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Association of Diurnal Patterns in Salivary Cortisol with All-Cause and Cardiovascular Mortality: Findings from the Whitehall II Study
Open accessAbstract
Context: 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. Design: 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: Participants included 4047 men and women aged 61 yr on average at baseline. Outcomes: 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.
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“Elevated levels of cortisol in the evening are associated with increased mortality risk from cardiovascular disease 32.”
From Type 2 diabetes mellitus and psychological stress — a modifiable risk factor (2017) · cites this paper as [32]
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Metadata
- Authors
- Kumari, M., Shipley, M., Stafford, M., & Kivimaki, M.
- Affiliations
- Department of Epidemiology and Public Health, University College London, London WC1E 6BT, United Kingdom
- University College London (GB)
- ORCID
- Stafford, Mai
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2011-05-01
- Volume
- 96
- Issue
- 5
- Pages
- 1478-1485
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC3085201
- OpenAlex
- W2059693239
- Cited by
- 343
- References
- 32
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 8 · 2023: 20 · 2022: 18 · 2021: 17 · 2020: 31 · 2019: 25 · 2018: 28 · 2017: 33 · 2016: 48 · 2015: 25 · 2014: 26 · 2013: 21 · 2012: 23
- FWCI
- 9.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institute for Health and Care Research
- British Heart Foundation (HS06516, RG/07/008/23674)
- University College London
- European Commission
- Health and Safety Executive
- Academy of Finland
- National Institutes of Health (-0001)
- Agency for Healthcare Research and Quality (HS06516)
- Medical Research Council (HS06516, WC1E 6BT)
- Economic and Social Research Council (RES 596-28-0001)
- National Institute on Aging (AG 13196, R37AG013196, R01AG013196)
- National Heart, Lung, and Blood Institute (HS06516, HL36310, R01HL036310)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- salivary cortisol, cardiovascular mortality, all-cause mortality, cortisol awakening response, morning cortisol, circadian rhythm, public sector employees, Whitehall II study
- MeSH terms
- Age Factors, Aged, Cardiovascular Diseases, Circadian Rhythm, Female, Follow-Up Studies, United Kingdom, Humans, Hydrocortisone, Male, Middle Aged, Mortality, Prospective Studies, Risk Factors, Saliva, Sex Factors, Socioeconomic Factors, Stress, Psychological, Cohort Studies, Health Behavior
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