Relationship Between the Cortisol Awakening Response and Other Features of the Diurnal Cortisol Rhythm: the Multi-Ethnic Study of Atherosclerosis

Cumulative cortisol burden is known to influence neuropsychiatric and metabolic disorders. To better understand the relationship between daily cortisol exposure and measures of the diurnal circadian cortisol rhythm, we examined the cross-sectional association of the cortisol awakening response (CAR) with wake-up cortisol, bedtime cortisol, diurnal slope, and total cortisol area under the curve (AUC). Up to 18 salivary cortisol samples were collected over 3 days from 935 White, Hispanic, and Black individuals (mean age 65 ± 9.8 years) in the Multi-Ethnic Study of Atherosclerosis. Outcome measures included awakening cortisol, CAR (awakening to 30 min post-awakening), early decline (30 min to 2h post-awakening), late decline (2h post-awakening to bedtime), and the corresponding AUCs. Total cortisol AUC was a summary measure of cumulative cortisol exposure. Higher CAR was associated with significantly lower wake-up cortisol (β=-0.56; 95% CI: -0.59 to -0.53) and a higher early decline AUC (β=0.38; 95% CI: 0.34-0.42) but was not associated with total cortisol AUC (β=0.04; 95% CI: -0.01 to 0.09), or other diurnal cortisol curve components following multivariable adjustment. Total cortisol AUC was significantly and positively associated with wake-up cortisol (β=0.36; 95% CI: 0.32-0.40), bedtime cortisol (β=0.61; 95% CI: 0.58-0.64), and other AUC measures, following multivariable adjustment. Associations were similar by sex, race/ethnicity, and age categories. We conclude that bedtime cortisol showed the strongest correlation with total cortisol AUC, suggesting it may be a marker of daily cortisol exposure.