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Can an improvement in sleep positively impact on health?
Sleep Medicine Reviews 14 (2010) 405e410
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Sleep Medicine Reviews journal homepage: www.elsevier.com/locate/smrv
COMMENTARY
Can an improvement in sleep positively impact on health? Daniel J. Buysse a, e, Ron Grunstein b, f, Jim Horne c, *, Peretz Lavie d, g a
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Sleep and Circadian Group Woolcock Institute of Medical Research, University of Sydney, Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia c Sleep Research Centre, Loughborough University, Leicestershire LE11 3TU, United Kingdom d Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel b
a r t i c l e i n f o
s u m m a r y
Article history: Received 2 October 2009 Received in revised form 28 January 2010 Accepted 2 February 2010 Available online 28 April 2010
Reports from a large number of studies document significant associations between sleep duration and various health problems such as cardiovascular events, risk of stroke, incident artery calcification, changes in inflammatory markers and many more. Furthermore, some sleep duration studies have shown that shorter sleep precedes some adverse health outcomes, although a causal relationship has yet to be demonstrated. Whilst clinical studies have shown that de-fragmenting (reducing awakenings and improving sleep continuity) sleep can reverse the harmful consequences of sleep apnea, and other studies have demonstrated that adjunctive treatment of insomnia improves depression, evidence that treatment of insomnia results in health benefit is more controversial. This article documents the debate session from the 6th International Sleep Disorders Forum e The Art of Good Sleep, held in Toronto, Canada in September 2008; the topic of which was “Does an improvement in sleep positively impact on health?” Ó 2010 Elsevier Ltd. All rights reserved.
Keywords: Daytime sleepiness Sleep deficit Sleep need Health Sleeping time Performance
Introduction
Statements PRO
The 6th International Sleep Disorders Forum e The Art of Good Sleep was held in Toronto, Canada in September 2008 and was attended by an international mix of sleep specialists. The meeting was held under the theme of Sleep & Society and focused on increasing the awareness of sleep disorders as an important health issue for society, and the relationship between sleep disorders and other common comorbid conditions. As part of the program a debate session was conducted on the topic “Does an improvement in sleep positively impact on health?”: the PRO argument was provided by Drs Ron Grunstein and Peretz Lavie, and the CON argument was presented by Drs Jim Horne and Daniel Buysse. Each author presented their arguments in the sequence PRO, CON, PRO, CON, followed by rebuttals, and the session was concluded with a general audience discussion. The following article summarizes the discussions that took place.
Ron Grunstein
* Corresponding author. Tel.: þ44 (0)1509 223004; fax: þ44 (0)15 0922 8480. E-mail addresses: [email protected] (D.J. Buysse), [email protected] (R. Grunstein), [email protected] (J. Horne), [email protected] (P. Lavie). e Tel.: þ1 412 246 6413; fax: þ1 412 246 5300. f Tel.: þ61 2 9515 8630; fax: þ61 2 9515 7070. g Tel.: þ972 4 8295234; fax: þ972 4 8343934. 1087-0792/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.smrv.2010.02.001
The specifics of the debate topic were clarified from the perspective of the ‘PRO’ argument: an “improvement in sleep” was defined as increasing sleep length (for instance by decreasing sleep latency), reducing arousals and sleep fragmentation, and improved perception of sleep quality; “positively impacts on health” was defined as an improvement of markers or endpoints of good health, a decrease in markers or endpoints of ill health, and better qualityof-life (QOL) or work productivity. Laboratory studies have shown increasingly poor performance with a decrease in sleep duration1,2 and a correlation has been established between workplace accidents caused by people falling asleep while at work and short sleep duration.3,4 Whilst it is unknown whether improved sleep would have helped to prevent the accidents from occurring, the value of recovery sleep has been demonstrated in a randomized study investigating the effect of restricted nocturnal sleep schedules with and without diurnal naps on psychomotor vigilance test performance.5 The study showed that the total daily sleep duration, whether consolidated or split, is the primary determinant of neurobehavioural function (psychomotor performance including alertness, vigilance, etc) over days.
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Clinical studies have shown that restricted sleep is a risk factor for certain comorbidities, whilst recovery sleep improves health.6e8 Outside clinical studies, the best way to measure whether restricted sleep has a negative impact on health would be to randomize people to short sleep versus longer sleep and measure accidents or medical errors by health professionals, but this is not ethically possible. The Harvard Work Hours Study,9,10 which randomized hospital interns to longer versus shorter work hours, showed that the longer a person works, the less sleep they get and the more errors they make. Interns made 36% more serious medical errors during a traditional work schedule than during an intervention schedule that eliminated extended work shifts.9,10 Furthermore, short-term experimental studies of short versus longer sleep have shown that short sleep is associated with impaired appetite control and glucose regulation,11 which has stimulated much investigation. However, an association between short sleep duration and health risk is not as clear because, despite some quite strong paediatric data, most of the evidence available to date is based on cross-sectional rather than longitudinal data.12e14 Clinical studies have also demonstrated that fragmented sleep worsens health,15 whilst de-fragmenting sleep (reducing awakenings and improving sleep continuity) improves health.16 Data on sleep apnoea are clear: positive airway pressure (PAP) is effective in reducing sleepiness, increasing QOL and improving sleep quality in moderate to severe OSA (but is not proven in mild OSA and in patients with certain comorbidities).17e27 Additionally, randomized, controlled trial data show that PAP increases growth hormone and results in better simulated driving,15,28 and strong observational data exist showing an association between restless legs syndrome/periodic limb movements in sleep and car crashes29 or cardiovascular endpoints.30 However, evidence that treatment of insomnia results in health benefit is more controversial31: there are no well-designed, longterm, randomized, controlled trials to clearly answer this. A randomized long-term study in patients with chronic primary insomnia showed that 6 months of zolpidem improved next-day concentration and morning sleepiness compared with placebo,32 and adjunctive treatment of insomnia has been shown to have positive effects on health in patients with depression.33e35 Improvement in health following sleep de-fragmenting may be modulated by genotype, phenotype and environmental factors, but this does not counter the general positive effect. It is also important to note the dangers of generalization: whilst approximately 7 h sleep is average in adults, inter-individual variations in sleep need exist outside this average.36 Peretz Lavie The debate topic can be answered with an unequivocal yes with respect to obstructive sleep apnea, so focus will be given to sleep quality and insomnia. Although insomnia is associated with reduced QOL and may predict depression, subjective complaint of insomnia has not been shown to be causally associated with adverse outcomes.37 In contrast with studies relying on subjective reports on insomnia that failed to show association with adverse outcomes, two studies reported that polysomnographic sleep quality variables predict mortality.38,39 In both studies, sleep latency was an independent predictor of all-cause mortality. Although two studies have shown that treating insomnia improves depression,33,34 it is not yet known whether treating insomnia or altering sleep duration will improve longevity. Future studies should elaborate the underlying relationship between sleep duration and mortality and whether modifying sleep duration can modify mortality risks.
A literature search revealed that there has been a recent dramatic increase in the number of papers that examined the relationship between sleep duration and health-related effects and with mortality. Notably, very few have been written by sleep researchers (mostly written by epidemiologists, diabetes researchers, and others in the public health domain). Whilst there are documented health effects associated with sleep duration, it is not yet known why the number of sleep hours correlates with bad health later in life. A total of 26 studies investigated the association between sleep duration and mortality (all-cause and causespecific), all of which examined sleep duration by participant self-report. Thirteen studies estimated the risk of short sleep after adjustment for comorbidities and 10 of these studies showed an increase in mortality related to short sleep.40e52 Also, 14 studies estimated the risk of long sleep after adjustment for comorbidities, of which 11 showed an increase in mortality related to long sleep.40e53 Many of the above studies reported that both short sleep and long sleep were associated with mortality. In most cases the nadir mortality was reported for people sleeping 7e8 h. A large number of studies documented significant associations between sleep duration and numerous health problems such as cardiovascular events, risk of stroke, incident artery calcification, changes in inflammatory markers, and many more. Statements CON Jim Horne If poor sleep is defined in terms of excessive daytime sleepiness (EDS), then an improvement in sleep will certainly impact on health as, for example, the greatest danger with EDS is probably falling asleep while driving. However, if a person complains about poor sleep without EDS, is this sleep really poor? While fragmented sleep is unhealthy, the argument should concentrate on whether shorter or longer sleep length is unhealthy. Approximately 7 h of sleep appears to be enough for most adults (around 10 h for children). This has remained unchanged historically,54 despite claims to the contrary; however, newer evidence challenging this can be misleading, especially as sleep debt surveys are often confounded by leading questions.55 It is not enough to ask a person if they want more sleep, but they should also be asked about what waking activities they would be prepared to give up in order to sleep more. Tiredness or fatigue are not the same as sleepiness 56 and are not always overcome with more sleep. Super-sensitive laboratory tests, may not be so relevant to the everyday issues of how much sleep a person needs because they are too sensitive. Studies in people with poor sleep without EDS have shown that more sleep may not make them more alert and happier, and executive functions are not usually improved.54 However, a study by Totterdell and colleagues57 demonstrated that mood may be improved by an earlier bed-time e without extending sleep. Also, in people with poor sleep without EDS, short/inadequate sleep is unlikely to cause obesity or metabolic syndrome58 [see for critical review]: obesity risk only becomes more apparent when sleep is atypically short (5 h/day),59e63 which comprises only 5e8% of the adult population.64 Additionally, although acute 4 h/day sleep has been shown to produce glucose intolerance,65 such little sleep is unsustainable and would inevitably lead to severe EDS. There is no solid epidemiological evidence to support the theory that people who sleep for 6 h/day, and are without daytime sleepiness, are at any real risk of ill health.52 Studies claiming increased morbidity or mortality in people sleeping less than 7 h (versus more than 7 h), include those sleeping less than 5 h
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(where there is a risk), but such studies do not provide actual evidence of risk for 6e7 h sleepers, despite implying that this is so (i.e., the ‘less than 7 h grouping’ is too wide). Moreover, few obese adults or children are short sleepers and few short-sleeping adults or children are obese.58 If an improvement in sleep positively impacts on health, would better or more sleep be effective in treating obesity, metabolic syndrome and diabetes? Probably not. Concerning claims that short sleep is a cause of obesity, the ‘best’ evidence points to short sleepers (<6 h) putting on less that 1.5 kg fat per year as a result of short sleep.58 Thus: if an obese person does not have EDS and wants to lose 1.5 kg over a year, then instead of sleeping 2 h more per day they would be better off using the extra time to exercise instead. The comparison is more dramatic, as time-wise, only about 9 min of that 2 h sleep would be required for brisk walking, to produce the same weight loss. That is, over one year: 52 h of brisk walking ¼ 730 h more sleep ¼ 1.5 kg loss of fat ¼ about 13,000 Calories! Better still, would be a Calorie reduced diet. It must also be pointed out that most 6-h ‘good sleepers’ will not develop diabetes or hypertension58,66 and there is no evidence that hypnotics alone are effective in producing weight reduction or in treating diabetes. Finally, studies in children and adults that show correlations between short sleep and obesity67,68 or hypertension69 demonstrate only small statistically significant differences and may not, therefore, be clinically significant. Daniel J Buysse There is clearly a relationship between various adverse health outcomes and short sleep durations. A cursory Medline search reveals over 100 articles dealing with sleep duration and morbidities including sleepiness, inflammation, immune function, hypertension, diabetes, depression, and many others. However, data are currently lacking to show that changing the number of hours that a person sleeps will alter the risk for morbidity associated with poor sleep. More importantly, it is not even known whether it is possible to increase or decrease sleep duration in individuals, especially since behavior is extremely hard to change and the determinants of sleep duration are unknown. It is also important to consider that changing sleep duration may even cause adverse consequences. A single, long, uninterrupted night-time sleep period e which we have come to accept as “normal” in humans e is essentially unknown among other mammals, the majority of whom demonstrate polyphasic sleep interrupted by periods of wakefulness.70 The great apes have relatively consolidated night-time sleep, but with at least one mid-day nap. Thus monophasic sleep may not even be “normal” for humans.71 In the case of sleep disorders, there is less evidence than might at first be believed to demonstrate that improved sleep actually leads to improved health or reduced risk. For instance, treating insomnia in comorbid depression and generalized anxiety disorder improves sleep, but the evidence in terms of improving psychiatric outcomes is mixed.33,72 It has not been shown in observational studies that treating insomnia alone reduces the risk of future depression or any other adverse outcomes, although properly-conducted prospective studies remain to be conducted. Even in the case of sleep apnea, while it is clear that having sleep apnea is associated with an increased risk of adverse health outcomes, it is less clear that treating sleep apnea reduces those risks over time. Randomized trials have shown that treatment of sleep apnea is associated with reduced hypertension and sleepiness, and observational studies indicate reduced mortality versus untreated patients with severe disease.16,20,73,74 On the other hand, there are also some data suggesting that treatment of sleep apnea can have adverse health consequences, such as weight gain 75 and the survival benefits of
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treating less severe disease are less clear. In any case, one might reasonably argue in this situation whether potential improvements in health are related to changes in sleep or changes in breathing. A model of risk factors by Kraemer and colleagues explains the importance of being precise about the language of risk and causality.76 In looking at risk factors, an orderly sequence of causation and proof needs to be established before a risk factor can be demonstrated to be causal for an adverse outcome. Just because a factor is associated with an outcome may make it a correlate, but not a risk factor. In order to prove causation we need to prove that the factor precedes the outcome and that by manipulating the factor the outcome can be changed. A causal risk factor is not the same as a cause; for example, in the case of AIDS, unprotected sex, intravenous drug use and contaminated blood products are all causal risk factors, but not the cause of AIDS (which is the HIV virus). Whilst some sleep duration studies show that shorter sleep precedes some adverse health outcomes (thus making it a risk factor), it is unknown whether that factor can be changed or manipulated. Even if reduced sleep was demonstrated to be a causal risk factor, it still hasn't been determined to be a cause of adverse outcomes. This is important because the public are constantly barraged by stories in the medical literature raising apprehension and fear, from which inappropriate conclusions are drawn. For instance, it is inappropriate to make the logical leap from shortterm studies of sleep restriction in healthy young adults showing impaired glucose regulation to the inference that longer sleep can address the tide of increasing obesity and diabetes in the general population e a claim that has been made even in health-oriented news sources (e.g., “Sleep More to Fight Obesity; Obesity Tied to Lack of Sleep, Say Researchers,” WebMD Health News, Nov. 16, 2004). Extrapolating the results from short-term laboratory studies to the general population is premature. We do our field (and the public) a disservice if premature claims are made that cannot be supported with rigorous science and, thus, have to be retracted later. Replies to the statements e PRO Ron Grunstein: the debate highlighted that, whilst the evidence is clearer that lack of sleep is quite harmful in children (although children were not mentioned in the debate), there is a need for trials comparing the outcomes related to individuals randomized to different sleep lengths before this question can be definitively answered in adults. Peretz Lavie: there is evidence that if you ask people how they feel then follow-up with them over a long period, 20 years later you will find that those who say they feel ‘lousy’ die rather earlier than those who say ‘great’. Therefore, it is hard to believe that if you improve a person's health (and sleep duration is a surrogate of health) that you don't improve mortality. Thus, it is possible that hours of sleep, either too short or too long, are surrogates for “bad health.” We need more objective data, similar to that reported by Dew et al.38 and Lavie and Lavie39 to examine the relationship between health and mortality and sleep quality and sleep duration. Replies to the statements e CON Daniel Buysse: while acute sleep deprivation has a negative impact on mood and other health outcomes, this is beside the point of the current discussion. This debate should not focus on the shortterm symptoms because long-term data provide the most important, consequential results. What we need to know is whether increasing a person's duration of sleep over the long term actually positively impacts on a person's health.
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Jim Horne: I'd like to re-iterate that whilst the acid test for insufficient sleep is EDS, this level sleepiness is greater than that usually found from super-sensitive tests able to eke out the last quantum of sleepiness, which may only reveal a level of sleepiness that people in their everyday lives find quite acceptable. Also, one needs to be cautious about interpreting statistically significant findings from large epidemiological studies of sleep duration in relation to mortality or morbidity. It is all too easy to assume that what may be small albeit statistically significant differences are also clinically significant, when they are actually of minor clinical relevance. Moreover, ‘odds ratios’ and ‘relative risks’ can be quite misleading; one should view these in conjunction with absolute differences. Concerning insomnia itself, there is no evidence that a ‘happy short sleeper’ without EDS will die earlier or have more illness. On the other hand, short sleepers who are ‘miserable and tired’ may have problems with their waking lives and attribute these largely to their apparently inadequate sleep. Simply providing sufferers with more sleep is not the answer to a better life.77 Furthermore, by the media extolling the need for at least 8 h sleep a night, and the dangers to health of having less, this only feeds their anxieties about sleep. As Dr Buysse pointed out, an apparent lack of sleep (in the absence of EDS) is unlikely to cause mental illness, particularly depression. If this was the case, why then does this ‘primary insomnia’ have to persist for so many years before the depression sets in?65 Sustained attempts to extend or improve this sleep, alone, by pharmacological methods, without dealing with the problems within the individual's waking life (e.g., via Cognitive Behavirol Therapy (CBT)), have yet to be shown to offset eventual depression. Of course, hypnotics can be of adjunctive help in dealing with sleep problems associated with depression.
Practice points PRO A decrease in sleep duration or consolidation is associated with increasingly poor performance and more errors There is a relationship (of undetermined causality) between various adverse health outcomes and shorter sleep durations Fragmented sleep worsens health, whilst de-fragmenting sleep improves health (e.g., sleep apnea) Chronic insomnia is associated with reduced qualityof-life and may predict (but not necessarily cause) depression Seven to eight hours of sleep appear to be the optimal sleep duration for most adults (approximately 10 h for children) CON Tiredness/fatigue is not the same as sleepiness and are not always improved/reduced with more sleep More sleep may not make people with poor sleep without EDS more alert and happier, or improve executive functions Mood may be improved by an earlier bed-time in people with poor sleep without EDS Short/inadequate sleep without EDS is unlikely to cause obesity or metabolic syndrome. Exercise is a far more effective treatment for these latter problems than is extended sleep Most 6-h good sleepers will not develop diabetes or hypertension
Audience perspective During the course of the debate, the audience e an international mix of sleep specialists e contributed their opinion to the debate via interactive keypads. When asked the question “Does an improvement in sleep positively impact on health?” immediately before the debate, 89% answered ‘Yes’ and 11% answered ‘No’. When asked the same question immediately after the presentations (but before the rebuttals), audience opinion had shifted: 66% supporting the affirmative statement, while 34% didn't. At the end of the rebuttals and general discussion the final vote was 64% for ‘Yes’ and 36% for ‘No’, which suggests that while the proportion of those who supported the debate question decreased, the majority of participants felt that improving sleep positively impacts on health. Conclusions/summary Whilst results from a large number of studies document significant associations between sleep duration and various health problems, a causal relationship remains to be demonstrated, and convincing evidence that treatment of ‘insufficient’ sleep results in health benefits is lacking. Before the question of whether an improvement in sleep positively impacts on health can be definitively answered in adults, there is a need for more detailed investigation into long-term outcomes and the potential for causality. These must include better designed observational studies with objective verification of sleep length and even experimental studies exposing individuals to realistic patterns of sleep loss. Advocating the virtue of ‘more sleep’ has to be tempered with us still not knowing enough about its functions, and whether the increasing use of psychostimulants to suppress or even replace part of sleep is, in the long-term, foolhardy or safe.
Research agenda Establish determinants of sleep duration Determine individual sleep needs Perform longitudinal studies to prove a correlation between short and long sleep hours and health risk Perform studies to determine whether it is possible to increase or decrease sleep duration in individuals without causing adverse consequences Determine whether changing the number of hours that a person sleeps alters the risk for morbidity associated with poor sleep Determine whether improved sleep leads to improved health Determine why the number of sleep hours, both long and short, correlates with bad health later in life
Acknowledgements Medical writing assistance for the preparation of this manuscript was provided by Wolters Kluwer Health Medical Communications. This assistance was funded by Sanofi-aventis. Conflict of interest Dr. Buysse serves as a consultant for the following: Actelion, Arena, Cephalon, Eli Lilly, GlaxoSmithKline, Merck, Neurocrine, Neurogen, Pfizer, Respironics, sanofi-aventis, Sepracor, Servier, Somnus Therapeutics, Stress Eraser, Takeda and Transept Pharmaceuticals, Inc.
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Sleep duration and coronary heart disease mortality among Chinese adults in Singapore: a populationbased cohort study. Am J Epidemiol 2008;168:1367e73. 52. Tamakoshi A, Ohno Y. Self-reported sleep duration as a predictor of all-cause mortality: results from the JACC study. Japan. Sleep 2004;27:51e4. 53. Qureshi AI, Giles WH, Croft JB, Bliwise DL. Habitual sleep patterns and risk for stroke and coronary heart disease: a 10-year follow-up from NHANES I. Neurology 1997;48:904e11. 54. Horne J. Is there a sleep debt? Sleep 2004;27:1047e9. 55. Anderson C, Horne JA. Do we really want more sleep? A population-based study evaluating the strength of desire for more sleep. Sleep Med 2008;9:184e7. 56. Horne J. Sleepiness as a need for sleep: when is enough, enough? Neurosci Biobehav Rev 2010;34:108e18.
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57. Totterdell P, Reynolds S, Parkinson B, Briner RB. Associations of sleep with everyday mood, minor symptoms and social interaction experience. Sleep 1994;17:466e75. *58. Horne J. Short sleep is a questionable risk factor for obesity and related disorders: statistical versus clinical significance. Biol Psychol 2008;77:266e76. 59. Bjorvatn B, Sagen IM, Oyane N, Waage S, Fetveit A, Pallesen S, et al. The association between sleep duration, body mass index and metabolic measures in the Hordaland Health Study. J Sleep Res 2007;16:66e76. 60. Chaput JP, Despres JP, Bouchard C, Tremblay A. Short sleep duration is associated with reduced leptin levels and increased adiposity: results from the Quebec family study. Obesity (Silver Spring) 2007;15:253e61. 61. Gangwisch JE, Malaspina D, Boden-Albala B, Heymsfield SB. Inadequate sleep as a risk factor for obesity: analyses of the NHANES I. Sleep 2005;28:1289e96. 62. Hasler G, Buysse DJ, Klaghofer R, Gamma A, Ajdacic V, Eich D, et al. The association between short sleep duration and obesity in young adults: a 13year prospective study. Sleep 2004;27:661e6. 63. Patel SR, Malhotra A, White DP, Gottlieb DJ, Hu FB. Association between reduced sleep and weight gain in women. Am J Epidemiol 2006;164:947e54. 64. Groeger JA, Zijlstra FR, Dijk DJ. Sleep quantity, sleep difficulties and their perceived consequences in a representative sample of some 2000 British adults. J Sleep Res 2004;13:359e71. 65. Spiegel K, Knutson K, Leproult R, Tasali E, Van Cauter E. Sleep loss: a novel risk factor for insulin resistance and Type 2 diabetes. J Appl Physiol 2005;99:2008e19. 66. Ayas NT, White DP, Al-Delaimy WK, Manson JE, Stampfer MJ, Speizer FE, et al. A prospective study of self-reported sleep duration and incident diabetes in women. Diabetes Care 2003;26:380e4.
67. Lumeng JC, Somashekar D, Appugliese D, Kaciroti N, Corwyn RF, Bradley RH. Shorter sleep duration is associated with increased risk for being overweight at ages 9 to 12 years. Pediatrics 2007;120:1020e9. 68. von Kries R, Toschke AM, Wurmser H, Sauerwald T, Koletzko B. Reduced risk for overweight and obesity in 5- and 6-y-old children by duration of sleepea cross-sectional study. Int J Obes Relat Metab Disord 2002;26:710e6. 69. Gottlieb DJ, Redline S, Nieto FJ, Baldwin CM, Newman AB, Resnick HE, et al. Association of usual sleep duration with hypertension: the Sleep Heart Health Study. Sleep 2006;29:1009e14. 70. Zepelin H, Siegel JM, Tobler I. Mammalian sleep. In: Kryger MH, Roth T, Dement WC, editors. Principles and practice of sleep medicine. 4th ed. Philadelphia: Elsevier/Saunders; 2005. p. 91e100. 71. Ekirch AR. At day's close: night in time's past. New York: W.W. Norton & Company, Inc.; 2005. 72. Fava M, Asnis GM, Shrivastava R, Lydiard B, Bastani B, Sheehan D, et al. Zolpidem extended-release improves sleep and next-day symptoms in comorbid insomnia and generalized anxiety disorder. J Clin Psychopharmacol 2009;29:222e30. 73. Giles TL, Lasserson TJ, Smith BH, White J, Wright J, Cates CJ. Continuous positive airways pressure for obstructive sleep apnoea in adults. Cochrane Database Syst Rev 2006;3. CD001106. 74. Young T, Finn L, Peppard PE, Szklo-Coxe M, Austin D, Nieto FJ, et al. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep 2008;31:1071e8. 75. Redenius R, Murphy C, O'Neill E, Al-Hamwi M, Zallek SN. Does CPAP lead to change in BMI? J Clin Sleep Med 2008;4:205e9. 76. Kraemer HC, Kazdin AE, Offord DR, Kessler RC, Jensen PS, Kupfer DJ. Coming to terms with the terms of risk. Arch Gen Psychiatry 1997;54:337e43. 77. Horne J. Primary insomnia: a disorder of sleep, or primarily one of wakefulness? Sleep Med Rev 2010;14:3e7.
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COMMENTARY
Can an improvement in sleep positively impact on health? Daniel J. Buysse a, e, Ron Grunstein b, f, Jim Horne c, *, Peretz Lavie d, g a
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Sleep and Circadian Group Woolcock Institute of Medical Research, University of Sydney, Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia c Sleep Research Centre, Loughborough University, Leicestershire LE11 3TU, United Kingdom d Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel b
a r t i c l e i n f o
s u m m a r y
Article history: Received 2 October 2009 Received in revised form 28 January 2010 Accepted 2 February 2010 Available online 28 April 2010
Reports from a large number of studies document significant associations between sleep duration and various health problems such as cardiovascular events, risk of stroke, incident artery calcification, changes in inflammatory markers and many more. Furthermore, some sleep duration studies have shown that shorter sleep precedes some adverse health outcomes, although a causal relationship has yet to be demonstrated. Whilst clinical studies have shown that de-fragmenting (reducing awakenings and improving sleep continuity) sleep can reverse the harmful consequences of sleep apnea, and other studies have demonstrated that adjunctive treatment of insomnia improves depression, evidence that treatment of insomnia results in health benefit is more controversial. This article documents the debate session from the 6th International Sleep Disorders Forum e The Art of Good Sleep, held in Toronto, Canada in September 2008; the topic of which was “Does an improvement in sleep positively impact on health?” Ó 2010 Elsevier Ltd. All rights reserved.
Keywords: Daytime sleepiness Sleep deficit Sleep need Health Sleeping time Performance
Introduction
Statements PRO
The 6th International Sleep Disorders Forum e The Art of Good Sleep was held in Toronto, Canada in September 2008 and was attended by an international mix of sleep specialists. The meeting was held under the theme of Sleep & Society and focused on increasing the awareness of sleep disorders as an important health issue for society, and the relationship between sleep disorders and other common comorbid conditions. As part of the program a debate session was conducted on the topic “Does an improvement in sleep positively impact on health?”: the PRO argument was provided by Drs Ron Grunstein and Peretz Lavie, and the CON argument was presented by Drs Jim Horne and Daniel Buysse. Each author presented their arguments in the sequence PRO, CON, PRO, CON, followed by rebuttals, and the session was concluded with a general audience discussion. The following article summarizes the discussions that took place.
Ron Grunstein
* Corresponding author. Tel.: þ44 (0)1509 223004; fax: þ44 (0)15 0922 8480. E-mail addresses: [email protected] (D.J. Buysse), [email protected] (R. Grunstein), [email protected] (J. Horne), [email protected] (P. Lavie). e Tel.: þ1 412 246 6413; fax: þ1 412 246 5300. f Tel.: þ61 2 9515 8630; fax: þ61 2 9515 7070. g Tel.: þ972 4 8295234; fax: þ972 4 8343934. 1087-0792/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.smrv.2010.02.001
The specifics of the debate topic were clarified from the perspective of the ‘PRO’ argument: an “improvement in sleep” was defined as increasing sleep length (for instance by decreasing sleep latency), reducing arousals and sleep fragmentation, and improved perception of sleep quality; “positively impacts on health” was defined as an improvement of markers or endpoints of good health, a decrease in markers or endpoints of ill health, and better qualityof-life (QOL) or work productivity. Laboratory studies have shown increasingly poor performance with a decrease in sleep duration1,2 and a correlation has been established between workplace accidents caused by people falling asleep while at work and short sleep duration.3,4 Whilst it is unknown whether improved sleep would have helped to prevent the accidents from occurring, the value of recovery sleep has been demonstrated in a randomized study investigating the effect of restricted nocturnal sleep schedules with and without diurnal naps on psychomotor vigilance test performance.5 The study showed that the total daily sleep duration, whether consolidated or split, is the primary determinant of neurobehavioural function (psychomotor performance including alertness, vigilance, etc) over days.
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Clinical studies have shown that restricted sleep is a risk factor for certain comorbidities, whilst recovery sleep improves health.6e8 Outside clinical studies, the best way to measure whether restricted sleep has a negative impact on health would be to randomize people to short sleep versus longer sleep and measure accidents or medical errors by health professionals, but this is not ethically possible. The Harvard Work Hours Study,9,10 which randomized hospital interns to longer versus shorter work hours, showed that the longer a person works, the less sleep they get and the more errors they make. Interns made 36% more serious medical errors during a traditional work schedule than during an intervention schedule that eliminated extended work shifts.9,10 Furthermore, short-term experimental studies of short versus longer sleep have shown that short sleep is associated with impaired appetite control and glucose regulation,11 which has stimulated much investigation. However, an association between short sleep duration and health risk is not as clear because, despite some quite strong paediatric data, most of the evidence available to date is based on cross-sectional rather than longitudinal data.12e14 Clinical studies have also demonstrated that fragmented sleep worsens health,15 whilst de-fragmenting sleep (reducing awakenings and improving sleep continuity) improves health.16 Data on sleep apnoea are clear: positive airway pressure (PAP) is effective in reducing sleepiness, increasing QOL and improving sleep quality in moderate to severe OSA (but is not proven in mild OSA and in patients with certain comorbidities).17e27 Additionally, randomized, controlled trial data show that PAP increases growth hormone and results in better simulated driving,15,28 and strong observational data exist showing an association between restless legs syndrome/periodic limb movements in sleep and car crashes29 or cardiovascular endpoints.30 However, evidence that treatment of insomnia results in health benefit is more controversial31: there are no well-designed, longterm, randomized, controlled trials to clearly answer this. A randomized long-term study in patients with chronic primary insomnia showed that 6 months of zolpidem improved next-day concentration and morning sleepiness compared with placebo,32 and adjunctive treatment of insomnia has been shown to have positive effects on health in patients with depression.33e35 Improvement in health following sleep de-fragmenting may be modulated by genotype, phenotype and environmental factors, but this does not counter the general positive effect. It is also important to note the dangers of generalization: whilst approximately 7 h sleep is average in adults, inter-individual variations in sleep need exist outside this average.36 Peretz Lavie The debate topic can be answered with an unequivocal yes with respect to obstructive sleep apnea, so focus will be given to sleep quality and insomnia. Although insomnia is associated with reduced QOL and may predict depression, subjective complaint of insomnia has not been shown to be causally associated with adverse outcomes.37 In contrast with studies relying on subjective reports on insomnia that failed to show association with adverse outcomes, two studies reported that polysomnographic sleep quality variables predict mortality.38,39 In both studies, sleep latency was an independent predictor of all-cause mortality. Although two studies have shown that treating insomnia improves depression,33,34 it is not yet known whether treating insomnia or altering sleep duration will improve longevity. Future studies should elaborate the underlying relationship between sleep duration and mortality and whether modifying sleep duration can modify mortality risks.
A literature search revealed that there has been a recent dramatic increase in the number of papers that examined the relationship between sleep duration and health-related effects and with mortality. Notably, very few have been written by sleep researchers (mostly written by epidemiologists, diabetes researchers, and others in the public health domain). Whilst there are documented health effects associated with sleep duration, it is not yet known why the number of sleep hours correlates with bad health later in life. A total of 26 studies investigated the association between sleep duration and mortality (all-cause and causespecific), all of which examined sleep duration by participant self-report. Thirteen studies estimated the risk of short sleep after adjustment for comorbidities and 10 of these studies showed an increase in mortality related to short sleep.40e52 Also, 14 studies estimated the risk of long sleep after adjustment for comorbidities, of which 11 showed an increase in mortality related to long sleep.40e53 Many of the above studies reported that both short sleep and long sleep were associated with mortality. In most cases the nadir mortality was reported for people sleeping 7e8 h. A large number of studies documented significant associations between sleep duration and numerous health problems such as cardiovascular events, risk of stroke, incident artery calcification, changes in inflammatory markers, and many more. Statements CON Jim Horne If poor sleep is defined in terms of excessive daytime sleepiness (EDS), then an improvement in sleep will certainly impact on health as, for example, the greatest danger with EDS is probably falling asleep while driving. However, if a person complains about poor sleep without EDS, is this sleep really poor? While fragmented sleep is unhealthy, the argument should concentrate on whether shorter or longer sleep length is unhealthy. Approximately 7 h of sleep appears to be enough for most adults (around 10 h for children). This has remained unchanged historically,54 despite claims to the contrary; however, newer evidence challenging this can be misleading, especially as sleep debt surveys are often confounded by leading questions.55 It is not enough to ask a person if they want more sleep, but they should also be asked about what waking activities they would be prepared to give up in order to sleep more. Tiredness or fatigue are not the same as sleepiness 56 and are not always overcome with more sleep. Super-sensitive laboratory tests, may not be so relevant to the everyday issues of how much sleep a person needs because they are too sensitive. Studies in people with poor sleep without EDS have shown that more sleep may not make them more alert and happier, and executive functions are not usually improved.54 However, a study by Totterdell and colleagues57 demonstrated that mood may be improved by an earlier bed-time e without extending sleep. Also, in people with poor sleep without EDS, short/inadequate sleep is unlikely to cause obesity or metabolic syndrome58 [see for critical review]: obesity risk only becomes more apparent when sleep is atypically short (5 h/day),59e63 which comprises only 5e8% of the adult population.64 Additionally, although acute 4 h/day sleep has been shown to produce glucose intolerance,65 such little sleep is unsustainable and would inevitably lead to severe EDS. There is no solid epidemiological evidence to support the theory that people who sleep for 6 h/day, and are without daytime sleepiness, are at any real risk of ill health.52 Studies claiming increased morbidity or mortality in people sleeping less than 7 h (versus more than 7 h), include those sleeping less than 5 h
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(where there is a risk), but such studies do not provide actual evidence of risk for 6e7 h sleepers, despite implying that this is so (i.e., the ‘less than 7 h grouping’ is too wide). Moreover, few obese adults or children are short sleepers and few short-sleeping adults or children are obese.58 If an improvement in sleep positively impacts on health, would better or more sleep be effective in treating obesity, metabolic syndrome and diabetes? Probably not. Concerning claims that short sleep is a cause of obesity, the ‘best’ evidence points to short sleepers (<6 h) putting on less that 1.5 kg fat per year as a result of short sleep.58 Thus: if an obese person does not have EDS and wants to lose 1.5 kg over a year, then instead of sleeping 2 h more per day they would be better off using the extra time to exercise instead. The comparison is more dramatic, as time-wise, only about 9 min of that 2 h sleep would be required for brisk walking, to produce the same weight loss. That is, over one year: 52 h of brisk walking ¼ 730 h more sleep ¼ 1.5 kg loss of fat ¼ about 13,000 Calories! Better still, would be a Calorie reduced diet. It must also be pointed out that most 6-h ‘good sleepers’ will not develop diabetes or hypertension58,66 and there is no evidence that hypnotics alone are effective in producing weight reduction or in treating diabetes. Finally, studies in children and adults that show correlations between short sleep and obesity67,68 or hypertension69 demonstrate only small statistically significant differences and may not, therefore, be clinically significant. Daniel J Buysse There is clearly a relationship between various adverse health outcomes and short sleep durations. A cursory Medline search reveals over 100 articles dealing with sleep duration and morbidities including sleepiness, inflammation, immune function, hypertension, diabetes, depression, and many others. However, data are currently lacking to show that changing the number of hours that a person sleeps will alter the risk for morbidity associated with poor sleep. More importantly, it is not even known whether it is possible to increase or decrease sleep duration in individuals, especially since behavior is extremely hard to change and the determinants of sleep duration are unknown. It is also important to consider that changing sleep duration may even cause adverse consequences. A single, long, uninterrupted night-time sleep period e which we have come to accept as “normal” in humans e is essentially unknown among other mammals, the majority of whom demonstrate polyphasic sleep interrupted by periods of wakefulness.70 The great apes have relatively consolidated night-time sleep, but with at least one mid-day nap. Thus monophasic sleep may not even be “normal” for humans.71 In the case of sleep disorders, there is less evidence than might at first be believed to demonstrate that improved sleep actually leads to improved health or reduced risk. For instance, treating insomnia in comorbid depression and generalized anxiety disorder improves sleep, but the evidence in terms of improving psychiatric outcomes is mixed.33,72 It has not been shown in observational studies that treating insomnia alone reduces the risk of future depression or any other adverse outcomes, although properly-conducted prospective studies remain to be conducted. Even in the case of sleep apnea, while it is clear that having sleep apnea is associated with an increased risk of adverse health outcomes, it is less clear that treating sleep apnea reduces those risks over time. Randomized trials have shown that treatment of sleep apnea is associated with reduced hypertension and sleepiness, and observational studies indicate reduced mortality versus untreated patients with severe disease.16,20,73,74 On the other hand, there are also some data suggesting that treatment of sleep apnea can have adverse health consequences, such as weight gain 75 and the survival benefits of
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treating less severe disease are less clear. In any case, one might reasonably argue in this situation whether potential improvements in health are related to changes in sleep or changes in breathing. A model of risk factors by Kraemer and colleagues explains the importance of being precise about the language of risk and causality.76 In looking at risk factors, an orderly sequence of causation and proof needs to be established before a risk factor can be demonstrated to be causal for an adverse outcome. Just because a factor is associated with an outcome may make it a correlate, but not a risk factor. In order to prove causation we need to prove that the factor precedes the outcome and that by manipulating the factor the outcome can be changed. A causal risk factor is not the same as a cause; for example, in the case of AIDS, unprotected sex, intravenous drug use and contaminated blood products are all causal risk factors, but not the cause of AIDS (which is the HIV virus). Whilst some sleep duration studies show that shorter sleep precedes some adverse health outcomes (thus making it a risk factor), it is unknown whether that factor can be changed or manipulated. Even if reduced sleep was demonstrated to be a causal risk factor, it still hasn't been determined to be a cause of adverse outcomes. This is important because the public are constantly barraged by stories in the medical literature raising apprehension and fear, from which inappropriate conclusions are drawn. For instance, it is inappropriate to make the logical leap from shortterm studies of sleep restriction in healthy young adults showing impaired glucose regulation to the inference that longer sleep can address the tide of increasing obesity and diabetes in the general population e a claim that has been made even in health-oriented news sources (e.g., “Sleep More to Fight Obesity; Obesity Tied to Lack of Sleep, Say Researchers,” WebMD Health News, Nov. 16, 2004). Extrapolating the results from short-term laboratory studies to the general population is premature. We do our field (and the public) a disservice if premature claims are made that cannot be supported with rigorous science and, thus, have to be retracted later. Replies to the statements e PRO Ron Grunstein: the debate highlighted that, whilst the evidence is clearer that lack of sleep is quite harmful in children (although children were not mentioned in the debate), there is a need for trials comparing the outcomes related to individuals randomized to different sleep lengths before this question can be definitively answered in adults. Peretz Lavie: there is evidence that if you ask people how they feel then follow-up with them over a long period, 20 years later you will find that those who say they feel ‘lousy’ die rather earlier than those who say ‘great’. Therefore, it is hard to believe that if you improve a person's health (and sleep duration is a surrogate of health) that you don't improve mortality. Thus, it is possible that hours of sleep, either too short or too long, are surrogates for “bad health.” We need more objective data, similar to that reported by Dew et al.38 and Lavie and Lavie39 to examine the relationship between health and mortality and sleep quality and sleep duration. Replies to the statements e CON Daniel Buysse: while acute sleep deprivation has a negative impact on mood and other health outcomes, this is beside the point of the current discussion. This debate should not focus on the shortterm symptoms because long-term data provide the most important, consequential results. What we need to know is whether increasing a person's duration of sleep over the long term actually positively impacts on a person's health.
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Jim Horne: I'd like to re-iterate that whilst the acid test for insufficient sleep is EDS, this level sleepiness is greater than that usually found from super-sensitive tests able to eke out the last quantum of sleepiness, which may only reveal a level of sleepiness that people in their everyday lives find quite acceptable. Also, one needs to be cautious about interpreting statistically significant findings from large epidemiological studies of sleep duration in relation to mortality or morbidity. It is all too easy to assume that what may be small albeit statistically significant differences are also clinically significant, when they are actually of minor clinical relevance. Moreover, ‘odds ratios’ and ‘relative risks’ can be quite misleading; one should view these in conjunction with absolute differences. Concerning insomnia itself, there is no evidence that a ‘happy short sleeper’ without EDS will die earlier or have more illness. On the other hand, short sleepers who are ‘miserable and tired’ may have problems with their waking lives and attribute these largely to their apparently inadequate sleep. Simply providing sufferers with more sleep is not the answer to a better life.77 Furthermore, by the media extolling the need for at least 8 h sleep a night, and the dangers to health of having less, this only feeds their anxieties about sleep. As Dr Buysse pointed out, an apparent lack of sleep (in the absence of EDS) is unlikely to cause mental illness, particularly depression. If this was the case, why then does this ‘primary insomnia’ have to persist for so many years before the depression sets in?65 Sustained attempts to extend or improve this sleep, alone, by pharmacological methods, without dealing with the problems within the individual's waking life (e.g., via Cognitive Behavirol Therapy (CBT)), have yet to be shown to offset eventual depression. Of course, hypnotics can be of adjunctive help in dealing with sleep problems associated with depression.
Practice points PRO A decrease in sleep duration or consolidation is associated with increasingly poor performance and more errors There is a relationship (of undetermined causality) between various adverse health outcomes and shorter sleep durations Fragmented sleep worsens health, whilst de-fragmenting sleep improves health (e.g., sleep apnea) Chronic insomnia is associated with reduced qualityof-life and may predict (but not necessarily cause) depression Seven to eight hours of sleep appear to be the optimal sleep duration for most adults (approximately 10 h for children) CON Tiredness/fatigue is not the same as sleepiness and are not always improved/reduced with more sleep More sleep may not make people with poor sleep without EDS more alert and happier, or improve executive functions Mood may be improved by an earlier bed-time in people with poor sleep without EDS Short/inadequate sleep without EDS is unlikely to cause obesity or metabolic syndrome. Exercise is a far more effective treatment for these latter problems than is extended sleep Most 6-h good sleepers will not develop diabetes or hypertension
Audience perspective During the course of the debate, the audience e an international mix of sleep specialists e contributed their opinion to the debate via interactive keypads. When asked the question “Does an improvement in sleep positively impact on health?” immediately before the debate, 89% answered ‘Yes’ and 11% answered ‘No’. When asked the same question immediately after the presentations (but before the rebuttals), audience opinion had shifted: 66% supporting the affirmative statement, while 34% didn't. At the end of the rebuttals and general discussion the final vote was 64% for ‘Yes’ and 36% for ‘No’, which suggests that while the proportion of those who supported the debate question decreased, the majority of participants felt that improving sleep positively impacts on health. Conclusions/summary Whilst results from a large number of studies document significant associations between sleep duration and various health problems, a causal relationship remains to be demonstrated, and convincing evidence that treatment of ‘insufficient’ sleep results in health benefits is lacking. Before the question of whether an improvement in sleep positively impacts on health can be definitively answered in adults, there is a need for more detailed investigation into long-term outcomes and the potential for causality. These must include better designed observational studies with objective verification of sleep length and even experimental studies exposing individuals to realistic patterns of sleep loss. Advocating the virtue of ‘more sleep’ has to be tempered with us still not knowing enough about its functions, and whether the increasing use of psychostimulants to suppress or even replace part of sleep is, in the long-term, foolhardy or safe.
Research agenda Establish determinants of sleep duration Determine individual sleep needs Perform longitudinal studies to prove a correlation between short and long sleep hours and health risk Perform studies to determine whether it is possible to increase or decrease sleep duration in individuals without causing adverse consequences Determine whether changing the number of hours that a person sleeps alters the risk for morbidity associated with poor sleep Determine whether improved sleep leads to improved health Determine why the number of sleep hours, both long and short, correlates with bad health later in life
Acknowledgements Medical writing assistance for the preparation of this manuscript was provided by Wolters Kluwer Health Medical Communications. This assistance was funded by Sanofi-aventis. Conflict of interest Dr. Buysse serves as a consultant for the following: Actelion, Arena, Cephalon, Eli Lilly, GlaxoSmithKline, Merck, Neurocrine, Neurogen, Pfizer, Respironics, sanofi-aventis, Sepracor, Servier, Somnus Therapeutics, Stress Eraser, Takeda and Transept Pharmaceuticals, Inc.
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