Sex Differences in the Association Between Inflammatory Biomarkers (Hs-CRP, IL-6, IL-10, TNF-α) and Frailty in Hospitalized Adults Aged ≥65 in Taizhou, China: A Cross-Sectional Study

Purpose: Frailty is a prevalent geriatric syndrome that is strongly related to systemic inflammation; nevertheless, sex differences in its association with inflammation remain poorly understood. We aimed to investigate sex-specific associations between inflammatory biomarkers and frailty in a large cohort of hospitalized older adults. Patients and Methods: This cross-sectional study with 4,438 older adults aged ≥ 65 years was conducted at Taizhou First People’s Hospital (Taizhou, China) between 23/08/2024 and 31/05/2025. The 28-item Frailty Index (FI-28, score ≥ 0.25 indicates frail) was used to measure frailty. High-sensitivity CRP (hs-CRP) (immunofluorescence), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-α) (flow cytometry) were measured; biomarkers underwent ln-transformation. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for frailty per 1 standard deviation (SD) rise in ln-transformed biomarkers, controlling for confounders. Sex-specific differences were evaluated using interaction tests. Results: Women experienced frailty at a higher rate than men did (37.68% vs 22.8%, P < 0.001). After adjustment, high levels of IL-6, hs-CRP, and IL-10 in frail older adults were significantly linked to frailty risk (all P < 0.001). Nevertheless, TNF-α did not (p = 0.983). The relationship of frailty with IL-6, hs-CRP, and IL-10 was found to be significantly altered by sex, according to interaction tests (P interaction < 0.001). The relationship of inflammatory markers with frailty risk differed by sex. In women, raised hs-CRP, IL-6, and IL-10 (all P < 0.001) levels showed a strong link to greater frailty risk. In men, though these markers were significantly related to frailty, their strength was lower: hs-CRP, IL-6, and IL-10 (all P < 0.001). TNF-α showed no independent association in either group. Conclusion: In older adults, elevated levels of hs-CRP, IL-6, and IL-10 are associated with higher frailty risk; the associations are significantly stronger in women than in men. These findings emphasize considering sex differences in frailty management; however, longitudinal studies are required to confirm causality. Keywords: frailty syndrome, biomarkers, inflammatory, sex differences, aging, disability evaluation, healthy aging