Irregular sleep and all-cause mortality: A large prospective cohort study

Published:October 10, 2022DOI:



      Previous studies using objective parameters have shown that irregular sleep is associated with the disease incidence, progression, or mortality. This study aimed to determine the association between subjective sleep duration and sleep regularity, with mortality in a large population.


      Participants were from the Japan Multi-Institutional Collaborative Cohort study. We obtained information from each participant on sleep duration, sleep regularity, and demographics and overall lifestyle using self-administered questionnaires. We defined sleep regularity according to participants' subjective assessment of sleep/wake time regularity. Participants (n = 81,382, mean age: 58.1 ± 9.1years, males: 44.2%) were classified into 6 groups according to sleep duration and sleep regularity. Hazard ratios (HR) for time-to-event of death were calculated using the Cox proportional hazards model.


      The mean follow-up period was 9.1 years and the mean sleep duration was 6.6 h/day. Irregular sleep significantly increased the risk of all-cause mortality in all models compared with regular sleep (HR 1.30, 95% confidence interval; CI, 1.18-1.44), regardless of sleep duration. Multivariable analysis of the 6 groups by sleep pattern (sleep regularity and duration) showed irregular sleep and sleep durations of <6 h/day, 6 to <8 h/day, or ≥8 h/day were associated with a 1.2-1.5-fold increases in mortality, compared to regular sleep and sleep duration of 6 to <8 h/day.


      Our study shows an association between sleep irregularity and all-cause mortality in a large Japanese population. Our findings provide further confirmation of the need to consider not only sleep duration, but also the regularity aspect of sleep schedules.


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        • Buysse DJ.
        Sleep health: can we define it? Does it matter?.
        Sleep. 2014; 37: 9-17
        • Gallicchio L
        • Kalesan B.
        Sleep duration and mortality: a systematic review and meta-analysis.
        J Sleep Res. 2009; 18: 148-158
        • Kronholm E
        • Laatikainen T
        • Peltonen M
        • Sippola R
        • Partonen T.
        Self-reported sleep duration, all-cause mortality, cardiovascular mortality and morbidity in Finland.
        Sleep Med. 2011; 12: 215-221
        • Ikehara S
        • Iso H
        • Date C
        • et al.
        Association of sleep duration with mortality from cardiovascular disease and other causes for Japanese men and women: the JACC study.
        Sleep. 2009; 32: 295-301
        • Ma QQ
        • Yao Q
        • Lin L
        • Chen GC
        • Yu JB.
        Sleep duration and total cancer mortality: a meta-analysis of prospective studies.
        Sleep Med. 2016; 27-28: 39-44
        • Huang T
        • Redline S.
        Cross-sectional and prospective associations of actigraphy-assessed sleep regularity with metabolic abnormalities: the multi-ethnic study of atherosclerosis.
        Diabetes Care. 2019; 42: 1422-1429
        • Sohail S
        • Yu L
        • Bennett DA
        • Buchman AS
        • Lim AS.
        Irregular 24-hour activity rhythms and the metabolic syndrome in older adults.
        Chronobiol Int. 2015; 32: 802-813
        • Yin J
        • Jin X
        • Shan Z
        • et al.
        Relationship of sleep duration with all-cause mortality and cardiovascular events: a systematic review and dose-response meta-analysis of prospective cohort studies.
        J Am Heart Assoc. 2017; 6
        • Scheer FA
        • Michelson AD
        • Frelinger 3rd, AL
        • et al.
        The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors.
        PLoS One. 2011; 6: e24549
        • Wyatt JK
        • Ritz-De Cecco A
        • Czeisler CA
        • Dijk DJ.
        Circadian temperature and melatonin rhythms, sleep, and neurobehavioral function in humans living on a 20-h day.
        Am J Physiol. 1999; 277 (Pt 2): R1152-R1163
        • Erren TC
        • Lewis P.
        Hypothesis: ubiquitous circadian disruption can cause cancer.
        Eur J Epidemiol. 2019; 34: 1-4
        • Huang T
        • Mariani S
        • Redline S.
        Sleep irregularity and risk of cardiovascular events: the multi-ethnic study of atherosclerosis.
        J Am Coll Cardiol. 2020; 75: 991-999
        • Vyas MV
        • Garg AX
        • Iansavichus AV
        • et al.
        Shift work and vascular events: systematic review and meta-analysis.
        Bmj. 2012; 345: e4800
        • Wegrzyn LR
        • Tamimi RM
        • Rosner BA
        • et al.
        Rotating night-shift work and the risk of breast cancer in the Nurses' Health Studies.
        Am J Epidemiol. 2017; 186: 532-540
        • Gooley JJ.
        How much day-to-day variability in sleep timing is unhealthy?.
        Sleep. 2016; 39: 269-270
        • De Bacquer D
        • Van Risseghem M
        • Clays E
        • Kittel F
        • De Backer G
        • Braeckman L.
        Rotating shift work and the metabolic syndrome: a prospective study.
        Int J Epidemiol. 2009; 38: 848-854
        • Taylor BJ
        • Matthews KA
        • Hasler BP
        • et al.
        Bedtime variability and metabolic health in midlife women: the SWAN Sleep Study.
        Sleep. 2016; 39: 457-465
        • Parsons MJ
        • Moffitt TE
        • Gregory AM
        • et al.
        Social jetlag, obesity and metabolic disorder: investigation in a cohort study.
        Int J Obes (Lond). 2015; 39: 842-848
        • Ogura Y
        • Koyama T
        • Ozaki E
        • Omichi C
        • Uehara R.
        Subjective irregular sleep is associated with metabolic syndrome: a cross-sectional study.
        Prev Med Rep. 2022; 28101844
        • Takeuchi K
        • Naito M
        • Kawai S
        • et al.
        Study profile of the japan multi-institutional collaborative cohort (J-MICC) study.
        J Epidemiol. 2021; 31: 660-668
        • Wakai K
        • Hamajima N
        • Okada R
        • et al.
        Profile of participants and genotype distributions of 108 polymorphisms in a cross-sectional study of associations of genotypes with lifestyle and clinical factors: a project in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.
        J Epidemiol. 2011; 21: 223-235
        • Hara M
        • Higaki Y
        • Taguchi N
        • et al.
        Effect of the PPARG2 Pro12Ala polymorphism and clinical risk factors for diabetes mellitus on HbA1c in the Japanese general population.
        J Epidemiol. 2012; 22: 523-531
        • Hamajima N.
        The Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study) to detect gene-environment interactions for cancer.
        Asian Pac J Cancer Prev. 2007; 8: 317-323
        • Banks S
        • Dinges DF.
        Behavioral and physiological consequences of sleep restriction.
        J Clin Sleep Med. 2007; 3: 519-528
        • Knutson KL
        • Spiegel K
        • Penev P
        • Van Cauter E.
        The metabolic consequences of sleep deprivation.
        Sleep Med Rev. 2007; 11: 163-178
        • Cappuccio FP
        • Cooper D
        • D'Elia L
        • Strazzullo P
        • Miller MA
        Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies.
        Eur Heart J. 2011; 32: 1484-1492
        • Benca RM
        • Obermeyer WH
        • Thisted RA
        • Gillin JC.
        Sleep and psychiatric disorders. a meta-analysis.
        Arch Gen Psychiatry. 1992; 49 (discussion 669-670): 651-668
        • Tamakoshi A
        • Ohno Y.
        Self-reported sleep duration as a predictor of all-cause mortality: results from the JACC study, Japan.
        Sleep. 2004; 27: 51-54
        • Cappuccio FP
        • D'Elia L
        • Strazzullo P
        • Miller MA
        Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies.
        Sleep. 2010; 33: 585-592
        • Bertisch SM
        • Pollock BD
        • Mittleman MA
        • et al.
        Insomnia with objective short sleep duration and risk of incident cardiovascular disease and all-cause mortality: Sleep Heart Health Study.
        Sleep. 2018; 41
        • Vgontzas AN
        • Liao D
        • Pejovic S
        • et al.
        Insomnia with short sleep duration and mortality: the Penn State cohort.
        Sleep. 2010; 33: 1159-1164
        • Svensson T
        • Inoue M
        • Saito E
        • et al.
        The association between habitual sleep duration and mortality according to sex and age: the japan public health center-based prospective study.
        J Epidemiol. 2021; 31: 109-118
        • Dijk DJ
        • Czeisler CA.
        Contribution of the circadian pacemaker and the sleep homeostat to sleep propensity, sleep structure, electroencephalographic slow waves, and sleep spindle activity in humans.
        J Neurosci. 1995; 15 (Pt 1): 3526-3538
        • Phillips AJK
        • Clerx WM
        • O'Brien CS
        • et al.
        Irregular sleep/wake patterns are associated with poorer academic performance and delayed circadian and sleep/wake timing.
        Sci Rep. 2017; 7: 3216
        • Bei B
        • Wiley JF
        • Trinder J
        • Manber R.
        Beyond the mean: A systematic review on the correlates of daily intraindividual variability of sleep/wake patterns.
        Sleep Med Rev. 2016; 28: 108-124
        • Morris CJ
        • Purvis TE
        • Mistretta J
        • Hu K
        • Scheer F.
        Circadian misalignment increases C-reactive protein and blood pressure in chronic shift workers.
        J Biol Rhythms. 2017; 32: 154-164
        • Leproult R
        • Holmbäck U
        • Van Cauter E.
        Circadian misalignment augments markers of insulin resistance and inflammation, independently of sleep loss.
        Diabetes. 2014; 63: 1860-1869
        • McElroy H
        • O'Leary B
        • Adena M
        • Campbell R
        • Monfared AAT
        • Meier G
        Comparative efficacy of lemborexant and other insomnia treatments: a network meta-analysis.
        J Manag Care Spec Pharm. 2021; 27: 1296-1308
        • Nakayama-Ashida Y
        • Takegami M
        • Chin K
        • et al.
        Sleep-disordered breathing in the usual lifestyle setting as detected with home monitoring in a population of working men in Japan.
        Sleep. 2008; 31: 419-425
        • Omichi C
        • Kadotani H
        • Sumi Y
        • et al.
        Prolonged sleep latency and reduced REM latency are associated with depressive symptoms in a japanese working population.
        Int J Environ Res Public Health. 2022; 19