Tang Xiaoyan, Liu Jie, Li Hongwei, Chen Zili, Yang Li, Du Rui
Department of Cardiology, General Hospital of Central Theater Command, Wuhan, Hubei, China.
Department of Ultrasound, International Mongolian Hospital of Inner Mongolia, Hohhot, Inner Mongolia, China.
Ann Med. 2025 Dec;57(1):2534091. doi: 10.1080/07853890.2025.2534091. Epub 2025 Jul 17.
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; = 0.031, Q4: β = -41.03; 95% CI: -80.27, -1.78; = 0.046). Sex-stratified analysis showed a stronger inverse association in females (Q3: β = -73.13; 95% CI: -123.58, -22.69; = 0.006, Q4: β = -99.79; 95% CI: -154.68, -44.89; < 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.
血浆致动脉粥样硬化指数（AIP）是脂质失衡和心血管风险的标志物，而α-klotho是一种参与氧化应激和炎症调节的抗衰老蛋白。尽管两者都与心血管和代谢健康有关，但AIP与α-klotho之间的关系，尤其是性别差异方面，仍不清楚。
我们对来自美国国家健康与营养检查调查（NHANES）连续五个周期（2007年1月至2016年12月）的社区队列进行了横断面分析。共纳入4897名年龄在40至79岁之间的参与者。加权多元线性回归模型评估了AIP与血清α-klotho（SαKl）水平之间的关联，并对人口统计学和临床协变量进行了调整。性别分层分析探讨了潜在的效应修正。
女性的平均±标准误SαKl水平为869.9±8.6 pg/mL，男性为826.6±10.2 pg/mL；平均±标准误AIP值分别为-0.09±0.01和0.05±0.01。在完全调整模型中，处于AIP第三四分位数（Q3）和第四四分位数（Q4）的参与者的SαKl显著低于Q1中的参与者（Q3：β=-40.3²；95%置信区间：-75.89，-4.75；P=0.031，Q4：β=-41.03；95%置信区间：-80.27，-1.78；P=0.046）。性别分层分析显示女性的负相关更强（Q3：β=-73.13；95%置信区间：-123.58，-22.69；P=0.006，Q4：β=-99.79；95%置信区间：-154.68，-44.89；P<0.001），而在男性中未观察到显著关系。
在这个基于社区的队列中，AIP与SαKl呈负相关，尤其是在女性中，这表明血脂异常可能以性别特异性方式导致较低的SαKl水平。AIP有助于识别有SαKl缺乏风险的个体，尤其是女性。有必要进行前瞻性研究以证实因果关系，并确定改善血脂状况是否可以维持SαKl及相关健康结果。
