Cleveland HeartLab 2013 Symposium

1. The Power of Sleep
a key to
addressing inflammation
& optimizing health
Param Dedhia, MD

2. Disclosures
• No third party relationship influences
this presentation
• I have no financial relationships related
to this presentation
• No off-label medications or treatments
are included in this presentation

3. A Wake Up Call: The Objectives
 Present the Power of Sleep as a
Key for Optimal Health
 Illuminate the
Sleep-Inflammation Connection
↓ Sleep → ↑ Inflammation
↑ Inflammation → ↓ Sleep
 Offer Tips and Clinical Pearls for
Best Sleep

4. The Function of Sleep
10. Pay off sleep debt
9. Replete energy stores
8. Enhance neuroplasticity
7. Regulate ion channels
6. Cool brain and body
5. Optimize physiological repair, growth & function
4. Improve memory formation and consolidation
3. Soothe emotions and mental fatigue
2. Promote endogenous antioxidant defense
1. Reduce inflammatory markers

5. Optimal Sleep
 Quantity
 Quality

7. Sleep Myths
• We all wish that we could
sleep like a baby
Teenagers are the “best” sleepers
• We need less sleep as we get older
– Most ALL adults need 7-9 hours…
– Sleep changes in adults
↓ Deep Sleep
↑ Arousable
↑ “Cope” with Arousals

9. How much sleep do you need or want?
• Studies that paid people to sleep
Participants asked to be “well rested”
• Definition of “well rested”
Not being able to fall asleep
in a darkened room mid-day
• TAKE HOME POINT
Most adults need 7 - 9 hours of sleep

10. GOAL: 7-9 hours of sleep
Debate:
•All At Once vs. Naps
•All At Night = Gold Standard
Naps =
• Good Option in order to reach 7-9 hours
• Consider Power Nap (10 - 30 minutes)
• Longer Naps may disrupt night time sleep

11. Stages of Sleep
Wake
= resting,
eyes closed
Stage 1 = transitional sleep
Stage 2 = typical sleep
Stage 3 = “deep” sleep
R.E.M. = “dream” sleep

12. Normal Sleep Cycles
Awake
REM
1
2
3
Hours
8
0
1
2
3
4
5
6
7

13. Disruptors from Consolidated Sleep
Arousals & Awakenings
• Sleep Apnea/Snoring
• Comorbid Conditions
• Periodic Leg Movements
- Psychiatric,
(Depression/ Anxiety)
• Bruxism (Teeth Grinding)
- Hormonal, Menopausal
• Pain & Discomfort
- Urological (Bladder*)
• Caffeine/ Drugs/ ETOH
• Room Environment
(light, noise, etc.)
- Neurological
- Cardiovascular
- Autoimmune
- Inflammatory

14. Sleep-Inflammation
Connection
↓ Sleep → ↑ Inflammation
↑ Inflammation → ↓ Sleep

15. Poor Sleep → Comorbidities
Sleep Restriction/
Insufficient Sleep Recovery
Chronic Hypoxia &/or
Frequent Arousals
Stress & Autonomic System Activation
↑ Cortisol, Catecholamines, Blood Pressure, Blood Glucose
↑ Leukocytes, Inflammatory Cytokines, CRP, Oxidative Stress
Pro-inflammatory Status & Endothelial Injury
Cardiovascular Comorbidities

16. DISORDERED SLEEP
MECHANISM
RISK FACTORS
OUTCOMES
•
•
•
•
•
•
•
•
•
•
•
•
Inflammation
Metabolic
Vascular
Hormonal
Hypertension
Obesity
Diabetes
Hyperlipidemia
CHD & CVD
Stroke
Dementia
Death

17. OSA and Inflammation
Control
Mild OSA
Severe OSA
BMI
28.3 ± 1.3
27.9 ± 1.0
28.1 ± 0.06
AHI
3.3 ± 0.6
11.0 ± 0.9
48.4 ± 0.04
Low SaO2
95.2 ± 2.6
83.7 ± 1.7
75.7 ± 2.1
CRP (mg/L)
0.90 ± 0.2
1.5 ± 0.3
2.8 ± 0.4
IL-6 (pg/mL)
0.91 ± 0.15
1.23 ± 0.14
2.25 ± 0.28
IL-18 (pg/mL)
181.9 ± 20.3
209.7 ± 27.0
273.5 ± 16.8
Minoguichi, Am J Respir Crit Care Med 2005
OSA = Obstructive Sleep Apnea

18. Sleep Duration & Inflammation
• Elevated hs-CRP & IL-6
– U Shaped Impact
• Short Sleep Duration < 5 hours
• Long Sleep Duration > 9 hours
– Stronger correlation in women than men
Miller, Sleep 2009
Rohde, Am J Cardiol 1999
Sesso, Hypertension 2007

19. Sleep Duration & Adipokines
Each hour of reduced sleep time
•
6 % increase in leptin (p = 0.01)
•
↑ Leptin
• Potential furthering of
leptin resistance
14 % increase in visfatin (p = 0.02)
Each hour of reduced REM
•
15 % increase in leptin (p = 0.01)
•
31 % increase in visfatin (p = 0.05)
↑ Visfastin
• Competitive inhibition of
insulin receptor binding
Other studies note
increased IL-6, TNF α, &
adiponectin
Hayes, Sleep 2011

20. Glucose and Sleep
Advanced Glycation End-Products (AGE)
Insulin Resistance → AGE
High Caloric, High Saturated Fat → AGE
Oxidative Injury from Sleep Apnea → AGE
Tan, Sleep 2006
Veasey, Sleep 2006
Wautier, Am J Physiol Endo Metab 2001

21. Sleep & Hypertension
• Sleep-related Breathing Disorders
promote non-dipping of
nocturnal blood pressure
• Even mild OSA associated with
increased risk of developing hypertension
in 4 years
– (OR 1.42: [1.13-1.78])
• Moderate to Severe even greater risk
– (OR 2.9: [1.5- 5.6])
Wisconsin Sleep Cohort, Sleep 2008

22. Syndrome X → “Syndrome Z”
• “Syndrome Z”: Syndrome X + Sleep Disturbance
– Proposed Model Fit with Syndrome X
– Sleep Disturbance:
Model Fit (0.82 ± 0.03; p < 0.01)
greater model fit than
• Insulin Resistance (0.67 ± 0.05; p < 0.01)
• Hypertension (0.64 ± 0.04; p < 0.01)
• Dyslipidemia (0.60 ± 0.05; p < 0.01)
– Obesity:
Model Fit (0.85 ± 0.02; p < 0.01)
Nook, Sleep 2011

23. Sleep Duration & Pneumonia
• Both Short and Long Duration promote
Pneumonia Risk in Women
– U Shaped Impact
• Short Sleep Duration < 5 hours
– (RR 1.39: [1.06-1.82])
• Long Sleep Duration > 9 hours
– (RR 1.38: [1.04–1.84])
– Perceived Insufficient Sleep
– (RR 1.50: [1.29-1.74])
Patel, Sleep 2012

24. Sleep Duration and Immunity
• Short Sleep Duration (< 6 hours)
Negative effect in vivo
antibody response to novel antigen
– Hepatitis B Vaccination
– Influenza Vaccination
– Possible explanation for poor sleep with
increased susceptibility to infectious disease
Prather, Sleep 2012

25. Sleep Duration & Mortality
• Both Short and Long Duration associated
with increased all-cause mortality
– U Shaped Impact
• Short Sleep Duration < 6 hours
– (RR 1.12: [1.06-1.18])
• Long Sleep Duration > 9 hours
– (RR 1.38: [1.22–1.38])
Cappuccio, Sleep 2010

26. Insomnia
• Prevalence of insomnia 21.4 % (18 to 65 years)
• Adjusted OR 2.2 in setting of medical disorders
•
Heart Disease (1.6: [1.2-23])
•
Migraine (1.8: [1.5-2.1])
•
Hypertension (1.5: [12-18])
•
Asthma (1.6: [1.3-2.0])
•
Diabetes (1.4: [20-105])
•
COPD (1.9: [1.5-2.5])
•
Gastric Ulcers (2.1: [1.6-2.7])
•
Neurological (2.0: [1.5-2.7])
•
Arthritis (1.8: [1.5-2.2])
•
Menstrual (1.7: [1.3-2.1])
Budhiraja, Sleep 2011

27. Sleepy U.S.
• National Sleep Foundation
Survey, 2005
– 21 % think they have “sleep problems”
• Of these, 75% have some problem
– Only 45% would ask their doctor about it

28. Sleepiness doesn't kill but
Sleep Apnea does
OPEN
AIRWAY
COLLAPSED
AIRWAY
ABCs of Life
Airway
Breathing
Circulation

29. Sleep Apnea & the Heart
Very High Mortality
Similar risk as smoking
> 50% increase in cardiovascular events
2 - 3 times increased risk for myocardial infarction
Higher Risk of Major Medical Conditions
–
–
–
–
Arrhythmia
Sudden Cardiac Death
Hypertension
Stroke
− Dementia
− Elevated Blood Sugar
− Depression
− Traumatic Injury

30. Who Gets Apnea?
 Large neck: >17” men & >16” women
 Nasal congestion or fracture
 Small chin
 Family History
 Alcohol or sedatives
 Men of all ages and Women after menopause

31. Signs & Symptoms of Apnea
 Mouth Breathing and/or
Airway Crowding
 Morning Complaint of
Dry Mouth or Headache
 Sleepy, Tired, Irritable,
Poor Performance
 Hypertension (requiring >1 meds)
 Arrhythmia (atrial fibrillation; repeat cardioversion)

32. Crowded Airway: Sleep Apnea
•
•
•
•
Class I
Class II
Class III
Class IV
View Soft Palate, Fauces, Uvula, Tonsillar Pillars
View Soft Palate and Fauces, Uvula Tip Obscured
View Soft Palate
View Hard Palate Only

33. Tonsils: Sleep Apnea
Narrowing of Lateral Airway

34. Treatment for Sleep Apnea
Sleep Position
(Side vs. Back)
CPAP
Treat
Stuffy Nose
Dental
Device
Surgery
Provent
Alcohol
Weight
Loss
(Timing at Night)
GOLD
STANDARD

35. Consequences of Poor Sleep:
Sleepiness !

36. It is NOT “normal” to:
• Fall asleep if reading quietly in the afternoon
• “Drift off” at afternoon meetings
• Sleep on airplanes
• Fall asleep watching TV in the early evenings
• Sleep when you are a passenger in a car
• “Drift off” while waiting at red lights

37. Chronic Sleep Deprivation
16
14
12
10
8
6
4
2
0
Time In Bed
0h TIB
4h TIB
6h TIB
8h TIB
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Number of Errors
14 days of sleep restriction
days of sleep restriciton
Van Dongen HP. Sleep 2003

38. Alcohol
General rule: per drink
1 hour of sedation…
followed by 1 hour of arousal/withdrawal

39. Sleep Interference
• Caffeine:
– The biggest one:
– Half life =7 hours,
i.e. ¼ of am coffee still there at 10 PM
8 AM
3 PM
Full
Half
10 PM
Quarter

40. Steps to Better Sleep
• Appreciate Sleep as Time Well Spent
• Reduce Body Activity and Temperature
• Slow Down a Busy Brain
• Make the Bedroom a Sanctuary
• Create Rituals

41. Tip for Better Sleep
• Appreciate Sleep as Time Well Spent
As much setting aside “Me Time” is vital,
sleep is of top priority– it will provide better ‘Me Time”
If sleeping were a pill,
its label would list:
- antioxidant
- anti-inflammatory
- antidepressant
- libido enhancement
- heart smart

42. Tip for Better Sleep
• Reduce Body Activity and Temperature
The act of cooling down the core body temperature
promotes the transition to DEEP sleep
- Warm Shower
- Exercise Earlier in the day
up a 3 hours before bed time
- Cool (not cold) room
yet, extremities need to be warm

43. Tip for Better Sleep
• Slow Down a Busy Brain
Advice to think of nothing rarely works
The brain is a “factory of thoughts”
Stream of consciousness is default mode
Seek a recitation–
this creates stillness of mind & body
-Recite a poem, prayer or hymn
-Count or watch breaths
-Progressive muscle relaxation

44. Tip for Better Sleep
• Make the Bedroom a Sanctuary
Sight – Lighting
Smell – Aromatherapy
Sound – Quiet or White Noise
Touch – Temperature & Comfort
The bed is only for:
(1)Intimacy
(2)Sleep
NOT for work, worry, or
problem solving

45. Tip for Better Sleep
• Create Rituals
Start winding down 1-2 hours before bed
Dim the lights & turn off the screens
Time the liquids before bed
- water
- alcohol
- caffeine

46. Tip for Better Sleep
• Create Rituals
Enjoy reading, stretch or gentle yoga
Warm shower
Set wake up time

47. Tip for Better Sleep
• Create Rituals
If cannot get to sleep or get back to sleep in 20 minutes…
GET OUT OF BED
-Avoid TV and Computer
-Recite poem, prayer or hymn
-Count breaths
-Progressive relaxation
-Read
-Stretch
-Gentle Yoga

48. Prescription for Optimal Health
Param Dedhia, MD
Internal Medicine
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49. THANK YOU
Param Dedhia, MD
pdedhia@gmail.com