Klotho蛋白与充血性心力衰竭的关联及炎症的介导作用

Association of Klotho protein with congestive heart failure and mediating role of inflammation

目的:探讨Klotho蛋白与充血性心力衰竭(CHF)的关联及炎症的介导作用。方法:选取美国国家健康与营养调查2007-2016年的10762例研究对象(男5240例,女5522例),根据Klotho蛋白的四分位数将研究对象分为4组(Q1、Q2、Q3、Q4组),采用Logistic回归模型分析Klotho蛋白及炎症生物标志物与CHF的关系,采用广义线性模型分析Klotho蛋白与炎症生物标志物的关联,中介分析用于评估炎症生物标志物在Klotho蛋白与CHF关联中的中介效应。结果:Klotho蛋白可降低CHF风险(OR=0.695,95%CI为0.513~0.942),且在男性中更显著(OR=0.604,95%CI为0.406~0.898)。炎症生物标志物在Klotho蛋白与CHF的关联中具有中介效应,其中中性粒细胞计数与淋巴细胞计数比值的中介作用最大,在总人群和男性中分别为11.93%和9.92%,中介效应β(95%CI)分别为-0.047(-0.078~-0.026)和-0.050(-0.093~-0.021)。结论:高水平的Klotho蛋白、低水平的炎症生物标志物可降低CHF风险。炎症生物标志物部分介导了Klotho蛋白对CHF的保护作用。

Aim:To investigate the relationship between Klotho protein and congestive heart failure(CHF)and the mediating role of inflammation.Methods:A total of 10762 individuals(5240 men and 5522 women)from American National Health and Nutrition Examination Survey 2007-2016 were selected and divided into Q1,Q2,Q3,Q4 groups according to Klotho protein quartiles.Logistic regression model was used to analyze the association of Klotho protein and inflammatory markers with CHF.Generalized linear models were used to analyze the association between Klotho protein and inflammatory markers.Mediation analysis was used to assess the mediating effect of inflammatory markers in the association of Klotho protein with CHF.Results:Klotho protein decreased the risk of CHF(OR=0.695,95%CI was 0.513-0.942)and was more significant in men(OR=0.604,95%CI was 0.406-0.898).Inflammatory markers had mediating effects in the association between Klotho protein and CHF,with neutrophil-to-lymphocyte ratio having the largest mediating effect,11.93%in the total population and 9.92%in men.The mediation effectβ(95%CI)was-0.047(-0.078--0.026)and-0.050(-0.093--0.021),respectively.Conclusion:High level of Klotho protein and low levels of inflammatory biomarkers could reduce the risk of CHF.Inflammatory biomarkers may partially mediate the protective effect of Klotho protein against CHF.