Correlation of the weight-adjusted waist circumference index with Klotho in the United States: differences by sex

The relationship between the weight-adjusted waist circumference index (WWI) and the senescence-inhibitory protein Klotho remains unknown. Therefore, this study aimed to investigate the relationship between WWI and soluble Klotho (s-Klotho). This study analyzed 9,928 participants based on the 2007-2016 National Health and Nutrition Examination Survey (NHANES). Three multiple linear regression models and a restricted cubic spline (RCS) were constructed to assess the association between WWI and s-Klotho levels. Further stratified analyses and interaction tests were performed to evaluate the stability of this association. Piecewise multivariate regression modeling was applied to detect threshold effects. The fully adjusted model showed a negative correlation between continuous WWI and s-Klotho levels (β = -23.65, 95% CI: -36.55, -10.76, P < 0.001). When WWI was grouped into quartiles, participants in the highest quartile had significantly lower circulating s-Klotho levels than those in the lowest quartile (β = -40.65, 95% CI: -64.20, -17.10, P = 0.001). The RCS curves showed a linear negative correlation between WWI and s-Klotho. Further stratified analyses showed that the correlation between WWI and s-Klotho remained stable in most conditions, except for gender. A nonlinear relationship and saturation effect were observed between WWI and s-Klotho in females, with an inflection point of 11.38 cm/√kg (P for overall < 0.001; P for non-linearity = 0.013). However, no significant correlation was observed in males. There is a significant negative correlation between WWI and s-Klotho levels. Proper management of central obesity in middle-aged and older women may be beneficial in delaying senescence.