Age-related changes in hypothalamic-pituitary-adrenal axis activity in patients with manifest arterial disease

Reports on age-related changes of hypothalamic-pituitary-adrenal (HPA) axis activity are equivocal. In addition, subtle changes in HPA axis activity are associated with cardiovascular risk factors. This study evaluates the effect of age in a large sample of patients with arterial disease on several parts of the circadian rhythm of the HPA axis. Within the Second Manifestations of Arterial Disease-Magnetic Resonance (SMART-MR) study, a prospective cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 419 patients (age 63 +/- A 9 years). Circadian cortisol rhythm was assessed with six saliva samples, collected at awakening and 30, 45, and 60 min thereafter and at 10 and 11 pm. Furthermore, a low dose of dexamethasone (0.5 mg) was administered at 11 pm, and saliva was sampled the next morning to test the cortisol suppression. Linear regression analyses adjusted for sex, awakening time, workday, smoking, blood pressure, BMI, diabetes mellitus, and dyslipidemia showed that older age was associated with a blunted cortisol awakening response. Per year increase, the rise (beta = -0.15 nmol/l; 95%CI -0.25 to -0.05) and diurnal pattern (beta = -0.14 nmol/l; 95%CI -0.25 to -0.02) decreased. Furthermore, older age was associated with higher evening levels (beta log transformed = 0.01; 95%CI 0.01-0.02) and higher mean cortisol after dexamethasone (beta log transformed = 0.01; 95%CI 0.002-0.02). In patients with arterial disease, HPA axis activity showed reduced variability with older age, independent of cardiovascular risk factors.