Association between sex-hormone binding globulin and cardiovascular events in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a common systemic autoimmune disease characterized by progressive deterioration of bone and cartilage. Sex hormone-binding globulin (SHBG), a glycoprotein integral to the regulation of sex hormone bioavailability, may have a pivotal role in the pathogenesis of RA. This study aims to investigate the relationship between SHBG concentrations and the risk of RA, as well as the occurrence of related cardiovascular complications.

The analysis included 25,051 adult participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2023. Frailty was assessed using a 49-item frailty index, while medical conditions were self-reported via questionnaire. Logistic regression and mediation analyses were employed to evaluate these associations. Additionally, Kaplan-Meier survival curves were constructed to compare survival probabilities across different subgroups.

Elevated SHBG levels were identified as a significant risk factor for RA. Both the frailty index and C-reactive protein (CRP) levels demonstrated positive correlations with RA. Importantly, the frailty index partially mediated the association between SHBG and RA, accounting for approximately 24.47% of this relationship. Furthermore, RA patients with higher SHBG concentrations exhibited markedly reduced survival rates, an effect that was especially pronounced in male patients.

Serum SHBG concentrations are inversely correlated with survival outcomes in individuals diagnosed with RA. These findings suggest that routine monitoring of SHBG levels in RA patients may enhance prognostic assessments and inform clinical management strategies. Key Points • SHBG represents a significant risk factor for the development of RA. • The frailty index partially mediates the relationship between SHBG and RA, explaining approximately 24.47% of this association. • Male RA patients with elevated SHBG levels experience significantly decreased survival rates.