Association of Antiaging Protein Klotho with Stroke: A Population Study Based on NHANES

Background: Stroke, a debilitating condition often leading to long-term disability, poses a substantial global concern and formidable challenge. Aims and Objectives: The association of klotho with stroke was inconclusive, and we aimed to clarify the role of klotho in stroke. Materials and Methods: The data of 10,737 samples and 16 variables were collected from National Health and Nutrition Examination Surveys 2009–2016. Logistic regression analyses were performed to explore the association between klotho and stroke, followed by an importance evaluation of klotho. Then the association between klotho and other variables was explored by logistic regression and Spearman analyses, and important variables correlated with klotho were determined. Furthermore, mediation analyses based on population and mendelian randomization (MR) were performed to assess the mediating effect of klotho involved in stroke. Results: The level of klotho was lower in the stroke group than in the nonstroke group ( P < 0.001). Regression analysis showed that klotho significantly correlated with the stroke risk (OR = 0.253, P < 0.001). After adjusting for different variables, their independent association was still significant (all P < 0.05). Among all the variables, the importance of klotho involved in stroke ranked first. In addition, smoking status, age, alcohol use, and hypertension significantly correlated with klotho level (all P < 0.05), suggesting the mediating role of klotho on the association between these variables and stroke. The population study only indicated the mediating effects of klotho on the association of smoking/age and stroke (all P < 0.05). However, the mediation MR did not support its mediating effect. Conclusion: Klotho was significantly associated with stroke, but their causal relationship needed further investigation.