Sex differences in mortality risk and U-shaped relationship with klotho levels: A long-term cohort study

It remains unclear whether there are sex differences in the correlation between klotho and mortality risk. The purpose of our study is to investigate the relationship between klotho levels and all-cause mortality, specifically examining potential sex disparities.

The study utilized data from the National Health and Nutrition Examination Survey. The study employed the Cox proportional hazards model and Kaplan-Meier survival curves to conduct multivariate analyses investigating the associations between klotho and mortality. The impact of klotho level on mortality was assessed by a restricted cubic spline curve.

Our study included 13,748 participants. The hazard ratios (HR) for all-cause mortality were found to be higher in males compared to females. The risk of all-cause mortality decreased until the klotho level reached 959 pg/mL in all-cause mortality, then increased thereafter in females (P value for nonlinearity = 0.01, P overall = 0.02); no curved relationship was observed in males.

Klotho levels and mortality follow a U-shaped curve, with sex differences in the relationship. Males with higher klotho levels have a higher risk of all-cause death than females.