Sleep and Health Patrick J. Strollo, Jr., M.D. University of Pittsburgh Medical Center PMBC SLEEP...
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Transcript of Sleep and Health Patrick J. Strollo, Jr., M.D. University of Pittsburgh Medical Center PMBC SLEEP...
Sleep and Health
Patrick J. Strollo, Jr., M.D.University of Pittsburgh Medical
Center
PMBC SLEEP WORKSHOP 2006
Goals
• Review how disturbed sleep impacts physiology in healthy humans
• Examine the data relating disturbed sleep to morbidity and mortality
• Understand how a common sleep disorder (Sleep Apnea) may the contribute to cardiovascular risk
• Appreciate the complex interaction between disturbed sleep and physiologic risk in patient populations
Function of Sleep
• Consolidate memory• Improve
concentration• Improve mood• Enhance creativity
• Hormonal control of appetite
• Immune function & systemic inflammation
Brain Systemically
Sleep Medicine 2004 5:225-30Nature 2004 430:27-28J Am Coll Cardiol 2004 43:678-83J Clin Endocrinol Metab 2004 89:5762-71
NREM WAKE
Interaction between Sleep and Wake States
REM
Sleep Med2005 6:23-27
Effect of insufficient sleep on unadjusted prevalence rates for HRQOL among adults aged 18 or older (n = 79,625)
> 14 / 30 days insufficient sleep
< 14 / 30 days insufficient sleep
The Cumulative Cost of Additional Wakefulness: Dose-Response Effects on Neurobehavioral Functions and Sleep Physiology From Chronic Sleep Restriction and Total Sleep Deprivation
SLEEP 20032:117-126
Aim: Assess whether human sleep can be chronically reduced without consequencesDesign: The chronic sleep restriction experiment involved randomization to 1 of 3sleep doses (4 h, 6 h, or 8 h time in bed per night), which were maintained for 14 consecutive days. The total sleep deprivation experiment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days.Subjects: A total of n = 48 healthy adults (ages 21–38)Results: Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks.Conclusion: Chronic restriction of sleep to 6 h or less per night produced cognitive performance deficits equivalent to up to 2 nights of total sleep deprivation,relatively moderate sleep restriction can seriously impair waking neurobehavioralfunction in healthy adults.
Sleepiness
Sympathovagal Balance
Evening cortisol concentrations
Time in Bed4 8 12
Impact of Sleep Debt on Metabolic And Endocrine FunctionLancet 1999 354:1435-39
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Aim: Examine the effect of sleep debton metabolic and hormonal function Subjects: 11 Males (18 -27 yrs)Design:• Baseline - 3 nights 8 hrs in bed• Sleep Debt - 6 nights 4 hrs in bed• Recovery – 7 nights 12 hrs in bedResults: In the Sleep Debt Condition• Glucose tolerance & thryrotropin concentrations were decreased• Evening cortisol concentrations were increased• Sympathetic nervous system activity was increased
p < 0.0001
p < 0.02
p < 0.007
After 2 d of
4-h sleep time
After 2 d of 10-h sleep time
After 2 d of 10-h sleep time
After 2 d of 10-h sleep time
After 2 d of4-h sleep time
After 2 d of4-h sleep time
After 2 d of4-h sleep time
After 2 d of 10-h sleep time
Sleep Curtailment in Healthy Young Men Is Associated with Decreased Leptin Levels, Elevated Ghrelin Levels, andIncreased Hunger and AppetiteAnn Intern Med 2004 141:846-850
Aim: To determine whether partial sleep curtailment, alters appetiteSubjects: 12 normal weight malesBMI 23.6 + 2.0 / Age 22 + 2 yrsDesign: Randomized, 2 period, 2 condition crossover clinical studyIntervention: 2 days of sleep restrictionand 2 days of sleep extensionResults: Sleep restriction was associatedwith – • Decreased Leptin (anorexigenic) 18%• Increased Ghrelin (orexigenic) 24%• Increased Hunger 24%• Increased appetite* 23% *calorie dense high carbohydrate food
Arch Intern Med. 2005165:25-30
Aim: Examine the association between restricted sleep and obesityin a heterogeneous adult primarycare populationDesign: Prospective cohort, involving questionnaires and measurement of BMI in 4 primary care offices (n = 1001)Conclusion: Reduced amountsof sleep are associated with overweight and obese status
The association between total sleep time and body weight in primary care
Results:
The Obesity Epidemic Worldwide
Nature 2000
Obesity and the Risk of Heart failure
NEJM 2002347:305-13
Men
Goals
• Review how disturbed sleep impacts physiology in healthy humans
• Examine the data relating disturbed sleep to morbidity and mortality
• Understand how a common sleep disorder (Sleep Apnea) may the contribute to cardiovascular risk
• Appreciate the complex interaction between disturbed sleep and physiologic risk in patient populations
Relative Risk of CHD across 10 Years according to Self-Reported Sleep Duration*: Nurses Health Study
1
1.05
1.11.15
1.2
1.25
1.31.35
1.4
1.45
1.5
6 7 8 > 9
N = 76,617* *
Covariates: shift work, depression, high cholesterol, diabetes, hypertension, BMI, smoking, snoring, exercise, alcohol consumption, aspirin use, postmenopausal hormone use, family history of MI.
Arch Int Med 2003 163:205-209
< 5
Impact of Sleep on Survival
Sleep Latency Sleep Efficiency
Latency < 30 min
Latency > 30 min
Efficiency > 80 %
Efficiency < 80 %
Su
rviv
al
Weeks Weeks
Psychosomatic Medicine 2003 65:63–73
Brain, Behavior, and Immunity2003 17: 350–364
Stress
JACC 200443:678–83
Effect of Partial Sleep Deprivation on C-Reactive Protein
(n = 5)(n = 4)
Sleep Complaints Heart Failure Patients vs. General Population
0 10 20 30 40 50 60
Trouble sleeping
Hypnotics
Sleep Maintenance
Difficulty Initiating Sleep
Early AM Awakening
RLS
Stop BreathingHeart Failure
General Population
Percentage AACN Clinical Issues2003 14:477-87
n = 84Male (59%)Age = 54.1 + 10.8NYHA = 2.8 + 0.8LVEF (%) = 21.7 + 6.3
*
****
*
Impact of Sleep Difficulties on the Minnesota Living with Heart Failure Questionnaire
J Cardiovasc Nurs 200419: 234–242
Aim: To describe self-assessed sleep difficulties, daytime sleepiness, and theirrelation to HRQOL in men and women with HF, as well as to make a comparisonto data from a norm population.Design: Cross-sectional design including 223 patients with HF, New York HeartAssociation classification II–IV, assessed using the Uppsala Sleep Inventory-ChronicHeart Failure, the Epworth Sleepiness Scale, Medical Outcomes Study 36-Item Short Form Health Survey, and Minnesota Living With Heart Failure Questionnaire.
Conclusion: Patients with HF have a reduced HRQOL especially if difficulties maintaining sleep, initiating sleep, and early morning awakenings are involved.
Results:
Goals
• Review how disturbed sleep impacts physiology in healthy humans
• Examine the data relating disturbed sleep to morbidity and mortality
• Understand how a common sleep disorder (Sleep Apnea) may the contribute to cardiovascular risk
• Appreciate the complex interaction between disturbed sleep and physiologic risk in patient populations
ROS
Xanthine Oxidase Mitochondrial Dysfunction Homocysteine
Activation of Transcription Factors
Monocyte Activation
Lymphcyte Activation
Endothelial cell Activation
Adhesion Molecule Expression
Monocyte Lymphocyte / Endothelial Adhesion
Endothelial Dysfunction
Vascular Disease
Intermittent Hypoxia
Sleep Med Rev2003 7:35-51
OSDB: Effect on Nocturnal BP and CO
Thorax 1998
53:416-418
Sympathetic Neural Activity OSA vs. Normals
J Clin Invest 199596:1897-1904
10 sec
Awake
Normal OSA
Effect of OSA on Inflammatory Markers
Circulation 2003107:1129-34
C-Reactive Protein IL-6
Effect of Activated Monocytes on the Endothelium
Nature 2002420: 868-74
ROS
Cytokines MMPs
Tissue Factor
Sleep Apnea Impacts on Insulin and Glucose Independent of Obesity
J Intern Med 2003254:32-44
Effect of Long-term Intermittent Hypoxia on
Brain Structure and Function • Adult male C57BL/6J mice• 8 week protocol: LTIH during
sleep period• Conditions
– Sham Intermittent Hypoxia– Intermittent Hypoxia
• MSLT performed after 2 weeks of recovery
• Basal forebrain and brainstem– Elevated isoprostane (22%)– Increased protein carbonylation
50%– Increased nitration 200%– Induction of antioxidant enzymes 0
2
4
6
8
10
12
14
LTIH(n =19)
Sham LTIH(n = 16)
Mean Sleep Latency
*
8.9 + 1.0
12.7 + 0.5
Significant oxidative injuries in the sleep-wakeregions of the brain after LTIH are associatedwith “residual hypersomnolence”
Day–Night Pattern of Sudden Death in Obstructive Sleep Apnea
N Engl J Med 2005352:1206-14.
< 5 5 -39 > 40
Apnea Hypopnea Index
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6:00 AM – 1:59 PM
2:00 PM –9:59 PM
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AIM: Observational study to compare incidence of fatal and non-fatal cardiovascular events in simple snorers, patients with untreated OSA,patients treated with CPAP, and healthy men recruited from the general population.Design: Prospective observational cohort. 264 healthy men, 377 simple snorers, 403 with untreated mild-moderate OSA (AHI 5-30), 235 with untreated severe OSA (AHI > 30), and 372 with OSA and treated with CPAP
Lancet 2005 365: 1046–53
MonthsMonths
.
Conclusion: In men, severe OSA significantly increases the risk of fatal and non-fatalcardiovascular events. CPAP treatment reduces this risk.
Long-term cardiovascular outcomes in men with OSA
Goals
• Review how disturbed sleep impacts physiology in healthy humans
• Examine the data relating disturbed sleep to morbidity and mortality
• Understand how a common sleep disorder (Sleep Apnea) may the contribute to cardiovascular risk
• Appreciate the complex interaction between disturbed sleep and physiologic risk in patient populations
Obesity
Sleep Apnea Diabetes
LV Hypertrophy
Pleiotrophic Effects of Adiopkines on Vascular Risk
Adipokines & Leptin
J Appl Physiol 98: 2226–2234, 2005.
Healthy Controls (n = 10)
OSA Subjects (n =16)
Arch Intern Med. 2006;166:1709-171
Proposed Model Integrating Sleep Disordered Breathing, Psychological Stress and Nocturnal Physiology as Predictors of CVD Risk Factors
Heart SCORESleep SCORE
Sleep Disordered Breathing
Nocturnal Physiology• Non SDB sleep Characteristics• Urinary catecholamines• Autonomic function• BP dipping status
Psychological stress• Acute & chronic life events• Ambient stress
Established CV Risk Factors• Cholesterol• Hyperglycemia• Blood Pressure • Smoking Cardiovascular
Morbidity & Mortality• Coronary calcification• Brachial artery size• Endothelial dysfunction• MI• Stroke • Death
Emerging CV Risk Factors• Inflammation• Metabolic Syndrome• Renal Insufficiency
Sleep
Heart Failure
Sympathetic Activation
Inflammation
CRT
Wake DriveSleep Drive
Sleep and Heart Failure: The role of Autonomic Activation and Inflammation
NREM WAKE
Interaction between Sleep and Wake States
REM
Summary
• Impaired sleep affects a number of physiologic parameters.
• Concomitant primary sleep disorders can “gain up” the stress response.
• Understanding the relative contribution of psychological stress vs. metabolic stress is crucial when investigating patient populations.
• A collaborative / translational approach is essential to understand mechanisms and advance the field.
• Think about sleep when caring for patients and planning research questions.
“Never, ever, think outside of the box.”