BSc (Hons), PhD, MAcadMEd
Reader of Biochemical Medicine
University of Warwick,
Warwick Medical School,
5th April 2011
Insufficient Sleep
(Sleep Deprivation)
Neurobehavioral deficits
Fragmented Sleep
(Sleep Disruption)
Performance deficits
Increased Morbidity / Mortality
Decreased Quality of Life
Is there a link between the growing obesity epidemic
and the decline in sleeping time?
Average Body Mass Index
in US adults in the last century
Average sleep duration (hours)
in US adults in the last century
Forest plot of the risk of obesity amongst short sleepers in children (age 2
to 20 years).
Short sleep if obese
Short sleep if lean
Odds Ratio
(95% CI)
First author
Year
Country
Sample size
Locard
1992
France
1,031
2.25 (1.27 to 3.97)
BenSlama
2002
Tunisia
167
11.02 (4.75 to 25.60)
Sekine
2002
Japan
8,941
1.19 (0.99 to 1.41)
Von Kries
2002
Germany
6,645
2.16 (1.55 to 3.01)
Agras
2004
USA
150
1.99 (0.79 to 5.01)
Giugliano
2004
Brazil
165
5.64 (0.72 to 44.17)
Padez
2005
Portugal
4,390
1.15 (0.93 to 1.43)
Reilly
2005
UK
6,426
1.45 (1.19 to 1.76)
Chaput
2006
Canada
422
2.64 (1.25 to 5.56)
Chen
2006
Taiwan
656
1.75 (1.28 to 2.40)
Seicean
2007
USA
509
2.23 (0.87 to 5.70)
29,502
1.89 (1.46 to 2.43)
Combined effect: p<0.0001
Heterogeneity: Q=46.6; p<0.001
Begg’s test: p=0.12
0.1
1
10
Odds Ratio (log scale)
Cappuccio FP, Taggart FM, Kandala NB, Currie A, Peile E,
Stranges S, Miller MA. Sleep 2008; 31: 619-26
4
Forest plot of the risk of obesity amongst short sleepers in adults
(age 15 to 102 years).
First author
Year
Country
Sample size
Vioque
2000
Spain
1,772
3.35 (2.22 to 5.06)
Shigeta
2001
Japan
437
1.97 (1.03 to 3.77)
Kripke
2002
USA
497,037
1.52 (1.46 to 1.58)
Cournot
2004
France
3,127
1.38 (0.97 to 1.96)
Short sleep if obese
Short sleep if lean
Odds Ratio
(95% CI)
Hasler
2004
Switzerland
457
10.8 (0.99 to 118.1)
Bjorkelund
2005
Sweden
1,460
1.52 (0.68 to 3.40)
Gangwisch 1
2005
USA
3,682
1.84 (1.40 to 2.42)
Gangwisch 2
2005
USA
3,324
1.38 (1.07 to 1.78)
Gangwisch 3
2005
USA
2,582
0.95 (0.67 to 1.35)
Singh
2005
USA
3,158
1.70 (1.27 to 2.28)
Moreno
2006
Brazil
4,878
1.22 (1.06 to 1.40)
Vahtera
2006
Finland
26,468
1.43 (1.35 to 1.52)
Watari (men)
2006
Japan
19,894
1.95 (1.20 to 3.19)
Watari (women)
2006
Japan
5,418
2.97 (0.77 to 11.50)
Bjortvan
2007
Norway
8,860
1.88 (1.22 to 2.89)
Chaput (men)
2007
Canada
323
4.01 (1.73 to 9.33)
Chaput (women)
2007
Canada
417
2.64 (1.25 to 5.56)
Ko
2007
Hong Kong
4,793
1.30 (1.13 to 1.49)
Tuomilehto
2007
Finland
2,770
1.30 (1.05 to 1.61)
Fogelholm (men)
2007
Finland
3,377
1.46 (1.13 to 1.89)
Fogelholm (women)
2007
Finland
4,264
1.75 (1.36 to 2.26)
Stranges
2008
UK
5,021
2.01 (1.56 to 2.60)
603,519
1.55 (1.43 to 1.68)
Combined effect: p<0.0001
Heterogeneity: Q=64.0, p<0.001
Begg’s test: p=0.09
0.1
1
10
Odds Ratio (log scale)
Cappuccio FP, Taggart FM, Kandala NB, Currie A, Peile E,
Stranges S, Miller MA. Sleep 2008; 31: 619-26
5
Ferrie JE et al. Sleep 2007: 30: 1659-66
Cappuccio FP, Miller MA et al. Sleep 2010;
Cappuccio et al. Diabetes care 2010;
6
Outcomes
Risk factors
Mechanisms
Short sleep
Inflammation
Appetite
Neuro
Endocrine
Hypertension
Diabetes
Obesity
High cholesterol
High trigs
Low HDL-chol
Metabolic synd.
Death
CHD
Stroke
Heart failure
8
•
•
Leptin
Ghrelin
•
•
Insulin: increased sympathetic tone/ changes in cortisol
Adiponectin
•
•
E-selectin
Soluble intercellular adhesion molecules- (sICAM-1)
•
•
•
•
C-reactive Protein (CRP)
Interleukin 6 (IL-6)
Tumor necrosis factor  (TNF-)
Fibrinogen
•
•
•
Von Willebrand Factor
Factor VII
Fibrinogen
9
Men (n=3,428)
Women (n=1,249)
Geometric Mean Ratio (95% CI)
Geometric Mean Ratio (95% CI)
2
2
P=0.70 non-linear
P=0.43 linear
1.8
1.8
1.6
1.6
1.4
1.4
1.2
1.2
1
1
0.8
0.8
0.6
P=0.04 non-linear
P=0.71 linear
0.6
< 5h
(n=105)
6h
(n=708)
7h
(n=1671)
8h
(n=857)
> 9h
(n=87)
< 5h
(n=56)
6h
(n-269)
7h
(n=578)
8h
(n=303)
> 9h
(n=43)
Adjusted for age, marital status, BMI, smoking, SBP and triglycerides
Miller, Sleep. 2009; 32(7):857-64.
10
Risk of developing or dying of stroke amongst short sleepers (top) and long sleepers (bottom).
Short-sleepers: 210,978 participants with 3,163 fatal and non-fatal stroke events.
Long-sleepers includes 210,978 participants with 3,208 fatal and non-fatal stroke events
Reference
Short sleep
Relative Risk
(95% CI)
First author
Year
Country
Qureshi
1997
USA
1.00 (0.69 to 1.45)
Amagai (men)
2004
Japan
1.30 (0.18 to 9.58)
Amagai (women)
2004
Japan
3.19 (0.98 to 10.34)
Chen
2008
USA
1.14 (0.97 to 1.33)
Ikehara (men)
2009
Japan
1.55 (0.81 to 2.96)
Ikehara (women)
2009
Japan
1.07 (0.60 to 1.93)
1.15 (1.00 to 1.31)
Combined effect: p=0.047
Heterogeneity: I2=0%;, p=0.50
Egger’s test: p=0.30
0.1
1
10
Relative Risk (log scale)
Reference
Relative Risk
(95% CI)
Long sleep
First author
Year
Country
Qureshi
1997
USA
1.51 (1.12 to 2.02)
Amagai (men)
2004
Japan
1.20 (0.49 to 2.95)
Amagai (women)
2004
Japan
2.51 (0.79 to 7.98)
Chen
2008
USA
1.70 (1.34 to 2.15)
Ikehara (men)
2009
Japan
1.67 (1.32 to 2.11)
Ikehara (women)
2009
Japan
1.68 (1.28 to 2.21)
1.65 (1.45 to 1.87)
Combined effect: p<0.0001
Heterogeneity: I2=0%; p=0.92
Egger’s test: p=0.96
0.1
1
10
Relative Risk (log scale)
Cappuccio, Miller EHJ 2011
11
Cross-sectional relationship between VWF, Factor VII and Fibrinogen and
duration of sleep by gender.
1.05
1.1
1.15
Female
1
Adjusted Geom. means of VWF
Male
<=6H
7H
8+H<=6H
7H
8+H
Sleep in hours
Adjusted Geom. means of VWF
Adjusted Geom. means of VWF
Upper 95%CI/Lower 95%CI
Female
1
1.05
1.1
Male
.95
AdjustedGeom. meansof Factor7
Graphs by sex
<=6H
7H
8+H<=6H
7H
8+H
Sleep in hours
Adjusted Geom. means of Factor7
Adjusted Geom. means of Factor7
Male
No major associations between sleep
and either factor VII or fibrinogen were
observed.
Female
.98
1
1.02
1.04
In women, there was a significant nonlinear association with the highest levels
mainly been observed in the long
sleepers, irrespective of menopausal
status.
Upper 95%CI/Lower 95%CI
Graphs by sex
Adjusted Geom. means of fibrinogen
Both short and long sleeping men had
higher vWF levels than those that slept
7h.
<=6H
7H
8+H<=6H
7H
8+H
Sleep in hours
Adjusted Geom. means of fibrinogen
Adjusted Geom. means of fibrinogen
Upper 95%CI/Lower 95%CI
Graphs by sex
Adj
Adj:: age, employment, BMI, smoking, alcohol,
systolic blood pressure, physical score,
mental score, insulin, time sample taken
Longitudinal studies are required to fully
investigate possible temporal
relationships between sleep and vWF.
Miller et al. Arterioscler Thromb Vasc Biol. 2010 Oct;30(10):2032-8.
12
(E.g. Gender differences,
healthy ageing)
(E.g. Inflammation,
thrombosis, lipids)
(E.g. shift work,
Junior doctors)
(E.g. Depression,
Cognition (Boston – UoW))
(E.g. Maternal and
Foetal Outcomes)
Research-Led Teaching
(E.g. CVD, Diabetes,
Hypertension, stroke)
(E.g. SSM Sleep Medicine)
Visits:
14
As the course progressed I started
to appreciate more the importance
and relevance of such a field to
other medical fields and to daily
life
After studying this
very interesting,
innovative and
informative module,
my opinion
regarding sleep has
changed hugely
It was an excellent
introduction to the
subject and I
thoroughly
enjoyed it
Thanks to the
SSM, I know the
value of sleep
I admire the
dedication of
both tutors
The highlighting factors
for me were our visits to
Loughborough and
Leicester sleep
laboratories
sleepresearch@warwick.ac.uk
Leads:
FP Cappuccio & MA Miller
Warwick Team:
E Peile, S Stranges, NN-B Kandala, FM Taggart,
C Ji, G Ward, A Bakewell
Bakewell,, A Currie, A Lowe, D Cooper
Collaborators:
Warwick
R.C.P.
U.C.L.
Boston (Harvard)
Naples (Federico II)
Avellino (CNR)
Buffalo (SUNY)
Funding:
S Williams, S Weich
R Pounder
MG Marmot, E Brunner, M Kumari
Kumari,, M Shipley, JE Ferrie
Ferrie,,
M Kivimaki
C Czeisler
Czeisler,, SW Lockley, CP Landrigan, JP Sullivan
P Strazzullo, L D’
D’Elia
G Barba
J Dorn, R Donhaue,
Donhaue, M Trevisan
Cephalon Inc., Wingate Foundation, Whitehall II,
RDF University of Warwick, NHS Workforce
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Cappuccio FP, Cooper D, D'Elia L, Strazzullo P, Miller MA. Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of
prospective studies. Eur Heart J. 2011
Miller MA, Kandala NB, Kumari M, Marmot MG, Cappuccio FP. Relationships between sleep duration and von Willebrand factor, factor VII, and
fibrinogen: Whitehall II study. Arterioscler Thromb Vasc Biol. 2010 Oct;30(10):2032-8.
Cappuccio FP, D'Elia L, Strazzullo P, Miller MA. Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies.
Sleep. 2010 May 1;33(5):585-92. Review.
Stranges S, Dorn JM, Cappuccio FP, Donahue RP, Rafalson LB, Hovey KM, Freudenheim JL, Kandala NB, Miller MA, Trevisan M. A population-based
study of reduced sleep duration and hypertension: the strongest association may be in premenopausal women. J Hypertens. 2010 May;28(5):896-902.
Cappuccio FP, D'Elia L, Strazzullo P, Miller MA. Quantity and quality of sleep and incidence of type 2 diabetes: a systematic review and meta-analysis.
Diabetes Care. 2010 Feb;33(2):414-20.
Miller MA, Kandala NB, Kivimaki M, Kumari M, Brunner EJ, Lowe GD, Marmot MG, Cappuccio FP. Gender differences in the cross-sectional
relationships between sleep duration and markers of inflammation: Whitehall II study. Sleep. 2009 Jul 1;32(7):857-64.
Stranges S, Dorn JM, Shipley MJ, Kandala NB, Trevisan M, Miller MA, Donahue RP, Hovey KM, Ferrie JE, Marmot MG, Cappuccio FP. Correlates of
short and long sleep duration: a cross-cultural comparison between the United Kingdom and the United States: the Whitehall II Study and the Western New
York Health Study. Am J Epidemiol. 2008 Dec 15;168(12):1353-64.
Cappuccio FP, Taggart FM, Kandala NB, Currie A, Peile E, Stranges S, Miller MA. Meta-analysis of short sleep duration and obesity in children and
adults. Sleep. 2008 May 1;31(5):619-26.
Ferrie JE, Shipley MJ, Cappuccio FP, Brunner E, Miller MA, Kumari M, Marmot MG. A prospective study of change in sleep duration: associations with
mortality in the Whitehall II cohort. Sleep. 2007 Dec 1;30(12):1659-66.
Stranges S, Cappuccio FP, Kandala NB, Miller MA, Taggart FM, Kumari M, Ferrie JE, Shipley MJ, Brunner EJ, Marmot MG. Cross-sectional versus
prospective associations of sleep duration with changes in relative weight and body fat distribution: the Whitehall II Study. Am J Epidemiol. 2008 Feb
1;167(3):321-9. .
Cappuccio FP, Stranges S, Kandala NB, Miller MA, Taggart FM, Kumari M, Ferrie JE, Shipley MJ, Brunner EJ, Marmot MG. Gender-specific
associations of short sleep duration with prevalent and incident hypertension: the Whitehall II Study. Hypertension. 2007 Oct;50(4):693-700.
Miller MA, Cappuccio FP. Inflammation, sleep, obesity and cardiovascular disease. Curr Vasc Pharmacol. 2007 Apr;5(2):93-102. Review.
Cappuccio FP, Bakewell A, Taggart FM, Ward G, Ji C, Sullivan JP, Edmunds M, Pounder R, Landrigan CP, Lockley SW, Peile E; Warwick EWTD
Working Group. Implementing a 48 h EWTD-compliant rota for junior doctors in the UK does not compromise patients' safety: assessor-blind pilot
comparison. QJM. 2009 Apr;102(4):271-82. Epub 2009 Jan 27.
Currie A, Cappuccio FP. Sleep in children and adolescents: a worrying scenario: can we understand the sleep deprivation-obesity epidemic? Nutr Metab
Cardiovasc Dis. 2007 Mar;17(3):230-2.
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