The mediating role of sleep quality in the association between inflammatory disease activity and health-related quality of life in rheumatoid arthritis

Background: Sleep disturbance is highly prevalent in rheumatoid arthritis (RA) and is a key determinant of patient-reported outcomes. However, the mechanistic pathways linking systemic inflammation and metabolic dysregulation, defined in this study as insulin resistance and adverse cardiometabolic indices, and sleep quality remain poorly defined. This study aimed to investigate the interplay between inflammatory/metabolic markers and sleep quality, and to determine whether sleep quality mediates the relationship between disease activity by DAS28-ESR and health-related quality of life. Methods: In this cross-sectional study, 128 patients with RA and 115 healthy controls were evaluated. Systemic inflammation and metabolic stress were characterized using ESR, CRP, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and indices including the TyG index and cardiometabolic index. Sleep was assessed via the Pittsburgh Sleep Quality Index and HRQoL via the Short Form-36. Mediation analyses (5,000 bootstrap resamples), adjusted for age, sex, smoking status, education level, and disease duration, and sensitivity analyses were performed to quantify the indirect effects of sleep quality on HRQoL domains. Results: = 0.002). Mediation analyses revealed that sleep quality may significantly mediate the association between disease activity and life quality, accounting for 24.4% of the effect of DAS28-ESR on Mental Health (Indirect Effect = -1.42; 95% CI - 2.38 to -0.62) and 23.6% on General Health. Sensitivity analyses confirmed these mediating effects were robust across BMI and gender subgroups. Conclusion: Sleep quality may represent a critical mechanistic link through which inflammatory disease activity translates into impaired HRQoL in RA. These findings suggest that nearly one-quarter of the disease's psychological burden may be statistically mediated through sleep disruption. Integrating systematic sleep assessment and Vitamin D optimization into routine care may help mitigate the patient-perceived disease burden. Given the cross-sectional design, these findings should be interpreted as evidence of statistical mediation rather than confirmed causal pathways.