8 th hypertension masterclass sleep deprivation and chronic disease francesco p cappuccio md msc...
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88thth Hypertension Masterclass Hypertension Masterclass
Sleep Deprivation and Chronic DiseaseSleep Deprivation and Chronic Disease
Francesco P Cappuccio MD MSc FRCP FFPH FAHA
Professor of Cardiovascular Medicine & EpidemiologyClinical Sciences Research Institute
Warwick Medical School, Coventry, UK
88thth Hypertension Masterclass Hypertension Masterclass
How many hours per night How many hours per night do you usually sleep?do you usually sleep?
0
50
Les
s th
an 5
h 6
h 7
h 8
h
9h o
r more
0% 0% 0%0%0%
1. Less than 5h
2. 6h
3. 7h
4. 8h
5. 9h or more
88thth Hypertension Masterclass Hypertension Masterclass
Sleep Duration Time Trends in US AdultsSleep Duration Time Trends in US Adults
9.0
7.56.8
0.01.02.03.04.05.06.07.08.09.0
10.0
1910 1975 2005
Hrs per night
National Sleep Foundation. Sleep in America Poll
88thth Hypertension Masterclass Hypertension Masterclass
Sleep duration in British Adults Sleep duration in British Adults (1967/2003)(1967/2003)
Groeger JA et al. J Sleep Res. 2004; 13:359-71
19671967
20032003
88thth Hypertension Masterclass Hypertension Masterclass
How much did you score How much did you score at the ESS questionnaire?at the ESS questionnaire?
0
50
10
or le
ss
11-
16
17
or m
ore
0% 0%0%
1. 10 or less
2. 11-16
3. 17 or more
88thth Hypertension Masterclass Hypertension Masterclass
Fragmented SleepFragmented Sleep(Sleep Disruption)(Sleep Disruption)
Insufficient SleepInsufficient Sleep(Sleep Deprivation)(Sleep Deprivation)
Excessive Daytime Sleepiness (EDS)Excessive Daytime Sleepiness (EDS)
Neurobehavioral Neurobehavioral deficitsdeficits
cognitive/executive function cognitive/executive function attention/concentration attention/concentration
Cardio-metabolicCardio-metabolicappetite regulationappetite regulation
high blood pressurehigh blood pressure
Increased Morbidity / MortalityIncreased Morbidity / Mortality
Decreased Quality of LifeDecreased Quality of Life
Performance deficitsPerformance deficitserrors/accuracyerrors/accuracy
88thth Hypertension Masterclass Hypertension Masterclass
Cardio-Metabolic Risk FactorsCardio-Metabolic Risk Factors
• Obesity/body fat distribution Obesity/body fat distribution
• Type 2 Diabetes MellitusType 2 Diabetes Mellitus
• HypertensionHypertension
Total and Cause-Specific MortalityTotal and Cause-Specific Mortality
Coronary Heart DiseaseCoronary Heart Disease
Short Sleep Duration & Chronic Diseases Short Sleep Duration & Chronic Diseases
88thth Hypertension Masterclass Hypertension Masterclass
Cardio-Metabolic Risk Factors:Cardio-Metabolic Risk Factors:
ObesityObesity
88thth Hypertension Masterclass Hypertension Masterclass
ObesityObesity Epidemic and Sleep Duration Epidemic and Sleep Duration
7.56.8
9.0
0.01.02.03.04.05.06.07.08.09.0
10.0
1910 1975 2005
Sleep duration in US adults Sleep duration in US adults
25.2
26.9
23.0
21.0
22.0
23.0
24.0
25.0
26.0
27.0
28.0
1910 1975 2005
BMI in US adultsBMI in US adults
88thth Hypertension Masterclass Hypertension Masterclass
Short Sleep Duration and Short Sleep Duration and Metabolic HormonesMetabolic Hormones
Taheri S et al. PLoS Med. 2004; 1:210-7
LeptinLeptin GhrelinGhrelin
-15.5%
+14.9%
88thth Hypertension Masterclass Hypertension Masterclass
Sleep Deprivation and Sleep Deprivation and Appetite RegulationAppetite Regulation
-18% leptin; +28% ghrelin-18% leptin; +28% ghrelin+24% hunger/appetite+24% hunger/appetite
Spiegel K et al. Ann Intern Med. 2004; 141:846-50
88thth Hypertension Masterclass Hypertension Masterclass
Short Sleep Duration (<10h) and Short Sleep Duration (<10h) and ObesityObesityMeta-analysis of Cross-Sectional StudiesMeta-analysis of Cross-Sectional Studies
Cappuccio FP et al. Sleep 2008; in press
Odds Ratio 0.72 1 1.89 11
Combined
Seicean (2007)
Chen (2006)
Chaput (2006)
Reilly (2005)
Padez (2005)
Giugliano (2004)
Agras (2004)
Von Kries (2002)
Sekine (2002)
BenSlama (2002)
Locard (1992)
OR & 95% CI
2.25 (1.27; 3.98)
11.00 (4.75; 25.49)
1.19 (1.00; 1.42)
2.17 (1.57; 3.00)
2.00 (0.80; 5.02)
5.63 (0.72; 44.06)
1.15 (0.93; 1.43)
1.45 (1.20; 1.76)
2.63 (1.24; 5.58)
1.75 (1.28; 2.39)
2.23 (0.87; 5.73)
Children, n=29,502Children, n=29,502
1.89 1.89 (1.46-2.43)(1.46-2.43)
88thth Hypertension Masterclass Hypertension Masterclass
Odds Ratio 0.67 1 1.55 10
Combined
Stranges (2008) Fogelholm (Women) (2007)
Fogelholm (men) (2007) Tuomilehto (2007)
Ko (2007) Chaput (women) (2007)
Chaput (men) (2007) Bjorvatn (2007)
Watari (women) (2006) Watari (men) (2006)
Vahtera (2006) Moreno (2006)
Singh (2005) Gangwisch3 (2005) Gangwisch2 (2005) Gangwisch1 (2005)
Bjorkelund (2005) Hasler (2004)
Cournot (2004) Kripke (2002)
Shigeta (2001) Vioque (2000)
Short Sleep Duration (<5h) and Short Sleep Duration (<5h) and ObesityObesityMeta-analysis of Cross-Sectional StudiesMeta-analysis of Cross-Sectional Studies
Cappuccio FP et al. Sleep 2008; in press
Adults, n=603,519Adults, n=603,519
1.55 1.55 (1.43-1.68)(1.43-1.68)
OR & 95% CI
3.36 (2.24; 5.03)1.98 (1.03; 3.81)1.52 (1.46; 1.58)1.38 (0.98; 1.95)10.80 (0.99; 117.4)1.52 (0.68; 3.41)1.84 (1.40; 2.41)1.38 (1.06; 1.79)0.95 (0.67; 1.34)1.70 (1.26; 2.29)1.22 (1.07; 1.40)1.43 (1.34; 1.52)1.96 (1.19; 3.22)2.98 (0.77; 11.57)1.87 (1.22; 2.86)4.01 (1.72; 9.34)2.65 (1.27; 5.54)1.30 (1.14; 1.48)1.30 (1.06; 1.60)1.46 (1.13; 1.88)1.75 (1.36; 2.25)2.02 (1.57; 2.60)
88thth Hypertension Masterclass Hypertension Masterclass
Sleep Deprivation & Obesity:Sleep Deprivation & Obesity:Potential MechanismsPotential Mechanisms
ObesityObesitySleep Sleep DeprivationDeprivation
Patel SR et al. Obesity; 2008; in press
88thth Hypertension Masterclass Hypertension Masterclass
-2
-1.5
-1
-0.5
0
0.5
1
1.5
2
<=5 6 7 8 9+
0
0.5
1
1.5
2
2.5
<=5 6 7 8 9+
Hours of sleep
Stranges S et al. Am J Epidemiol. 2008; 167: 321-9
BMI BMI
OR Obesity OR Obesity
Short Sleep Duration and Short Sleep Duration and ObesityObesityThe Whitehall II Study/The Whitehall II Study/Cross-SectionalCross-Sectional (n=5,021) (n=5,021)
-0.35 (-0.57;-0.12)P <0.001
1.65 1.65 (1.22-2.24)(1.22-2.24)
88thth Hypertension Masterclass Hypertension Masterclass
-0.6
-0.4
-0.2
0
0.2
0.4
0.6
<=5 6 7 8 9+
0
0.5
1
1.5
2
2.5
3
<=5 6 7 8 9+
Hours of sleep
Stranges S et al. Am J Epidemiol. 2008; 167: 321-9
BMI BMI
OR Obesity OR Obesity
Short Sleep Duration and Short Sleep Duration and ObesityObesityThe Whitehall II Study/The Whitehall II Study/ProspectiveProspective
0.03 (-0.03; 0.08)P = 0.36
1.05 1.05 (0.60-1.82)(0.60-1.82)
88thth Hypertension Masterclass Hypertension Masterclass
Cardio-Metabolic Risk Factors:Cardio-Metabolic Risk Factors:
Type 2 DiabetesType 2 Diabetes
88thth Hypertension Masterclass Hypertension Masterclass
Sleep Duration and Risk of Sleep Duration and Risk of DiabetesDiabetesThe Massachusetts Male Aging Study (n=1,139)The Massachusetts Male Aging Study (n=1,139)
0
1
2
3
4
5
6
<=5 6 7 8 >8Hours of Sleep
Rel
ativ
e R
isk
Yaggi HK et al. Diabetes Care 2006; 29:657-61
1.95 1.95 (0.95-4.01)(0.95-4.01)
3.12 3.12 (1.53-6.37)(1.53-6.37)
88thth Hypertension Masterclass Hypertension Masterclass
Sleep Duration and Risk of Sleep Duration and Risk of DiabetesDiabetesThe Nurses’ Health Study (n=70,026)The Nurses’ Health Study (n=70,026)
0
0.5
1
1.5
2
<=5 6 7 8 >8Hours of Sleep
Rel
ativ
e R
isk
Ayas NT et al. Diabetes Care 2003; 26:380-4
1.18 1.18 (0.96-1.44)(0.96-1.44)
1.29 1.29 (1.05-1.59)(1.05-1.59)
88thth Hypertension Masterclass Hypertension Masterclass
• Elevation of evening cortisol levels predisposing to Elevation of evening cortisol levels predisposing to
insulin resistanceinsulin resistance
• Increase in sympathetic tone, inhibiting pancreatic Increase in sympathetic tone, inhibiting pancreatic
function and leading to increased glucose intolerancefunction and leading to increased glucose intolerance
• Weight gain and reduction in leptinWeight gain and reduction in leptin
• Reduction of testosterone levelsReduction of testosterone levels
Sleep Deprivation & Diabetes:Sleep Deprivation & Diabetes:Potential MechanismsPotential Mechanisms
88thth Hypertension Masterclass Hypertension Masterclass
Cardio-Metabolic Risk Factors:Cardio-Metabolic Risk Factors:
HypertensionHypertension
88thth Hypertension Masterclass Hypertension Masterclass
Sleep duration and Sleep duration and incidentincident Hypertension Hypertension NHANES-INHANES-I
0
0.5
1
1.5
2
2.5
<=5 6 7 to 8 =>9
Hours of Sleep
Haz
ard
Rat
io
Gangwish JE et al. Hypertension 2006; 47:833-9
Men & Women, 32-59 years, n=3,620Men & Women, 32-59 years, n=3,6201.60 1.60
(1.19-2.14)(1.19-2.14)
88thth Hypertension Masterclass Hypertension Masterclass Cappuccio FP et al. Hypertension 2007:50:694-701
Sleep duration and Sleep duration and prevalent prevalent HypertensionHypertension The Whitehall II StudyThe Whitehall II Study
0.701.00.92
0.74
0.0
0.5
1.0
1.5
2.0
Rel
ativ
e R
isk
0.86 0.921.01.12
0.88
0.0
0.5
1.0
1.5
2.0
<=5 6 7 8 >=9
Re
lati
ve
Ris
k
Hours sleepHours sleep
Women, n=1,567Women, n=1,567
Men, n=4,199Men, n=4,199
1.72 1.72 (1.07-2.75)(1.07-2.75)
P = 0.037
88thth Hypertension Masterclass Hypertension Masterclass Cappuccio FP et al. Hypertension 2007:50:694-701
Sleep duration and Sleep duration and incidentincident HypertensionHypertension The Whitehall II StudyThe Whitehall II Study
1.42
0.99 1.071.31
1.0
0.0
0.5
1.0
1.5
2.0
Rel
ativ
e R
isk
1.11
0.13
0.89 1.01.02
0.0
0.5
1.0
1.5
2.0
<=5 6 7 8 >=9
Re
lati
ve
Ris
k
Hours sleepHours sleep
Women, n=1,005Women, n=1,005
Men, n=2,686Men, n=2,686
88thth Hypertension Masterclass Hypertension Masterclass Stranges S et al. 2008; (under review)
Sleep duration and Sleep duration and prevalent prevalent HypertensionHypertension The Western New York Health StudyThe Western New York Health Study
0.691.0
0.0
0.5
1.0
1.5
2.0
Rel
ativ
e R
isk
1.01.39
0.88
0.0
0.5
1.0
1.5
2.0
Re
lati
ve
Ris
k
Hours sleepHours sleep
Women, n=1,710Women, n=1,710
Men, n=1,317Men, n=1,317
1.61 1.61 (1.08-2.41)(1.08-2.41)
<6 6-8 >8
88thth Hypertension Masterclass Hypertension Masterclass
• Increased BP load resulting from prolongation of higher Increased BP load resulting from prolongation of higher
BP whilst awakeBP whilst awake
• Truncation of the BP dip during sleepTruncation of the BP dip during sleep
• Prolonged activation of sympathetic nervous systemProlonged activation of sympathetic nervous system
• Increased renal sodium retentionIncreased renal sodium retention
• Gender-specific effects?Gender-specific effects?
• Confounding?Confounding?
Sleep Deprivation & Hypertension:Sleep Deprivation & Hypertension:Potential MechanismsPotential Mechanisms
88thth Hypertension Masterclass Hypertension Masterclass
Total and cause-specific mortalityTotal and cause-specific mortality
88thth Hypertension Masterclass Hypertension Masterclass Kripke DF et al. Arch Gen Psychiatry 2002;59:131-136
The U-Shaped Association between The U-Shaped Association between Sleep Duration and Sleep Duration and TotalTotal MortalityMortality
The Cancer Prevention Study IIThe Cancer Prevention Study II
Women, n=636,095Women, n=636,095 Men, n=480,841Men, n=480,841
88thth Hypertension Masterclass Hypertension Masterclass
All-CauseAll-Cause mortality by mortality by hours of sleephours of sleepThe Whitehall II StudyThe Whitehall II Study
0
1
2
3
4
< 5h(56 deaths)
7h(256 deaths)
8h(87 deaths)
Hazard Ratio (95% CI)
Age-adjustedFully adjusted
6h(160 deaths)
> 9h(7 deaths)
Phase 1 (1985-88) n=9,781
0
1
2
3
4
< 5h(29 deaths)
7h(112 deaths)
8h(74 deaths)
Hazard Ratio (95% CI)
Age-adjustedFully adjusted
6h(61 deaths)
> 9h(16 deaths)
Phase 3 (1991-93) n=7,729
Ferrie JE et al. Sleep 2007; 30:1659-66
88thth Hypertension Masterclass Hypertension Masterclass
All-CauseAll-Cause mortality from Phase 3 by mortality from Phase 3 by changes in changes in hours sleephours sleep between Phase 1 and Phase 3 between Phase 1 and Phase 3
0
1
2
3
4
RefIncrease from 5 or 6h(55 deaths)
Decrease from 6, 7 or 8h(57 deaths)
Increase from 7 or 8h(58 deaths)
Hazard Ratio (95% CI)
Age-adjustedFully adjusted
Ferrie JE et al. Sleep 2007; 30:1659-66
88thth Hypertension Masterclass Hypertension Masterclass
0
1
2
3
4
RefIncrease from 5 or 6h(16 deaths)
Decrease from 6, 7 or 8h(24 deaths)
Increase from 7 or 8h(12 deaths)
Hazard Ratio (95% CI)
Age-adjustedFully adjusted
CVDCVD mortality from Phase 3 by mortality from Phase 3 by changes in hours changes in hours sleepsleep between Phase 1 and Phase 3 between Phase 1 and Phase 3
Ferrie JE et al. Sleep 2007; 30:1659-66
88thth Hypertension Masterclass Hypertension Masterclass
0
1
2
3
4
RefIncrease from 5 or 6h(38 deaths)
Decrease from 6, 7 or 8h(33 deaths)
Increase from 7 or 8h(45 deaths)
Hazard Ratio (95% CI)
Age-adjustedFully adjusted
Non-CVDNon-CVD mortality from Phase 3 by mortality from Phase 3 by changes in changes in hours sleephours sleep between Phase 1 and Phase 3 between Phase 1 and Phase 3
Ferrie JE et al. Sleep 2007; 30:1659-66
88thth Hypertension Masterclass Hypertension Masterclass
SummarySummary
• Either a Either a decreasedecrease in sleep duration from a regular 6, 7 in sleep duration from a regular 6, 7 or 8h per night or an or 8h per night or an increaseincrease from a regular 7 or 8h from a regular 7 or 8h per night predict per night predict all-cause mortalityall-cause mortality
• A A decreasedecrease in sleep duration affects all-cause in sleep duration affects all-cause mortality via increases in mortality via increases in cardiovascular deathscardiovascular deaths
• An An increaseincrease in sleep duration affects overall mortality in sleep duration affects overall mortality via an increase in via an increase in non-cardiovascular deathsnon-cardiovascular deaths
• Sleep changesSleep changes over time may represent more reliable over time may represent more reliable measures to assess the impact of sleep on healthmeasures to assess the impact of sleep on health
88thth Hypertension Masterclass Hypertension Masterclass
Coronary Heart DiseaseCoronary Heart Disease
88thth Hypertension Masterclass Hypertension Masterclass
Coronary Heart DiseaseCoronary Heart Disease by by hours of sleephours of sleepThe MONICA StudyThe MONICA Study
1.401.341.05 1.0
0.0
0.5
1.0
1.5
2.0
2.5
3.0
Rel
ativ
e R
isk
1.051.22
1.071.01.13
0.0
0.5
1.0
1.5
2.0
<=5 6 7 8 >=9
Re
lati
ve
Ris
k
Hours sleepHours sleep
Women, n=3,388Women, n=3,388
Men, n=3,508Men, n=3,508
2.98 2.98 (1.48-6.03)(1.48-6.03)
Meisinger C et al. Sleep 2007; 30:1121-27
88thth Hypertension Masterclass Hypertension Masterclass
Coronary Heart DiseaseCoronary Heart Disease by by hours of sleephours of sleepThe Nurses’ Health StudyThe Nurses’ Health Study
1.091.181.0
0.0
0.5
1.0
1.5
2.0
<=5 6 7 8 >=9
Rela
tive
Risk
Hours sleepHours sleep
1.45 1.45 (1.10-1.92)(1.10-1.92)
Ayas NT et al. Arch Intern Med 2003; 163:205-9
1.38 1.38 (1.03-1.86)(1.03-1.86)
Women, n=71,617Women, n=71,617
88thth Hypertension Masterclass Hypertension Masterclass
SummarySummary
• Both short and long sleep duration may be associated Both short and long sleep duration may be associated with more detrimental effects on cardiovascular health with more detrimental effects on cardiovascular health in women than menin women than men
• The biological mechanisms underlying these The biological mechanisms underlying these associations are unclearassociations are unclear
• High blood pressure may represent one mechanism High blood pressure may represent one mechanism linking short sleep duration with increased risk of CHD, linking short sleep duration with increased risk of CHD, at least in women at least in women
88thth Hypertension Masterclass Hypertension Masterclass
Co-morbidities of sleep disorders (psychiatric/chronic conditions)Co-morbidities of sleep disorders (psychiatric/chronic conditions)
Bidirectional relationship (reverse causality/temporality?)Bidirectional relationship (reverse causality/temporality?)
Confounding by other lifestyle behaviorsConfounding by other lifestyle behaviors
Sleep as marker of health status vs. risk factorSleep as marker of health status vs. risk factor
Biological plausibilityBiological plausibility
Objective assessment of sleep changes over timeObjective assessment of sleep changes over time
Unresolved issuesUnresolved issues
88thth Hypertension Masterclass Hypertension Masterclass
SLEEP, HEALTH & SOCIETYUniversity of Warwick Medical School
sleepresearch@warwick.ac.uk
Leads: FP Cappuccio & E Peile
Warwick Team: MA Miller, S Stranges, N-B Kandala, FM Taggart, C Ji, A Currie,
G Ward, A Bakewell, A Lowe, D Cooper
Collaborators:
Warwick: S Williams, D Banejee,
RCP: R Pounder
UCL: MG Marmot, E Brunner, M Kumari, M Shipley, JE Ferrie
Surrey: D-J Djik, S Archer
Harvard: C Czeisler, S Lockley, C Landrigan
Naples: P Strazzullo, G Barba
Buffalo: JM Dorn, RP Donahue, M Trevisan
Funding: Cephalon Inc., Wingate Foundation, Whitehall II,
RDF University of Warwick, NHS Workforce
88thth Hypertension Masterclass Hypertension Masterclass Groeger JA et al. J Sleep Res. 2004; 13:359-71
Average sleep duration in a survey Average sleep duration in a survey of ~2,000 British Adultsof ~2,000 British Adults
88thth Hypertension Masterclass Hypertension Masterclass
Co-morbidities of Sleep Disorders Co-morbidities of Sleep Disorders
Sleep disordersSleep disorders Co-morbiditiesCo-morbidities
InsomniaInsomnia Psychiatric DisordersPsychiatric Disorders
Sleep ApnoeaSleep Apnoea Cardiopulmonary DiseaseCardiopulmonary Disease
Restless Legs SyndromeRestless Legs Syndrome Musculoskeletal ConditionsMusculoskeletal Conditions
Short sleep duration Short sleep duration ((behavioural)) CancerCancer
88thth Hypertension Masterclass Hypertension Masterclass
Co-morbidities of Sleep Disorders Co-morbidities of Sleep Disorders
36.0
52
69
0
10
20
30
40
50
60
70
80
None 1 to 3 4 or more
Number of Medical Conditions
% S
leep
pro
ble
ms
Foley D et al. Psychosom Res. 2004; 56:497-502
88thth Hypertension Masterclass Hypertension Masterclass
Regression coefficient: β (unit of BMI per h sleep per night)
-0.86 -0.57 -0.35 -0.12 0
Combined
Stranges (2008)
Kohatsu (2006)
Gangwisch1 (2005)
Bjorkelund (2005)
Hasler (2004)
Cournot (2004)
Vioque (2000)
Sleep Duration and Sleep Duration and BMIBMIMeta-analysis of Cross-Sectional StudiesMeta-analysis of Cross-Sectional Studies
Cappuccio FP et al. Sleep 2008; in press
Adults, n=16,509Adults, n=16,509 β & 95% CI
-0.60 (-0.75; -0.45)
-0.01 (-0.03; 0.00)
-0.45 (-0.71; -0.19)
-0.18 (-0.36; 0.00)
-0.36 (-0.52;-0.20)
-0.52 (-0.86; -0.18)
-0.39 (-0.51; -0.27)
-0.35 (-0.57;-0.12)
Equivalent to approx 1.4 kg per
hour
88thth Hypertension Masterclass Hypertension Masterclass Gale SM et al. J Nutr 2004; 134:295-8
LACK OF SLEEPLACK OF SLEEP
lessless
moremore
88thth Hypertension Masterclass Hypertension Masterclass
Objective assessment of sleep changes over timeObjective assessment of sleep changes over time
More prospective evidenceMore prospective evidence
Better understanding of determinants of sleep durationBetter understanding of determinants of sleep duration
Better control for confounders/co-morbiditiesBetter control for confounders/co-morbidities
Experimental evidence on biological plausibilityExperimental evidence on biological plausibility
Need for further research…Need for further research…
88thth Hypertension Masterclass Hypertension Masterclass
Short sleep durationShort sleep duration Long sleep Long sleep durationduration
Low SES/Unhealthy lifestyle/ Poor general health status Co-Morbidities/Elderly
Appetite dysregulation/ Impaired glucose
homeostasis
CVD/Metabolic alterations
Increased morbidity/mortality/ Increased morbidity/mortality/ Reduced quality of life Reduced quality of life
Inflammatory/neurovegatative/ hormonal responses
Depression/ Poor general
health status
Putative pathwaysPutative pathways
88thth Hypertension Masterclass Hypertension Masterclass
Sleep Deprivation & Diabetes:Sleep Deprivation & Diabetes:Potential MechanismsPotential Mechanisms
Spiegel K et al. J Appl Physiol. 2005; 99: 2008-19
DiabetesDiabetes
Acute sleep Acute sleep deprivationdeprivation
Chronic sleep Chronic sleep deprivationdeprivation
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