Sleep Disorders and Cardiovascular Disease

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Sleep Disorders and Cardiovascular Disease

• Alan M. Blaker, MD, FACC, FACP
• Pee Dee Cardiology Associates

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Disclosure and Off Label Use

• Nothing to disclose
• No off label drug use

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Sleep Apnea

• Obstuctive Sleep Apnea (OSA)
• Repetitive interruption of ventilation during
  sleep due to collapse of the upper airway
• Central Sleep Apnea (CSA)
• Recurrent interruption of ventilation during
  sleep due to loss of ventilatory drive

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OSA Sleep Disordered Breathing

• Intermittent snoring
• Disruptive snoring
• Hypopnea
• Apnea obstructive, central, mixed
• AHI apneas hypopneas / hour
• RDI apneas hypopneas snore arousals/
  (Respiratory Disturbance Index) hour

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Apnea/Hypopnea

• Apnea
• Cessation of airflow gt 10 secs
• Hypopnea
• Reduction of airflow to lt 50 with desaturation
  and/or sleep arousals

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Obstructive Apnea
Normal Airway
Obstructed Airway
S. Javaheri MD, Univ of Cincinnati, JAAC 2007,
www.indianasleep.com/uploads/Vienna
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Partial and complete airway obstruction resulting
in hypopnea and apnea, respectively
Somers, V. K. et al. J Am Coll Cardiol
200852686-717
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OSA Prevalence

• More common in men than women
• Estimated to affect 15 million Americans
• About 1/5 have mild 1/15 mod. to severe
• Prevalence increased 2-3 times with
  cardiovascular disease
• Prevalence of cardiovascular disease higher with
  OSA

AHA, 2008
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OSA Prevalence Study

• Random sample of 602 men and women between 30 and
  60 years received sleep studies (NPSG)
• Male and obesity strongly associated OSA
• Male and female snorers associated OSA
• Male 24 AHI gt5, 15 gt 10, 9.1 gt 15
• Female 9 AHI gt5, 5gt 10, 4 gt 15

NEJM 1993 3281230-
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http//sleepzine.com/tag/carbon_dioxide/
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OSA Signs, Symptoms

• Disruptive snoring
• Witnessed apnea or gasping
• Morning Headache
• Hypersomnolence
• Sexual dysfunction
• Behavioral changes
• Obesity, enlarged (crowded) neck

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Sleep Apnea Diagnosis

• HP
• Holter monitoring
• Overnight oximetry
• Home monitoring
• Overnight Polysomnography (sleep study)
• Gold standard

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http//www.peaceful-river.com/osa/cartoon.htm
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OSA Snoring O2 sat.
J. Burk MD, Texas Pulmonary and CC Consultants,
www.texaspulmonary.com, 2003
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OSA CVPathophysiological - acute

• Intermittent hypoxia - ischemia-reperfusion
• Reduced myocardial oxygen delivery
• Decreased cardiac output
• Increased myocardial oxygen demand
• Sympathetic nervous system activation
• Increase in left ventricular afterload due to
  negative intrathoracic pressure and increased
  blood pressure

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OSA CVPathophysiological - acute

• Increased heart rate
• Increased catecholamines
• Nocturnal myocardial ischemia
• Nocturnal pulmonary edema
• Cardiac arrhythmias

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OSA CVPathophysiology - chronic

• Autonomic cardiovascular derangements
• Sympathetic nervous system activation
• Reduced heart rate variability
• Impaired baroreflex control of heart rate
• Systemic hypertension nocturnal diurnal
• Myocardial effects
• Left ventricular hypertrophy
• Left ventricular dysfunction and failure

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OSA CVPathophysiology - chronic

• Increased platelet aggregability and blood
  hypercoagulability
• Increases blood viscosity
• Increased susceptibility to thrombotic and
  embolic cardiac and cerebrovascular events
• Increased generation of O2 free radicals

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Pathophysiology of OSA on the CV System
Am J Respir Crit Care Med, 164, 2147-2165, 2001.
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OSA CardiovascularCLINICAL DISORDERS

• Hypertension
• Stroke
• Ischemic Heart Disease
• Congestive Heart Failure
• Arrythmias Atrial and Ventricular

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Mechanisms Contributing to Risk of Cardiovascular
Disease
Shamsuzzaman, A. S. M. et al. JAMA
20032901906-1914.
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Prevalence Of SDB in CVD Patients
Sanner et al. Clin Cardiology 2001
Schafer et al. Cardiology 1999
Nieto et al. JAMA 2000
Javaheri et al. Circulation 1999
Logan et al. J. Hypertension 2001
ResMed
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OSA Hypertension

• Hypertension affects 20 of USA adults
• Major risk factor for coronary artery disease,
  CHF, stroke, and renal disease
• Secondary cause found in 5-10 of hypertensives
• Effective therapy reduces risk of developing CAD,
  CHF, CVA and renal disease

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OSA Hypertension

• Sleep Heart Health Study (6132 pts) and Wisconsin
  Sleep Cohort Study (1069 pts)
• Independent association of OSA and HBP
• Adjusted odds ratio of increased risk 1.37- 3.1
  with AHI gt30
• At 4-8 years of follow-up (893 pts) the odds
  ratio of new onset hypertension was 2.89 with AHI
  gt15
• Medically refractory HBP, 87 had OSA

JAMA, 2000, 283, 1829 Arch Intern Med., 1997,
157,1746 J. Hyperten.,2001.
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OSA - Hypertension

• Pathophysiologic studies followed in animals and
  humans since 1980s
• Intermittent hypoxia ?Sympathetic activation?
  vasoconstriction
• Dippers vs Nondippers in BP variability
• Normal 15 nocturnal drop (dippers)
• Nondipping assoc. with CV complications
• Consider OSA in nondippers (10/11 one study)
• Elimination of OSA and Beta Blockers helpful

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OSA Hypertension
J. Burk MD, Texas Pulmonary and CC Consultants,
www.texaspulmonary.com, 2003
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OSA Blood Pressure CPAP
J. Burk MD, Texas Pulmonary and CC Consultants,
www.texaspulmonary.com, 2003
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OSA Stroke

• Stroke is third leading cause of death in USA and
  leading cause of disability
• Hypertension associated with CVA and OSA
• Hypercoagulability and increased platelet
  aggregation associated with OSA/hypoxia
• Decreased cerebral blood flow associated with
  decreased cardiac output due to OSA
• Cerebral vasodilatation associated with
  hypercapnia, ie. morning headaches

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OSA Stroke

• Habitual snoring independent risk factor for
  stroke with odds ratio of 2.1 to 3.3
• Odds of stroke 1.58 greater with AHI gt11
• In patients with stroke, OSA is prevalent in 43
  to 91 (62.5) and is negative prognosticly
• OSAgtgt CSA (lt10)
• Central sleep apnea may be increased immediately
  post-stroke then improves
• 10 yr f/u increased mortality post CVA with OSA,
  not CSA

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OSA - Stroke and Patent Foramen Ovale (PFO)

• 78 pts with OSA, RDI 60/hr, tested for pfo by
  bubble echo during Valsalva, and without known
  cardiac or vascular disease
• 10 subjects then studied during npsg with bubble
  echo during normal breathing, hypopneas, and
  apneas
• no pfo events during normal breathing, hypopneas,
  or apneas lt16 sec. Cont.

Sleep 200225856-, J. Burk MD, Texas Pulmonary
and CC Consultants, www.texaspulmonary.com, 2003
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OSA - Stroke via Patent Foramen Ovale, cont.

• Microembolic bubble echo events during extended
  sleep apneas and awake Valsalva correlated
  (plt0.001)
• Maximal bubble intensity within 7 sec of apnea
  termination (mean 3.9 sec)
• other variables did not correlate including O2
  sat.

Sleep 200225856-, J. Burk MD, Texas Pulmonary
and CC Consultants, www.texaspulmonary.com, 2003
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OSA CAD, Ischemia and MI

• Intermittent hypoxemia, increased BP,
  vasoconstriction, endothelial dysfunction,
  increased platelet aggregation, all potential
  triggers for ischemia/MI and seen with SDB
• Modest association of OSA and CAD with odds ratio
  of 1.27 in Sleep Heart Health Study cohort
• Study gt200 pts with electron beam CT showed more
  coronary Ca2 with OSA
• More nocturnal angina, better with CPAP
• Most studies observational

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OSA CAD, Ischemia and MI

• 5 yr f/u of pts with CAD and sleep apnea
  significant increase in death, MI and
  cerebrovascular events both men and women
• (AM J Resp Crit Care Med, 2001)
• Men 28 with SDB, 14 without
• Women 20 with SDB, 14 without
• Increase in odds for AMI with OSA and worsens
  with severity (Lancet, 1990)
• Higher incidence of sudden cardiac death
  10PM-6AM with OSA, c/w 6AM-11AM without OSA
  (NEJM, 2005)

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OSA and Arrhythmias

• More frequent with Sleep apnea and worsens with
  severity of apnea
• Reported in up to 50 of patients with OSA
• Bradycardia, NSVT, second degree AV block and
  Freq PVCs most common
• Increased likelihood of A. Fib.

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OSA and Arrhythmias (cont.)

• Prolonged apnea and hypoxia lead to dive reflex,
  increased vagal tone
• AV block, bradycardia and asystole.
• Normal conducting system by EP studies
• Bradycardia and AV block pts., OSA present 70
• CPAP reverses
• Consider OSA before pacemaker, if nocturnal
• European Sleep Trial, OSA in 68 with AV block
  and prior pacemaker
• Atrial overdrive pacing not shown to improve SDB

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OSA and A. Fib.

• Study of pts admitted for cardioversion (Circ.,
  2004)
• 50 had OSA c/w 30 in general cardiology clinic
  population
• Retrospective study gt3500 pts obesity and OSA
  independent predictors of PAF (JACC, 2007)
• Post op A Fib more likely with OSA
• OSA associated with enlarged LA, unproven
  hypothesis as cause for PAF with OSA
• Untreated OSA after cardioversion, 82 recurrence
  at 1 yr
• double the risk c/w treated OSA

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Heart Failure

• OSA frequently detected
• 218 pts for CHF (JACC, 2007)
• AHIgt15 found in 26
• OSA reported in up to 50 with diastolic
  dysfunction
• 3 months of CPAP showed improvement
• Likely contributing factors Hypoxemia,
  Hypertension, LVH, LV dilation, increased
  afterload (peripheral sympathetic activation)

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Heart Failure (cont.)

• Worsening CHF ? Worsening OSA
• Fluid retention, reduced activity, airway
  resistance
• Secondary pulmonary hypertension can result
  leading to Cor Pulmonale
• Treatment of CHF may reduce OSA severity, no
  specific drug
• EF can improve with CPAP, Pulmonary pressure
  improves, mortality benefit not clear

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Central Sleep Apnea

• Much less frequent than OSA
• More common over age 65 5-10
• More often DM, CHF and stroke
• Consequence of stroke and CHF as opposed to OSA
  which may be causative
• Snoring, daytime somnolence, obesity less common

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Central Sleep Apnea (cont.)

• For CHF, ACEI may reduce AHI
• Optimize CHF treatment
• Nocturnal supplemental O2
• Short term benefit of acetazolamide (diamox)
  before bed, no data long term
• Mixed results with CPAP, not routine
• Cardiac resynchronization therapy reduced AHI
  with CM and CSA, prelim. data

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CHF and CSA
Am J Respir Crit Care Med, 164, 2147-2165, 2001.
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Treatment Options for OSA

• Weight Loss
• Oral appliances
• Behavioral changes such as sleeping on side
• CPAP
• Surgery
• Tracheostomy, Uvulopalatopharyngoplasty, laser
  assisted uvuloplasty

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CPAP
S. Javaheri MD, Univ of Cincinnati, JAAC 2007,
www.indianasleep.com/uploads/Vienna
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http//www.peaceful-river.com/osa/cartoon.htm
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Conclusions
Somers, V. K. et al. J Am Coll Cardiol
200852686-717
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References

• Sleep Apnea and Cardiovascular Disease, Am J
  Respir Crit Care, Vol 164., 2001, 2147-2165.
• Sleep Apnea and Cardiovascular Disease AHA/ACC
  Scientific Statement, JACC,52, 2008, 686-717.
  Also published in Circulation

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Thank You