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...

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Main Authors: Xiaoyan Tang, Jie Liu, Hongwei Li, Zili Chen, Li Yang, Rui Du
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Annals of Medicine
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Online Access:https://www.tandfonline.com/doi/10.1080/07853890.2025.2534091
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author Xiaoyan Tang
Jie Liu
Hongwei Li
Zili Chen
Li Yang
Rui Du
author_facet Xiaoyan Tang
Jie Liu
Hongwei Li
Zili Chen
Li Yang
Rui Du
author_sort Xiaoyan Tang
collection DOAJ
description 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 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.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.
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spelling doaj-art-36448b0a2e2d4de5953dd7e3dd8df62e2025-08-20T03:13:22ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602025-12-0157110.1080/07853890.2025.2534091Sex differences in the association between atherogenic index of plasma and α-klotho: insights from a community-based cohortXiaoyan Tang0Jie Liu1Hongwei Li2Zili Chen3Li Yang4Rui Du5Department of Cardiology, General Hospital of Central Theater Command, Wuhan, Hubei, ChinaDepartment of Ultrasound, International Mongolian Hospital of Inner Mongolia, Hohhot, Inner Mongolia, ChinaDepartment of Procurement Management, General Hospital of Central Theater Command, Wuhan, Hubei, ChinaDepartment of Ultrasound, General Hospital of Central Theater Command, Wuhan, Hubei, ChinaDepartment of Ultrasound, General Hospital of Central Theater Command, Wuhan, Hubei, ChinaDepartment of Ultrasound, General Hospital of Central Theater Command, Wuhan, Hubei, ChinaBackground 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 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.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.https://www.tandfonline.com/doi/10.1080/07853890.2025.2534091Atherogenic index of plasmaα − klothoaging biomarkerscross-sectional studyNHANES
spellingShingle Xiaoyan Tang
Jie Liu
Hongwei Li
Zili Chen
Li Yang
Rui Du
Sex differences in the association between atherogenic index of plasma and α-klotho: insights from a community-based cohort
Annals of Medicine
Atherogenic index of plasma
α − klotho
aging biomarkers
cross-sectional study
NHANES
title Sex differences in the association between atherogenic index of plasma and α-klotho: insights from a community-based cohort
title_full Sex differences in the association between atherogenic index of plasma and α-klotho: insights from a community-based cohort
title_fullStr Sex differences in the association between atherogenic index of plasma and α-klotho: insights from a community-based cohort
title_full_unstemmed Sex differences in the association between atherogenic index of plasma and α-klotho: insights from a community-based cohort
title_short Sex differences in the association between atherogenic index of plasma and α-klotho: insights from a community-based cohort
title_sort sex differences in the association between atherogenic index of plasma and α klotho insights from a community based cohort
topic Atherogenic index of plasma
α − klotho
aging biomarkers
cross-sectional study
NHANES
url https://www.tandfonline.com/doi/10.1080/07853890.2025.2534091
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