Experimental sleep restriction causes endothelial dysfunction in healthy humans

Andrew D Calvin, Naima Covassin, Walter K Kremers, Taro Adachi, Paula Macedo, Felipe N Albuquerque, Jan Bukartyk, Diane E Davison, James A Levine, Prachi Singh, Shihan Wang, Virend K Somers, Andrew D Calvin, Naima Covassin, Walter K Kremers, Taro Adachi, Paula Macedo, Felipe N Albuquerque, Jan Bukartyk, Diane E Davison, James A Levine, Prachi Singh, Shihan Wang, Virend K Somers

Abstract

Background: Epidemiologic evidence suggests a link between short sleep duration and cardiovascular risk, although the nature of any relationship and mechanisms remain unclear. Short sleep duration has also been linked to an increase in cardiovascular events. Endothelial dysfunction has itself been implicated as a mediator of heightened cardiovascular risk. We sought to determine the effect of 8 days/8 nights of partial sleep restriction on endothelial function in healthy humans.

Methods and results: Sixteen healthy volunteers underwent a randomized study of usual sleep versus sleep restriction of two-thirds normal sleep time for 8 days/8 nights in a hospital-based clinical research unit. The main outcome was endothelial function measured by flow-mediated brachial artery vasodilatation (FMD). Those randomized to sleep restriction slept 5.1 hours/night during the experimental period compared with 6.9 hours/night in the control group. Sleep restriction was associated with significant impairment in FMD (8.6±4.6% during the initial pre-randomization acclimation phase versus 5.2±3.4% during the randomized experimental phase, P=0.01) whereas no change was seen in the control group (5.0±3.0 during the acclimation phase versus 6.73±2.9% during the experimental phase, P=0.10) for a between-groups difference of -4.40% (95% CI -7.00 to -1.81%, P=0.003). No change was seen in non-flow mediated vasodilatation (NFMD) in either group.

Conclusion: In healthy individuals, moderate sleep restriction causes endothelial dysfunction.

Clinical trial registration url: ClinicalTrials.gov. Unique identifier: NCT01334788.

Keywords: cardiovascular risk; endothelial dysfunction; sleep deprivation.

© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1.
Figure 1.
Effect of sleep restriction on endothelial function—endothelial function, assessed by percentage change in flow‐mediated dilatation (FMD), was impaired by sleep restriction while non‐flow‐mediated vasodilatation (NFMD) was not. Those randomized to sleep restriction showed an impairment in FMD (8.6±4.6% during the acclimation phase vs 5.2±3.4% during the experimental phase, P=0.01) whereas no change was seen in the control group (5.0%±3.0 during the acclimation phase vs 6.73±2.9% during the experimental phase, P=0.10) for a between groups difference of −4.40% (95% CI −7.00 to −1.81%, P=0.003). In contrast, no change was seen in NFMD.

References

    1. Kojima M, Wakai K, Kawamura T, Tamakoshi A, Aoki R, Lin Y, Nakayama T, Horibe H, Aoki N, Ohno Y. Sleep patterns and total mortality: a 12‐year follow‐up study in Japan. J Epidemiol. 2000; 10:87-93.
    1. Kripke DF, Garfinkel L, Wingard DL, Klauber MR, Marler MR. Mortality associated with sleep duration and insomnia. Arch Gen Psychiatry. 2002; 59:131-136.
    1. 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.
    1. Patel SR, Ayas NT, Malhotra MR, White DP, Schernhammer ES, Speizer FE, Stampfer MJ, Hu FB. A prospective study of sleep duration and mortality risk in women. Sleep. 2004; 27:440-444.
    1. Wingard DL, Barrett‐Connor EL, Scheidt‐Nave C, McPhillips JB. Prevalence of cardiovascular and renal complications in older adults with normal or impaired glucose tolerance or NIDDM. A population‐based study. Diabetes Care. 1993; 16:1022-1025.
    1. Chien KL, Chen PC, Hsu HC, Su TC, Sung FC, Chen MF, Lee YT. Habitual sleep duration and insomnia and the risk of cardiovascular events and all‐cause death: report from a community‐based cohort. Sleep. 2010; 33:177-184.
    1. Ferrie JE, Shipley MJ, Cappuccio FP, Brunner E, Miller MA, Kumari M, Marmot MG. A prospective study of change in sleep duration: associations with mortality in the Whitehall II cohort. Sleep. 2007; 30:1659-1666.
    1. Shankar A, Koh WP, Yuan JM, Lee HP, Yu MC. Sleep duration and coronary heart disease mortality among Chinese adults in Singapore: a population‐based cohort study. Am J Epidemiol. 2008; 168:1367-1373.
    1. Ikehara S, Iso H, Date C, Kikuchi S, Watanabe Y, Wada Y, Inaba Y, Tamakoshi A. 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.
    1. Ayas NT, White DP, Manson JE, Stampfer MJ, Speizer FE, Malhotra A, Hu FB. A prospective study of sleep duration and coronary heart disease in women. Arch Intern Med. 2003; 163:205-209.
    1. Krueger PM, Friedman EM. Sleep duration in the United States: a cross‐sectional population‐based study. Am J Epidemiol. 2009; 169:1052-1063.
    1. Ross R. Atherosclerosis–an inflammatory disease. N Engl J Med. 1999; 340:115-126.
    1. Kinlay S, Ganz P. Role of endothelial dysfunction in coronary artery disease and implications for therapy. Am J Cardiol. 1997; 80:11I-16I.
    1. Amir O, Alroy S, Schliamser JE, Asmir I, Shiran A, Flugelman MY, Halon DA, Lewis BS. Brachial artery endothelial function in residents and fellows working night shifts. Am J Cardiol. 2004; 93:947-949.
    1. 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; 27:223-227.
    1. Sauvet F, Leftheriotis G, Gomez‐Merino D, Langrume C, Drogou C, Van Beers P, Bourrilhon C, Florence G, Chennaoui M. Effect of acute sleep deprivation on vascular function in healthy subjects. J Appl Physiol. 2010; 108:68-75.
    1. Sekine T, Daimon M, Hasegawa R, Toyoda T, Kawata T, Funabashi N, Komuro I. The impact of sleep deprivation on the coronary circulation. Int J Cardiol. 2009; 144:266-267.
    1. Tasali E, Leproult R, Ehrmann DA, Van Cauter E. Slow‐wave sleep and the risk of type 2 diabetes in humans. Proc Natl Acad Sci USA. 2008; 105:1044-1049.
    1. Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999; 354:1435-1439.
    1. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jr, Jones DW, Materson BJ, Oparil S, Wright JT, Jr, Roccella EJ. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA. 2003; 289:2560-2571.
    1. Calvin AD, Carter RE, Adachi T, Macedo PG, Albuquerque FN, van der Walt C, Bukartyk J, Davison DE, Levine JA, Somers VK. Effects of experimental sleep restriction on caloric intake and activity energy expenditure. Chest. 2013; 144:79-86.
    1. Caples SM, Rosen CL, Shen WK, Gami AS, Cotts W, Adams M, Dorostkar P, Shivkumar K, Somers VK, Morgenthaler TI, Stepanski EJ, Iber C. The scoring of cardiac events during sleep. J Clin Sleep Med. 2007; 3:147-154.
    1. Otto ME, Svatikova A, Barretto RB, Santos S, Hoffmann M, Khandheria B, Somers V. Early morning attenuation of endothelial function in healthy humans. Circulation. 2004; 109:2507-2510.
    1. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non‐invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992; 340:1111-1115.
    1. Corretti MC, Plotnick GD, Vogel RA. Technical aspects of evaluating brachial artery vasodilatation using high‐frequency ultrasound. Am J Physiol. 1995; 268:H1397-H1404.
    1. Kato M, Roberts‐Thomson P, Phillips BG, Haynes WG, Winnicki M, Accurso V, Somers VK. Impairment of endothelium‐dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation. 2000; 102:2607-2610.
    1. Anderson TJ. Assessment and treatment of endothelial dysfunction in humans. J Am Coll Cardiol. 1999; 34:631-638.
    1. Motoyama T, Kawano H, Kugiyama K, Hirashima O, Ohgushi M, Yoshimura M, Ogawa H, Yasue H. Endothelium‐dependent vasodilation in the brachial artery is impaired in smokers: effect of vitamin C. Am J Physiol. 1997; 273:H1644-H1650.
    1. Kawano H, Motoyama T, Hirashima O, Hirai N, Miyao Y, Sakamoto T, Kugiyama K, Ogawa H, Yasue H. Hyperglycemia rapidly suppresses flow‐mediated endothelium‐dependent vasodilation of brachial artery. J Am Coll Cardiol. 1999; 34:146-154.
    1. Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol. 2003; 23:168-175.
    1. Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, Ganz P, Hamburg NM, Luscher TF, Shechter M, Taddei S, Vita JA, Lerman A. The assessment of endothelial function: from research into clinical practice. Circulation. 2012; 126:753-767.
    1. Halcox JP, Donald AE, Ellins E, Witte DR, Shipley MJ, Brunner EJ, Marmot MG, Deanfield JE. Endothelial function predicts progression of carotid intima‐media thickness. Circulation. 2009; 119:1005-1012.
    1. Rossi R, Nuzzo A, Olaru AI, Origliani G, Modena MG. Endothelial function affects early carotid atherosclerosis progression in hypertensive postmenopausal women. J Hypertens. 2011; 29:1136-1144.
    1. Gokce N, Keaney JF, Jr, Hunter LM, Watkins MT, Nedeljkovic ZS, Menzoian JO, Vita JA. Predictive value of noninvasively determined endothelial dysfunction for long‐term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol. 2003; 41:1769-1775.
    1. Dettoni JL, Consolim‐Colombo FM, Drager LF, Rubira MC, Souza SB, Irigoyen MC, Mostarda C, Borile S, Krieger EM, Moreno H, Jr, Lorenzi‐Filho G. Cardiovascular effects of partial sleep deprivation in healthy volunteers. J Appl Physiol (1985). 2012; 113:232-236.
    1. Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C, Luscher TF. Nitric oxide is responsible for flow‐dependent dilatation of human peripheral conduit arteries in vivo. Circulation. 1995; 91:1314-1319.
    1. Drake CL, Roehrs T, Richardson G, Walsh JK, Roth T. Shift work sleep disorder: prevalence and consequences beyond that of symptomatic day workers. Sleep. 2004; 27:1453-1462.
    1. Meier‐Ewert HK, Ridker PM, Rifai N, Regan MM, Price NJ, Dinges DF, Mullington JM. Effect of sleep loss on C‐reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol. 2004; 43:678-683.
    1. Buxton OM, Cain SW, O'Connor SP, Porter JH, Duffy JF, Wang W, Czeisler CA, Shea SA. Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption. Sci Transl Med. 2012; 4:129ra143
    1. Unhealthy sleep‐related behaviors–12 states, 2009. MMWR Morb Mortal Wkly Rep. 2011; 60:233-238.
    1. National Sleep Foundation. 2011 Sleep in America poll: communications technology and sleep . Published March 7, 2011. Accessed March 1, 2013.

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