Association of diurnal patterns in salivary cortisol with all-cause and cardiovascular mortality: findings from the Whitehall II study.

Abstract

Evidence for the association of cortisol with mortality or disease events is mixed, possibly due to a failure to consider diurnal cortisol patterns. Our objective was to examine the association of diurnal cortisol patterns throughout the day with cardiovascular and noncardiovascular mortality in a community-dwelling population. This was a prospective cohort study among 4047 civil servants, the Whitehall II study, United Kingdom. We measured diurnal cortisol patterns in 2002-2004 from six saliva samples obtained over the course of a normal weekday: at waking, +30 min, +2.5 h, +8 h, +12 h, and bedtime. Participants were subsequently followed for all-cause and cause-specific mortality until January 2010. Participants included 4047 men and women aged 61 yr on average at baseline. We assessed all-cause, cardiovascular, and noncardiovascular death. There were 139 deaths, 32 of which were deaths due to cardiovascular disease, during a mean follow-up period of 6.1 yr. Flatter slopes in cortisol decline across the day were associated with increased risk of all-cause mortality (hazard ratio for 1 sd reduction in slope steepness 1.30; 95% confidence interval (CI) = 1.09-1.55). This excess mortality risk was mainly driven by an increased risk of cardiovascular deaths (hazard ratio = 1.87; 95% confidence interval = 1.32-2.64). The association with cardiovascular deaths was independent of a wide range of covariates measured at the time of cortisol assessment. There was no association between morning cortisol, the cortisol awakening response, and mortality outcomes. These findings demonstrate, for the first time, the relationship between a flatter slope in cortisol levels across the day and an increased risk of cardiovascular disease mortality in a nonclinical population.