Background/Purpose: C-reactive protein (CRP) is used to assess disease activity in rheumatoid arthritis (RA), and previous work suggests that adiposity also impacts CRP levels. This study assessed associations between BMI and CRP, hypothesizing that increasing levels of obesity are associated with elevations of CRP independent of RA disease activity, paralleling what is seen in the general population.

Methods: Associations between BMI and CRP were assessed in two RA cohorts – 1) a cross-sectional Body Composition (BC) cohort (N = 451) pooled from 3 independent studies from US academic centers that included whole-body DXA measures of fat mass index, and 2) the longitudinal Veterans Affairs Rheumatoid Arthritis (VARA) registry (N = 1652). For comparison, associations were also evaluated in the general population using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 (N = 10,813). Linear and logistic regression analyses (defining high CRP as CRP > 1.0 mg/dL and using generalized estimating equations to incorporate repeated measures in VARA) were stratified by sex and adjusted for age, race, and smoking. Sequential models assessed the impact of adjustment for disease activity (swollen/tender joints, patient global score), and fat mass in BC only as this measure was not available for VARA.

Results: In all three cohorts (NHANES, VARA, BC), women in higher BMI categories had significantly higher CRP (all p < 0.001; BMI ≥ 35 vs 20-25 kg/m²) (Figure). This association remained after adjusting for joint counts and patient global scores (p < 0.001 in BC; p < 0.01 in VARA) but was completely attenuated when adjusted for fat mass in BC. Women with BMI ≥ 35 kg/m² were also more likely to have an elevated CRP (Table 1).  Again associations remained after adjusting for disease activity (BC: OR 4.05, p = 0.02; VARA: OR 2.82, p = 0.01), but were attenuated with adjustment for fat mass in the BC cohort (OR 0.99, p = 1). Among men, BMI ≥ 35 (vs BMI 20-25 kg/m²) was not associated with higher CRP in VARA or BC (Figure). In VARA, but not in controls, men with low BMI <20 kg/m² had higher CRP and greater odds of an elevated CRP (all p < 0.01). In BC, fat mass index was associated with a greater odds of an elevated CRP in women (OR 1.69 per standard deviation, p < 0.01) but a lower odds in men (OR 0.60, p < 0.01).

Conclusion: Morbid obesity is associated with greater CRP in women with RA, similar to what is seen in the general population. This association is related to fat mass and not RA disease activity, necessitating caution when interpreting CRP among women with a high BMI. Causes of high CRP in low BMI men with RA require further study.