Klotho mediates the association between serum testosterone and severe abdominal aortic calcification: a cross-sectional study from the NHANES database

Severe abdominal aortic calcification (SAAC) is acknowledged as a significant contributor to cardiovascular morbidity and mortality, yet its relationship with sex steroid hormones remains unclear. Here, the unexplored link between serum sex steroid hormone levels and SAAC was investigated within the National Health and Nutrition Examination Survey (NHANES) cohort. This study utilized data from NHANES 2013-2014. SAAC was determined using the abdominal aortic calcification 24-point scale. Serum sex steroid hormones were categorized into quintiles 1-5 for analysis. Multivariable logistic regression and subgroup analyses were employed to investigate the potential relationship between serum sex steroid hormones and SAAC risk. Moreover, the Johnson-Neyman plot was applied to identify the presence of any threshold effects. Finally, to reveal the potential pathophysiological mechanism, mediation analyses were performed. A total of 1852 enrolled individuals were included, and the prevalence of SAAC stood at 8.00%. After adjusting for potential confounding factors, multivariate analysis suggested the association of higher level of serum testosterone with a reduced incidence of SAAC (AOR = 0.33, 95%CI:0.13-0.87, P = 0.0247 for quintile 5, P for trend = 0.025). Subgroup analyses demonstrated the negative associations were more significant in participants aged >= 60 (AOR = 0.20, 95%CI:0.07-0.56, P = 0.0023 for quintile 5) and non-hypertensive population (AOR = 0.29, 95%CI:0.09-0.96, P = 0.0436 for quintile 5). The restricted cubic spline curve indicated that among the non-hypertensive male population aged >= 60, there was a dose-response relationship between serum testosterone and SAAC risk. Furthermore, Johnson-Neyman plot showed that sex hormone binding globulin exhibited a threshold effect on the modulation of the association between serum testosterone and SAAC. Finally, mediation analysis identified the role of Klotho in mediating high levels of serum testosterone's association with SAAC. This study reported that serum testosterone was inversely associated with SAAC, and further highlighted the mediation effect of anti-ageing protein Klotho on that association. Our findings have positive implications for the prevention and treatment of SAAC.