Hypothalamic-pituitary-adrenal-axis dysregulation and double product increases potentiate ischemic heart disease risk in a Black male cohort: The SABPA study

Emotional distress has been associated with a poorer prognosis in myocardial infarction patients. Elevated adrenocorticotrophic hormone (ACTH), lower cortisol, dehydroepiandrosterone sulfate (DHEAS) and cortisol:DHEAS, as measures of emotional distress, might correlate with silent myocardial ischemia (SMI) and workload. Thus, we assessed the relationship between emotional distress, SMI and double product (systolic blood pressure (SBP) × heart rate). Cross-sectional South African biethnic single-set cohorts (N=378), aged 44.7±9.52 years, were investigated. Depressive symptoms (Patient Health Questionnaire-9), anthropometric, fasting blood, 24-h double product and 24-h 2-lead electrocardiogram (ST-segment depression) values were obtained. Blacks, mostly men, had increased depressive symptoms, hyperglycemia, SMI, double product, SBP hypertension and ACTH but lower cortisol, DHEAS and cortisol:DHEAS than their White counterparts. Black men had the highest combined SBP hypertension and below-median cortisol prevalence, 38%, compared with 5.9-13.8% in the other groups. Their SMI was associated with ACTH and cortisol:DHEAS (adj. R 0.29; β 0.27-0.31 (0.12-0.64); P≤ 1/20.05), double product (adj. R 0.29; β 0.38 (0.18-0.57); P=0.050) and SBP hypertension (area under the curve: 0.68 (95% CI: 0.56, 0.80); P=0.042; sensitivity/specificity 49/85%). Double product was positively associated with central obesity in all sex groups and with cortisol in the Black men (P\u3c0.05). A dysregulated hypothalamic-pituitary-adrenal-axis (HPAA) showed signs of a hyporesponsive adrenal cortex, suggesting chronic emotional stress in the Black male cohort. In this cohort, HPAA dysregulation and compensatory increases in double product occur as a potential defense mechanism to alleviate perfusion deficits, thereby potentiating ischemic heart disease risk. 2