OSA is a systemic disease

1. OBSTRUCTIVE SLEEP
APNEA IS A SYSTEMIC
DISEASE
ImanGalal, MD
Assistant Professor Pulmonary Medicine
AinShams University

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47#, Verse 25#Furqan, Chapter -Al

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ObstructiveSleepApneaSyndrome&Metabolic
Syndrome.
ObstructiveSleepApneaSyndrome&Cardiovascular
Diseases.
EffectofContinuousPositiveAirwayPressuretreatment.
Content:

5. Page 
Obstructive Sleep Apnea:

6. Page 
Obstructive
Sleep
Apnea
Memory
Problems
Increased
Insulin
Resistance
Stroke
Increased
Traffic
Accidents
Cardiac
Problems
Hypertension

7. Page 
Introduction:
Obstructivesleepapnea,a
highly prevalent
disease,affecting4%ofmen
&2%ofwomen,isadisorder
characterizedbyrecurrent
episodesofupperairway
obstruction,&isassociated
with reductions in
ventilation,resultingin
recurrentarousals&episodic
oxyhemoglobindesaturations
duringsleep.

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AvarietyofphenomenaareimplicatedinOSASsuchas
modifications in the autonomic nervous
system,hypoxemia–reoxygenationcycles,inflammation,&
coagulation–fibrinolysisimbalance.
OSASpatientsalsopresentincreasedlevelsofcertain
biomarkerslinkedtoendocrine-metabolic&cardiovascular
alterationsamongothersystemicconsequences.
Introduction:

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Metabolic Syndrome:
TheNationalCholesterolEducationProgram(NCEP)AdultTreatment
PanelIII(ATPIII)reportrecommendedtheuseof5variables:
1)AbdominalObesity:waistcircumference(≥102cmin,≥88cmin
)
2)↑TG(≥150mg/dLordrugtreatment)
3)↓HDL(<40mg/dLin,<50mg/dLin,ordrugtreatment)
4)Hypertension:BP(systolicBP≥130mmHg,ordiastolicBP≥85
mmHg,ordrugtreatmentforhypertension)
5)GlucoseIntolerance:fastingglucose(≥100mg/dLordrugtreatment)
Subjects meeting 3 of these 5 criteria are classified as having
Metabolic Syndrome.
Grundy et al. Circulation 2005; 112: 285-90

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Metabolic Syndrome:
InternationalDiabetesFederation(IDF)ConsensusDefinition
2005CriteriaforIdentificationoftheMS:
Alberti, Lancet 2005
Abdominal Obesity: (waist circumference)
ethnicity specific
for Europids: Men >94 cm
Women >80 cm
Plus anyTwo of the following
Triglycerides ≥150 mg/dL
HDL cholesterol
Men <40 mg/dL
Women <50 mg/dL
Blood Pressure ≥130 / ≥85mmHg
Fasting Glucose ≥100mg/dL or Type II Diabetes

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Themetabolicdisturbancesinpatientswithobstructive
sleepapneasyndrome(OSAS)includeinsulinresistance&
elevatedlevelsofpro-inflammatorycytokines&vascular
adhesionmolecules,aswellasanelevationofhormones
derivedfromtheadiposetissueasleptin.
OSA & Metabolic Syndrome
“Syndrome Z”

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OSA & MS in Adults
Reference Design Results
Coughlin et al.,2004
Case controlled (matched for BMI)
OSA: AHI > 15
Control subjects: AHI < 5
MS: NCEP (ATP III) criteria
Independent* associations between:
1.OSA & MS
2.OSA& systolic and diastolic blood pressure, fasting
insulin, triglyceride, HDL, total/HDL cholesterol
Gruber et al., 2006
Case controlled
OSA: AHI criteria not given
MS: International Diabetes
Federation criteria
Independent* association between:
1.OSA & MS
2.No independent association between OSA & insulin
resistance (assessed by HOMA)
Lam et al., 2006
Community based
OSA: AHI > 5
MS: NCEP (ATP III) criteria
OSA and MS
Independent association between OSA & waist, diastolic
blood pressure*, fasting glucose*, MS*
Independent determinants of OSA: age, gender, BMI, MS
Sasanabe et al.,2006
OSA: AHI > 15
Control subjects: AHI < 5
MS: criteria for Japanese population
Independent* association between OSA & MS in not in
Parish et al., 2007 Retrospective PSG & chart review Higher prevalence of MS in patients with OSA (60 vs.40%)
Coughlin et al., 2007
Randomized, controlled study
MS: NCEP (ATP III) criteria
No change in proportion of subjects with MS with CPAP
Significant ↓ in blood pressure

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OSA & Obesity:
OSASoftencoexistswithobesity.
OSASispresentinapproximately
40%ofobeseindividuals,&about
70%ofOSASpatientsareobese.
Inrecentyears,muchattentionhas
beenfocusedontheinteraction
betweenOSAS&productsreleasedby
adiposetissuesuchasLeptin,
Adiponectin,Resistin&Ghrelin.

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OSA & Obesity:
Gateetal.,JNutr2004

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Leptinisanadipocyte-derivedhormonethatsuppresses
appetite&promotessatiety.
SeveralstudieshaveshownincreasedlevelsofLeptinin
OSAS,suggestingresistancetothemetaboliceffectsofleptin
(LeptinResistance).
Obesityisamajorconfoundingfactorintheassociation
betweenLeptin&OSA.
TreatmentwithCPAPreducesleptinlevels&alsomaybe
associatedwithdecreasedvisceralfataccumulation.
OSA & Obesity:

16. Page 
Sleep Apnea & Visceral Fat
AHI
Visceral Fat (cm
2
)
SaO
2
nadir
%
0
20
40
60
80
100
50 150 250 350 450
r = .70
p =.00
0
20
40
60
80
100
50 150 250 350 450
r = -.61
p =.001
0
100
200
300
400
OSA Obese
Controls
*
Abdominal Fat
Distribution (cm
2
)
Subcutaneous Fat
Visceral Fat
Vgontzas et al. J Clin Endocrin Metab 2000; 85: 1151-8

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Effect of CPAP on Visceral Fat
Fat accumulation (cm
2
)
BW= BW
0
BW= BW
100
200
300
* *
*
Visceral Subcutaneous
Chin et al., Circulation 1999; 100: 706-12

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OSA & Obesity:
Increased Leptin:
Chin et al., Circulation1999;100: 706-12.
Ip et al., Chest2000;118: 580-6.
Schafer et al., Chest2002;122: 829-39 (Obesity+)
Shimizu et al., Thorax2002;57: 429-34.
Ozturk et al.,Arch Otolaryngol Head Neck Surg2003;129: 538-40.
Sanner et al.,Eur Respir J2004;23: 601-4.
Shimura et al., Chest2005;127: 543-9 (Hypercapnia+)
Barcelo et al.,Am J Respir Crit Care Med2005;171: 183-7 (Obesity+)
Tatsumi et al., Chest2005;127: 716-21.
Ulukavak Ciftci et al., Respiration2005;72: 395-401.

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Adiponectinisanadipocyte-derivedcytokinewith
regulatoryfunctionsinbothglucose&lipidmetabolism.
Inaddition,Adiponectinhasprofoundanti-inflammatory
&antiatherogeniceffects.
PlasmalevelsofAdiponectindecreasesinobesity&
metabolicsyndromese.g.,OSAS.
CPAPtreatmentofOSASdoesnoteffectivelynormalize
Adiponectinlevels.
OSA & Obesity:
Harsch et al, Respiration 2004; 10: 710-580-6
Zhang et al, Chin Med J 2004; 117: 1603-1606

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Resistinisawhiteadiposetissuehormonewhose
physiologicalfunctionhasnotyetbeenestablished.
Inastudyof20obeseOSApatients,therewasaweaklink
betweenResistin&InsulinSensitivity.
CPAPtreatmentofOSAhadnosignificantinfluenceon
Resistinlevels.
OSA & Obesity:
Harsch et al, Med Sci Monit 2004; 10: 510-5

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OSA & Obesity:
Adiponectin:variable results
Zhang et al.,Chin Med J2004;117: 1603-1606
Harsch et al., Respiration2004;71: 580-586 (obesity+)
Wolk et al.,Obes Res2005;13: 186-190
Zhang et al.,Respiration2006;73: 73-77
Makino et al.,Clin Endocrinol2006;64:12-19
Resistin:
Harsch et al.,Med Sci Monit2004;10: 510-5 (insulin sensitivity , inflammation+)
Ghrelin:variable results
Harsch et al.,Eur Respir J2003;22:251-257
Ulukavak et al.,Respiration2005;72: 395-401 =

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OSA & Obesity:
OSAislessprevalentinthan,yetthisdifferencediminishes
aftermenopause2rytothedeclineinestrogen&progesterone.
Accordingly,estrogenreplacementtherapyinmenopausal
lessenstheprevalenceofOSAS.
OSASin causesreducedpituitary-gonadalfunction
(possibly2rytoobesity)→declineinmorningserum
testosteronelevels,reducedandrogensecretion&libido.In
addition,↑leptin→impairedtesticularLeydingcellfunction.
Anttalainen et al., Acta Obstet Gynecol Scand 2006; 85: 1381-8
Wesstrom et al., Acta Obstet Gynecol Scand 2005; 84: 54-7
Teloken et al., Urology2006; 76:1033-7
Luboshitzky et al., Obes Res2005;13:780-6
Ishikawa et al., Andrologia2007;39:22-7

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Insulin Resistance
Kasuga, J Clin Invest 2006
Normal
Normal
Increased
Normal or IGT Diabetes mellitus
Decreased
Pancreatic
Islets
cell compensation cell failure
Insulin
secretion
by cells
Blood
glucose

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Insulin Signaling in Cells
Kasuga, J Clin Invest 2006

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Relation between OSA, MS & Type II DM
Tasali & Ip, he Proceedings of the American Thoracic Society 2008;5:207-17

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OSA & Diabetes Mellitus:
In2001,ElMasry&co-workersprovedthattheprevalence
ofsevereOSAwassignificantlyhigherindiabeticpatients
thaninnormoglycaemicsubjectindependentofBMI.
Althoughobesityisthemainriskfactorfordiabetes,yet
coexistentsevereOSAmayaddtothisrisk.
El Masry et al., J Intern Med. 2001; 249: 153-61

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Reference
TTT
Period
Study Population Measures of Glucose Main Results
Brooks et al.,19944 ms
10 severely obese pts
with DM with OSA
Hyperinsulinemic
euglycemic clamp
Improvement in
insulin sensitivity
Harsh et al.2004 3 ms
40 Pts without DM
with OSA
Hyperinsulinemic
euglycemic clamp
Improvement in
insulin sensitivity
Harsh et al.2004 3 ms
9 Pts with DM with
OSA
Hyperinsulinemic
euglycemic clamp
Improvement in
insulin sensitivity
Babu et al.,2005 3 ms
25 Pts with DM with
OSA
72-h interstitial
glucoseHemoglobin A1c
Improvement in 1h
postprandial glucose
& decrease in
hemoglobin A1c
Hassaballa et al.,20053-4 ms
38 Pts with DM with
OSA
Hemoglobin A1c
Slight decrease in
hemoglobin A1c
Lindberg et al.,2006 3 wks
28 with OSA
28 Matched control
Fasting insulin &
HOMA
Reductions in fasting
insulin levels & IR
Effect of CPAP on Glucose Metabolism:

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Reference
TTT
Period
Study
Population
Measures of Glucose Main Results
Saini et al.,19931 Night8 pts with OSA
Profiles of glucose &
insulin at night
No change in nocturnal glucose & insulin
profiles
Cooper et al.1995 1 Night
6 Obese Pts
without DM
with OSA
Profiles of glucose &
insulin at night
No change in nocturnal glucose & insulin
profiles
Stoohs et al.2004 2 ms 5 Pts with OSA
Fasting glucose & insulin
Profiles of glucose &
insulin at night
↑in fasting & nocturnal glucose levels
No change in fasting or nocturnal insulin
levels
Saarlainen et al.,19973 ms 7 Pts with OSA
Hyperinsulinemic
euglycemic clamp
No improvement in insulin sensitivity
Ip et al.,2000 6 ms 9 Pts with OSA Fasting glucose & insulinNo change in fasting glucose & insulin levels
Sumurra et al.,2006 2 ms
16 pts with
OSA
Hyperinsulinemic
euglycemic clamp
OGTT
No change in insulin sensitivity & glucose
tolerance
Czupryniak et al.,20051 Night
9 pts without
DM with OSA
Nocturnal Intestinal
glucose
Fasting insulin & HOMA
↑in nocturnal glucose
No difference in fasting insulin levels & IR
Coughlin et al.,2007 6 wks
34 Obese pts
with OSA
HOMA
No change in insulin sensitivity with
therapeutic CPAP vs. with placebo CPAP
Effect of CPAP on Glucose Metabolism:

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OSA & Cardiovascular System:
TheassociationofOSAS&cardiovascularconsequencescan
beaddressedby3keyquestions:
First:IsOSAanindependentcardiovascularriskfactor?
Second:Ifso,doestreatmentofOSAreduce
cardiovascularrisk,morbidity&mortality?
Third:IsscreeningforOSASindicatedforpatientsatrisk
forcardiovasculardisease?

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Cardiovascular Events In OSA:
Abu et al, JAMA.2003;290:1906-1914

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OSA & Cardiovascular System:
Somers et al, N Engl J Med. 1993;328:303-307
Inhealthyindividuals,physiologicnormalsleepis
associatedwithdistinctsleepstage–relatedchangesin
cardiovascularregulation.
Sympatheticnervetraffictomuscles,aswellasHR,BP,SV,
COP,&SVR,alldecreaseprogressivelyduringdeeperstages
ofNREMsleep.
However,REMsleepisaccompaniedbystrikingincreases
insympatheticdrive.

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OSA & Cardiovascular System:
Narkiewicz et al, Circulation 1998;97:943–945
Themechanismforincreasedsympatheticactivationisnot
known.
OnepossibilityisthatincreasedchemoreflexgaininOSA
resultsintonicchemoreflexactivationevenduring
normoxia,withconsequentincreasedsympatheticactivity.
Administrationof100%oxygen(toeliminatetonic
chemoreflexdrive)significantlylowerssympatheticactivity,
HR,&BPinOSApatientsduringdaytimewakefulness.

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Neural & Circulatory Changes in OSA:
Somers et al, J Clin Invest. 1995;96:1897-1904

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Somers et al, J Clin Invest 1995
Neural & Circulatory Changes in OSA:

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Impaired Cardiovascular Variability:
Narkiewicz et al, Circulation 1998;98:1071–77
Singh et al, Hypertension 1998;32:293–97
Fratolla et al, J Hypertens 1993;11:1133–37
Comparedwithsimilarlyobesecontrolsubjects,resting
awakeOSApatientshavediminishedheartratevariability&
increasedBPvariability.
TheFraminghamHeartStudyhasimplicatedlowerHR
variabilityasaprecursortothedevelopmentoffuture
hypertension,&increasedBPvariabilityhasbeen
implicatedinincreasedriskofend-organdamagein
patientswithhypertension.

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Heart Rate Variability in OSA:
Thurnbeer, Swiss Med Wkly 2007; 137: 217-22
Var: HR variability, variability of > 6 bpm

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InOSA,thecombinationofrepetitivehypoxemia&sleep
deprivationmaybeassociatedwithincreasedlevelsofplasma
cytokinese.g.,IL-6,α-TNF,CAMs,serumamyloidA,&CRP.
CRPcontributetovasculardisease&dysfunctionby
inhibitingnitricoxidesynthase&increasingexpressionofcell
adhesionmolecules.
Adhesionofcirculatingleukocytestotheendothelialcellsis
consideredoneoftheinitialstepsinthepathogenesisof
atherosclerosis.
OSA & Inflammation:
Vgontzas et al, J Clin Endocrinol Metab. 1997;82:1313-16
Shamsuzzaman et al, Circulation. 2002;105:2462-64
Venugopa et al, Circulation. 2002;106:1439-41
Ross et al, Nature;1993;362:801-809

38. Page 0
0.5
1
1.5
2
2.5
3
pg/mL
Normal OSA NarcolepsyIdiopathic
Hypersomnia
TNF
IL
-
6
**
Normal OSANarcolepsy
Idiopathic
Hypersomnia
Cytokines & Disorders of EDS:
Vgontzas et.al., 1997

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OSA & Adhesion Molecules:
Galal IH (2007)0
100
200
300
400
500
600
700
0 1 2 3 4
sICAM-1
ng/mL 0
500
1000
1500
2000
2500
3000
3500
0 1 2 3 4
sVCAM-1
ng/mL

40. Page 
InOSA,thehypoxia/reoxygenationphenomenonthat
occursinresponsetoapneasfollowedbyhyperventilation,
mayelicitincreasedvascularoxidativestress.
Lowoxygentensionisatriggerforactivationof
polymorphonuclearneutrophils,whichadheretothe
endothelium&releasefreeoxygenradicals.
PreventionofOSAbyCPAPreducesproductionof
superoxide.
OSA & Oxidative Stress:
Schulz et al, Am J Respir Crit Care Med. 2000;162:566-70
Prabhakar et al, Am J Respir Crit Care Med. 2002;165:859-60

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HypercoagulabilityinOSASresultsfromtheimbalance
betweencoagulation&fibrinolysis.
Increasesinhematocrit,nocturnal&daytimelevelsof
fibrinogen,plateletaggregation, blood
viscosity,FVIIa,FXIIa,VWF,D-dimer&fibrinolysis-
inhibitingenzymeplasminogeninhibitor(PAI-1)in
OSA,likelycontributetopredispositiontoclotformation&
atherosclerosis.
CPAPtherapycanalleviatesomeoftheseabnormalities&
canreducefactorVIIclottingactivity.
OSA & Hpercoagulability:
Hoffstein al, Chest. 1994;106:787-91
Chin et al, Am J Resp Crit Care Med. 1996;153:1972-76
Nobil et al, Clin Hemorheol Microcirc. 2000;22:21-27
Wessendorf et al, Am J Resp Crit Care Med. 2000;162:2039-42

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OSA & Endothelial Dysfunction:
Thehypoxia,hypercapnia,&pressorsurgesaccompanyingobstructive
apneiceventsserveaspotentstimulifor↑inthereleaseofendothelin&
↓inNO→endothelialdysfunction.
EndothelialdysfunctionisoftenseenwithOSAcomorbidites
e.g.,HTN,hyperlipidemia,DM,orsmoking→↑riskofcardiovascular
events.
Inaddition,OSAitselfmaybeanindependentriskfactorforthe
developmentofendothelialdysfunction.
CPAPtreatmentplaysanimportantroleintheimprovement&
protectionofvascularendothelialdysfunction.
Zhang et al, Chin Med J.200;116:844-7
Zamarron et al., Eur J Inten Med.2008;19:390-8

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Cardiovascular Events In OSA:
Abu et al, JAMA.2003;290:1906-14

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Itisestimatedthat50%ofOSA
patientsarehypertensive,&
30%ofhypertensivepatients
alsohaveOSA, often
undiagnosed.
OSA & Hypertension:
Silverberg et al, Curr Opin Nephrol Hypertens. 1998;7:353–7
Fletcher et al., Ann Intern Med. 1985;103:190 –5

45. Page 
OSASisidentifiedasanindependentriskfactorforthe
onsetofarterialhypertension.
Acleardose-effectisevident:themoreapneas/hrofsleep,
thehigherthechanceforbecominghypertensive.
In2003,the“JointNationalCouncilonHighBlood
Pressure”listedOSAasthefirstidentifiablecauseofarterial
hypertension.
Harsch et al, Med Sci Monit 2004; 10: 510-5
OSA & Hypertension:

46. Page 
Potential mechanisms linking OSA with HTN:
Hoffmann et al, Minerva Med. 2004;95:281-90
Obstructive Sleep Apnea
HYPERTENSION
Chemoreflex activation
Baroreflex dysfunction
Arousals
Intrathoracic pressure changes
Sympathetic activation
Leptin R
Insulin R
Inflammation
Oxidative
stress
Obesity
RAS
activation
Endothelial
dysfunction

47. Page 
Drug-ResistantHypertension:(clinicalbloodpressure
of>140/90mmHgwhiletakingasensiblecombinationof≥
antihypertensivedrugs)ahighprevalenceofOSAShasbeen
reported.
(FletcherEC1985,IsakssonH,1991)
Inagroupof41patientstakingameanof3.6different
antihypertensive medications daily:
96%ofthemen&65%ofthewomenhadOSAS,withmen
sufferingfrommoresevereOSAS(AHI32vs.14).
(LoganAG,2001)
OSA & Hypertension:

48. Page 60
80
100
120
140
MAP (mmHg)
baseline
effective nCPAP
7
15
pm 11
15
pm 3
15
am 7
15
am3
15
pm 11
15
am
Becker, Circulation 2003
Effect of nCPAP on Blood Pressure in OSA:-25
-20
-15
-10
-5
0
5
10
15
mmHg
* *
*
MAP systolic diastolic

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OSA & Heart Failure:
Marin et al., Lancet. 2005; 365:1 046 –53
OSAcontributetotheprogressionofheartfailure
throughseveralpathologicalmechanisms:
1)byelicitinggreatersympatheticoutflowtotheheart,kidney,&
resistancevesselsduringwakefulness&sleep.
2)byincreasingleftventricularafterloadbothacutely&chronically.
3)byinducinghypoxia&2ryincreasesinrightventricularafterload.
4)byincreasingtheriskofmyocardialinfarction.
However,yettobeestablishediswhetherOSAcancause
heartfailure.Inaddition,whetherthepresenceofOSAin
Heartfailureacceleratesmortalityremainsunclear.

50. Page 
HeartfailurepatientswithCPAP-treatedOSAhavelow
mortalityratecomparedwithuntreatedOSA.
Effect of treatment on OSA on HF:
Wang et al., J Am Coll Cardiol. 2007;49:1625-31

51. Page 
EpidemiologicaldatasuggestthatOSAisoverrepresented
inpatientswithCAD.
Conversely,theclinicalcourseofCADisinitiated(or)
acceleratedbythepresenceofOSA.
Morethanhalfofsuddencardiacdeathsinpatientswith
provenOSAoccurduringthesleepinghours(between10
PM&6AM).Thus,OSAappearstoaffectthetimingof
suddencardiacdeath.
OSA & CAD:
Hedner et al., 2005
Somers et al., JACC 2008;52:686–717

52. Page 
InpatientswithcombinedOSA&CAD,treatmentofOSA
wasassociatedwithadecreaseintheoccurrenceofnew
cardiovascularevents.
Repotsfrompatients’spousesdescribemarkedchangesin
sleeppatterns,snoringseverity,&witnessedapneasafter
bypasssurgeryandsometimesevenafterangioplasty.
Effect of treatment on OSA & CAD:
Milleron et al., Eur Heart J. 2004;25:728 –34
Somers et al., JACC 2008;52:686–717

53. Page 
OSA & Arrhythmia:
Zwillich et al, J Clin Invest. 1982;69:1286-92
Somers et al., JACC 2008;52:686–717
Nocturnalarrhythmiashavebeen
reportedinupto50%ofpatientswith
OSAeveninabsenceofpre-existing
cardiacdisease.
Themostcommonarrhythmiasinclude
2
nd
degreeheartblock,AF,
ventricularextrasystole&sinus
bradycardia,representinginpartthe
divingreflexresponsetoapnea&
hypoxia

54. Page 
Recurrence of AF After Cardioversion:0
10
20
30
40
50
60
70
80
90
100
Controls (n=79)Treated OSA
(n=12)
Untreated Osa
(n=27)
% Recurrence
at 12 Months
**
Kanagola et al, Circ 107:2589, 2003

55. Page 
InsmallseriesofpatientswithOSA(withoutclinical
historyofchronicobstructivepulmonarydisorder)the
reporteddaytimepulmonaryarterialhypertensionwas
foundin20-42%ofcases
ThemostlikelyprimarymechanismOSA-relatedPAHis
hypoxemia,whichisknowntoreflexivelyinduceanacute
increaseinPAP.
OSA & PAH:
Yamakawa et al, Psychiatry Clin Neurosci.,2002;56:311–12
Voelkel, Am Rev Respir Dis. 1986;133:1186 –95

56. Page 
Buchner et al. AJRCCM 2007
CPAP Treatment & Cardiovascular Risk:

57. Page 
*
Cardiovascular Disease & Mortality in OSAS:
Doherty et al. Chest 2005; 127: 2076-84

58. Page 
Memoriesareformedinthemammillarybodies.
WhenUCLAneuroscientists*scannedthebrainsof43sleepapnea
patients&66healthyvolunteersusingmagneticMRI,theydiscovered
thattheOSApatients’mammillarybodieswerenearly20%smallerthan
thoseoftheuntroubledsleepers.
OSA & Memory Affection:
*Newswise: Study Links Common Sleep Disorder to Memory LossRetrieved on June 11, 2008

59. Page 
StrokehasbeenlinkedtoOSA&sleepapneaishighly
prevalentinpatientswithstroke.
Mechanismsthathavebeenimplicatedinanyincreasedrisk
ofstrokeinOSAincludeBPswings,reductionincerebral
bloodflow,alteredcerebralautoregulation,impaired
endothelialfunction,acceleratedatherogenesis,&
prothrombotic&proinflammatorystates.
OSA & Stroke:
Somers et al., JACC 2008;52:686–717

60. Page 
OSA & Stroke:
Bassetti & Aldrich, Sleep 22:217, 19990
5
10
15
20
25
30
35
Stroke (n=48) TIA (n=32) Controls (n=25)
Average AHI (Episodes/hour)

61. Page 
TheprevalenceofOSAinESRDrangedfrom40%-60%.
Long-standingOSAcontributestotheoriginofESRDby
inducingchronicelevationsinBP&increasingsympathetic
nervedischargedirectedatthekidney&othervascular
beds.
OSA & End-Stage Renal Disease:
Hanly, Semin Dial. 2004;17:109 –14

62. Page 
Conclusion

63. Page 
Zamarron, Eur J Int Med 2008; 19:390-98

64. Page 
The Association of OSAS with
Endocrine-Metabolic &
Cardiovascular Alternations
indicates that, More than a Local
Abnormality, OSAS should be
considered a Systemic Disease.

65. Page 

66. Page 
23#, Verse 30#Room, Chapter -Ar

67. Page 