Correlation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with serum α-klotho levels in US middle-aged and older individuals: Results from NHANES 2007-2016

Background: The alpha-klotho (alpha Kl) is widely accepted as an anti-aging and anti-inflammatory protein. However, it is rarely reported on the function and mechanism of alpha Kl in the overall population (including healthy people and those with history of chronic disease). The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are established as predictors of systemic inflammation. This study aims to investigate the relationship between NLR, PLR, and alpha Kl levels in the overall population. Methods: Data from 10,124 adults aged 40 years old and above, collected from NHANES 2007-2016, were analyzed. Associations between NLR, PLR, and alpha Kl levels were assessed by weighted multivariate linear regression analyses, adjusting for potential confounders. Subgroup analysis was conducted by gender, age, diabetes, cardiovascular disease, and chronic kidney disease. Results: Weighted linear regression models showed that a significant negative correlation was observed between both NLR and PLR with alpha Kl levels. Subgroup analysis revealed that the negative correlation between NLR and serum alpha Kl levels was not significant in individuals aged 40-59 years and males, while this relationship remained stable across most other subgroups. The negative correlation between PLR and serum alpha Kl levels was consistent across most subgroups but not significant in individuals with cardiovascular disease. Conclusion: Our study revealed a significant negative relationship between inflammatory markers (NLR and PLR) and serum alpha Kl levels, suggesting systemic inflammation may be linked to reduced alpha Kl expression. Subgroup analyses showed that the relationship varies across different demographic and health-related factors. We provided insight into the significance of managing inflammation and preserving alpha Kl levels.