Canadian Journal of Cardiology
Clinical Research| Volume 34, ISSUE 5, P683-689, May 2018

Download started.


Investigating Cortisol Production and Pattern as Mediators in the Relationship Between Shift Work and Cardiometabolic Risk

Published:February 09, 2018DOI:



      Shift work is a risk factor for many diseases, including cardiovascular disease. Although the biological pathways are still unclear, it is hypothesized that cortisol disruption during night work is an intermediate. The objective of this study is to determine whether total cortisol production and cortisol pattern mediate the relationship between current shift work and cardiometabolic risk (CMR) among female hospital employees.


      A cross-sectional study was conducted among 326 female employees (166 rotating shift workers, 160 day workers), recruited from a hospital in Southeastern Ontario, Canada, during 2011 to 2014. Participants completed a baseline interview, questionnaire, and clinical exam. Urine samples were collected over two 24-hour periods and used to analyze creatinine-adjusted cortisol, which was then used to calculate total cortisol production (AUCG), and pattern (AUCI). Mediation analysis was performed to test the mediating effect of cortisol in the relationship between shift work and a continuous CMR score.


      Current shift work is associated with a 0.52 higher CMR score (95% CI: 0.15, 0.89), a lower cortisol output (AUCG), and a flatter pattern (AUCI) over a 2-day period. AUCG is a partial mediator in the relationship between shift work and CMR, whereas AUCI is not. AUCG is also associated with CMR while controlling for shift work, suggesting that lower total cortisol production is also linked to CMR in non-shift workers.


      Total cortisol production is a partial mediator in the relationship between rotating shift work and CMR among female hospital employees, whereas cortisol pattern is not a mediator.



      Le travail par roulement est un facteur de risque de nombreuses maladies, y compris les maladies cardiovasculaires. Bien que les mécanismes biologiques en cause ne soient pas encore élucidés, une hypothèse voudrait que la perturbation du métabolisme du cortisol pendant le travail de nuit soit un mécanisme intermédiaire. L’objectif de cette étude est de déterminer si la production de cortisol total et le profil du cortisol assurent la médiation du lien entre le travail par roulement en cours et le risque cardiométabolique (RCM) chez des femmes travaillant dans un hôpital.


      Une étude transversale a été menée auprès de 326 employées (166 employées ayant un travail en rotation et 160 employées de jour) recrutées dans un hôpital du sud-est de l’Ontario (Canada) entre 2011 et 2014. Les participantes ont passé une entrevue initiale, elles ont répondu à un questionnaire et passé un examen clinique. Des échantillons d’urine ont été recueillis pendant deux périodes de 24 heures aux fins d’analyse des taux de cortisol corrigés selon la créatinine; ces taux ont ensuite servi à calculer la production de cortisol total (ASCG) et le profil du cortisol (ASCI). Une analyse a été réalisée pour tester l’effet médiateur du cortisol dans le contexte du lien existant entre le travail par roulement et un score de RCM continu.


      Le travail par roulement en cours est associé à un score de RCM plus élevé de 0,52 (intervalle de confiance [IC] à 95 %: 0,15 à 0,89), à une élimination inférieure du cortisol (ASCG) et à un profil plus plat (ASCI) du cortisol sur une période de deux jours. L’ASCG est un médiateur partiel du lien entre le travail par roulement et le RCM, ce qui n’est pas le cas de l’ASCI. L’ASCG est également associée au RCM lorsqu’une correction est apportée en fonction du travail par roulement, ce qui indique que la production inférieure de cortisol total est également liée au RCM chez les personnes n’ayant pas un travail par roulement.


      Contrairement au cycle du cortisol, la production de cortisol total est un médiateur partiel du lien existant entre le travail en rotation et le RCM chez les employées de l’hôpital de l’étude.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Canadian Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Stevens R.G.
        • Hansen J.
        • Costa G.
        • et al.
        Considerations of circadian impact for defining “shift work” in cancer studies: IARC Working Group Report.
        Occup Environ Med. 2011; 68: 154-162
        • Vyas M.
        • Garg A.
        • Iansavichus A.
        • et al.
        Shift work and vascular events: systematic review and meta-analysis.
        BMJ. 2012; 345
        • Wong I.S.
        • McLeod C.B.
        • Demers P.A.
        Shift work trends and risk of work injury among Canadian workers.
        Scand J Work Environ Health. 2011; 37: 54-61
        • Vetter C.
        • Devore E.E.
        • Wegrzyn L.R.
        • et al.
        Association between rotating night shift work and risk of coronary heart disease among women.
        JAMA. 2016; 315: 1726-1734
        • Mottillo S.
        • Filion K.B.
        • Genest J.
        • et al.
        The metabolic syndrome and cardiovascular risk: a systematic review and meta-analysis.
        J Am Coll Cardiol. 2010; 56: 1113-1132
        • Wang F.
        • Zhang L.
        • Zhang Y.
        • et al.
        Meta-analysis on night shift work and risk of metabolic syndrome.
        Obes Rev. 2014; 15: 709-720
        • Proper K.I.
        • van de Langenberg D.
        • Rodenburg W.
        • et al.
        The relationship between shift work and metabolic risk factors: a systematic review of longitudinal studies.
        Am J Prev Med. 2016; 50: e147-e157
        • Knutsson A.
        • Bøggild H.
        Shiftwork and cardiovascular disease: review of disease mechanisms.
        Rev Environ Health. 2000; 15: 359-372
        • Puttonen S.
        • Harma M.
        • Hublin C.
        Shift work and cardiovascular disease – pathways from circadian stress to morbidity.
        Scand J Work Environ Health. 2010; 36: 96-108
        • Fries E.
        • Dettenborn L.
        • Kirschbaum C.
        The cortisol awakening response (CAR): Facts and future directions.
        Int J Psychophysiol. 2009; 72: 67-73
        • Archer S.N.
        • Oster H.
        How sleep and wakefulness influence circadian rhythmicity: effects of insufficient and mistimed sleep on the animal and human transcriptome.
        J Sleep Res. 2015; 24: 476-493
        • Hung E.W.M.
        • Aronson K.J.
        • Leung M.
        • Day A.
        • Tranmer J.
        Shift work parameters and disruption of diurnal cortisol production in female hospital employees.
        Chronobiol Int. 2016; 33: 1045-1055
        • Fekedulegn D.
        • Burchfiel C.M.
        • Violanti J.M.
        • et al.
        Associations of long-term shift work with waking salivary cortisol concentration and patterns among police officers.
        Ind Health. 2012; 50: 476-486
        • Niu S.-F.
        • Chung M.-H.
        • Chu H.
        • et al.
        Differences in cortisol profiles and circadian adjustment time between nurses working night shifts and regular day shifts: A prospective longitudinal study.
        Int J Nurs Stud. 2015; 52: 1193-1201
        • Charles L.E.
        • Fekedulegn D.
        • Burchfiel C.M.
        • et al.
        Shiftwork and diurnal salivary cortisol patterns among police officers.
        J Occup Environ Med. 2016; 58: 542-549
        • Vogelzangs N.
        • Beekman A.T.F.
        • Milaneschi Y.
        • Bandinelli S.
        • Ferrucci L.
        • Penninx B.W.J.H.
        Urinary cortisol and six-year risk of all-cause and cardiovascular mortality.
        J Clin Endocrinol Metab. 2010; 95: 4959-4964
        • Kumari M.
        • Shipley M.
        • Stafford M.
        • Kivimaki M.
        Association of diurnal patterns in salivary cortisol with all-cause and cardiovascular mortality: Findings from the Whitehall II study.
        J Clin Endocrinol Metab. 2011; 96: 1478-1485
        • Desantis A.S.
        • Diezroux A.V.
        • Hajat A.
        • et al.
        Associations of salivary cortisol levels with metabolic syndrome and its components: the Multi-Ethnic Study of Atherosclerosis.
        Psychoneuroendocrinology. 2011; 96: 3483-3492
      1. Mayo Clinic. COCRU-Clinical: Cortisol/Cortisone, Free, Random, Urine. Available at: Accessed May 20, 2017.

        • DeBoer M.D.
        • Gurka M.J.
        Clinical utility of metabolic syndrome severity scores: consideration for practitioners.
        Diabetes Metab Syndr Obes. 2017; 10: 65-72
        • Hillier T.A.
        • Rousseau A.
        • Lange C.
        • et al.
        Practical way to assess metabolic syndrome using a continuous score obtained from principal components analysis.
        Diabetologia. 2006; 49: 1528-1535
        • Gurka M.J.
        • Lilly C.L.
        • Oliver M.N.
        • et al.
        An examination of sex and racial/ethnic differences in the metabolic syndrome among adults: a confirmatory factor analysis and a resulting continuous severity score.
        Metabolism. 2014; 63: 218-225
        • Agarwal S.
        • Jacobs D.R.
        • Vaidya D.
        • et al.
        Metabolic syndrome derived from principal component analysis and incident cardiovascular events: the Multi-Ethnic Study of Atherosclerosis (MESA) and Health, Aging, and Body Composition (Health ABC).
        Cardiol Res Pract. 2012; 2012: 1-9
        • D’Agostino Sr., R.B.
        • Grundy S.
        • Sullivan L.M.
        • Wilson P.
        • CHD Risk Prediction Group
        Validation of the Framingham coronary heart disease prediction scores.
        JAMA. 2001; 286: 180-187
        • Ridker P.M.
        • Buring J.E.
        • Rifai N.
        • Cook N.R.
        Development and validation of improved algorithms for the assessment of global cardiovascular risk in women.
        JAMA. 2007; 297: 611-619
        • Pruessner J.C.
        • Kirschbaum C.
        • Meinlschmid G.
        • Hellhammer D.H.
        Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change.
        Psychoneuroendocrinology. 2003; 28: 916-931
        • Fekedulegn D.B.
        • Andrew M.E.
        • Burchfiel C.M.
        • et al.
        Area under the curve and other summary indicators of repeated waking cortisol measurements.
        Psychosom Med. 2007; 69: 651-659
        • Preacher K.J.
        • Hayes A.F.
        Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models.
        Behav Res Methods. 2008; 40: 879-891
        • Lemche E.
        • Chaban O.S.
        • Lemche A.V.
        Neuroendorine and epigentic mechanisms subserving autonomic imbalance and HPA dysfunction in the metabolic syndrome.
        Front Neurosci. 2016; 10: 142
        • Chung S.
        • Hoon Son G.
        • Kim K.
        Circadian rhythm of adrenal glucocorticoid: Its regulation and clinical implications.
        BBA-Mol Basis Dis. 2011; 1812: 581-591
        • Arnaldi G.
        • Scandali V.M.
        • Trementino L.
        • Cardinaletti M.
        • Appolloni G.
        • Boscaro M.
        Pathophysiology of dyslipidemia in Cushing’s syndrome.
        Neuroendocrinology. 2010; 92: 86-90
        • Macfarlane D.P.
        • Forbes S.
        • Walker B.R.
        Glucocorticoids and fatty acid metabolism in humans: fuelling fat redistribution in the metabolic syndrome.
        J Endocrinol. 2008; 197: 189-204
        • Dekker M.J.
        • Koper J.W.
        • van Aken M.O.
        • et al.
        Salivary cortisol is related to atherosclerosis of carotid arteries.
        J Clin Endocrinol Metab. 2008; 93: 3741-3747
        • Troxler R.
        • Sprague E.
        • Albanese R.
        • Fuchs R.
        • Thompson A.
        The association of elevated plasma cortisol and early atherosclerosis as demonstrated by coronary angiography.
        Atherosclerosis. 1977; 26: 151-162
        • Korsiak J.
        • Tranmer J.
        • Day A.
        • Aronson K.
        Sleep duration as a mediator between an alternating day and night shift work schedule and metabolic syndrome among female hospital employees.
        Occup Environ Med. 2018; 75: 132-138
        • Buxton O.M.
        • Cain S.W.
        • O’Connor S.P.
        • et al.
        Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption.
        Sci Transl Med. 2012; 4: 129ra43
        • Rao M.N.
        • Blackwell T.
        • Redline S.
        • et al.
        Association between sleep duration and 24-hour urine free cortisol in the MrOS Sleep Study.
        PLoS One. 2013; 8e75205
        • Van Cauter E.
        • Spiegel K.
        • Tasali E.
        • Leproult R.
        Metabolic consequences of sleep and sleep loss.
        Sleep Med. 2008; 1: S23-S28
        • Leung M.
        • Tranmer J.
        • Hung E.
        • Korsiak J.
        • Day A.G.
        • Aronson K.J.
        Shift work, chronotype, and melatonin patterns among female hospital employees on day and night shifts.
        Cancer Epidemiol Prev Biomarkers. 2016; 25: 830-838
        • Karasek R.A.
        Job Content Questionnaire and User's Guide.
        Lowell: University of Massachusetts Lowell, Department of Work Environment. 1985;
        • Alberti K.
        • Eckel R.H.
        • Grundy S.M.
        • et al.
        Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity.
        Circulation. 2009; 120: 1640-1645