Managing Sleep Health in Primary Care 1 Managing Sleep Health in Primary Care Paul P. Doghramji, MD, FAAFP Family Practice Physician Collegeville Family Practice & Pottstown Medical Specialists, Inc. Medical Director of Health Services, Ursinus College – Collegeville, PA Attending Family Practice Physician, Pottstown Memorial Medical Center – Pottstown, PA Learning Objectives ▪ Communicate risk factors associated with not getting enough sleep ▪ Explain the sleep/wake cycle and circadian rhythms ▪ Identify common sleep disorders in primary care ▪ Use appropriate diagnostic tools to assess patients’ sleep health
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Managing Sleep Health in Primary Care
1
Managing Sleep Health in Primary Care
Paul P. Doghramji, MD, FAAFP
Family Practice Physician
Collegeville Family Practice & Pottstown Medical Specialists, Inc.
Medical Director of Health Services, Ursinus College – Collegeville, PA
Attending Family Practice Physician, Pottstown Memorial Medical Center – Pottstown, PA
Learning Objectives
▪ Communicate risk factors associated with not getting
enough sleep
▪ Explain the sleep/wake cycle and circadian rhythms
▪ Identify common sleep disorders in primary care
▪ Use appropriate diagnostic tools to assess patients’
sleep health
Managing Sleep Health in Primary Care
2
Agenda
▪ What is sleep?
▪ Sleep stages
▪ Sleep physiology
▪ Dreaming
▪ Sleepiness
▪ Sleep disorders
▪ Insomnia and comorbidities
Sleep Perspectives
▪ Behavioral
▪ Reversible
▪ Perceptual disengagement from, and unresponsiveness to, the environment
▪ Neurophysiological
▪ Two distinct states: REM sleep and NREM
▪ Actively produced, not a result of passive inactivity
▪ Highly regulated by homeostatic and circadian processes
▪ Produces changes in the entire organism, not just the CNS
▪ Teleological
▪ Necessary for survival; deprivation leads to functional impairments and eventual death
▪ Important for clearance of neurotoxic waste products (e.g., beta amyloid) that accumulate in
the brain during wakefulness
NREM = non-rapid eye movement
Carskadon MA, Dement WC (2005), Normal human sleep: an overview. In: Principles and Practice of Sleep Medicine, 4th ed., Kryger MH et al., eds. Philadelphia: Elsevier/Saunders, pp13-23. Science vol 342, 18 Oct 2013.
Managing Sleep Health in Primary Care
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Why is sleep important?
▪ Cognition and performance
▪ Mood regulation
▪ Mental health
▪ Physical health
▪ Safety
Fig. 4 Aβ plaque deposition after chronic sleep restriction and chronic orexin receptor blockade in transgenic mice (A) Mice that underwent chronic sleep restriction for 21 days showed significantly greater Aβ plaque deposition in multiple subregions of the cortex compared to age-matched control mice.
The glymphatic system supports interstitial solute and fluid clearance from the brain.
Sci Transl Med 2012;4:147ra111
Managing Sleep Health in Primary Care
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Sleep Stages
SLEEP REST
Managing Sleep Health in Primary Care
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Two States of Sleep
Rapid eye movement (REM) sleep
▪ When dreaming occurs
▪ “Active brain in a paralyzed body”
Hours 1
N 1
& REM
N 2
N3
2 3 4 5 6 7 8
Non-REM sleep
▪ 3 stages
▪ Based primarily on EEG
Typical Sleep Architectural Pattern of a Young Human Adult
Adapted from Hauri P. The Sleep Disorders. Kalamazoo, Mich: Upjohn;1982:8.
Stage I & REM sleep (red) are graphed on the same level because their EEG patterns are very similar
Sleep Architecture
▪ Sleep is entered through stage N1
▪ Orderly progression from stage N1 to N3 and, typically within 90
minutes of sleep onset, to the 1st REM period
▪ 90-minute cycle of REM-NREM repeats throughout sleep
▪ As the night progresses
▪ REM periods increase in duration and density of eye movements
▪ N3 sleep becomes less prominent in the 2nd half of the night
1. Soldatos CR, et al. Sleep Med. 2005;6:5-13; 2. Baldwin CM, et al. Sleep. 2004;27:305-311; 3. Pallesen S, et al. Sleep. 2007;30:619-624.
Worldwide Prevalence of ESS Scores >10
Managing Sleep Health in Primary Care
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Categories of Sleepiness
▪ Insufficient sleep
▪ Factitious
▪ Insomnia
▪ Poor quality sleep
▪ Obstructive sleep apnea
▪ Restless Legs Syndrome
▪ Disturbed timing of sleep
▪ Circadian rhythm disorders
▪ Medications and substances
▪ Rx, OTC, herbals
▪ Illicit drugs, alcohol
▪ Brain “damage”
▪ MS, Parkinson’s, TBI, stroke,
Alzheimer's
▪ Narcolepsy
Sleep Disorders
Managing Sleep Health in Primary Care
16
Restless Legs Syndrome6
10%-15%
Comorbid Insomnias4
6%
Narcolepsy5
0.06%†
Obstructive Sleep Apnea1
3%-28%
Sleep-Wake Disorders: Prevalence in Adults
*Among night and rotating shift workers; †Prevalence of hypersomnias such as narcolepsy without cataplexy may be higher.
1. Young T, et al. Am J Respir Crit Care Med. 2002;165:1217-1239. 4. Ohayon MM. Sleep Med Rev. 2002;6:97-111.2. Drake CL, et al. Sleep. 2004;27:1453-1462. 5. Silber MH, et al. Sleep. 2002;25:197-202.3. Strine DP, et al. Sleep Med. 2005;6:23-27. 6. Merlino G et al. Neurol Sci. 2007;28:S37-S46. †Mignot E, et al. Brain. 2006;129:1609-1623. †Singh M, et al. Sleep. 2006;29:890-895.
Shift Work Disorder2
8%-32%* Insufficient Sleep
Syndrome3
26%
How to Diagnose the Cause of Sleepiness
▪ Get detailed sleep/wake history
▪ Determine whether sleepy, fatigue, or depression
▪ Quantify degree of sleepiness: ESS
▪ Start probing for the causes, looking for clues
▪ Insufficient Sleep Syndrome: doesn’t get enough sleep
▪ OSA: loud snoring, waking up choking, witnesses apneas, waking with
sore throat, headache, enuresis, nocturia
▪ RLS: uncomfortable feelings in legs prevent sleep, need to move them to
Odds of OSA increase >2-fold for every 1-point increase
Class I Class II Class III Class IV
Restless Leg Syndrome (RLS)
Symptoms
▪ Irresistible urge to move legs usually with unpleasant sensations
▪ Relief with movement
▪ Worse at night
▪ Worse with rest
Etiology
▪ Dopaminergic dysfunction
▪ Iron deficiency
▪ Renal insufficiencies
▪ Peripheral neuropathies
▪ 25% secondary
Treatment
▪ Dopaminergic agents
▪ Iron if deficient
▪ Sedative hypnotics
▪ Anticonvulsants
▪ Opiates
▪ Sleep hygiene
Allen RP, Sleep Med, 2003.
Managing Sleep Health in Primary Care
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Periodic Limb Movement Disorder (PLMD) vs. RLS
▪ Substantial overlap
▪ Up to 85% of RLS patients have PLMD
▪ 30% of PLMD patients have RLS
▪ RLS diagnosis is made clinically
▪ PLMD diagnosis is made via PSG
▪ No other daytime clues, just sleepiness
▪ Treatments are the same
Insomnia and Comorbidities
Managing Sleep Health in Primary Care
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Insomnia
As a disorder:
▪ Trouble getting to sleep and/or
▪ Trouble staying asleep and/or
▪ Waking up too early and/or
▪ Occurring more days of the week than not
▪ Ongoing for over 3 months
Why Should PCP’s be Proactive about Insomnia?
▪ Very prevalent in primary care
▪ But patients don’t tell you
▪ Serious consequences
▪ Day to day life
▪ Poor outcome on mental and
physical health
▪ Insomnia is a clue
▪ Most insomnia is co-morbid
▪ Easy to identify
Treatment
▪ Relieves an upsetting symptom
▪ Improves next day
consequences
▪ Improves outcome of
co-morbidity
▪ Psychiatric
▪ Medical
▪ Majority is done by PCP
Managing Sleep Health in Primary Care
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Insomnia Risk Factors
▪ Age (older)
▪ Sex (especially post-1 and perimenopausal2 females)
▪ Divorce / separation / widowhood
▪ Psychiatric illness (mood and anxiety disorders)
▪ Medical conditions
▪ Cigarette smoking
▪ Alcohol and coffee consumption
▪ Certain prescription drugs
1. NIH Consens State Sci Statements. 2005;22:1-30.
2. Young T, et al. Sleep. 2003;26:667-672.
Insomnia Screening and Follow-up
▪ Sleep Schedule: Do you have trouble getting to sleep, staying asleep, or waking
up too early?
▪ Daytime consequences: Do you feel like you have slept well throughout the day?
▪ Sleep timing: When do you go to bed? …Wake up? …Middle of the night
awakening? …How long does it take you to fall back to sleep?
▪ Treatments: What remedies have you tried? Any previous Rx’s?
▪ Sleep hygiene/lifestyle issues: Alcohol? Smoking? Exercise? Medications that
cause insomnia?
▪ Duration, frequency, prior: How long has this been going on?...How often?...
Have you had it before?...
Sateia MJ, Doghramji K, Hauri PJ, Morin MM. Sleep. 2000;23:1-66.
Erman MK. In: Sleep Disorders: Diagnosis and Treatment. Totowa, NY: Humana Press; 1998:21-51.
Managing Sleep Health in Primary Care
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How Frequent are Comorbidities?
Terzano MG, et al. Sleep Med. 2004;5:67-75. Katz DA, McHorney CA. (1998).
Clinical correlates of insomnia in patients with chronic illness. Arch Intern Med 158(10):1099-1107.
35
28
19 17 15 1411
0
10
20
30
40
50
30
47
37 39
50
3842
106
17
2522
1215
0
10
20
30
40
50
InsomniaSevere insomnia
Pre
vale
nce
%
Medical Conditions in Primary
Care Patients with InsomniaInsomnia with Medical Conditions
How Does Inadequate Sleep Increase CVD?
▪ Total sleep time (TST) < 5 hours compared to TST > 5 hours
▪ Higher glucose & cortisol levels
▪ HPA-associated endocrine & metabolic imbalances
▪ Hypercholesterolemia even after controlling for other risk factors
▪ Night time BP: Nighttime SBP higher and day-to-night SBP dipping was lower
(-8% vs -15%, P < 0.01) in insomniacs
▪ Atherosclerosis: Total sleep time (P = 0.005), and sleep quality (P = 0.05)
contributed to increased carotid intima-media thickness
▪ Inflammation: Serum CRP levels higher and increased at a steeper rate
Lanfranchi, PA, et al. (2009). Nighttime blood pressure in normotensive subjects with chronic insomnia: implications for cardiovascular risk. Sleep 32(6): 760-766.
Nakazaki, C, et al. (2012). Association of insomnia and short sleep duration with atherosclerosis risk in the elderly."Am J Hypertens 25(11): 1149-1155. Parthasarathy,
S, et al. (2015). Persistent insomnia is associated with mortality risk. Am J Med 128(3): 268-275 e262. Lin, CL, et al. (2016). The relationship between insomnia with short
sleep duration is associated with hypercholesterolemia: a cross-sectional study. J Adv Nurs 72(2): 339-347. Farina, B., et al. (2014). Heart rate and heart rate variability
modification in chronic insomnia patients. Behav Sleep Med 12(4): 290-306. de Zambotti, M., et al. (2011). Sleep onset and cardiovascular activity in primary insomnia.
J Sleep Res 20(2): 318-325.
Managing Sleep Health in Primary Care
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Does insomnia contribute to development of hypertension?
Lewis, P. E., et al. (2014). Risk of type II diabetes and hypertension associated with chronic insomnia among active component, U.S. Armed Forces,
1998-2013. MSMR 21(10): 6-13.
Prospective Follow-up
▪ Active duty in US Military
▪ Excluded: Chronic
insomnia prior to
1/1/1998
▪ Without hypertension at
baseline
▪ Chronic insomnia led to
higher risk of
hypertension (aHR 2.00)
Rate of Developing
Hypertension(per 10,000 person-years)
46.2
95.6
0
20
40
60
80
100
Controls Insomnia
Does Insomnia Increase Risk of CVDs?
1.681.85
1.4 1.3
0
0.5
1
1.5
2
aOR of CV Event
0.961.35
4.53
0
1
2
3
4
5
1 2 3
aOR for CHF
1st CV Event
# Insomnia Symptoms
Hsu, CY, et al. (2015). The Association Between Insomnia and Increased Future Cardiovascular Events: A Nationwide Population-Based Study.
Psychosom Med 77(7): 743-751. Laugsand, LE, et al. (2014). Insomnia and the risk of incident heart failure: a population study. Eur Heart J 35(21):
1382-1393. Canivet, C, et al. (2014). Insomnia increases risk for cardiovascular events in women and in men with low SES: a longitudinal, register-
based study. J Psychosom Res 76(4): 292-299.
Managing Sleep Health in Primary Care
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How Much Does Insomnia Contribute to CV Mortality?
Health Professionals Follow-Up Study
▪ US men free of cancer
▪ Insomnia symptoms in 2004, followed through 2010
▪ Adjusted for age, lifestyle factors, and common chronic conditions
Metaanalysis of 13 Prospective Studies
▪ 122,501 subjects followed for 3-20 yrs
▪ Insomnia increased risk by 45% of developing or dying from CVD ▪ (RR 1.45, 1.29-1.62; p < 0.00001)
Li, Y, et al. (2014). "Association between insomnia symptoms and mortality: a prospective
study of U.S. men." Circulation 129(7): 737-746. Sofi, F, et al. (2014). Insomnia and risk of
cardiovascular disease: a meta-analysis. Eur J Prev Cardiol 21(1): 57-64.
1.25
1.091.04
1
1.25
1.5
Total Mortality CVD MortalityDifficulty Initiating & Nonrestorative
Pykkönen A-J, et al. (2012) Subjective Sleep Complaints Are
Associated With Insulin Resistance in Individuals Without Diabetes.
Diabetes Care 35:2271–8.
aORs for HbA1c >= 6.0%
6.79
3.96
2.33
0
2
4
6
8
Kachi, Y., et al. (2011). Association between insomnia symptoms and
hemoglobin A1c level in Japanese men. PLoS One 6(7): e21420.
Males 22-69 years old with no hx of diabetes
Difficulty maintaining
sleep
Lasting 2+wks
Early AM
awakening
Some-times
Some-times
Japanese company annual health check-up
Managing Sleep Health in Primary Care
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Does Treating Insomnia Lower Blood Pressure?
Standard BP treatment + estazolam
vs.
Standard BP treatment + placebo
▪ Insomnia treatment efficacy
▪ Estazolam: 67.3% (P < 0.001)
▪ Placebo: 14.0%
▪ Goal BP(< 140/90 mmHg)
▪ Estazolam: 74.8% (P < 0.001)
▪ Placebo: 50.5%
Li, Y, et al. (2017). "The impact of the improvement of insomnia on blood
pressure in hypertensive patients." J Sleep Res 26(1): 105-114.
Blood Pressure Reduction
from Baseline
-2.6 -2.8-2.5
-3.4
0
-2.3-2
-2.5 -2.7
-0.7
-2.8
-5
-7.1
0
-2.5
-3.7
-5.4
-8
-6
-4
-2
07 14 21 28 7 14 21 28
Placebo Estazolam
Systolic Diastolic
N = 202N = 200
Days of Treatment
Does Insomnia Increase Risk of Psychiatric Disorders?
31.1
35.9
30
14.4
5
21
18
10
0
5
10
15
20
25
30
35
40
Pati
en
ts (%
)
Incidence (%) over 3.5 years
Insomnia (n=240)
No Insomnia (n=739)
Breslau N, Roth T, Rosenthal L, Andreski P. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry. 1996;39:411-418.
Managing Sleep Health in Primary Care
26
Does Treating Insomnia Improve Comorbidities?
0
20
40
60
80
100
4 Months 16 Months
Poor Good
0
20
40
60
80
100
4 Months 16 MonthsControl Tai Chi
By Sleep Quality
%
4 months
CBT .21 (.03-1.47) p<.10
TCC NS
16 months
CBT .06 (.005-.669) p<.01
TCC .10 (.008-1.29) p<.05
ORs of Remaining
at High Risk
2-hour group sessions
weekly for 4 mo with a
16-mo evaluationRisk score based on 8 biomarkers: HDL, LDL, triglycerides,
C-reactive protein, fibrinogen, HA1c, glucose, insulin• High risk = 4 or more abnormal
By Intervention
% Remaining at High Risk
Carroll, JE, et al. (2015). Improved sleep quality in older adults with insomnia reduces biomarkers of disease risk: pilot results from a randomized controlled comparative
How is Insomnia Best Conceptualized to Guide Treatment?
▪ Genetic: heritability 42% - 57% in chronic insomnia
▪ Final common pathway: Autonomic and CNS hyperarousal
▪ Greater whole-brain metabolism during both sleep and wake periods
▪ Increased secretion of corticotropin and cortisol throughout sleep-wake cycle
▪ Sleep-wake regulation imbalance
▪ Overactivity of arousal systems
▪ Hypoactivity of sleep-inducing systems
▪ Both
▪ Failure of wake-promoting structures to deactivate during the transition
from waking to sleep states
Riemann D., et al. (2015). The neurobiology, investigation, and treatment of chronic insomnia. Lancet Neurol 14(5): 547-558. Vgontzas, AN, et al. (2013).
Insomnia with objective short sleep duration: the most biologically severe phenotype of the disorder. Sleep Med Rev 17(4): 241-254. Vgontzas et al.
Nofzinger et al. Am J of Psychiatry. 2004;161:2126-2128.
Managing Sleep Health in Primary Care
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1. Kupfer DJ, Reynolds CF III. N Engl J Med. 1997;336:341-346.