Ageing mediates the association between serum testosterone and severe abdominal aortic calcification
Authors: Lai Shengwei , Cao Long , Zhang Hongpeng , Guo Wei 
Published: December 2023

Abstract
BackgroundAbdominal aortic calcification (AAC) is acknowledged as a significant contributor to cardiovascular morbidity and mortality. However, the association between sex steroid hormones and the AAC is not well defined.
PurposeOur study aims to investigate the previously unexplored link between serum sex steroid hormone levels and severe AAC within the National Health and Nutrition Examination Survey (NHANES) cohort, potentially shedding light on innovative treatment approaches.
Methods The cross-sectional study utilized data from NHANES conducted between 2013-2014. A total of 1852 participants were included in the study. The severity of AAC was determined using the AAC 24-point scale, also known as the Kauppila calcification score. The serum sex steroid hormones assessed in this study included testosterone, estradiol, and sex hormone binding globulin (SHBG). These hormones were categorized into quintiles for subsequent analysis. Weighted multiple regression analyses were employed to investigate the potential relationship between serum sex steroid hormones and the occurrence of severe AAC. Additionally, subgroup and mediation analyses were conducted to ensure the robustness and validity of the findings.
ResultsFor 1852 enrolled individuals, the prevalence of severe AAC stood at 8.00%. Serum sex steroid hormones levels were stratified into quintiles. The average values of testosterone by quintiles were 9.90 ng/dL, 19.45 ng/dL, 116.14 ng/dL, 338.21 ng/dL, and 558.86 ng/dL respectively. The averages of estradiol by quintiles were 3.45 pg/mL, 10.71 pg/mL, 19.63 pg/mL, 27.30 pg/mL, and 105.00 pg/mL respectively. The averages of SHBG by quintiles were 24.19 nmol/L, 37.49 nmol/L, 50.10 nmol/L, 67.49 nmol/L, and 117.34 nmol/L respectively. Analytical results from univariate and multivariate analysis suggested a link between higher levels of serum testosterone and a reduced incidence of severe AAC (odds ratio [OR] = 0.33, 95% confidence interval [CI] 0.13, 0.87, P = 0.0247 for quintile 5, P for trend = 0.025). A similar connection was observed with higher serum SHBG levels, which correlated with diminished severe AAC (OR = 0.47, 95% CI 0.23, 0.93, P = 0.0315 for quintile 5, P for trend = 0.034). Further subgroup analysis found that the inverse association between serum testosterone and severe AAC was more significant (OR = 0.32, 95% CI 0.11, 0.95, P = 0.0397 for quintile 4, OR = 0.22, 95% CI 0.07, 0.67, P = 0.0073 for quintile 5, P for trend = 0.010)in the older adults (age group = 63-79), and the negative association between serum SHBG and severe AAC was more stronger (OR = 0.26, 95% CI 0.11, 0.64, P = 0.0030 for quintile 4, OR = 0.31, 95% CI 0.11, 0.93, P = 0.0366 for quintile 5, P for trend = 0.028) in male. Finally, mediated analysis found that serum Klotho, a well-recognized anti-aging-related protein, may mediate the association between higher testosterone levels and decreased severe AAC.
Conclusion This study highlights the potential negative association of serum testosterone with AAC, particularly among older individuals, and the effect may be exerted through Klotho.