Overweight and Obesity Increase Risk of Rheumatoid Arthritis in Women in a Large Prospective Study

Background/Purpose: Several case-control studies have suggested that overweight and obesity may increase the risk of rheumatoid arthritis (RA), but the evidence is conflicting. We examined the relationship between pre-existing overweight or obesity in development of future RA in two large prospective cohorts, the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII).

Methods: The NHS is a prospective cohort study established in 1976 that enrolled 121,700 US female registered nurses, ages 30–55 years. NHSII began in 1989, enrolling 116,608 female nurses aged 25–42 years. Lifestyle and environmental exposures and anthropometric measures have been collected through biennial questionnaires. The incident RA cases were identified using the previously validated connective tissue disease screening questionnaire followed by a medical record review, according to the 1987 ACR criteria. Body Mass Index (BMI) was calculated as weight /height ² (kg/m²).  Overweight and obesity were defined as 25.0≤BMI<30 kg/m² and BMI≥30.0 kg/m² respectively based on World Health Organization classification. We assessed the exposure variable using a time-varying status of overweight and obesity since baseline updated every two years up to 2006/2007. Cox proportional hazards models were used to estimate hazard ratios (HR) of RA, seropositive RA, and seronegative RA phenotypes after adjusting for potential confounders.

Results: During 2,769,593 person-years of follow-up from 1976 to 2008 in NHS and 2,139,702 person-years of follow-up from 1989 to 2009 in NHSII, 1292 incident cases of RA developed (903 in NHS, 389 in NHSII). The age-adjusted incidence rates of RA ranged from 30 to 36 /100,000 person-years in NHS, and 12 to 26 /100,000 person-years in NHSII across increasing levels of BMI. Overweight and obese women have increased risk of RA compared with women with BMI<25 (Table). The multivariate hazard ratios of RA in NHS were 1.19 (95% CI, 1.03-1.38) for overweight and 1.18 (95% CI, 0.98-1.42) for obesity respectively (p trend = 0.029). Consistent with the NHS, the HRs in NHSII were 1.78 (95% CI, 1.40-2.26) for overweight, and 1.73 (95% CI, 1.34-2.23) for obesity (p trend <0.001). Further stratified analyses in NHS demonstrated that the effect of overweight and obesity on RA risk was stronger in seronegative RA than in seropositive RA. The multivariate HRs of seronegative RA were 1.30 (95% CI, 1.03-1.63) for overweight and 1.34 (95% CI, 1.01-1.77) for obese, while the HRs of seropositive RA were 1.12 (95% CI, 0.92-1.36) for overweight and 1.08 (95% CI, 0.84-1.38).

Conclusion: In this long-term prospective cohort study of women, we found overweight and obesity were significantly associated with increased risk of developing future RA compared to women with BMI <25kg/m².  Future studies are needed to confirm our findings in other populations.