Measures of Adiposity and Risk of Rheumatoid Arthritis in Middle-Aged UK Women: A Prospective Cohort Study

Objectives: To estimate the association between various indicators of obesity-related health risk and the incidence of rheumatoid arthritis (RA) in a large cohort of women. Methods: The UK Women's Cohort Study is a prospective cohort of 35,372 middle-aged women (aged 35-69 at recruitment) initiated in 1995-1998. Obesity was assessed using body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), categorised according to WHO and NICE guidelines, as well as clothing size. Incident RA cases were identified via Hospital Episode Statistics (HES) linkage up to March 2019. Cox regression models were used to estimate RA risk, adjusting for demographics, reproductive factors, and lifestyle factors. Non-linear associations were examined using restricted cubic splines. Results: Among 27,968 eligible subjects with complete data linkage (625,269 person-years of follow-up), there were 255 incident RA cases. Obesity (≥30.0 kg/m²) was associated with increased RA risk (HR (95% CI) 1.48 (1.02, 2.17), as were abdominal obesity (WC > 88 cm: 1.58 (1.10, 2.27)), WHR ≥ 0.85 (1.56 (1.03, 2.36)), and WHtR ≥ 0.6 (2.25 (1.34, 3.80)). Each 2.5 kg/m² increase in BMI was associated with a 9% higher risk of RA; each 5 cm increase in WC with 6%; each 0.1 increase in WHR with 20%, and each 0.1 increase in WHtR with 27%. Larger clothing sizes were associated with a greater RA risk: for each onesize increment in blouse size and skirt size, the HRs were 1.13 (95% CI: 1.04, 1.22) and 1.13 (95% CI: 1.05, 1.22), respectively. Notably, skirt size ≥ 20 was associated with a 2.36-fold increased risk of RA. There was evidence of effect modification by weight change and menopausal status in obesity-related RA risk. Conclusions: Our findings suggest that managing obesity and central adiposity in middle-aged women may be associated with the risk of developing RA. WHtR may serve as a practical alternative to BMI in assessing RA risk. Clothing size, particularly skirt size, could provide a simple, cost-effective proxy for identifying at high risk of RA.