L-shaped association between serum klotho and prefrailty in physical frailty phenotype among adults in US: result from 2007 to 2016 National Health and Nutrition Examination Survey

Frailty is a state of being physically weak and vulnerable, with reduced functional reserve and resilience, while prefrailty represents an intermediate reversible stage. However, the association between serum α-klotho levels and frailty or prefrailty, particularly in prefrail individuals, remains uncertain. This study aimed to investigate the potential relationship between serum klotho levels and the prevalence of frail or prefrail among adults in the USA. Cross-sectional data from individuals aged 40-79 years who participated in the NHANES between 2007 and 2016 were analyzed. Multivariate logistic regression models were employed to assess the association between klotho and frailty or prefrailty. Restricted cubic splines were used to explore potential non-linearity relationships and dose-response association. Additionally, stratified and interaction analyses were performed to evaluate the stability of the relationship in different subgroups. The study included 6868 participants, with 52.9% (3630/6868) classified as -prefrail. Compared to individuals in the lower ln(klotho) consumption quartile (Q1,≤6.462), the adjusted OR values for ln(klotho) and prefrailty in Q2 (6.463-6.666), Q3 (6.667-6.882), and Q4 (>6.882) were 0.75 (95% CI: 0.64-0.87, p<0.001), 0.87 (95% CI: 0.75-1.01, p=0.063), and 0.81(95% CI: 0.70-0.95, p= 0.008), respectively. An L-shaped curve between ln(klotho) and prefrailty was observed (p=0.001). In two piecewise regression models, the adjusted OR for prefrailty was 0.41 (95% CI: 0.28-0.60; p<0.001) when ln(klotho)<6.68, while no association was found with ln(klotho)≥6.68. Subgroup and stratified analyses consistently confirmed the strength of the relationship. The findings of this study reveal an L-shaped relationship between serum klotho and prefrailty, indicating a significant inflection point at approximately 6.68. These results suggest that integrating the assessment of prefrailty into clinical practice could offer clinicians a valuable tool for early identification and management of this condition.