Age modifies the prognostic relevance of extracellular water-to-total body water ratio in rheumatoid arthritis: a retrospective cohort study

BACKGROUND: Clinicians often recognise broader deterioration in a patient's overall condition that is not fully captured by conventional disease-specific measures. Ageing is associated with reduced physiological reserve and altered body fluid distribution. However, objective markers that capture these changes remain limited. Because the extracellular water-to-total body water ratio (ECW/TBW) reflects fluid distribution, we hypothesised that its prognostic relevance is age-dependent rather than uniform. METHODS: In this retrospective cohort study, 186 adults with rheumatoid arthritis underwent bioelectrical impedance analysis in 2017 and were followed until December 2025. The primary outcome was a composite of all-cause death or transition to do-not-attempt-resuscitation/best supportive care (DNAR/BSC) status. Cox proportional hazards models including an age × ECW/TBW interaction term were used. Age-stratified analyses used the cohort median age (68 years). RESULTS: During a median follow-up of 95.2 months, 17 participants experienced death or transition to DNAR/BSC status. Age was strongly associated with risk (HR per 10-year increase 2.53, 95% CI 1.47-4.34; p < 0.001). In age-adjusted models, ECW/TBW was not independently associated with the outcome (HR per 0.01 increase 1.10, 95% CI 0.88-1.37; p = 0.40). In contrast, the age × ECW/TBW interaction was significant (HR 1.22, 95% CI 1.05-1.42; p = 0.010), suggesting that the association between ECW/TBW and the outcome differed according to age. Elevated ECW/TBW was associated with higher risk among older participants (HR 3.10, 95% CI 1.21-8.63; p = 0.018), but not among younger individuals. In competing-risk analyses, elevated ECW/TBW was associated with a higher cumulative incidence of non-planned admissions among older participants (Gray's test p = 0.014). CONCLUSIONS: The prognostic relevance of ECW/TBW appeared to vary by age, emerging primarily in later life rather than functioning as a uniform risk marker. These exploratory findings suggest that ECW/TBW may reflect aspects of age-related physiological vulnerability and may help identify older individuals at increased risk of non-planned hospitalisations and other unstable clinical trajectories. As a simple non-invasive measure, ECW/TBW may complement disease activity-centred assessment, although external validation is required.