Weight loss, the obesity paradox, and the risk of death in rheumatoid arthritis

Objective In contrast to what is observed in the general population, a low body mass index (BMI) has been associated with accelerated mortality in patients with rheumatoid arthritis (RA). The aim of this study was to assess whether weight loss might explain these seemingly paradoxical observations. Methods Our study included patients identified from the Veterans Affairs (VA) RA Registry. Dates of death were abstracted from VA electronic medical records. The BMI at each study visit and the change from the previous visit were determined. The maximum BMI of each patient was also obtained from medical records. The annualized rate of BMI loss was determined from the slope of change (per year) in BMI over visits within the preceding 13 months. Cox multivariable proportional hazards models were used to assess associations between BMI measures and mortality. Results In a sample of 1,674 patients, 312 deaths occurred over 9,183 person-years. A loss in BMI of ≥1 kg/m² was associated with a greater risk of death, after adjustment for demographics, comorbidities, BMI, smoking, and RA therapies (hazard ratio [HR] 1.99, 95% confidence interval [95% CI] 1.53-2.59, P<0.001). This association remained significant in a subsample analysis adjusting for C-reactive protein and physical function (HR 1.81, 95% CI 1.36-2.41, P<0.001). Weight loss at an annualized rate of ≥3 kg/m² was associated with the greatest risk of death (HR 2.49, 95% CI 1.73-3.57, P<0.001). Low BMI (<20 kg/m²) in patients with a history of obesity (>30 kg/m²) was associated with the greatest risk (HR 8.52, 95% CI 4.10-17.71, P<0.001). Conclusion Weight loss is a strong predictor of death in patients with RA. These observations may explain the observed obesity paradox and do not support a biologically protective role of obesity.