Sex differences in the association between atherogenic index of plasma and α-klotho: insights from a community-based cohort

BACKGROUND: The Atherogenic Index of Plasma (AIP) is a marker of lipid imbalance and cardiovascular risk, while α-Klotho is an anti-aging protein involved in oxidative stress and inflammation regulation. Although both are linked to cardiovascular and metabolic health, the relationship between AIP and α-Klotho, particularly regarding sex differences, remains unclear. METHODS: We performed a cross-sectional analysis of a community-based cohort drawn from five consecutive cycles of the NHANES (January 2007 - December 2016). A total of 4,897 participants aged 40 to 79 years were included. Weighted multivariate linear regression models assessed the association between AIP and serum α-Klotho (SαKl) levels, adjusting for demographic and clinical covariates. Sex-stratified analyses explored potential effect modification. RESULTS: < 0.001), whereas no significant relationship was observed in male. CONCLUSION: AIP is inversely associated with SαKl in this community-based cohort, particularly among females, suggesting dyslipidemia may contribute to lower SαKl levels in a sex-specific manner. AIP could help identify individuals-especially females-at risk of SαKl deficiency. Prospective studies are warranted to confirm causality and to determine whether improving lipid profiles can preserve SαKl and related health outcomes.