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

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.

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.

Mean ± SE SαKl level was 869.9 ± 8.6 pg/mL in females and 826.6 ± 10.2 pg/mL in males; mean ± SE AIP values were -0.09 ± 0.01 and 0.05 ± 0.01, respectively. In the fully adjusted model, participants in the third (Q3) and fourth (Q4) AIP quartiles had significantly lower SαKl than those in Q1 (Q3: β = -40.32; 95% CI: -75.89, -4.75; p = 0.031, Q4: β = -41.03; 95% CI: -80.27, -1.78; p = 0.046). Sex-stratified analysis showed a stronger inverse association in females (Q3: β = -73.13; 95% CI: -123.58, -22.69; p = 0.006, Q4: β = -99.79; 95% CI: -154.68, -44.89; p < 0.001), whereas no significant relationship was observed in male.

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.