). 2017 Apr 10. doi: 10.1002/acr.23229. [Epub ahead of print]