Lai Shengwei, Qin Handai, Wang Xinhao, Sun Guanchao, Cao Long, Fan Zheqi, Zhang Hongpeng, Guo Wei
Medical School of Chinese PLA, Beijing, 100853, China.
Department of Vascular Surgery, First Medical Centre of Chinese, PLA General Hospital, Beijing, 100853, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Mar 21. doi: 10.1007/s00210-025-04048-4.
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.
严重腹主动脉钙化（SAAC）被认为是心血管疾病发病率和死亡率的一个重要因素，但其与性甾体激素的关系仍不清楚。在此，在国家健康和营养检查调查（NHANES）队列中研究了血清性甾体激素水平与SAAC之间尚未探索的联系。本研究利用了NHANES 2013 - 2014年的数据。SAAC使用腹主动脉钙化24分制进行测定。血清性甾体激素被分为五分位数1 - 5进行分析。采用多变量逻辑回归和亚组分析来研究血清性甾体激素与SAAC风险之间的潜在关系。此外，应用约翰逊 - 内曼图来确定是否存在任何阈值效应。最后，为了揭示潜在的病理生理机制，进行了中介分析。总共纳入了1852名受试者，SAAC的患病率为8.00%。在调整潜在混杂因素后，多变量分析表明血清睾酮水平较高与SAAC发病率降低相关（五分位数5的AOR = 0.33，95%CI：0.13 - 0.87，P = 0.0247，趋势P = 0.025）。亚组分析表明，在年龄≥60岁的参与者（五分位数5的AOR = 0.20，95%CI：0.07 - 0.56，P = 0.0023）和非高血压人群（五分位数5的AOR = 0.29，95%CI：0.09 - 0.96，P = 0.0436）中，这种负相关更为显著。受限立方样条曲线表明，在年龄≥60岁的非高血压男性人群中，血清睾酮与SAAC风险之间存在剂量 - 反应关系。此外，约翰逊 - 内曼图显示性激素结合球蛋白对血清睾酮与SAAC之间关联的调节具有阈值效应。最后，中介分析确定了Klotho在介导高水平血清睾酮与SAAC关联中的作用。本研究报告血清睾酮与SAAC呈负相关，并进一步强调了抗衰老蛋白Klotho对该关联的中介作用。我们的研究结果对SAAC的预防和治疗具有积极意义。
