Sleep Deprivation and Chronic Disease
Francesco P Cappuccio MD MSc FRCP FFPH FAHA
Professor of Cardiovascular Medicine & Epidemiology
Clinical Sciences Research Institute
Warwick Medical School, Coventry, UK
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How many hours per night
do you usually sleep?
Less than 5h
6h
7h
8h
9h or more
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0%
or
m
or
e
0%
8h
0%
9h
Le
ss
th
an
5h
0
0%
7h
0%
6h
1.
2.
3.
4.
5.
50
Sleep Duration Time Trends in US Adults
Hrs per night
10.0
9.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0.0
9.0
7.5
6.8
1910
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1975
2005
National Sleep Foundation. Sleep in America Poll
Sleep duration in British Adults
(1967/2003)
1967
2003
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Groeger JA et al. J Sleep Res. 2004; 13:359-71
How much did you score
at the ESS questionnaire?
50
1. 10 or less
2. 11-16
3. 17 or more
or
m
or
e
0%
17
11
es
s
or
l
10
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0%
-1
6
0%
0
Insufficient Sleep
(Sleep Deprivation)
Fragmented Sleep
(Sleep Disruption)
Excessive Daytime Sleepiness (EDS)
Neurobehavioral
deficits
Performance deficits
Cardio-metabolic
errors/accuracy
appetite regulation
high blood pressure
cognitive/executive function
attention/concentration
Increased Morbidity / Mortality
Decreased Quality of Life
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Short Sleep Duration & Chronic Diseases
Cardio-Metabolic Risk Factors
• Obesity/body fat distribution
• Type 2 Diabetes Mellitus
• Hypertension
Total and Cause-Specific Mortality
Coronary Heart Disease
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Cardio-Metabolic Risk Factors:
Obesity
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Obesity Epidemic and Sleep Duration
BMI in US adults
28.0
26.9
27.0
26.0
25.2
25.0
24.0
23.0
23.0
22.0
21.0
1910
Sleep duration in US adults 10.0
9.0
2005
9.0
7.5
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0.0
6.8
1910
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1975
1975
2005
Short Sleep Duration and Metabolic Hormones
Leptin
Ghrelin
-15.5%
+14.9%
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Taheri S et al. PLoS Med. 2004; 1:210-7
Sleep Deprivation and Appetite Regulation
-18% leptin; +28% ghrelin
+24% hunger/appetite
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Spiegel K et al. Ann Intern Med. 2004; 141:846-50
Short Sleep Duration (<10h) and Obesity
Meta-analysis of Cross-Sectional Studies
Children, n=29,502
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)
Locard (1992)
BenSlama (2002)
Sekine (2002)
Von Kries (2002)
Agras (2004)
Giugliano (2004)
Padez (2005)
1.45 (1.20; 1.76)
2.63 (1.24; 5.58)
Reilly (2005)
Chaput (2006)
1.75 (1.28; 2.39)
2.23 (0.87; 5.73)
Chen (2006)
Seicean (2007)
1.89
Combined
0.72
1
1.89
Odds Ratio
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11
(1.46-2.43)
Cappuccio FP et al. Sleep 2008; in press
Short Sleep Duration (<5h) and Obesity
Meta-analysis of Cross-Sectional Studies
Adults, n=603,519
OR & 95% CI
Vioque (2000)
Shigeta (2001)
Kripke (2002)
Cournot (2004)
Hasler (2004)
Bjorkelund (2005)
Gangwisch1 (2005)
Gangwisch2 (2005)
Gangwisch3 (2005)
Singh (2005)
Moreno (2006)
Vahtera (2006)
Watari (men) (2006)
Watari (women) (2006)
Bjorvatn (2007)
Chaput (men) (2007)
Chaput (women) (2007)
Ko (2007)
Tuomilehto (2007)
Fogelholm (men) (2007)
Fogelholm (Women) (2007)
Stranges (2008)
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)
1.55
Combined
0.67
1
1.55
10
(1.43-1.68)
Odds Ratio
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Cappuccio FP et al. Sleep 2008; in press
Sleep Deprivation & Obesity:
Potential Mechanisms
Sleep
Deprivation
Obesity
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Patel SR et al. Obesity; 2008; in press
Short Sleep Duration and Obesity
The Whitehall II Study/Cross-Sectional (n=5,021)
2
1.5
-0.35 (-0.57;-0.12)
P <0.001
1
0.5
BMI
0
-0.5
-1
-1.5
-2
<=5
6
7
8
9+
6
7
8
9+
1.65
2.5
(1.22-2.24)
2
OR Obesity 1.5
1
0.5
0
<=5
Hours of sleep
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Stranges S et al. Am J Epidemiol. 2008; 167: 321-9
Short Sleep Duration and Obesity
The Whitehall II Study/Prospective
0.6
0.4
0.03 (-0.03; 0.08)
0.2
BMI
P = 0.36
0
-0.2
-0.4
-0.6
<=5
6
7
8
9+
6
7
8
9+
3
OR Obesity
2.5
1.05
(0.60-1.82)
2
1.5
1
0.5
0
<=5
Hours of sleep
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Stranges S et al. Am J Epidemiol. 2008; 167: 321-9
Cardio-Metabolic Risk Factors:
Type 2 Diabetes
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Sleep Duration and Risk of Diabetes
The Massachusetts Male Aging Study (n=1,139)
3.12
(1.53-6.37)
6
Relative Risk
5
1.95
(0.95-4.01)
4
3
2
1
0
<=5
6
7
Hours of Sleep
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8
>8
Yaggi HK et al. Diabetes Care 2006; 29:657-61
Sleep Duration and Risk of Diabetes
The Nurses’ Health Study (n=70,026)
2
1.29
(1.05-1.59)
1.18
Relative Risk
1.5
(0.96-1.44)
1
0.5
0
<=5
6
7
Hours of Sleep
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8
>8
Ayas NT et al. Diabetes Care 2003; 26:380-4
Sleep Deprivation & Diabetes:
Potential Mechanisms
• Elevation of evening cortisol levels predisposing to
insulin resistance
• Increase in sympathetic tone, inhibiting pancreatic
function and leading to increased glucose intolerance
• Weight gain and reduction in leptin
• Reduction of testosterone levels
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Cardio-Metabolic Risk Factors:
Hypertension
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Sleep duration and incident Hypertension
NHANES-I
2.5
1.60
(1.19-2.14)
Men & Women, 32-59 years, n=3,620
Hazard Ratio
2
1.5
1
0.5
0
<=5
6
7 to 8
=>9
Hours of Sleep
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Gangwish JE et al. Hypertension 2006; 47:833-9
Sleep duration and prevalent Hypertension
The Whitehall II Study
1.72
(1.07-2.75)
Relative Risk
2.0
Women, n=1,567
1.5
0.92
1.0
P = 0.037
1.0
0.74
0.70
0.5
0.0
Relative Risk
2.0
Men, n=4,199
1.5
1.0
0.88
0.86
<=5
6
1.0
1.12
0.92
0.5
0.0
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7
Hours sleep
8
>=9
Cappuccio FP et al. Hypertension 2007:50:694-701
Sleep duration and incident Hypertension
The Whitehall II Study
Relative Risk
2.0
1.5
1.31
1.42
Women, n=1,005
1.0
0.99
1.07
1.0
0.5
0.0
Relative Risk
2.0
Men, n=2,686
1.5
1.0
0.89
1.02
1.0
1.11
0.5
0.13
0.0
<=5
6
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7
Hours sleep
8
>=9
Cappuccio FP et al. Hypertension 2007:50:694-701
Sleep duration and prevalent Hypertension
The Western New York Health Study
Relative Risk
2.0
1.61
(1.08-2.41)
Women, n=1,710
1.5
1.0
0.69
1.0
0.5
0.0
2.0
Relative Risk
Men, n=1,317
1.5
1.0
0.88
1.0
1.39
0.5
0.0
<6
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6-8
Hours sleep
>8
Stranges S et al. 2008; (under review)
Sleep Deprivation & Hypertension:
Potential Mechanisms
• Increased BP load resulting from prolongation of higher BP
whilst awake
• Truncation of the BP dip during sleep
• Prolonged activation of sympathetic nervous system
• Increased renal sodium retention
• Gender-specific effects?
• Confounding?
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Total and cause-specific mortality
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The U-Shaped Association between
Sleep Duration and Total Mortality
The Cancer Prevention Study II
Women, n=636,095
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Men, n=480,841
Kripke DF et al. Arch Gen Psychiatry 2002;59:131-136
All-Cause mortality by hours of sleep
The Whitehall II Study
Phase 1 (1985-88) n=9,781
Phase 3 (1991-93) n=7,729
4 Hazard Ratio (95% CI)
4 Hazard Ratio (95% CI)
Age-adjusted
Fully adjusted
Age-adjusted
Fully adjusted
3
3
2
2
1
1
0
0
< 5h
(56 deaths)
6h
7h
8h
(160 deaths) (256 deaths) (87 deaths)
> 9h
(7 deaths)
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< 5h
(29 deaths)
6h
(61 deaths)
7h
8h
(112 deaths) (74 deaths)
> 9h
(16 deaths)
Ferrie JE et al. Sleep 2007; 30:1659-66
All-Cause mortality from Phase 3 by changes in
hours sleep between Phase 1 and Phase 3
4
Hazard Ratio (95% CI)
Age-adjusted
Fully adjusted
3
2
1
0
Increase from 5 or 6h
(55 deaths)
Ref
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Decrease from 6, 7 or 8h
(57 deaths)
Increase from 7 or 8h
(58 deaths)
Ferrie JE et al. Sleep 2007; 30:1659-66
CVD mortality from Phase 3 by changes in hours
sleep between Phase 1 and Phase 3
4
Hazard Ratio (95% CI)
Age-adjusted
Fully adjusted
3
2
1
0
Increase from 5 or 6h
(16 deaths)
Ref
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Decrease from 6, 7 or 8h
(24 deaths)
Increase from 7 or 8h
(12 deaths)
Ferrie JE et al. Sleep 2007; 30:1659-66
Non-CVD mortality from Phase 3 by changes in
hours sleep between Phase 1 and Phase 3
4
Hazard Ratio (95% CI)
Age-adjusted
Fully adjusted
3
2
1
0
Increase from 5 or 6h
(38 deaths)
Ref
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Decrease from 6, 7 or 8h
(33 deaths)
Increase from 7 or 8h
(45 deaths)
Ferrie JE et al. Sleep 2007; 30:1659-66
Summary
• Either a decrease in sleep duration from a regular 6, 7
or 8h per night or an increase from a regular 7 or 8h
per night predict all-cause mortality
• A decrease in sleep duration affects all-cause
mortality via increases in cardiovascular deaths
• An increase in sleep duration affects overall mortality
via an increase in non-cardiovascular deaths
• Sleep changes over time may represent more reliable
measures to assess the impact of sleep on health
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Coronary Heart Disease
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Coronary Heart Disease by hours of sleep
The MONICA Study
2.98
(1.48-6.03)
Relative Risk
3.0
Women, n=3,388
2.5
2.0
1.40
1.34
1.5
1.05
1.0
1.0
0.5
0.0
Relative Risk
2.0
Men, n=3,508
1.5
1.13
1.05
<=5
6
1.22
1.0
1.07
8
>=9
1.0
0.5
0.0
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7
Hours sleep
Meisinger C et al. Sleep 2007; 30:1121-27
Coronary Heart Disease by hours of sleep
The Nurses’ Health Study
Relative Risk
Women, n=71,617
2.0
1.45
1.38
(1.10-1.92)
1.5
(1.03-1.86)
1.18
1.09
1.0
1.0
0.5
0.0
<=5
6
7
8
>=9
Hours sleep
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Ayas NT et al. Arch Intern Med 2003; 163:205-9
Summary
• Both short and long sleep duration may be associated
with more detrimental effects on cardiovascular health
in women than men
• The biological mechanisms underlying these
associations are unclear
• High blood pressure may represent one mechanism
linking short sleep duration with increased risk of CHD,
at least in women
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Unresolved issues

Co-morbidities of sleep disorders (psychiatric/chronic conditions)

Bidirectional relationship (reverse causality/temporality?)

Confounding by other lifestyle behaviors

Sleep as marker of health status vs. risk factor

Biological plausibility

Objective assessment of sleep changes over time
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SLEEP, HEALTH & SOCIETY
University 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:
RCP:
UCL:
Surrey:
Harvard:
Naples:
Buffalo:
Funding:
S Williams, D Banejee,
R Pounder
MG Marmot, E Brunner, M Kumari, M Shipley, JE Ferrie
D-J Djik, S Archer
C Czeisler, S Lockley, C Landrigan
P Strazzullo, G Barba
JM Dorn, RP Donahue, M Trevisan
Cephalon Inc., Wingate Foundation, Whitehall II,
RDF University of Warwick, NHS Workforce
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Average sleep duration in a survey
of ~2,000 British Adults
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Groeger JA et al. J Sleep Res. 2004; 13:359-71
Co-morbidities of Sleep Disorders
Sleep disorders
Insomnia
Co-morbidities
Psychiatric Disorders
Sleep Apnoea
Cardiopulmonary Disease
Restless Legs Syndrome
Short sleep duration (behavioural)
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Musculoskeletal Conditions
Cancer
Co-morbidities of Sleep Disorders
80
69
% Sleep problems
70
60
52
50
40
36.0
30
20
10
0
None
1 to 3
4 or more
Number of Medical Conditions
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Foley D et al. Psychosom Res. 2004; 56:497-502
Sleep Duration and BMI
Meta-analysis of Cross-Sectional Studies
Adults, n=16,509
β & 95% CI
Vioque (2000)
-0.60 (-0.75; -0.45)
Cournot (2004)
-0.01 (-0.03; 0.00)
Hasler (2004)
-0.45 (-0.71; -0.19)
Bjorkelund (2005)
-0.18 (-0.36; 0.00)
Gangwisch1 (2005)
-0.36 (-0.52;-0.20)
Kohatsu (2006)
-0.52 (-0.86; -0.18)
Stranges (2008)
-0.39 (-0.51; -0.27)
-0.35 (-0.57;-0.12)
Combined
-0.86
-0.57
-0.35
Regression coefficient: β
(unit of BMI per h sleep per night)
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-0.12
0
Equivalent to approx
1.4 kg per hour
Cappuccio FP et al. Sleep 2008; in press
LACK OF SLEEP
less
more
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Gale SM et al. J Nutr 2004; 134:295-8
Need for further research…

Objective assessment of sleep changes over time

More prospective evidence

Better understanding of determinants of sleep duration

Better control for confounders/co-morbidities

Experimental evidence on biological plausibility
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Putative pathways
Low SES/Unhealthy lifestyle/
Poor general health status
Co-Morbidities/Elderly
Short sleep duration
Long sleep duration
Appetite dysregulation/
Impaired glucose homeostasis
Depression/
Poor general health status
Inflammatory/neurovegatative/
hormonal responses
CVD/Metabolic alterations
Increased morbidity/mortality/
Reduced quality of life
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Sleep Deprivation & Diabetes:
Potential Mechanisms
Acute sleep
deprivation
Chronic sleep
deprivation
Diabetes
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Spiegel K et al. J Appl Physiol. 2005; 99: 2008-19