Association of Systemic Inflammation with Balance and Falls in Older Adults: NHANES and Mendelian Randomization Study

Abstract Background Falls are a leading cause of morbidity in older adults, with emerging evidence suggesting that systemic inflammation may contribute to this risk. C-reactive protein (CRP), a biomarker of inflammation, has been linked to various health issues, including declines in physical function. However, its direct influence on balance and fall risk remains uncertain. This study investigates the association between CRP levels and balance using observational data and Mendelian Randomization (MR) to explore its causal role in fall risk. Methods We analyzed data from the 2021–2023 National Health and Nutrition Examination Survey (NHANES), including 1,215 participants aged 60 and older. CRP levels were measured using immunoturbidimetric assays, and balance was assessed via the Modified Romberg Test. We used multivariable ordinal logistic regression models to evaluate the relationship between CRP and balance, adjusting for demographic, health, and lifestyle factors. Genetic instruments for CRP were derived from genome-wide association studies (GWAS), and MR analysis was performed using fall risk summary statistics (2,215 cases, 6,289 controls). Results In the NHANES cohort, higher CRP levels were associated with poorer balance (β = −0.201, p = 0.007). This association was stronger in males but not in females. MR analysis confirmed a causal link between elevated CRP and increased fall risk (OR = 1.13, p = 8.96 × 10−8), with no evidence of pleiotropy or heterogeneity. Conclusions our findings highlight CRP as a key factor influencing balance and a causal contributor to fall risk in older adults, suggesting that anti-inflammatory interventions may help reduce fall risk.