Experimental sleep restriction causes endothelial dysfunction in healthy humans

Calvin AD, Covassin N, Kremers WK et al.
J Am Heart Assoc. 2014 Nov 25;3(6). pii: e001143. doi: 10.1161/JAHA.114.001143

Background

Several lines of evidence suggest a link between short sleep duration (<7 hours) and mortality [1-3], and higher frequency of cardiovascular events [4]. Also in people who voluntarily restrict the amount of sleep to 6 or fewer hours per night, have been found to be 24% more likely to have CV disease [5]. Sleep deprivation may thus be a common and preventable CV risk factor.
Vascular dysfunction may form a link between sleep deprivation and CV disease, as reduced flow-mediated dilation (FMD) has been observed after a single 24-hour work shift [6] or chronic stress with sleep restriction [7]. Also, a single night of <4 hours of sleep compared to >7 hours was associated with lower coronary flow reserve [8].
Because sleep restriction is largely voluntary and potentially correctable, this study aimed to better understand the mechanisms by which insufficient sleep promotes the development of CV disease. The hypothesis was tested that chronic partial sleep deprivation is associated with impaired endothelial function. To this extent, 17 healthy volunteers carried a digital actigraph with them during their usual activities for at least one week. Later, they participated in a 15-day and 14-night inpatient phase in which they consistently had to wake up at 6.00h. During the 8-day experimental phase, 8 participants were randomised to a bedtime and asked to stay awake between 06.00 and their bedtime.

Main results

• Total sleep time was an average of 6.5+1.1 hours/night during acclimation in the sleep-deprived group to 5.1+0.37 hours/night during restriction, while 7.4+1.2 hours/night and 6.9+0.8 hours/night respectively were seen in the control group.
• Sleep restriction was associated with increased caloric intake (sleep restriction: additional 542 kcal/day in the experimental phase (P=0.008), vs. a non-significant change of -118 kcal/day (P=0.52) in the control group).
  No change in activity-related energy expenditure or change in body weight was seen between the two groups.
• Significant impairment in FMD was seen in the sleep restricted group (5.2+3.4% in the experimental phase vs. 8.6+4.6% in the acclimation phase, P=0.01), while the control group showed no change (experimental: 6.73+2.9% vs. acclimation: 5.0+3.0%, P=0.10). A between-groups difference of -4.40% (95%CI: -7.00 to – 1.81%, P=0.003) was seen.
• Non-flow mediated (endothelium-independent) vasodilation (NFMD) did not change after sleep restriction, nor in the control group, and no between-groups difference was seen.
• Blood pressure increased somewhat after sleep restriction, while the control group showed a slight decrease, yielding a group BP difference of 3.08 (95%CI: -6.49 to 12.66, P=0.49)/-0.46 (95%CI: -7.19 to 6.27, P=0.88).
• Heart rate did not significantly change between the acclimation and experimental phase in either group, and no between-group difference was seen.

Conclusion

Moderate sleep restriction during 8 days was associated with a significant impairment in flow-mediated vasodilation, of a magnitude similar to that seen in people who smoke, have diabetes or who have coronary artery disease. This is important considering the high prevalence of voluntary sleep restriction. These findings may indicate that sleep deprivation selectively affects nitric oxide production, but does not attenuate the response of smooth muscle to it.

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