Abstract 4369461: Circulating Androgen Precursors and Cardiovascular Risk: Insights From NHANES 2017-2023

Background: Androgen precursors such as 17α-hydroxyprogesterone, androstenedione, and dehydroepiandrosterone (DHEA) play significant roles in endocrine and metabolic pathways, yet their relationships with cardiovascular outcomes remain underexplored. While androgens have been implicated in cardiometabolic risk, the impact of upstream precursors on heart failure (HF), coronary artery disease (CAD), or myocardial infarction (MI) is unclear. This study aimed to examine whether circulating levels of these androgen precursors are associated with incident cardiovascular events in a representative U.S. population sample. Methods: We conducted a cross-sectional analysis of 5,489 to 5,545 adults from the National Health and Nutrition Examination Survey (NHANES) with available serum levels of 17α-hydroxyprogesterone (ng/dL), androstenedione (ng/dL), and DHEA (µg/dL). Participants were stratified into quartiles (Q1–Q4) of hormone levels. Sex-specific and overall associations with cardiovascular events (HF, CAD, or MI) were evaluated using multivariate logistic regression models. Models were adjusted for age, sex, race, BMI, smoking status, diabetes mellitus, dyslipidemia, and hypertension. Results: There were no significant associations between 17α-hydroxyprogesterone levels and cardiovascular outcomes in either sex or the overall cohort. For androstenedione, a modest inverse association was observed in females at Q2 (OR 0.69; 95% CI: 0.48–1.00; P < 0.05), but not in males. Notably, DHEA showed robust, dose-dependent inverse associations with cardiovascular events. In the overall population, higher quartiles of DHEA were associated with significantly lower odds of events: Q2 (OR 0.74; 95% CI: 0.58–0.95; P < 0.05), Q3 (OR 0.57; 95% CI: 0.42–0.78; ** P < 0.001), and Q4 (OR 0.32; 95% CI: 0.19–0.54; ** P < 0.001). These associations remained significant in both males and females, with Q4 DHEA showing a strong protective effect in females (OR 0.20; 95% CI: 0.05–0.85; P < 0.05). Conclusions: Among the androgen precursors analyzed, DHEA was independently and significantly associated with lower odds of HF, CAD, or MI across sexes, suggesting a potential cardioprotective role. In contrast, 17α-hydroxyprogesterone and androstenedione showed limited or sex-specific associations. These findings support further investigation into DHEA as a biomarker or therapeutic target for cardiovascular risk reduction.