Prolonged hypothalamic-pituitary-adrenal axis activation after acute coronary syndrome in the GENESIS-PRAXY cohort

Background Glucocorticoid excess has been linked with cardiovascular disease. Little is known about the long-term cortisol response in patients after acute coronary syndrome. Design The objective of this study was to describe the distribution of salivary cortisol in the post-acute phase of acute coronary syndrome and to describe the association of late-night salivary cortisol with cardiovascular risk factors. Methods We used late-night salivary cortisol measurements post-discharge to estimate hypothalamic-pituitary-adrenal axis activity in 309 patients aged 18-55 years enrolled in the GENESIS-PRAXY study from January 2009-April 2013. We evaluated hypothalamic-pituitary-adrenal axis activity and its association with hypertension, dyslipidemia, diabetes, smoking, family history, prior acute coronary syndrome, psychiatric diseases, acute coronary syndrome severity, as well as mortality and rate of rehospitalization at 12 months. Results Persistently elevated late-night salivary cortisol>2.92nmol/l was seen in 99 (32.0%) patients: within the range of what may be seen in Cushing's disease. Elevated late-night salivary cortisol was associated with previous acute coronary syndrome (13.3% vs 24.2%, p=0.02), peripheral vascular disease (3.8% vs 13.1%, p=0.002), and smoking (32.9% vs 46.5% p=0.02). Elevated late-night salivary cortisol was associated with higher hemoglobin A1c values (5.63.0 vs 6.1 +/- 2.9, p=0.008) and lower high density lipoprotein values (0.94 +/- 0.53 vs 0.86 +/- 0.50, p=0.01). There were no differences in psychiatric symptom scores, acute coronary syndrome severity or mortality, and rate of rehospitalization at 12 months. Conclusions Many patients post-acute coronary syndrome have prolonged, marked activation of the hypothalamic-pituitary-adrenal axis. Late-night salivary cortisol co-associates with several cardiovascular risk factors. Further studies are needed to confirm the exact role of hypothalamic-pituitary-adrenal axis activity in the pathophysiology of cardiovascular disease.