ACE, Aspirin and CPAP

1
ACE, Aspirin and CPAP!

• Sherif Al-Farra, M.D., FC.C.P., D.A.B.S.M.
• Pulmonary and CCM

2
Obstructive Sleep Apnea
3
Apnea Hypopnea Index (AHI)

• Number of events/hours of sleep
• 5-15 Mild
• 15-30 Moderate
• 30 Severe

4
Prevelance

• An estimated 15 to 20 million American adults
  have obstructive sleep apnea (OSA), a prevalence
  comparable to diabetes.
• Young, T. N Engl J Med 328,1230-1235

5
Metabolic Syndrome

• Abdominal obesity
• Atherogenic dyslipidemia (high triglycerides, low
  HDL cholesterol and high LDL cholesterol)
• Hypertension
• Insulin resistance or glucose intolerance
• Prothrombotic state (e.g., high fibrinogen or
  plasminogen activator inhibitor1)
• Proinflammatory state (e.g., elevated C-reactive
  protein)

6
Metabolic Syndrome

• Other features
• Microalbuminuria
• Hypercoagulability
• Increased inflammation
• Endothelial dysfunction
• Poor cardiorespiratory fitness
• Sympathetic activation
• Reaven G. Circulation. 2002106286288.

7
Metabolic Syndrome

• 61 males with OSA
• 43 controls
• Overnight fast
• Glucose
• Insulin
• Lipids
• Blood pressure
• Coughlin S. Eur Heart J. 200425735741

8
Metabolic Syndrome

• Subjects with OSA
• More obese
• Higher BP
• Higher fasting insulin
• More insulin resistant
• Lower HDL cholesterol
• Increased incidence of metabolic syndrome (87
  vs. 35 P
• Coughlin S. Eur Heart J. 200425735741

9
Metabolic Syndrome

• Regression analysis adjusted for
• age
• BMI
• smoking
• alcohol consumption
• OSA independently associated with
• increased systolic and diastolic blood pressure
• higher fasting insulin and triglyceride
  concentrations
• decreased HDL cholesterol
• increased cholesterolHDL ratio
• trend towards higher HOMA values
• Coughlin S. Eur Heart J. 200425735741.

10
Metabolic Syndrome

• Metabolic syndrome was 9.1 times more likely to
  be present in subjects with OSA. (95 confidence
  interval 2.6-3.2 P
• Coughlin S. Eur Heart J. 200425735741.

11
Metabolic Syndrome

• Metabolic Syndrome
• Metabolic Syndrome 2P
• e a l S n e
• Sleep apnea

12
(No Transcript)
13
(No Transcript)
14
Obstructive Sleep Apnea
15
OSA pressure drops to -80 cm H2O
16
Cardiovascular Disease

• Cross-sectional epidemiologic studies
• Association between OSA and the risk for
• hypertension
• stroke
• congestive heart failure
• coronary artery disease
• Confounding factors difficult to establish causal
  relationships
• Exception of systemic hypertension
• Shahar, E. Am J Respir Crit Care Med
  2001163,19-25

17
Cardiovascular Risk

• Inspiratory efforts against an obstructed upper
  airway
• Reduction in intrathoracic pressure
• Acute changes in pulmonary arterial pressures and
  blood flow
• Increased cardiac afterload
• Bonsignore MR, Eur Respir J 19947786-805

18
Pathophysiology

• Sympathetic activation
• Endothelial dysfunction
• Oxidative stress
• Systemic inflammation
• Hypercoagulability
• Hyperleptinemia
• Insulin resistance
• Shamsuzzaman AS. JAMA. 200329019061914

19
Cardiovascular Risk

• Increased venous return
• Leftward intraventricular septal shift
• Shiomi T, Chest 1991100894-902
• Alterations in transmural cardiac pressures
• Virolainen J, J Appl Physiol 199579455-60
• Impedance of left ventricular filling
• Brinker JA, Circulation 198061626-33
• Increase in myocardial oxygen demand

20
Cardiovascular Risk

• Reduced levels of Nitric oxide
• Ip MS, Respir. Crit. Care Med
  20001622166-71
• Elevated serum endothelin levels
• Phillips BG, J Hypertens 19991761-6
• Increased CRP
• Shamsuzzaman AS, Circulation 20021052462-4.
• CRP decreased with CPAP
• Teramoto S, Circulation 2003107E40

21
Blood Pressure

• Normal sleep dipping
• Drop in arterial pressure
• Increase in parasympathetic mediated
  vasodilatation
• Decrease in cardiac output
• Apneic episodes and desaturation in OSA
• Elevated blood pressure during sleep

22
Hypertension

• OSA leads to an acute increase in nocturnal BP
  and sustained daytime hypertension
• Peppard PE, N Engl J Med 20003421378-84

23
Hypertension

• The Wisconsin Sleep Cohort Study
• Association between OSA at baseline and the
  incidence of new hypertension 4 years later
• Independent of obesity and other comorbidities
• Peppard, PE. N Engl J Med 2000342,1378-1384

24
Hypertension

• OSA in animal models
• A causal contributor to hypertension
• Brooks, D. J Clin Invest 199799,106-109
• Two randomized controlled studies
• Decreases in systolic and diastolic BP as soon as
  one week after initiation of CPAP therapy
• Robinson, GV.Thorax 2004,1089-1094
• Grote, L. J Hypertens 200018,679-685

25
Hypertension

• The seventh Joint National Committee on
  Hypertension guidelines
• Identifies OSA as a treatable cause of
  hypertension
• Patients with hypertension who are suspected of
  having OSA because of snoring, daytime
  sleepiness, or obesity, or because of resistant
  hypertension should be consider for an overnight
  sleep study and receive treatment if necessary
• Chobanian, AV. JAMA 2003289,2560-2572

26
CHF

• Contributes to 270,000 deaths per year
• Leading cause of hospitalization in patients 65
  years of age
• At a cost of 29 billion in 2004.
• Affects 1.5-2 of US population
• 6-10 in those above 65 years
• Annual death rate 30-40 in patients with NYHA
  class IV
• AHA Heart disease and stroke statistics-2004

27
CHF and OSA

• Epidemiological studies suggest a strong
  association between OSA CHF
• Sin DD, Am J Respir Crit Care Med
  19991601101-6
• Javaheri S, Circulation 1998972154-9
• Mechanism
• Hypoxemia
• Increased sympathetic drive
• Changes in intra-thoracic pressure
• Acute change in BP

28
CHF

• 40-80 of patients with Systolic heart failure
  have an apnea hypopnea index of 15/hour
• 5-32 OSA
• 30-60 CSA
• Sin DD, Resp Crit Care 19991601101-06
• Fries R, Pace 199922223-227

29
Cheyne-Stokes (CSA)
Paco2 and apnea threshold
30
Central Sleep Apnea

• Low PaCo2 Closer to apnea threshold
• Naughton M BD, Am Rev Respir Dis
  1993148330-8
• Breathing a Co2 rich gas abolishes CSA
• Lorenzi G, Respir Crit Care Med
  19991591490-8
• Patients complain of insomnia and sleep
  fragmentation and not EDS
• Bradley TD, Circulation 20031071822-6

31
Cheyne-Stokes (CSA)
32
Waxing and Waning Breathing Contributed by John
Kimoff, MD, ATS On Line
33
Consider PSG in CHF

• Nocturnal angina
• PND
• Restless sleep/maintenance insomnia
• Progressive ventricular dysfunction
• NYHA III or IV despite aggressive Rx
• Patients with implanted defibrillator
• On the transplant list

34
Cardiovascular Risk

• In patients with CAD
• OSA is an independent prognostic factor of
  recurrent cardiovascular disorders and survival.
• Mooe T, Resp Crit Care 20011641910-13
• Systolic Heart Failure
• OSA associated with lower EF
• EF improves with CPAP
• Mansfield , Resp Crit Care 2004169361-66

35
Cardiovascular Risk

• Observational studies suggest
• Significant increase in ischemic cardiac events
  in patients with untreated severe OSA
• Compared to those receiving treatment with CPAP
• Marin, JM. Lancet 2005365,1046-1053

36
Arrhythmias

• Patients with severe OSA (AHI30) when compared
  to normal (AHI
• Atrial fibrillation
• 4.8 versus 0.9 (p 0.003)
• Non sustained ventricular tachycardia
• 5.3 versus 1.2 (p 0.004)
• Ectopic ventricular beats
• 25.0 versus 14.5 (p 0.002)
• Mehra R, Respir Crit Care Med 2006173910-6

37
Arrhythmias

• Patients with arrhythmias and untreated sleep
  apnea had an arrhythmia recurrence double that of
  patients treated with CPAP
• Continuous cardiac monitoring reveals that 75 of
  persistent atrial fibrillation occurred between 8
  pm and 8 am
• Kanagala R, Circulation 20031072589-94

38
Atrial Fibrillation

• 59 patients with lone AF free of
• obesity
• hypertension
• diabetes
• heart disease
• One third of subjects had moderate-to-severe AHI
  (15/h)
• Porthan, KM. Chest 2004125,879-885.

39
Atrial Fibrillation

• 150 patients with established AF
• Presenting for electrocardioversion
• Risk for OSA identified by a validated sleep
  questionnaire
• Half of the AF patients at high risk for OSA
• One third of control subjects
• Odds ratio for the association between OSA and AF
  was 2.2
• Gami, AS. Circulation 2004110,364-367

40
Atrial Fibrillation

• Untreated sleep apnea in patients successfully
  cardioverted to normal sinus rhythm was
  accompanied by an 80 likelihood of recurrence of
  AF within 1 year
• recurrence rate less than half in patients in
  whom sleep apnea was appropriately treated
• Kanagala, R. Circulation 2003107,2589-2594

41
Treating OSA in CHF

• CPAP/Bi-PAP
• Therapy with
• Diuretics
• ACE
• Beta Blockers
• Oxygen

42
CPAP
43
CPAP

• CPAP/Bi-PAP
• Improves left ventricular EF
• Decreases BP
• Improve ventricular systolic volume
• Mansfield , Resp Crit Care 2004169361-66

44

• Cohort of 1600 men
• Higher incidence of fatal (top) and non-fatal
  (bottom) cardiovascular events observed in the
  36 with severe OSA who were noncompliant with
  CPAP treatment

Marin, JM. Lancet 2005365,1046-1053
45
Useful Reference

• Obstructive Sleep Apnea Implications for Cardiac
  and Vascular Disease Francisco Lopez-Jimenez, MD,
  MSc Fatima H. Sert Kuniyoshi, MSc Apoor Gami,
  MD and Virend K. Somers, MD, PhD, FCCP (Chest.
  2008 133793-804).

46
Recommendations

• Screening
• Screening
• Screening

47
ESS

• SituationChance of Dozing or Sleeping
• Sitting and reading____
• Watching TV____
• Sitting inactive in a public place____
• As a passenger in a car for an hour or more____
• Lying down in the afternoon ____
• Sitting and talking to someone ____
• Sitting quietly after lunch (no alcohol)____
• Stopped for a few minutes in traffic while
  driving ___
• Total score
• This is your Epworth score ____
• Snoring Y N
• Stop breathing Y N
• Wake up Gasping Y N

• 0 would never doze or sleep.
• 1 slight chance of dozing or sleeping
• 2 moderate chance of dozing or sleeping
• 3 high chance of dozing or sleeping

48
Consider PSG in CHF

• PND
• Restless sleep/maintenance insomnia
• Progressive ventricular dysfunction
• NYHA III or IV despite aggressive Rx
• Patients with implanted defibrillator
• On the transplant list

49
High Risk

• CHF
• Atrial Fibrillation
• Refractory to cardioversion
• Recurrent post cardioversion
• Refractory HTN
• Nocturnal angina