High anticipatory stress plasma cortisol levels and sensitivity to glucocorticoids predict severity of coronary artery disease in subjects undergoing coronary angiography

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and/or increased sensitivity of peripheral tissues to glucocorticoids may be associated with the dysmetabolic syndrome and its cardiovascular sequelae. In this prospective pilot clinical study, we examined possible associations between HPA axis activity and severity of cardiovascular disease. We measured morning serum cortisol and intima media thickness (IMT) of carotid and femoral arteries in 105 subjects before undergoing coronary angiography for suspected coronary artery disease (CAD). In a randomly selected 46 of these subjects, we obtained late afternoon and morning cortisol levels (after ultralow-dose dexamethasone [0.25 mg] treatment) and determined their genotype for the Bcl1 polymorphism of the glucocorticoid receptor gene, which has been associated with increased sensitivity to glucocorticoids. There was significant association between morning preangiography cortisol levels and the number of vessels with severe stenosis in the angiography, independently of age or sex (P = .002), and a trend for a positive correlation between morning cortisol and the IMT of the femoral artery (P = .057). Bcl1 G allele homozygotes had a significantly higher carotid IMT (P = .005) and a nonsignificant tendency for higher waist-hip ratio (P = .059). Hyperactivity of the HPA axis in anticipation of a stressful procedure, such as angiography, may be an index of CAD severity. Chronic HPA axis hyperreactivity combined with tissue hypersensitivity to glucocorticoids may contribute to more severe atherosclerosis and CAD.