Background/Purpose: Being overweight or obese increases the risk of rheumatoid arthritis (RA) among women, particularly among those diagnosed with RA at earlier ages.  Abdominal obesity is more associated with visceral fat and inflammation than overall obesity measured by body mass index (BMI). We investigated whether abdominal obesity predicts RA risk in two large prospective cohorts, the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII).

Methods: We followed 48,919 women in NHS (aged 40-67 years in 1986) and 47,220 women in NHSII (aged 29-48 years in 1993) without RA at baseline. Lifestyle and environmental exposures were collected through biennial questionnaires. Abdominal obesity was measured using waist circumference (WC) reported in 1986, 1996 and 2000 in NHS and 1993 and 2005 in NHS II. The cutoff point for abdominal obesity (WC≥88cm) was based on WHO recommendations for women. Incident RA cases were identified using the previously validated connective tissue disease screening questionnaire followed by a medical record review. RA serologic status was determined by positive rheumatoid factor (RF) or anti-citrullinated peptide antibodies (ACPA) in the medical record. Using pooled data from the two cohorts, we estimated hazard ratios (HR) for RA risk using time-varying Cox proportional hazards models. We repeated analyses restricted to young and middle aged women (age≤55 years) based on our pre-specified hypothesis.

Results: During 28 years of follow-up, we identified 803 incident RA cases (505 in NHS, 298 in NHSII). Women with WC>88cm had increased RA risk compared with women with WC<88cm (Table). The multivariable adjusted HR was 1.27(95% CI: 1.10-1.47). Further adjustment for BMI attenuated the association. Consistently, BMI was also associated with risk of RA (HR were 1.48 with 95% CI: 1.24-1.77) for BMI ≥30 kg/m² compared to BMI<25kg/m². Stratified analyses by serostatus demonstrated that the association of WC with RA risk was stronger for seropositive RA than for seronegative RA. Among young and middle aged women (age ≤ 55 years), abdominal obesity increased risk of all RA by 65%, and by 94% for seropositive RA. After further adjusting for BMI, abdominal obesity remained associated with risk of seropositive RA (HR 1.51, 95% CI :1.01-2.25).  

Conclusion: In this prospective cohort study of women followed up to 28 years, abdominal obesity was significantly associated with increased risk of developing RA. Abdominal obesity conferred the greatest risk for seropositive RA among women ≤55 years old independent of BMI.