CONSEQUENCES OF SLEEP APNEA SYNDROME

Yksel Peker MD, PhD, Associate Professor

Sleep Medicine Unit, Skaraborg Hospital, Skvde & University of Gothenburg, Sweden

Wife stabbed snoring husbandrescued by thoracic surgeons

OSA (Asymptomatic OSA; Non-sleepy sleep apnoeics)

OSAS (Symptomatic OSA; Sleepy sleep-apnoeics)

OBSTRUCTIVE SLEEP APNEA SYNDROME (OSAS)

OSA + Daytime sleepiness

Treatment indication

Prevalence (30-60 yrs)Men Women

OSA24 %9 %

OSAS 4 %2 %

The majority of the patients with OSA do not report daytime sleepiness

Eight-year follow-up AHI versus baseline AHI in the Wisconsin Sleep Cohort Study (n= 282) Young T et al, AJRCCM 2002OSA increases by age

Bixler et al, AJRCCM 1998%OSAS decreases after age of 64?Do theybecome asymptomatic? die?

OSA

Immediate changes

Long-term effects

OSA

Immediate changes

Long-term effects

Modified from Grote L, Schneider H, 1997

Acute Blood Pressure Changes in OSA - Mechanisms -

Part

SaO2

EMG

EEG

EOG

Flow

Effort

30 sec

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

Cardiovascular mechanisms (I)

Repeated nocturnal hypoxemiaCoccogna 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

Cardiovascular mechanisms (II)

Enhanced release of superoxide from polymorphonuclear neutrophils in OSA. Impact of CPAP. Schulz R et 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 T et al, Circulation 2003

TimeOxygen saturation %Pulse-oximetry

Heart rate50 %

OSA & CVD

Immediate changes

Long-term effects

Hypnogram

00:0002:0004:0006:0008:00S4S3S2S1REMWakeMTLights Out00:0001:0002:0003:0004:0005:0006:0007:00S4S3S2S1REMWakeMTLights OutNormalOSA

Long-term complications

Cognitive dysfunction

Cardiovascular dysfunction

AHI 30AHI 30AHI 30AHI 30AHI 30AHI 30

Long-term complications

Cognitive dysfunction

Cardiovascular dysfunction

Clinical and epidemiological aspects

Obstructive sleep apnea is associated withHypertensionCoronary heart diseaseCardiac arrhythmias Heart failureStrokeDiabetes and Insulin ResistanceMortality

CVD OSAOSAS

CVD OSAObesity

OSA & CAD

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

Prevalence of OSA in CAD clinic cohorts

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

Prognosis of CAD with concomitant OSA is WORSE than theprognosis of CAD patients without OSA

Peker et al, AJRCCM 2000

Mooe et al, AJRCCM 2001

Yumino et al, Am J Cardiol 2007

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

Peker et al, AJRCCM 2000

Hazard function of death estimated by use of Poisson modelPeker et al, AJRCCM 2000

Prognosis of CAD with concomitant OSA isNOT WORSE than the prognosis for CAD patientswithout 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

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

CAUSALITY

Incident CAD in OSA

Impact of treatment of the OSA on CAD

AJRCCM 2002All normotensive at baseline

FOURVARIABLES

6.56.756.8

4.16.727

3.3021.6

1.6016.2

Non OSA (n=122)

Efficiently treated OSA (n=15)

Incompletely treated OSA (n=37)

%

Blad1

OSA (ineffectively treated)OSA (effectively treated)Non OSA

Coronary Artery Disease804

Hypertension1015

Cardiovascular Disease2118

Non OSA (n=122)Efficiently treated OSA (n=15)Incompletely treated OSA (n=37)

Cardiovascular disease6.56.756.8

Hypertension4.16.727.0

Coronary artery disease3.3021.6

Cardiovascular event1.6016.2

CAD incidence in a sleep-clinic cohort at a 7-yr follow-up%Peker et al, ERJ 2006

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

Peker et al, ERJ 2006

OSA & Stroke

Prevalence of sleep apnea in acute stroke/TIA

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

Early neurologic worsening in acute stroke and sleep apnea

50 patients with acute stroke underwent polysomnography (first night)62% had AHI10Early neurologic worsening occurred in 30%Sleep apnea and serum glucose predicted early neurologic worseningNo difference in functional outcome after 6 months

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

Increased 6-month mortality (37%) in patients withstroke and sleep apnea

120 patients enrolled

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

OSA is a risk factor for death in patients with stroke

10-year follow-up132 patients (1995-1997) were enrolledObstructive Sleep Apnea (AHI15) in 23Central Sleep Apnea in 28116 had died at follow-upAdjusted OR for death was 1.76 (95% CI 1.05-2.95) for OSANo correlation with central sleep apnea

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

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

Arzt M et al, AJRCCM 2005; 172:1447-1451PREVALENCE of STROKE General population: 1475 subjects

Arzt M et al, AJRCCM 2005; 172:1447-1451INCIDENT STROKEGeneral population: 1189 subjects - at 4-yr follow-up

OSA & Mortality

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

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

%Cardiovascular events in men during 10 yearsmodified from Marin JM et al, Lancet 2005******

Fully adjusted Odds Ratios for cardiovascular death associated with clinical variables

OR (95% CI)p

Age, yrs1.09 (1.04-1.12)0.001Snoring1.03 (0.31-1.84)0.88Mild OSA1.15 (0.34-2.69)0.71Severe OSA2.87 (1.17-7.51)0.025CPAP1.05 (0.39-2.21)0.74Cardiovascular disease2.54 (1.31-4.99)0.005Marin JM et al, Lancet 2005

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)

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.

Thank you for your attention!

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