8 th hypertension masterclass sleep deprivation and chronic disease francesco p cappuccio md msc...

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


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


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


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


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


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


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


Cardio-Metabolic Risk Factors:Cardio-Metabolic Risk Factors:

ObesityObesity


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


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%


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


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)


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


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)


Sleep Deprivation & Obesity:Sleep Deprivation & Obesity:Potential MechanismsPotential Mechanisms

ObesityObesitySleep Sleep DeprivationDeprivation

Patel SR et al. Obesity; 2008; in press


-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)


-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)



Type 2 DiabetesType 2 Diabetes


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)


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)


• 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



HypertensionHypertension


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



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



Men, n=1,317Men, n=1,317

1.61 1.61 (1.08-2.41)(1.08-2.41)

<6 6-8 >8


• 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


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


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)



6h(61 deaths)

> 9h(16 deaths)

Phase 3 (1991-93) n=7,729

Ferrie JE et al. Sleep 2007; 30:1659-66


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)





0

1

2

3

4






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



0

1

2

3

4






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



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


Coronary Heart DiseaseCoronary Heart Disease


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



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


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


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)



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


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


SLEEP, HEALTH & SOCIETYUniversity of Warwick Medical School

[email protected]

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


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


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


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


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


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…


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


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

8 th hypertension masterclass sleep deprivation and chronic disease francesco p cappuccio md msc...

Documents