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CONSEQUENCES OF SLEEP APNEA SYNDROME Yüksel Peker MD, PhD, Associate Professor Sleep Medicine Unit, Skaraborg Hospital, Skövde & University of Gothenburg, Sweden. Wife stabbed snoring husband. rescued by thoracic surgeons. OSA (Asymptomatic OSA; “Non-sleepy sleep apnoeics”)

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CONSEQUENCES OF SLEEP APNEA SYNDROME Yüksel Peker MD, PhD, Associate Professor

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Consequences of sleep apnea syndrome y ksel peker md phd associate professor

CONSEQUENCES OF

SLEEP APNEA SYNDROME

Yüksel Peker

MD, PhD, Associate Professor

Sleep Medicine Unit, Skaraborg Hospital,

Skövde & University of Gothenburg, Sweden


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Wife stabbed snoring husband

rescued by thoracic surgeons


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

  • OSA (Asymptomatic OSA; “Non-sleepy sleep apnoeics”)

  • OSAS (Symptomatic OSA; “Sleepy sleep-apnoeics”)


Obstructive sleep apnea syndrome osas osa daytime sleepiness treatment indication

OBSTRUCTIVE SLEEP APNEA SYNDROME (OSAS) OSA + Daytime sleepinessTreatment indication


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Prevalence (30-60 yrs)Men Women OSA24 %9 % OSAS 4 %2 %The majority of the patients with OSA do not report daytime sleepiness


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

  • OSA increases by age

Eight-year follow-up AHI versus baseline AHI in the Wisconsin Sleep Cohort Study (n= 282) Young Tet al, AJRCCM 2002


Bixler et al ajrccm 1998

  • OSAS decreases after age of 64?

Bixleret al, AJRCCM 1998

%

Do they

  • become asymptomatic?

  • die?


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

OSA

  • Immediate changes

  • Long-term effects


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

OSA

  • Immediate changes

  • Long-term effects


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Grote L. et al., J. Cardiovasc. Pharmacol. 1994


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Cardiovascular mechanisms (I)

Repeated nocturnal hypoxemia

Coccogna G et al, 1972; Podszus T et al, 1986

Sympathetic nervous activity

Fletcher EC et al, 1987; Hedner J et al, 1988;

Narkiewicz K & Somers VK 2003

Vascular endothelial dysfunction

Carlson J et al, 1996; Remsburg S et al, 1999;

Kraiczi H et al, 2000


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Cardiovascular mechanisms (II)

Enhanced release of superoxide from polymorphonuclear neutrophils in OSA. Impact of CPAP.

Schulz Ret al, AJRCCM 2000

Plasma vascular endothelial growth factor in OSAS: Effects of CPAP.

Lavie L et al, AJRCCM 2002

Elevated levels of C-reactive protein and interleukin-6 in patients with OSAS are decreased by CPAP.

Yokoe Tet al, Circulation 2003


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Pulse-oximetry

Oxygen

saturation %

Heart rate

50 %

Time


Osa cvd

OSA & CVD

  • Immediate changes

  • Long-term effects


Hypnogram

Hypnogram

Lights Out

MT

Normal

Wake

REM

S1

S2

S3

S4

00:00

02:00

04:00

06:00

08:00

OSA

Lights Out

MT

Wake

REM

S1

S2

S3

S4

00:00

01:00

02:00

03:00

04:00

05:00

06:00

07:00


Long term complications

Long-term complications

  • Cognitive dysfunction

  • Cardiovascular dysfunction


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

AHI 30

AHI 30

AHI 30

AHI 30

AHI 30

AHI 30


Long term complications1

Long-term complications

  • Cognitive dysfunction

  • Cardiovascular dysfunction


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Clinical and epidemiological aspects

Obstructive sleep apnea is associated with

Hypertension

Coronary heart disease

Cardiac arrhythmias

Heart failure

Stroke

Diabetes and Insulin Resistance

Mortality


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

CVD

OSA

OSAS


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

CVD

OSA

Obesity


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

OSA & CAD


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Prevalence of CAD in Sleep Clinic Cohorts

CAD in 25% of unselected patients with OSA

More common in severe OSA

Maekawa M et al, Psychiatry Clin Neurosci 1998


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

First authorpubl yr

n

AHI10

controls

De Olazabal1982

Andreas1996

Mooe1996

Mooe 1996

Koehler1996

Peker1999

Moruzzi1999

Sanner2001

Mehra2006

Takama2007

Yumino2007

17

50

142

102

74

62

22

49

104

65

89

76 %

50 %

37 %

30 %

35 %

31 %

9 %

27 %

66 %

45 %

57 %

yes

yes

yes

Total

776

42%

Prevalence of OSA in CAD clinic cohorts


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Explanatory variables associated with CAD (multivariate analysis) _______________________________________________________________________________________Odds Ratio 95 % CI p values_______________________________________________________________________________________Current smoking9.82.6-36.50.001Diabetes mellitus4.21.1-17.10.045Obstructive sleep apnea3.11.2-8.30.025_______________________________________________________________________________________

Peker et al, ERJ 1999


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Prognosis of CAD with concomitant OSA is WORSE than the

prognosis of CAD patients without OSA

Peker et al, AJRCCM 2000

Mooe et al, AJRCCM 2001

Yumino et al, Am J Cardiol 2007


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Prognosis of CAD after PCI in patients with

concomitant OSA

89 consecutive patients with acute coronary syndrome who were successfully treated with PCI

OSA in 51 patients (57%); follow-up period 6 months

Major cardiac event (cardiac death, reinfarction, revascularization)

23.5 % in OSA, 5.3 % in non-OSA (p=0.020)

Odds ratio for OSA 11.6 (95% CI 2.2-62-2)

Yumino et al, Am J Cardiol 2007


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Peker et al, AJRCCM 2000


Hazard function of death estimated by use of poisson model

Hazard function of death estimated by use of Poisson model

Peker et al, AJRCCM 2000


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Prognosis of CAD with concomitant OSA is

NOT WORSE than the prognosis for CAD patients

without OSA

50 CAD patients (25 OSA, 25 non-OSA)

Follow-up period 10 years

Cardiac death in 4 versus 5 patients (ns)

Hagenah et al, Respir Med 2006


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Weak association between OSA & CAD

in a general population

Sleep Heart Health Study

Cross-sectional analysis (n=6,132)

Adjusted OR for OSA 1.27 (95% CI 0.99-1.62)

(AHI>11 versus AHI<1.4)

Shahar E et al, AJRCCM 2001


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

CAUSALITY

Incident CAD in OSA

Impact of treatment of the OSA on CAD


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

All normotensive at baseline

AJRCCM 2002


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

CAD incidence in a sleep-clinic cohort

at a 7-yr follow-up

%

Peker et al, ERJ 2006


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Probability of CAD incidence estimated by Poisson modelStart age 49 yrs, Systolic BP 133 mmHg and Sat. min 86%

Peker et al, ERJ 2006


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

OSA & Stroke


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

First authorpubl yr

n

AHI10

controls

Bassetti1996

Dyken1996

Bassetti1999

Wessendorf2000

Parra2000

Iranzo 2002

Hui2002

Turkington2002

Kaneko2003

Bassetti2006

59

24

128

147

161

50

51

120

61

152

69 %

71 %

63 %

44 %

71 %

62 %

67 %

61 %

72 %

58 %

yes

yes

Total

953

67%

Prevalence of sleep apnea in acute stroke/TIA


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Sleep apnea improves after the acute phase of stroke

Normalizing in 40% of the patients within 6 months

Bassetti CL et al, Stroke 2006; 37:967-972


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Early neurologic worsening in acute stroke and

sleep apnea

50 patients with acute stroke underwent polysomnography (first night)

62% had AHI10

Early neurologic worsening occurred in 30%

Sleep apnea and serum glucose predicted early neurologic worsening

No difference in functional outcome after 6 months

Iranzo A et al, Neurology 2002; 58:911-916


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Increased 6-month mortality (37%) in patients with

stroke and sleep apnea

120 patients enrolled

Turkington PM et al, Thorax 2004; 59: 367-371


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

OSA is a risk factor for death in patients with stroke

10-year follow-up

132 patients (1995-1997) were enrolled

Obstructive Sleep Apnea (AHI15) in 23

Central Sleep Apnea in 28

116 had died at follow-up

Adjusted OR for death was 1.76 (95% CI 1.05-2.95) for OSA

No correlation with central sleep apnea

Sahlin C et al, Arch Intern Med 2008; 168:297-301


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Association between OSA & stroke in a general population

Sleep Heart Health Study

Cross-sectional analysis (n=6,132)

Adjusted OR for OSA 1.58 (95% CI 1.02-2.46)

(AHI>11 versus AHI<1.4)

Shahar E et al, AJRCCM 2001


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

PREVALENCE of STROKE

General population: 1475 subjects

Arzt M et al, AJRCCM 2005; 172:1447-1451


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

INCIDENT STROKE

General population: 1189 subjects - at 4-yr follow-up

Arzt M et al, AJRCCM 2005; 172:1447-1451


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

OSA & Mortality


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Long-term cardiovascular outcomes in men with OSA with or without treatment with CPAP: an observational study

Marin JM et al

Lancet 2005; 365:1046-53


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

  • Long-term cardiovascular outcomes in men with OSA with or without CPAP

  • Sleep clinic (1992-1994), PSG 1465

  • Simple snorers (n=377)

  • OSA (n=1071)

  • CPAP recommended (n=667)

  • CPAP accepted (n=426)

  • Untreated severe OSA (AHI>30, n=235)

  • Healthy controls (n=264) individually matched with the severe untreated OSA for age and BMI (AHI<5)


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Cardiovascular events in men during 10 years

%

***

***

modified from Marin JM et al, Lancet 2005


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Fully adjusted Odds Ratios for cardiovascular death associated with clinical variables

OR (95% CI)p

Age, yrs1.09 (1.04-1.12)0.001

Snoring1.03 (0.31-1.84)0.88

Mild OSA1.15 (0.34-2.69)0.71

Severe OSA2.87 (1.17-7.51)0.025

CPAP1.05 (0.39-2.21)0.74

Cardiovascular disease2.54 (1.31-4.99)0.005

Marin JM et al, Lancet 2005


Conclusions i

CONCLUSIONS (I)

  • Recurrent obstructive events during sleep have harmful effects on daytime vigilance as well as on vascular structure and function

  • Epidemiological data suggest an independent association between OSA and CVD in the clinical cohorts while the association is weaker in the general population

  • Not only may OSA induce CVD but also the events in themselves may worsen the prognosis of an already existing CVD


Conclusions ii

CONCLUSIONS (II)

  • OSA should be included among factors considered in the primary and secondary prevention models of CVD.

  • OSA should be treated not only to eliminate daytime sleepiness. Treatment may also have a beneficial prognostic impact by reducing cardiovascular morbidity in OSA.


Consequences of sleep apnea syndrome y ksel peker md phd associate professor

Thank you for your attention!


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