Association of testosterone, cortisol, and CRP with miR-146a expression and cardiovascular risk indices in dyslipidemic and healthy men: a case–control study

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Cardiovascular disease remains a leading cause of mortality worldwide. Testosterone, cortisol, and C-reactive protein (CRP) have been implicated in cardiometabolic regulation, while miR-146a plays an important role in inflammatory signaling. This study investigated the associations of testosterone, cortisol, and CRP with miR-146a expression and advanced cardiovascular risk indices in men from the Kerman Coronary Artery Disease Risk Factors Study (KERCADRS). In this case–control study, 155 adult men were evaluated, including dyslipidemic ( n = 121) and healthy ( n = 34) participants. Serum testosterone, cortisol, and CRP levels were measured by the enzyme-linked immunosorbent assay (ELISA) method, and miR-146a expression was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Advanced cardiometabolic indices were calculated. Dyslipidemic men had significantly lower testosterone levels (4.91 ± 1.84 vs. 6.97 ± 1.48 ng/mL, P < 0.001) and higher miR-146a expression (1.53 ± 1.05 vs. 0.91 ± 0.31, P < 0.001) than healthy controls. Higher testosterone was associated with better lipid profiles and lower cardiometabolic risk indices. In multivariate analyses, testosterone remained independently and inversely associated with the Atherogenic Index of Plasma (AIP) in both groups, and with lower miR-146a expression in the dyslipidemic group ( P < 0.001). Cortisol independently predicted higher AIP in dyslipidemic participants, while CRP showed no significant independent associations. Unexpectedly, higher CRP levels were not linked to worse atherogenic indices. Higher testosterone levels were independently associated with more favorable cardiometabolic profiles and lower miR-146a expression in dyslipidemic men, while higher cortisol levels were associated with increased atherogenic risk. These findings suggest that testosterone, cortisol, and advanced atherogenic indices may aid in cardiovascular risk stratification among men with dyslipidemia. However, due to the observational nature of the study, causality cannot be inferred, and prospective longitudinal as well as interventional studies are needed to validate these associations and explore their potential clinical utility.