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Effects of sleep deprivation on endothelial function in adult humans: a systematic review


Sleep deprivation is highly prevalent and is associated with increased cardiovascular disease (CVD) morbidity and mortality. Age-related alterations in sleep and chronobiology may exaggerate CVD susceptibility in older individuals. The mechanisms responsible for the association between sleep deprivation and CVD are not fully understood, but endothelial dysfunction may play a central role. Our objective was to conduct a systematic literature review to evaluate the evidence on the effects of sleep deprivation on endothelial function (EF). This review adhered to the PRISMA guidelines and was pre-registered with PROSPERO (#CRD42020192485, 07/24/2020). We searched PubMed, Web of Science, Embase, and Cochrane Library for articles published through May 1, 2020. Eligibility criteria included publication in English and use of well-established EF methodologies in adult humans. Two investigators independently performed the literature search, study selection, data extraction, risk-of-bias assessment, and qualitative data synthesis. Out of 3571 articles identified, 24 articles were included in the systematic review. Main findings include the following: (1) shorter sleep duration is associated with lower macrovascular EF; (2) not sleeping 7–9 h/night is linked with impaired microvascular EF; (3) sleep restriction impairs micro- and macrovascular EF; (4) acute total sleep deprivation impairs micro- and macrovascular EF but data on macrovascular EF are less consistent; and (5) shift work impairs macrovascular EF. In conclusion, sleep deprivation impairs EF, which may explain the link between insufficient sleep and CVD. Future investigations should fully elucidate the underlying mechanisms and develop strategies to combat the adverse endothelial effects of sleep deprivation across the lifespan.

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  1. 1.

    Liu Y, Wheaton AG, Chapman DP, Cunningham TJ, Lu H, Croft JB. Prevalence of healthy sleep duration among adults--United States, 2014. MMWR Morb Mortal Wkly Rep. 2016;65(6):137–41.

  2. 2.

    St-Onge MP, Grandner MA, Brown D, Conroy MB, Jean-Louis G, Coons M, et al. Sleep duration and quality: impact on lifestyle behaviors and cardiometabolic health: a scientific statement from the American Heart Association. Circulation. 2016;134(18):e367–e86.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Hirshkowitz M, Whiton K, Albert SM, Alessi C, Bruni O, DonCarlos L, et al. National Sleep Foundation’s sleep time duration recommendations: methodology and results summary. Sleep Health. 2015;1(1):40–3.

    Article  PubMed  Google Scholar 

  4. 4.

    NSF. 2010 Bedroom Poll: Summary of Findings. 2012:1–79.

  5. 5.

    Foley DJ, Monjan AA, Brown SL, Simonsick EM, Wallace RB, Blazer DG. Sleep complaints among elderly persons: an epidemiologic study of three communities. Sleep. 1995;18(6):425–32.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Crowley K. Sleep and sleep disorders in older adults. Neuropsychol Rev. 2011;21(1):41–53.

    Article  PubMed  Google Scholar 

  7. 7.

    Duffy JF, Zitting KM, Chinoy ED. Aging and circadian rhythms. Sleep Med Clin. 2015;10(4):423–34.

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Harrington JJ, Lee-Chiong T Jr. Sleep and older patients. Clin Chest Med. 2007;28(4):673–84, v.

    Article  PubMed  Google Scholar 

  9. 9.

    Covassin N, Singh P. Sleep duration and cardiovascular disease risk: epidemiologic and experimental evidence. Sleep Med Clin. 2016;11(1):81–9.

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Song Q, Liu X, Wang X, Wu S. Age- and gender-specific associations between sleep duration and incident hypertension in a Chinese population: the Kailuan study. J Hum Hypertens. 2016;30(8):503–7.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Chandola T, Ferrie JE, Perski A, Akbaraly T, Marmot MG. The effect of short sleep duration on coronary heart disease risk is greatest among those with sleep disturbance: a prospective study from the Whitehall II cohort. Sleep. 2010;33(6):739–44.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Itani O, Jike M, Watanabe N, Kaneita Y. Short sleep duration and health outcomes: a systematic review, meta-analysis, and meta-regression. Sleep Med. 2017;32:246–56.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation. 2017;135(10):e146–603.

    Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Dhingra R, Vasan RS. Age as a risk factor. Med Clin North Am. 2012;96(1):87–91.

    Article  PubMed  Google Scholar 

  15. 15.

    deGoma EM, Knowles JW, Angeli F, Budoff MJ, Rader DJ. The evolution and refinement of traditional risk factors for cardiovascular disease. Cardiol Rev. 2012;20(3):118–29.

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Cirelli C, Tononi G. Is sleep essential? PLoS Biol. 2008;6(8):e216.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Rana S, Prabhu SD, Young ME. Chronobiological influence over cardiovascular function: the good, the bad, and the ugly. Circ Res. 2020;126(2):258–79.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Sato M, Matsuo T, Atmore H, Akashi M. Possible contribution of chronobiology to cardiovascular health. Front Physiol. 2013;4(409):409.

    Article  PubMed  Google Scholar 

  19. 19.

    Gupta NJ. Lifestyle and circadian health: where the challenges lie? Nutr Metab Insights. 2019;12:1178638819869024.

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Xie Y, Tang Q, Chen G, Xie M, Yu S, Zhao J, et al. New insights into the circadian rhythm and its related diseases. Front Physiol. 2019;10(682):682.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Ortman J, Velkoff V, Hogan H. An aging nation: the older population in the United States. US Census Bureau; 2014.

  22. 22.

    Miner B, Kryger MH. Sleep in the aging population. Sleep Med Clin. 2017;12(1):31–8.

    Article  PubMed  Google Scholar 

  23. 23.

    Wright KP Jr, Bogan RK, Wyatt JK. Shift work and the assessment and management of shift work disorder (SWD). Sleep Med Rev. 2013;17(1):41–54.

    Article  PubMed  Google Scholar 

  24. 24.

    Rajaratnam SM, Howard ME, Grunstein RR. Sleep loss and circadian disruption in shift work: health burden and management. Med J Aust. 2013;199(8):S11–5.

    Article  PubMed  Google Scholar 

  25. 25.

    Puttonen S, Harma M, Hublin C. Shift work and cardiovascular disease - pathways from circadian stress to morbidity. Scand J Work Environ Health. 2010;36(2):96–108.

    Article  PubMed  Google Scholar 

  26. 26.

    James SM, Honn KA, Gaddameedhi S, Van Dongen HPA. Shift work: disrupted circadian rhythms and sleep-implications for health and well-being. Curr Sleep Med Rep. 2017;3(2):104–12.

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004;109(23 Suppl 1):III27–32.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Ras RT, Streppel MT, Draijer R, Zock PL. Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta-analysis. Int J Cardiol. 2013;168(1):344–51.

    Article  PubMed  Google Scholar 

  29. 29.

    Inaba Y, Chen JA, Bergmann SR. Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis. Int J Cardiovasc Imaging. 2010;26(6):631–40.

    Article  PubMed  Google Scholar 

  30. 30.

    Matsuzawa Y, Kwon TG, Lennon RJ, Lerman LO, Lerman A. Prognostic value of flow-mediated vasodilation in brachial artery and fingertip artery for cardiovascular events: a systematic review and meta-analysis. J Am Heart Assoc. 2015;4(11).

  31. 31.

    Seals DR, Alexander LM. Vascular aging. J Appl Physiol (1985). 2018;125(6):1841–2.

  32. 32.

    Ghebre YT, Yakubov E, Wong WT, Krishnamurthy P, Sayed N, Sikora AG et al. Vascular aging: implications for cardiovascular disease and therapy. Transl Med (Sunnyvale). 2016;6(4).

  33. 33.

    Moher D, Liberati A, Tetzlaff J, Altman DG, Grp P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement (reprinted from Annals of Internal Medicine). Phys Ther. 2009;89(9):873–80.

    Article  PubMed  Google Scholar 

  34. 34.

    Bonsen T, Wijnstok NJ, Hoekstra T, Eringa EC, Serne EH, Smulders YM, et al. Sleep quality and duration are related to microvascular function: the Amsterdam Growth and Longitudinal Study. J Sleep Res. 2015;24(2):140–7.

    Article  PubMed  Google Scholar 

  35. 35.

    Bain AR, Weil BR, Diehl KJ, Greiner JJ, Stauffer BL, DeSouza CA. Insufficient sleep is associated with impaired nitric oxide-mediated endothelium-dependent vasodilation. Atherosclerosis. 2017;265:41–6.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Weil BR, Greiner JJ, Stauffer BL, Desouza CA. Self-reported habitual short sleep duration is associated with endothelial fibrinolytic dysfunction in men: a preliminary report. Sleep. 2013;36(2):183–8.

    Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Weil BR, Mestek ML, Westby CM, Van Guilder GP, Greiner JJ, Stauffer BL, et al. Short sleep duration is associated with enhanced endothelin-1 vasoconstrictor tone. Can J Physiol Pharmacol. 2010;88(8):777–81.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Hall MH, Mulukutla S, Kline CE, Samuelsson LB, Taylor BJ, Thayer JF et al. Objective sleep duration is prospectively associated with endothelial health. Sleep. 2017;40(1).

  39. 39.

    Aggarwal B, Makarem N, Shah R, Emin M, Wei Y, St-Onge MP et al. Effects of inadequate sleep on blood pressure and endothelial inflammation in women: findings from the American Heart Association Go Red for Women Strategically Focused Research Network. J Am Heart Assoc. 2018;7(12).

  40. 40.

    Behl M, Bliwise D, Veledar E, Cunningham L, Vazquez J, Brigham K, et al. Vascular endothelial function and self-reported sleep. Am J Med Sci. 2014;347(6):425–8.

    Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Grassi D, Socci V, Tempesta D, Ferri C, De Gennaro L, Desideri G, et al. Flavanol-rich chocolate acutely improves arterial function and working memory performance counteracting the effects of sleep deprivation in healthy individuals. J Hypertens. 2016;34(7):1298–308.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Wehrens SM, Hampton SM, Skene DJ. Heart rate variability and endothelial function after sleep deprivation and recovery sleep among male shift and non-shift workers. Scand J Work Environ Health. 2012;38(2):171–81.

    Article  PubMed  Google Scholar 

  43. 43.

    Sauvet F, Leftheriotis G, Gomez-Merino D, Langrume C, Drogou C, Van Beers P et al. Effect of acute sleep deprivation on vascular function in healthy subjects. J Appl Physiol (1985). 2010;108(1):68–75.

  44. 44.

    Sauvet F, Arnal PJ, Tardo-Dino PE, Drogou C, Van Beers P, Bougard C, et al. Protective effects of exercise training on endothelial dysfunction induced by total sleep deprivation in healthy subjects. Int J Cardiol. 2017;232:76–85.

    Article  PubMed  Google Scholar 

  45. 45.

    Sauvet F, Bourrilhon C, Besnard Y, Alonso A, Cottet-Emard JM, Savourey G, et al. Effects of 29-h total sleep deprivation on local cold tolerance in humans. Eur J Appl Physiol. 2012;112(9):3239–50.

    Article  PubMed  Google Scholar 

  46. 46.

    Yang H, Durocher JJ, Larson RA, Dellavalla JP, Carter JR. Total sleep deprivation alters cardiovascular reactivity to acute stressors in humans. J Appl Physiol (1985). 2012;113(6):903–8.

  47. 47.

    Sekine T, Daimon M, Hasegawa R, Toyoda T, Kawata T, Funabashi N, et al. The impact of sleep deprivation on the coronary circulation. Int J Cardiol. 2010;144(2):266–7.

    Article  PubMed  Google Scholar 

  48. 48.

    Calvin AD, Covassin N, Kremers WK, Adachi T, Macedo P, Albuquerque FN, et al. Experimental sleep restriction causes endothelial dysfunction in healthy humans. J Am Heart Assoc. 2014;3(6):e001143.

    Article  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Takase B, Akima T, Uehata A, Ohsuzu F, Kurita A. Effect of chronic stress and sleep deprivation on both flow-mediated dilation in the brachial artery and the intracellular magnesium level in humans. Clin Cardiol. 2004;27(4):223–7.

    Article  PubMed  Google Scholar 

  50. 50.

    Dettoni JL, Consolim-Colombo FM, Drager LF, Rubira MC, Souza SB, Irigoyen MC et al. Cardiovascular effects of partial sleep deprivation in healthy volunteers. J Appl Physiol (1985). 2012;113(2):232–6.

  51. 51.

    Sauvet F, Drogou C, Bougard C, Arnal PJ, Dispersyn G, Bourrilhon C, et al. Vascular response to 1 week of sleep restriction in healthy subjects. A metabolic response? Int J Cardiol. 2015;190:246–55.

    Article  PubMed  Google Scholar 

  52. 52.

    Garcia-Fernandez R, Garcia Perez-Velasco J, Milian AC, Peix Gonzalez A, Garcia-Barreto D. Endothelial dysfunction in cardiologists after 24 hours on call. Rev Esp Cardiol. 2002;55(11):1202–4.

    Article  PubMed  Google Scholar 

  53. 53.

    Zheng H, Patel M, Hryniewicz K, Katz SD. Association of extended work shifts, vascular function, and inflammatory markers in internal medicine residents: a randomized crossover trial. JAMA. 2006;296(9):1049–50.

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Tarzia P, Milo M, Di Franco A, Di Monaco A, Cosenza A, Laurito M, et al. Effect of shift work on endothelial function in young cardiology trainees. Eur J Prev Cardiol. 2012;19(5):908–13.

    Article  PubMed  Google Scholar 

  55. 55.

    Shimada K, Fukuda S, Maeda K, Kawasaki T, Kono Y, Jissho S, et al. Aromatherapy alleviates endothelial dysfunction of medical staff after night-shift work: preliminary observations. Hypertens Res. 2011;34(2):264–7.

    Article  PubMed  Google Scholar 

  56. 56.

    Kim W, Park HH, Park CS, Cho EK, Kang WY, Lee ES, et al. Impaired endothelial function in medical personnel working sequential night shifts. Int J Cardiol. 2011;151(3):377–8.

    Article  PubMed  Google Scholar 

  57. 57.

    Amir O, Alroy S, Schliamser JE, Asmir I, Shiran A, Flugelman MY, et al. Brachial artery endothelial function in residents and fellows working night shifts. Am J Cardiol. 2004;93(7):947–9.

    Article  PubMed  Google Scholar 

  58. 58.

    Sterne JA, Hernan MA, Reeves BC, Savovic J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919.

    Article  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.

    Article  PubMed  Google Scholar 

  60. 60.

    McGuinness LA, Higgins JPT. Risk-of-bias VISualization (robvis): an R package and shiny web app for visualizing risk-of-bias assessments. Res Synth Methods. 2020.

  61. 61.

    Slomko J, Zawadka-Kunikowska M, Kozakiewicz M, Klawe JJ, Tafil-Klawe M, Newton JL, et al. Hemodynamic, autonomic, and vascular function changes after sleep deprivation for 24, 28, and 32 hours in healthy men. Yonsei Med J. 2018;59(9):1138–42.

    Article  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Akdemir I, Altunbas G, Ercan S, Arslan S, Davutoglu V. Impact of acute sleep deprivation on aortic elastic properties in healthy workers. Turk J Med Sci. 2013;43:279–82.

    Article  Google Scholar 

  63. 63.

    Anujuo K, Stronks K, Snijder MB, Jean-Louis G, Rutters F, van den Born BJ, et al. Relationship between short sleep duration and cardiovascular risk factors in a multi-ethnic cohort - the helius study. Sleep Med. 2015;16(12):1482–8.

    Article  PubMed  Google Scholar 

  64. 64.

    Anujuo K, Stronks K, Snijder MB, Jean-Louis G, van den Born BJ, Peters RJ, et al. Relationship between sleep duration and arterial stiffness in a multi-ethnic population: the HELIUS study. Chronobiol Int. 2016;33(5):543–52.

    Article  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Cao X, Zhou J, Yuan H, Chen Z. Association between sleep condition and arterial stiffness in Chinese adult with nonalcoholic fatty liver disease. J Thromb Thrombolysis. 2016;42(1):127–34.

    Article  PubMed  Google Scholar 

  66. 66.

    Chen S, Yang Y, Cheng GL, Jia J, Fan FF, Li JP, et al. Association between short sleep duration and carotid atherosclerosis modified by age in a Chinese community population. J Epidemiol Community Health. 2018;72(6):539–44.

    Article  PubMed  Google Scholar 

  67. 67.

    Cooper DC, Ziegler MG, Milic MS, Ancoli-Israel S, Mills PJ, Loredo JS, et al. Endothelial function and sleep: associations of flow-mediated dilation with perceived sleep quality and rapid eye movement (REM) sleep. J Sleep Res. 2014;23(1):84–93.

    Article  PubMed  Google Scholar 

  68. 68.

    Culver MN, Langan SP, Carreker J, Flatt AA, Ratchford SM, Grosicki GJ. Self-reported sleep quality is associated with central hemodynamics in healthy individuals. Sleep Breath. 2020;24(3):1083–8.

    Article  PubMed  Google Scholar 

  69. 69.

    Dominguez F, Fuster V, Fernandez-Alvira JM, Fernandez-Friera L, Lopez-Melgar B, Blanco-Rojo R, et al. Association of sleep duration and quality with subclinical atherosclerosis. J Am Coll Cardiol. 2019;73(2):134–44.

    Article  PubMed  Google Scholar 

  70. 70.

    Hijmans JG, Levy M, Garcia V, Lincenberg GM, Diehl KJ, Greiner JJ, et al. Insufficient sleep is associated with a pro-atherogenic circulating microRNA signature. Exp Physiol. 2019;104(6):975–82.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Kim CW, Chang Y, Zhao D, Cainzos-Achirica M, Ryu S, Jung HS, et al. Sleep duration, sleep quality, and markers of subclinical arterial disease in healthy men and women. Arterioscler Thromb Vasc Biol. 2015;35(10):2238–45.

    CAS  Article  PubMed  Google Scholar 

  72. 72.

    Logan JG, Kang H, Lobo JM, Sohn MW, Lin GM, Lima JAC, et al. Actigraphy-based sleep characteristics and aortic stiffness: the multi-ethnic study of atherosclerosis. J Am Soc Hypertens. 2018;12(12):841–9.

    Article  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Martinez-Gomez D, Eisenmann JC, Gomez-Martinez S, Hill EE, Zapatera B, Veiga OL, et al. Sleep duration and emerging cardiometabolic risk markers in adolescents. The AFINOS study Sleep Med. 2011;12(10):997–1002.

    Article  PubMed  Google Scholar 

  74. 74.

    Morita N, Kambayashi I, Okuda T, Oda S, Takada S, Nakajima T, et al. Inverse relationship between sleep duration and cardio-ankle vascular index in children. J Atheroscler Thromb. 2017;24(8):819–26.

    Article  PubMed  PubMed Central  Google Scholar 

  75. 75.

    Nagai M, Hoshide S, Nishikawa M, Shimada K, Kario K. Sleep duration and insomnia in the elderly: associations with blood pressure variability and carotid artery remodeling. Am J Hypertens. 2013;26(8):981–9.

    Article  PubMed  Google Scholar 

  76. 76.

    Sands MR, Lauderdale DS, Liu K, Knutson KL, Matthews KA, Eaton CB, et al. Short sleep duration is associated with carotid intima-media thickness among men in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Stroke. 2012;43(11):2858–64.

    Article  PubMed  PubMed Central  Google Scholar 

  77. 77.

    Tsai TC, Wu JS, Yang YC, Huang YH, Lu FH, Chang CJ. Long sleep duration associated with a higher risk of increased arterial stiffness in males. Sleep. 2014;37(8):1315–20.

    Article  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Weil BR, Maceneaney OJ, Stauffer BL, Desouza CA. Habitual short sleep duration and circulating endothelial progenitor cells. J Cardiovasc Dis Res. 2011;2(2):110–4.

    Article  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Yoshioka E, Saijo Y, Kita T, Okada E, Satoh H, Kawaharada M, et al. Relation between self-reported sleep duration and arterial stiffness: a cross-sectional study of middle-aged Japanese civil servants. Sleep. 2011;34(12):1681–6.

    Article  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Zonoozi S, Ramsay SE, Papacosta O, Lennon L, Ellins EA, Halcox JPJ, et al. Self-reported sleep duration and napping, cardiac risk factors and markers of subclinical vascular disease: cross-sectional study in older men. BMJ Open. 2017;7(6):e016396.

    Article  PubMed  PubMed Central  Google Scholar 

  81. 81.

    Aggarwal S, Loomba RS, Arora RR, Molnar J. Associations between sleep duration and prevalence of cardiovascular events. Clin Cardiol. 2013;36(11):671–6.

    Article  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Hirshkowitz M, Whiton K, Albert SM, Alessi C, Bruni O, DonCarlos L, et al. National Sleep Foundation’s updated sleep duration recommendations: final report. Sleep Health. 2015;1(4):233–43.

    Article  PubMed  PubMed Central  Google Scholar 

  83. 83.

    Toda N. Age-related changes in endothelial function and blood flow regulation. Pharmacol Ther. 2012;133(2):159–76.

    CAS  Article  PubMed  Google Scholar 

  84. 84.

    Anderson TJ, Charbonneau F, Title LM, Buithieu J, Rose MS, Conradson H, et al. Microvascular function predicts cardiovascular events in primary prevention: long-term results from the Firefighters and Their Endothelium (FATE) study. Circulation. 2011;123(2):163–9.

    Article  PubMed  Google Scholar 

  85. 85.

    Limberg JK, Casey DP, Trinity JD, Nicholson WT, Wray DW, Tschakovsky ME, et al. Assessment of resistance vessel function in human skeletal muscle: guidelines for experimental design, Doppler ultrasound, and pharmacology. Am J Physiol Heart Circ Physiol. 2020;318(2):H301–H25.

    CAS  Article  PubMed  Google Scholar 

  86. 86.

    Thijssen DHJ, Bruno RM, van Mil A, Holder SM, Faita F, Greyling A, et al. Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans. Eur Heart J. 2019;40(30):2534–47.

    Article  PubMed  Google Scholar 

  87. 87.

    Huang AL, Silver AE, Shvenke E, Schopfer DW, Jahangir E, Titas MA, et al. Predictive value of reactive hyperemia for cardiovascular events in patients with peripheral arterial disease undergoing vascular surgery. Arterioscler Thromb Vasc Biol. 2007;27(10):2113–9.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  88. 88.

    Thosar SS, Butler MP, Shea SA. Role of the circadian system in cardiovascular disease. J Clin Invest. 2018;128(6):2157–67.

    Article  PubMed  PubMed Central  Google Scholar 

  89. 89.

    Charles LE, Zhao S, Fekedulegn D, Violanti JM, Andrew ME, Burchfiel CM. Shiftwork and decline in endothelial function among police officers. Am J Ind Med. 2016;59(11):1001–8.

    Article  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Folkard S. Do permanent night workers show circadian adjustment? A review based on the endogenous melatonin rhythm. Chronobiol Int. 2008;25(2):215–24.

    Article  PubMed  Google Scholar 

  91. 91.

    Tahara Y, Shibata S. Entrainment of the mouse circadian clock: effects of stress, exercise, and nutrition. Free Radic Biol Med. 2018;119:129–38.

    CAS  Article  PubMed  Google Scholar 

  92. 92.

    Mullington JM, Haack M, Toth M, Serrador JM, Meier-Ewert HK. Cardiovascular, inflammatory, and metabolic consequences of sleep deprivation. Prog Cardiovasc Dis. 2009;51(4):294–302.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  93. 93.

    Mullington JM, Simpson NS, Meier-Ewert HK, Haack M. Sleep loss and inflammation. Best Pract Res Clin Endocrinol Metab. 2010;24(5):775–84.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  94. 94.

    Solarz DE, Mullington JM, Meier-Ewert HK. Sleep, inflammation and cardiovascular disease. Front Biosci (Elite Ed). 2012;4:2490–501.

  95. 95.

    Meier-Ewert HK, Ridker PM, Rifai N, Regan MM, Price NJ, Dinges DF, et al. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol. 2004;43(4):678–83.

    CAS  Article  PubMed  Google Scholar 

  96. 96.

    Irwin MR, Wang M, Campomayor CO, Collado-Hidalgo A, Cole S. Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch Intern Med. 2006;166(16):1756–62.

    CAS  Article  PubMed  Google Scholar 

  97. 97.

    Irwin MR, Carrillo C, Olmstead R. Sleep loss activates cellular markers of inflammation: sex differences. Brain Behav Immun. 2010;24(1):54–7.

    CAS  Article  PubMed  Google Scholar 

  98. 98.

    Clapp BR, Hingorani AD, Kharbanda RK, Mohamed-Ali V, Stephens JW, Vallance P, et al. Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress. Cardiovasc Res. 2004;64(1):172–8.

    CAS  Article  PubMed  Google Scholar 

  99. 99.

    Schulz E, Gori T, Munzel T. Oxidative stress and endothelial dysfunction in hypertension. Hypertens Res. 2011;34(6):665–73.

    CAS  Article  PubMed  Google Scholar 

  100. 100.

    Bohm F, Pernow J. The importance of endothelin-1 for vascular dysfunction in cardiovascular disease. Cardiovasc Res. 2007;76(1):8–18.

    CAS  Article  PubMed  Google Scholar 

  101. 101.

    Dai DZ, Dai Y. Role of endothelin receptor A and NADPH oxidase in vascular abnormalities. Vasc Health Risk Manag. 2010;6:787–94.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  102. 102.

    Tobaldini E, Costantino G, Solbiati M, Cogliati C, Kara T, Nobili L et al. Sleep, sleep deprivation, autonomic nervous system and cardiovascular diseases. Neurosci Biobehav Rev. 2017;74(Pt B):321–9.

  103. 103.

    Bruno RM, Ghiadoni L, Seravalle G, Dell’oro R, Taddei S, Grassi G. Sympathetic regulation of vascular function in health and disease. Front Physiol. 2012;3:284.

    Article  PubMed  PubMed Central  Google Scholar 

  104. 104.

    Glos M, Fietze I, Blau A, Baumann G, Penzel T. Cardiac autonomic modulation and sleepiness: physiological consequences of sleep deprivation due to 40 h of prolonged wakefulness. Physiol Behav. 2014;125:45–53.

    CAS  Article  PubMed  Google Scholar 

  105. 105.

    Cedernaes J, Osler ME, Voisin S, Broman JE, Vogel H, Dickson SL, et al. Acute sleep loss induces tissue-specific epigenetic and transcriptional alterations to circadian clock genes in men. J Clin Endocrinol Metab. 2015;100(9):E1255–61.

    Article  PubMed  Google Scholar 

  106. 106.

    Paschos GK, FitzGerald GA. Circadian clocks and vascular function. Circ Res. 2010;106(5):833–41.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  107. 107.

    Thosar SS, Berman AM, Herzig MX, McHill AW, Bowles NP, Swanson CM, et al. Circadian rhythm of vascular function in midlife adults. Arterioscler Thromb Vasc Biol. 2019;39(6):1203–11.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  108. 108.

    Thosar SS, Berman AM, Herzig MX, Roberts SA, Lasarev MR, Shea SA. Morning impairment in vascular function is unrelated to overnight sleep or the inactivity that accompanies sleep. Am J Physiol Regul Integr Comp Physiol. 2018;315(5):R986–R93.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  109. 109.

    Elherik K, Khan F, McLaren M, Kennedy G, Belch JJ. Circadian variation in vascular tone and endothelial cell function in normal males. Clin Sci (Lond). 2002;102(5):547–52.

    CAS  Article  Google Scholar 

  110. 110.

    Shang X, Pati P, Anea CB, Fulton DJ, Rudic RD. Differential regulation of BMAL1, CLOCK, and endothelial signaling in the aortic arch and ligated common carotid artery. J Vasc Res. 2016;53(5–6):269–78.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  111. 111.

    Ungvari Z, Tarantini S, Sorond F, Merkely B, Csiszar A. Mechanisms of vascular aging, a Geroscience perspective: JACC focus seminar. J Am Coll Cardiol. 2020;75(8):931–41.

    CAS  Article  PubMed  Google Scholar 

  112. 112.

    Wehrens SMT, Christou S, Isherwood C, Middleton B, Gibbs MA, Archer SN, et al. Meal timing regulates the human circadian system. Curr Biol. 2017;27(12):1768–75 e3.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  113. 113.

    Fonken LK, Aubrecht TG, Melendez-Fernandez OH, Weil ZM, Nelson RJ. Dim light at night disrupts molecular circadian rhythms and increases body weight. J Biol Rhythm. 2013;28(4):262–71.

    Article  Google Scholar 

  114. 114.

    Wolff CA, Esser KA. Exercise timing and circadian rhythms. Curr Opin Physiol. 2019;10:64–9.

    Article  PubMed  PubMed Central  Google Scholar 

  115. 115.

    Boivin DB, Tremblay GM, James FO. Working on atypical schedules. Sleep Med. 2007;8(6):578–89.

    Article  PubMed  Google Scholar 

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DDC was supported by the National Institute on Aging of the National Institutes of Health [grant AG063143].

Author information




BJH and DDC conceived and designed the systematic review. BJH and SSL performed the literature search and screening, data extraction and synthesis, and risk-of-bias assessment. BJH wrote the initial draft of the manuscript. DDC, SSL, and DEJS critically revised the manuscript for intellectual content. All authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Demetra D. Christou.

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This systematic review was based on data acquired through previously published articles.

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Holmer, B.J., Lapierre, S.S., Jake-Schoffman, D.E. et al. Effects of sleep deprivation on endothelial function in adult humans: a systematic review. GeroScience 43, 137–158 (2021).

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  • Sleep deprivation
  • Endothelial function
  • Cardiovascular aging
  • Chronobiology