title: Association of diurnal patterns in salivary cortisol with all-cause and cardiovascular mortality: findings from the Whitehall II study.
abstract: BACKGROUND
  Evidence for the association of cortisol with mortality or disease events is mixed, possibly due to a failure to consider diurnal cortisol patterns.
  
  
  OBJECTIVE
  Our objective was to examine the association of diurnal cortisol patterns throughout the day with cardiovascular and noncardiovascular mortality in a community-dwelling population.
  
  
  METHODS
  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.
  
  
  METHODS
  Participants included 4047 men and women aged 61 yr on average at baseline.
  
  
  RESULTS
  We assessed all-cause, cardiovascular, and noncardiovascular death.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology and Public Health, University College London, London WC1E 6BT, United Kingdom. m.kumari@ucl.ac.uk
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.forename: Martin
authors.initials: M
authors.lastname: Shipley
authors.forename: Mai
authors.initials: M
authors.lastname: Stafford
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimaki
mesh_terms: D000367:Age Factors; D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality*; D002940:Circadian Rhythm / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015438:Health Behavior; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D011446:Prospective Studies; D012307:Risk Factors; D012463:Saliva / Q000378:metabolism*; D012737:Sex Factors; D012959:Socioeconomic Factors; D013315:Stress, Psychological / Q000378:metabolism / Q000401:mortality; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D006854:Hydrocortisone