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Intima-MediaThicknessinPatientsWithObstructiveSleepApneaWithoutComorbiditiesAgnieszkaGorzewskaKrzysztofSpecjalskiJacekDrozdowskiKatarzynaKunickaEwaSwierblewskaLeszekBieniaszewskiJanM.
SominskiEwaJassemReceived:21January2013/Accepted:16April2013/Publishedonline:14May2013TheAuthor(s)2013.
ThisarticleispublishedwithopenaccessatSpringerlink.
comAbstractBackgroundObstructivesleepapnea(OSA)isassociatedwithelevatedriskofcardiovascularevents.
Theearlystagesofvascularcomplicationscanbevisualizedbymeansofultrasound.
Intima-mediathickness(IMT)cor-relateswiththepresenceofriskfactorsofcardiovasculardiseasessuchashypertension,diabetes,tobaccosmoking,orhyperlipidemia.
However,littleisknownwhetherOSAitselfmaybethecauseofIMTthickening.
MethodsThestudygroupwascomposedof28patients(6women,22men;meanage=53.
8years,meanBMI=27.
1kg/m2,meanAHI=22.
4/h)withOSAwhohadnocomorbidities.
Thecontrolgroupconsistedof28healthysubjects(6women,22men;meanage=53.
9years;meanBMI=27.
5kg/m2).
InbothgroupsIMTwasassessedincommoncarotidarterieswiththeuseofultra-sonography.
Additionally,inpatientswithOSA,pulsewavevelocity,echocardiography,24-hautomatedbloodpressuremonitoring,clinicalsignsandsymptoms,andbloodtestswereperformedtoinvestigatepossiblecorre-lationswithIMT.
ResultsMedianIMTwas0.
41mminOSApatientsand0.
46mminthecontrolgroup(p=0.
087).
Echocardiographyrevealedleftventriclehypertrophyin21%,systolicdis-ordersin8%,anddiastolicdisordersin57%ofthepatients.
Inalargemajorityofpatients,pulsewavevelocitywasfoundtobenormal.
IMTcorrelatedwithage(r=0.
446,p=0.
017),totalcholesterol(r=0.
518,p=0.
005),daytimesystolicbloodpressure(r=0.
422,p=0.
025),pulsepressure24handdaytime(r=0.
424,p=0.
027andr=0.
449,p=0.
019),earlymitralow/atrialmitralow(E/A)(r=-0.
429,p=0.
023),andposteriorwalldiameter(PWD)(r=0.
417,p=0.
270).
ConclusionInarelativelynonobesegroupofpatients,nosignicantdifferenceswerefoundintheintima-mediathicknessbetweenOSApatientswithoutconcomitantcar-diovasculardiseasesandhealthycontrols.
ThismayleadtotheconclusionthatIMTdoesnotreectincreasedriskofcardiovasculareventsinpatientswithisolatedOSA.
KeywordsObstructivesleepapneaIntima-mediathicknessCardiovascularriskfactorsUltrasonographyIntroductionObstructivesleepapnea(OSA)ischaracterizedbyrecur-ringepisodesofcollapseoftheupperairways.
Atleastveepisodesperhour[Apnea-HypopneaIndex(AHI)[5]andcoexistenceofdaytimesleepinessmaybefoundinabout4%menand2%women30–60yearsofage[1].
OSAisassociatedwithsignicantimpairmentofqualityoflifeaswellashighermortality.
Heetal.
[2]reportedamortalityrateof40%inagroupofpatientswithsevereOSAduringthefollow-upperiodof8years.
InastudybyLavieetal.
[3],basedontheanalysisof1,620cases,theobserved/expectedmortalityratewas3.
33.
HighmortalityinOSApatientsresultspartiallyfromexcessivedaytimesleepinessA.
GorzewskaJ.
DrozdowskiJ.
M.
SominskiDepartmentofPneumonology,MedicalUniversityofGdansk,ul.
Debinki7,80-952Gdansk,PolandK.
Specjalski(&)E.
JassemDepartmentofAllergology,MedicalUniversityofGdansk,ul.
Debinki7,80-952Gdansk,Polande-mail:specjalski@gumed.
edu.
plK.
KunickaE.
SwierblewskaL.
BieniaszewskiDepartmentofCardiology,MedicalUniversityofGdansk,ul.
Debinki7,80-952Gdansk,Poland123Lung(2013)191:397–404DOI10.
1007/s00408-013-9471-7whichleadstocaraccidentsandaccidentsataworkplace[4,5].
Anothermechanismofmortalityisrelatedtotheincreasedriskofcardiovascularevents.
IthasbeenshownthatmyocardialinfarctionsandbrainstrokesaretwotothreetimesmorecommoninthepopulationwithOSAcomparedtohealthyindividualsofthesameage.
Thisisprobablyaconsequenceofarterialhypertension,endothe-liumdysfunction,coagulationdisorders,elevatedlevelsofinammatorymediators,andplateletactivationobservedinOSApopulation[6].
Anatomicalchangesinthevesselscanbevisualizedbymeansofultrasound.
However,ineverydaypractice,attentionisusuallypaidtoatheroscleroticplaquestypicalofadvancedatherosclerosiswithorgandysfunction.
Theearlystagesofcardiovasculardiseasecanbeevaluatedbytheintima-mediathickness(IMT).
IMTcorrelateswiththepresenceofriskfactorsofcardiovasculardiseases,suchashypertension,diabetes,tobaccosmoking,andhyperlipid-emia[7–9].
AnIMTofC0.
75mmisassociatedwithahigherriskofcardiovascularevents[10].
InpatientswithOSAandseveralcomorbidities,theintima-mediacomplexisthickerthanthatofcontrolswithoutOSAwhosharethesameriskfactorsofcardio-vascularevents[11].
Moreover,IMTintherstgroupstronglycorrelateswithfrequencyofdesaturationbelow90%[12].
However,littleisknownaboutIMTinpatientssufferingfromOSAalone.
Theaimofthisstudywastoinvestigatewhetherthereisanincreaseinintima-mediathicknessinOSApatientswithoutanycomorbidities(arterialhypertension,diabetes,andcoronaryarteriesdisease).
PatientsandMethodsThestudygroupwascomposedof28patientswithOSAwhohadnocomorbidities.
Ineverycase,OSAwascon-rmedbysleepmonitoringwiththeuseofaportablesleeprecorder(Stardust,PhilipsRespironics,theNetherlands)thatregisteredchestmovements,airow,saturation,heartrate,andbodyposition.
ForourstudyweadaptedtheAASMcriteria.
Hypopneawasfoundwhentherewasa30%reductionofairowaccompaniedby4%oxygendesaturationorwhentherewasa50%reductionofairowaccompaniedby3%desaturationorarousal.
Apneawasdiagnosedwhentherewascompletecessationofairow[13].
Alltheresultswerevisuallyreviewed.
SleepinesswasevaluatedwiththeEpworthscale.
Patientswereexcludediftheyhadcardiovasculardiseases,includingarterialhyper-tension,coronaryarterydisease,diabetes,andhypercho-lesterolemia;ahistoryofvascularevents(myocardialinfarction,transientischemicattack,andbrainstroke);currentorpasttherapywithmedicationstolowerbloodpressure,glucose,orcholesterollevel;elevatedbloodpressure;orabnormalitiesinlabtestsduringavisittotheclinic.
Thecontrolgroupof28subjectswasrecruitedfromthemembersofCityGuardsofGdanskandtheirfamilies.
Exclusioncriteriawereahistoryofrespiratoryorcardio-vasculardisease,includingdiabetes,hypertension,andhypercholesterolemia;symptomssuggestingOSA;andtak-ingmedicationforanyoftheabove-mentionedconditionscurrentlyorinthepast.
Inthecontrolgroup,assessmentofriskfactors(medicalhistoryandlaboratorytests)andIMTmeasurementwereperformedonthevisittotheclinic.
AssessmentofRiskFactorsMedicalhistorywastakenandaphysicalexaminationwasperformedineveryparticipantofthestudy.
Bodymassindex(BMI)andwaist/hipratio(WHR)werecalculated.
Subsequently,bloodspecimensweretakenfromeveryparticipantfordeterminationofglucose,HbA1c,andlipidlevels.
Patientswithnohistoryofcardiovasculardiseaseorsignicantabnormalitiesinlaboratorytestswereincludedinfurtherphasesofthestudy.
Intima-MediaThicknessMeasurementIMTwasassessedinthecommoncarotidarterieswiththeuseofultrasonography(ALOKA5000,AlokaCo.
,Japan)aspreviouslydescribed[14].
Themeasurementwasper-formedbilaterally,inanteriorandlateralplanes,1–3cmbelowthebulb,inlocationsthatwerefreeofatheroscle-roticplaques.
Imageswereacquiredattheendofdiastole,denedastheRwaveintheECG.
Theimageswereana-lyzedwithcvsver.
1ssoftware(TechnicalUniversityofGdansk,Poland),allowingforprecisemeasurementsintheselectedfragmentoftheimages.
Common,internal,andexternalcarotidarteriesaswellasvertebralarteriesweretestedwithDopplerultrasoundforthepresenceofatheroscleroticplaquesandhemody-namicallysignicantstenosis.
Theformerwasdenedaslocalstenosisof[1.
2mmnotoccupyingthewholecir-cumferenceofavesselandthelatterwasdenedasadecreaseofmorethan50%oftheinnerdiameterofthevessel.
PulseWaveVelocityAssessmentPulsewavevelocity(PWV)wasassessedinsubjectslyingsupineafter20minofrest.
Measurementswereperformedsimultaneouslyabovetherightcommoncarotidarteryandtherightfemoralartery.
Pulsesensors(TY-306,Philips,theNetherlands)wereplacedatpointswherethepulsewasthebestpalpable.
Pulsewavevelocitywascalculatedusingthe398Lung(2013)191:397–404123formula:PWV=L/dt,whereListhedistancebetweensensorsandDt(dt)isthedelaybetweentwopulsewaves.
Atotalof20measurementswereperformedforeverysubject.
Afterexclusionofbordervalues,themeanvaluewasusedforstatisticalanalysis.
24-hAutomatedBloodPressureMonitoringTwenty-four-hourautomatedbloodpressuremonitoringwasperformedbymeansofoscillometry(Spacelab90207,MontaraDolby,UK).
Bloodpressurewasregisteredevery20minduringthedaytime(6.
00–22.
00)andevery30minduringthenighttime(22.
00–6.
00).
Meanvaluesofsystolic(SBP)anddiastolicbloodpressure(DBP)aswellasheartratewerecalculatedforthe24-hperiodandperiodsrepresentativeofdaytimeandnighttime.
AccordingtoStaessen'scriteria,onlyresultswithmorethan90%oftechnicallyacceptableparameterswereanalyzed[15].
Asaconsequence,thefollowingdatahavebeenexcluded:heartratebelow40/minorabove150/min,pulsepressure(PP;differencebetweensystolicanddiastolicpressures)lowerthan10%SBP,SBPbelow50mmHgorabove240mmHg,andDBPbelow40mmHgorabove140mmHg.
EchocardiographyEchocardiographywasperformedwithAloka5000Ultra-sound(AlokaCo.
,Japan).
LuminaldiametersandwallthicknesseswereassessedinaccordancewiththePennconvention.
Alltheparametersweremeasuredthreetimesandthemeanvaluehasbeenpresented.
Leftventricledimensionsweredeterminedintheparasternalplane(M-mode).
Interventricularseptumdiameter(IVSD),pos-teriorwalldiameter(PWD),andleftventriclediastolicdiameter(LVDD)wereassessedonthelevelofchordaetendineaeofthemitralvalve.
Leftventricleend-systolicdiameter(LVDS)wasmeasuredatthemomentofthemax-imalfrontpositionoftheheart'sposteriorwall.
Diastolicfunctionoftheheartwasdescribedbythefollowingparameters:earlymitralow(E;cm/s),atrialmitralow(A;cm/s),E/Aratio,decelerationE(DecE;cm/s2),anddecel-erationEtime(DecTE;ms).
Systolicfunctionwasdescribedbyejectionfraction(EF)andfractionalshortening(FS).
Leftventriclemass(LVM)wascalculatedusingDevereuxandReichek'sformula[16].
Leftventriclemassindex(LVMI)wasdenedasthequotientofLVMandbodysurfacearea.
StatisticalAnalysisThedatawereanalyzedusingtheStatistica8.
0softwaresystem(StatSoft,Tulsa,OK,USA).
Inordertoverifythehypothesisofstandardnormaldistribution,theShapiro–Wilktest(W)wasapplied.
AnalysisoftherelationshipsbetweennormallydistributedvariableswasbasedonPearson'scorrelation.
Inothercases,Spearman'srankcorrelationwastested.
Theresultswerepresentedascor-relationcoefcient(r)andstatisticalsignicance(p).
Fortestingindependentsamples,theMann-WhitneyUtestwasapplied.
Apvalue\0.
05wasconsideredsignicant.
TheprotocolofthestudywasapprovedbytheInde-pendentEthicsCommitteeattheMedicalUniversityofGdansk(No.
NKEBN/8/2006).
Alltheparticipantsgaveinformedconsentbeforeinclusioninthestudy.
ResultsThestudygroupwascomposedof28patientswithOSA,including22menand6women29–69yearsold(meanage=53.
8years).
ThemeanBMIwas27.
1kg/m2andtheWHRwas0.
92.
Frequencyofapneaepisodeswasevalu-atedbymeansofpolysomnography.
MeanAHIwas22.
4(SD±11.
9).
MildOSA(AHIB15/h)wasdiagnosedin9(32%)patients,moderateOSA(AHI=15–30/h)in13(46%)patients,andsevereOSA(AHI[30/h)in6(22%)patients.
SleepinesswasevaluatedwiththeEpworthscale.
In11patients(39.
3%),theresultwasnormal(0–9points).
Moderatesleepinesswasfoundin11(39.
3%)patients,andseveredaytimesleepinesswasfoundin6(21.
4%)patients.
Thecontrolgroupcomprised28healthysubjects:22menand6women34–65yearsold(meanage=53.
9years).
Therewerenostatisticallysignicantdifferencesbetweenthetwogroupsintermsofage,BMI,andbloodcholesterollevel(Table1).
Pulsewavevelocitywasdeterminedinthestudygrouptoassesscomplianceofthearteries;resultsfrom7.
65to14.
1m/swereobtained(mean=10.
34m/s,SD=±1.
58).
Infourpatients,PWVexceeded12m/s.
Statisticalanalysisconrmedstandardnormaldistribution(W=0.
929,p=0.
06).
NocorrelationswerefoundbetweenPWVandage,BMI,orAHI.
Table1CharacteristicsofOSAandcontrolgroupsOSAgroupControlgrouppvalueAge(years)29–6934–65Age(mean±SD)53.
8±9.
5153.
9±6.
20.
434Gender(F:M)6:226:22BMI(kg/m2)22.
6–3615.
8–44.
2BMI(mean±SD)27.
1±3.
127.
5±5.
10.
737Cholesterollevel(mg/dl)138–310159–346Cholesterollevel(mean±SD)222.
2±47.
71231.
8±36.
90.
384Dataarepresentedasminimal–maximalvaluesormean±SDLung(2013)191:397–404399123Bloodpressurewasmeasuredconventionallyandmon-itoredautomaticallyfor24h.
Meanvaluesofsystolicanddiastolicbloodpressurewere120.
9±8.
86mmHgand78.
4±9.
02mmHginconventionalmeasurement;121.
1±15.
1mmHgand77.
4±8.
6mmHgin24hmonitoring.
Apartfromresultsgainedfromconventionalmeasurements,alltheparametershadanormaldistribu-tion.
Therewerenocorrelationsbetweenbloodpressureandage,BMI,orwaistcircumference.
EchocardiographywasperformedinpatientswithOSAalone.
CorrelationswerefoundbetweenEF,FS,PWDandage;E,E/A,IVSD,LVMandAHI;andLVMandwaist.
Detailedresultsof24-hbloodpressuremonitoringandechocardiographyaswellasalistofcorrelationsareavailableondemandfromthecorrespondingauthor.
Commoncarotidarterieswereassessedbymeansofultrasound.
Noabnormalitieswerefoundin16patients(57.
2%).
Wallirregularitieswerefoundin3patients(10.
7%)andatheromatousplaqueswererevealedin9patients(32.
1%).
Theywerenotassociatedwithhemo-dynamicallysignicantstenosisinanycase.
IMTwasmeasuredbilaterallyintwoplanes:anteriorandlateral.
InOSApatientsthehighestmedianIMTvaluewasregisteredintheleftcommoncarotidarteryinthelateralplane.
However,theonlysignicantdifferencewasobservedbetweenanteriorandlateralplanesinrightcommoncarotidartery(p\0.
05)(Fig.
1).
MedianIMTwas0.
41mminOSApatientsand0.
46mminthecontrolgroup.
Thedifferencewasnotstatisticallysignicant(p=0.
087)(Fig.
2).
TherewasnocorrelationbetweenIMTandOSAseverityeither.
InthegroupofpatientswithOSA,wesearchedforcorrelationsbetweenmeanIMTandalltheanthropometricdata,laboratoryndings,andcardiovascularparameters.
ItwasfoundthatIMTcorrelatedwithage,cholesterollevel,PP(24h),PPd,SBPd,E/A,andPWD.
Selectedcorrelationcoefcients(r)andcorrespondinglevelsofsignicance(p)aregiveninTable2.
DiscussionObstructivesleepapneahasbeenshowntocorrelatewithhighermortalityresultingfromcardiovascularevents.
AlthoughOSAandcardiovasculardiseasessharemanyriskfactors,epidemiologicalstudiesdemonstratedthatOSAisanindependentriskfactorofarterialhypertensionandatherosclerosis[17].
Themechanismsofthisrelationshiparenotfullyunderstood.
Theymaybepartlyexplainedbyconstantactivationofthesympatheticsystem,changesofpressureinthechest,andoxidativestress[18].
AtheroscleroticplaquescanbevisualizedonlyatthelatestagesofthediseasewhentheycoexistwithnumerousFig.
1IMTinpatientswithOSAandincontrolgroup(p=0.
087).
Dataarepresentedasmedian(centralsquare),25–75%(topandbottomofboxes),andminimal–maximalvalues(topandbottomofbars)Fig.
2MedianIMTinpatientswithOSAwithregardtothesideandplane.
LAleftcommoncarotidartery,anteriorplane,LLleftcommoncarotidartery,lateralplane,RArightcommoncarotidartery,anteriorplane,RLrightcommoncarotidartery,lateralplane,NSnotsignicant.
Dataarepresentedasmedian(centralsquare),25–75%(topandbottomofboxes)andminimal–maximalvalues(topandbottomofbars)400Lung(2013)191:397–404123comorbidities.
Thus,inmanypatientswithOSA,itisimpossibletoestimatewhetherthedevelopmentofplaquesisaconsequenceofrecurringhypoxiaonlyortheresultofcoexistingdiseases.
Thatiswhyassessmentoftheearlystagesofatheroscleroticchanges,suchasintima-mediathicknessmeasurement,seemstobeamuchbetterapproach.
Moreover,IMTdeterminationcouldbeavalu-abletoolineverydaypracticeasitiseasytodetermine,repetitive,andnoninvasive.
ItisparticularlyindicatedthatIMTshouldbemeasuredinpatientswitharterialhyper-tension,inwhomIMT[0.
9mmisregardedasasignoforgandysfunction.
Themaingoalofthepresentstudywastoassesswhe-therIMTiselevatedinOSApatientswithoutcomorbidities(hypertension,diabetes,andcoronaryarterydisease).
Whentakingepidemiologicaldataintoaccount,itisquiteclearthatrecruitmentofpatientswhomeetsuchinclusioncriteriahasbeenadifculttask.
Thevastmajorityofpatientswereexcludedbecauseofadvancedcardiovasculardiseases.
Finally,28patientswithsymptomaticOSA,conrmedbyportablesleeprecording,wereenrolled.
ThecontrolgroupwasrecruitedfromhealthyemployeesoftheCityGuardsofGdanskwhodidnothaveanychronicdiseases.
Nosignicantdifferenceswerefoundbetweenthegroupsintermsofage(53.
8vs.
53.
9yearsonaverage),gender(22menand6womeninbothgroups),andtotalcholesterollevel(222vs.
232mg/dl).
MeanBMIwas27.
5kg/m2inthecontrolgroupand27.
1kg/m2intheOSAgroup.
Inthelattergroup,25%ofpatientshadnormalBMI,in61%wereoverweight,and14%werediagnosedwithobesity.
Theseresultsareinlinewithpreviousepi-demiologicalstudiesconductedinthepopulationofnorthernPoland.
TheSOPKARDstudyshowedthepres-enceofoverweightorobesityin61and65%ofpatients,respectively,inthefthandsixthdecadesoflife[19].
IntheWOBASZstudy,overweightorobesitywasfoundin62%ofthePolishpopulation[20].
AccordingtotheNationalCholesterolEducationPro-gramAdultTreatmentPanelIII(NCEPATPIII),visceralobesityisdiagnosedwhenthewaistcircumferenceisgreaterthan102cminmenand88cminwomen[21].
Thiscriterionwasmetin6(21%)ofourpatientswithOSA.
TheresultwasthesamewhentheWHRwasusedtomakethediagnosis.
MedianIMTwas0.
41mminpatientswithOSAand0.
46mminhealthycontrols(p=0.
087).
Comparisonofthisresultwiththoseofpreviousstudiesistroublesomeastheyvarywithrespecttoselectionofparticipantsandmethodology.
MostofthestudieswerebasedontypicalpopulationsofpatientswithOSA,i.
e.
,theyhadnumerouscomorbidities.
Forexample,Silvestrinietal.
[11]measuredIMTin23patientswithsevere,untreatedOSA.
ThemeanBMIwas31kg/m2.
Mostofthepatientshadconcomitantdiseasessuchasarterialhypertension(65%),hyperlipid-emia(35%),diabetes(17%),andtobaccodependency(22%).
Acontrolofsimilarageandriskfactors(highBMI,smoking,hypertension,diabetes,andhyperlipidemia)wasassignedtoeverypatient.
ItwasfoundthatIMTwassignicantlyhigherintheOSAgroupcomparedtocontrols(1.
429±0.
34vs.
0.
976±0.
17;p\0.
0001)[11].
Kaynaketal.
[22]analyzed114caseswhoweresuspectedofhavingOSA.
Theyweredividedintothreesubgroups:37subjectswithnormalAHI(B5),41subjectswithmild-to-moderateOSA(5\AHI\30),and36subjectswithsevereOSA(AHI[30).
Therewerenosignicantdif-ferencesamongthegroupsintermsofage,hypertension,diabetes,smoking,andserumlevelsoftotalcholesterolandtriglycerides.
ItwasshownthatIMTwashigherinpatientswithOSAthaninthegroupwithnormalAHI.
Thedif-ferencesbetweenthegroupswithmild-to-moderateandsevereOSAwerealsosignicant(1.
78±0.
57vs.
1.
91±0.
39,respectively;p\0.
001).
ThemainlimitationofthatstudywasthatthegroupwithsevereOSA(AHI[30)wascharacterizedbyhigherBMI,whichcor-relatespositivelywithIMT.
Moreover,thepatientswithseveresymptomshadalongerofhistoryofOSA(8.
5yearsonaverage,comparedto7yearsinthegroupwithmild-to-moderateOSA)[22].
Bothstudies[11,22]showedtherelationshipbetweenOSAandthickeningofintima-mediacomplex.
However,theywerenotsufcienttoprovethatOSAitselfisresponsibleforthedevelopmentofearlyatheromatouschanges.
Everyriskfactor,particularlydiabetes,hyperlip-idemia,andhypertension,mightaffecttheserelationships.
Forexample,Savranskyetal.
[23]showedinananimalmodelthatatherosclerosisdevelopedonlyinmicesub-jectedtointermittentairandfedahigh-cholesteroldiet.
Thus,todeterminewhetherOSAleadstoanincreasedIMT,itwasnecessarytoconductstudiesinpatientswithnoconcomitantdiseases.
Table2RelationshipsbetweenIMTandselectedparametersinpatientswithobstructivesleepapneaIMTrpAge0.
4460.
017Cholesterol0.
5180.
005LDL0.
6410.
001PP24h0.
4240.
027PPd0.
4490.
019SBPd0.
4220.
025E/A-0.
4290.
023PWD0.
4170.
027Desaturation\90%time0.
1280.
17rcorrelationcoefcient,plevelofsignicanceLung(2013)191:397–404401123Drageretal.
[24]comparedtheIMTinagroupof30patientswithOSA(15withmild-to-moderateOSA,i.
e.
,meanAHI=16.
2,and15withsevereOSA,i.
e.
,AHI=55.
7)withthatof12healthycontrols.
Patientswithhypertension,diabetes,andhyperlipidemiawereexcludedfromthestudy.
IMTinthesevereOSAgroupwassignif-icantlyhigherthanthatinthemild-to-moderateOSAgroup(0.
722vs.
0.
580mm;p\0.
05)andincontrols(0.
604mm).
However,nodifferenceinIMTwasfoundbetweenthecontrolsandpatientswithmild-to-moderatesymptoms[24].
TheserelationshipswerealsoconrmedbyAltin[25].
Moreover,heobservedthatresultsregisteredintheleftcarotidarterywerehigherinallthegroups:patientswithsevereOSA(0.
8vs.
0.
97mm),mild-to-moderateOSA(0.
63vs.
0.
78mm),andhealthycontrols(0.
58vs.
0.
67mm).
However,thedifferenceswerenotstatisticallysignicant.
Inthepresentstudy,theIMTinpatientswithOSAandincontrolsweresimilar.
ThismaybebecausethemeanAHIinourgroupwaslowerthanthatinthepreviousstudies.
Asshownbefore,patientswithmildandmoderateOSAhadanIMTcomparabletothatofthehealthypop-ulation.
TherewerecleardifferencesonlybetweenpatientswithsevereOSAandhealthysubjects.
Wealsoconrmeddifferencesbetweenrightandleftcommoncarotidarteries.
Itmaybehypothesizedthatthisisassociatedwithana-tomicalconditionsthatleadtoahigherbloodpressureinleftcarotidarteries.
SignicantpositivecorrelationsbetweenIMTandageandtotalcholesterolwererevealed.
Suchrelationshipshavealsobeenshowninpreviousstudies[26–28].
Incontrasttothosestudies,wehavenotfoundanycorrelationbetweenIMTandBMI.
Thismaybebecausethepartici-pantsinourstudydidnothaveanyconcomitantdiseases.
Moreover,themeanBMI(27.
1kg/m2)inourstudywaslowerthanthatinthestudiesbyDrager(29kg/m2),Tan-riverdi(29.
8kg/m2),andAltin(30kg/m2inthegroupwithsevereOSAand27.
8kg/m2inthegroupwithmildOSA)[24,25,29].
AlthoughthemeanIMTinourstudygroupwasnotsignicantlyelevated,atheromatousplaqueswerefoundin32%ofpatients.
ThisishigherthanthatfoundinthestudiesbyTanriverdietal.
[29]andAltinetal.
[25](12.
5and14%,respectively).
Altinetal.
[25]suggestedthatthefrequencyandgradeofatheromatousstenosisishigherinpatientswithsevereOSAandhypothesizedthatahighAHIisanevenstrongerpredictorofatherosclerosisthanage.
Tanriverdietal.
[29]didnotconrmthisrelationship,whichisinlinewithourndings.
Pulsewavevelocitymeasurementwasusedinthestudybecausehasbeendemonstratedthatitsincreasecorrelateswiththegradeofatherosclerosis[30].
IthasalsobeenfoundthatanincreaseinPWVmayprecededevelopmentofarterialhypertension[2,31].
Sofar,therelationshipsbetweenPWVandOSAhavebeenrarelyinvestigated.
Drageretal.
[24]showedthatPWVcorrelatedpositivelywithAHI(r=0.
61,p\0.
0001).
PWVincaseswithsevereOSA(AHI[30)wassignicantlyhighercomparedtothatincasesofmild-to-moderateOSA(30[AHI[5)andcontrolgroups.
However,thedifferencebetweenpatientswithmild-to-moderateOSAandthecontrolgroupwasnotstatisticallysignicant[24].
Inthepresentstudy,themeanPWVwasnormal(10.
34m/s);PWVwaselevatedinonlyfourpatients.
NocorrelationshavebeenobservedbetweenPWVandbasicanthropometricparameters,IMT,orseverityofOSA.
ThismaybeexplainedinpartbythefactthatthemeanAHIinthestudygroupcouldbeclassiedasmild-to-moderateOSAaccordingtoDrager'scriteria.
Theresultsofpreviousstudiesonthisarecontradictoryandmakefurtherstudiesnecessary[32,33].
Epidemiologicalstudiesindicatethatarterialhyperten-sionstronglydependsonageandbodyweight.
TheFra-minghamHeartStudyshowedthatbeforetheageof60,bothsystolicanddiastolicbloodpressureareincreasing,whileafterthisageSBPisstillincreasingandDBPisdecreasing.
Asfarasbeingoverweightisconcerned,every10kgabovethenormalbodyweightisassociatedwithanincreaseinsystolicbloodpressureofabout3mmHg[34].
Thisiswhybloodpressurewasmonitoredinthepresentstudy,evenafterexcludingpatientswithdiagnosedhypertension.
Wefoundnoassociationbetweenanthro-pometricvariablessuchasage,BMI,andwaistcircum-ferenceandmeanbloodpressureatdaytimeornighttime.
However,IMTcorrelatedpositivelywith24-hpulsepressure(24hPP)anddaytimesystolicbloodpressure(SBPd).
Suchrelationshipshavealsobeenconrmedpre-viouslyinpopulationswitharterialhypertension.
Forexample,intheELSAstudy[35],SBP,PP,andagewerethestrongestfactorsthatdeterminedIMT.
Similarobser-vationsarebeingmadeinnormotensivepatientswithOSAforthersttimeandneedtobeinvestigatedinotherpopulations.
ThestructureoftheleftventriclewasevaluatedinaccordancewiththeEuropeanSocietyofHypertension/EuropeanSocietyofCardiology(ESH/ESC)guidelines[36].
Thecriterionofleftventriclehypertrophywasaleftventriclemassindex(LVMI)of[125g/m2inmenand[110g/m2inwomen.
Sixof28participants(21%)metthiscriterion.
Moreover,thePWDwaselevatedintwopatientsandtheIVSDwaselevatedinfourpatients.
Inepidemiologicalstudies,leftventriclehypertrophywasfoundin12–30%ofpatientswitharterialhyperten-sion.
ItwasalsooftenfoundinpatientswithOSA.
Clowardetal.
[37]foundleftventriclehypertrophyin92%ofhissubjectswithsevereOSA,denedasAHI[40,despite402Lung(2013)191:397–404123thefactthatonlyhalfofthegroupsufferedfromarterialhypertension.
Dursunogluetal.
[38]foundleftventriclehypertrophymoreofteninpatientswithsevereOSAthaninthegroupswithmildandmoderateforms.
Inthepresentstudy,AHIcorrelatedwithLVMandIVSD.
Besides,therewerepositivecorrelationsbetweenPWDandageaswellaswithLVMandwaistcircumfer-ence.
Theresultsconrmtheroleofageandobesityinthepathogenesisofhearthypertrophy[39].
Forassessmentofthesystolicfunctionoftheheart,fractionalshorteningandejectionfraction(EF)wereused.
Intwopatients(7%),EFwasbelow55%,andabnor-malitiesofFSwerefoundinvepatients(17%)(normalvaluesweredenedas28–44%)[40].
ThisisinlinewiththatfoundinastudybyLaabanetal.
[41]whodescribeddecreasedejectionfractionin7.
7%ofOSApatients.
TheCardiovascularHealthStudyconductedin5,201peoplefoundthatsystolicfunctiondisordersoccurin1.
8%ofwomenandin6.
3%ofmen.
Inthepopulationwithcar-diovasculardiseases,thefrequencyofthesedisordersis10.
5%[42].
Ourstudy'sresultof7%isonlyslightlyhigherthanthatobservedinthegeneralpopulation.
Ejec-tionfractionandfractionalshorteningcorrelatedwithagehasalreadybeendescribedpreviously[43].
Intheassessmentofdiastolicfunctionoftheheart,earlymitralow(E),atrialmitralow(A),E/Aratio,deceler-ationE(DecE),anddecelerationEtime(DecTE)wereanalyzed.
In16(57%)patients,therewasadecreaseintheE/Aratioof\1,andin6patients,DecTEexceeded240ms.
AccordingtotheguidelinesoftheCanadianCardiovascularSociety,allthesecasescouldbeclassiedasmilddiastolicdisorders[40].
TheresultsaresimilartothoseofthestudybyTanriverdietal.
TheyevaluatedmassandfunctionoftheleftventricleinOSApatientswithnoconcomitantcardiovasculardiseasesandfoundtheretobediastolicdisordersin52.
5%ofparticipants[29].
TheyalsofoundcorrelationsbetweenE,E/A,andAHIwhichwereconrmedbythepresentstudy.
NosignicantrelationshipshavebeenfoundbetweenIMTandselectedparametersofthesystolicfunctionoftheleftventricle.
However,IMTcorrelatednegativelywithE/AandpositivelywithPWD.
ThisisinlinewiththeresultsofParinello'sstudywhichindicatedthatahigherIMTwasoftenassociatedwithdiastolicdysfunctionandhearthypertrophy[44].
Thiswasobservedinagroupof142patientswithdiagnosedhypertension,whichwasanexclusioncriterioninourstudy.
Themainlimitationsofthisstudywereitscross-sec-tionalnature,relativelysmallsamplesize,andrecruitmentinasinglecenter.
Asobstructivesleepapneaisusuallyaccompaniedbymanycomorbidities,itwouldbenecessarytoconductmulticenterstudiestondasufcientnumberofpatientswithisolatedOSA.
ThediagnosisofOSAwasmadeusingportablesleepmonitoring,notpolysomnography,whichprovidesresearcherswithmoredata.
Anotherlimitationisthatnomarkersofinammationwererecorded.
ForabetterunderstandingoftherelationshipsbetweenOSAandvas-cularcomplications,monitoringoftheinammatorypro-cessseemstobenecessary.
ConclusionsInarelativelynonobesegroupofpatients,nosignicantdifferenceswerefoundtheinintima-mediathicknessbetweenOSApatientswithoutconcomitantcardiovasculardiseasesandhealthycontrols.
However,IMTcorrelatedwithage,totalcholesterol,LDL,daytimesystolicbloodpressure,pulsepressure(24handdaytime),E/A,andPWD.
ThismayleadtotheconclusionthatIMTdoesnotreectincreasedriskofcardiovasculareventsinpatientswithisolatedOSA.
ConictofinterestTheauthorshavenoconictsofinteresttodisclose.
OpenAccessThisarticleisdistributedunderthetermsoftheCreativeCommonsAttributionLicensewhichpermitsanyuse,dis-tribution,andreproductioninanymedium,providedtheoriginalauthor(s)andthesourcearecredited.
References1.
ShochatT,PillarG(2003)Sleepapnoeaintheolderadult:pathophysiology,epidemiology,consequencesandmanagement.
DrugsAging20:551–5602.
HeJ,KrygerMH,ZorickFJ(1988)Mortalityandapneaindexinobstructivesleepapnea:experiencein385malepatients.
Chest94:9–143.
LavieP,HererP,PeledRetal(1995)Mortalityinsleepapneapatients:amultivariateanalysisofriskfactors.
Sleep18:149–1574.
FriendleyLJ,LevinsonMP,BonnieRJ(1992)Drivingperfor-manceandautomobileaccidentsinpatientswithsleepapnea.
ClinChestMed13:427–4355.
BarbeF,PericasJ,MunozAetal(1998)Automobileaccidentsinpatientswithsleepapneasyndrome.
AmJRespirCritCareMed158:18–226.
KrumholzHM,LarsonM,LevyDetal(1995)PrognosisofleftventriculargeometricpatternsintheFraminghamheartstudy.
JAmCollCardiol25:879–8847.
PainvansaloM,SuramoI,RantalaAetal(1996)Prevalenceofcarotidatherosclerosisinmiddle-agedhypertensiveandcontrolsubjects.
Across-sectionalsystematicstudywithduplexultra-sound.
JHypertens14:1433–14398.
WagenknechtLE,D'AgostinoR,SavagePJetal(1997)Durationofdiabetesandcarotidwallthickness:Theinsulinresistanceatherosclerosisstudy(IRAS).
Stroke28:999–10059.
CuspidiC,ManciaG,ZanchettiAetal(2004)Leftventricularandcarotidstructureinuntreated,uncomplicatedessentialhypertension:resultsfromtheassessmentprognosticriskobser-vationalsurvey(APROS).
JHumHypertens18:891–896Lung(2013)191:397–40440312310.
AminbakhshA,ManciniGB(1999)Carotidintima-mediathicknessmeasurements:whatdenesanabnormalityAsys-tematicreview.
ClinInvestMed22:149–15711.
SilvestriniM,RizzatoB,PlacidiFetal(2002)Carotidarterywallthicknessinpatientswithobstructivesleepapneasyndrome.
Stroke33:1782–178512.
SuzukiT,NakanoH,MaekawaJetal(2004)Obstructivesleepapneaandcarotid-arteryintima-mediathickness.
Sleep27:129–13313.
RedlineS,BudhijaraR,KapurVetal(2007)Thescoringofrespiratoryeventsinsleep:reliabilityandvalidity.
JClinSleepMed3:169–20014.
YanaseT,NasuS,UkutaYetal(2006)Evaluationofanewcarotidintima-mediathicknessmeasurementbyB-modeultra-sonographyusinganinnovativemeasurementsoftware,intima-scope.
AmJHypertens19:1206–121215.
StaessenJ,BulpittCJ,O'BrienEetal(1992)Thediurnalbloodpressureprole.
Apopulationstudy.
AmJHypertens5:386–39216.
DeverexRB,ReichekN(1977)Echocardiographicdeterminationofleftventricularmassinman.
Circulation55:613–61817.
LavieP,HererP,HoffsteinV(2000)Obstructivesleepapneasyndromeasariskfactorforhypertension:populationstudy.
BMJ320:479–48218.
NarkiewiczK,PesekCA,KatoMetal(1998)Baroreexcontrolofsympatheticnerveactivityandheartrateinobstructivesleepapnea.
Hypertension32:1039–104319.
BabinskaZ,GnaciskaM,ZdrojewskiTetal(2002)Associationofoverweightandobesitywithelevatedbloodpressurein40-and50-year-oldinhabitantsofSopotinSopotCardiologyProphylaxisProgrammeSOPKARD.
NadcisnienieTetnicze4:2320.
[Noauthorslisted](2005)Regionalandnationalprevalenceofmaincardiovascularriskfactors.
ResultsofWOBASZstudyonhealthconditionofpopulationofPoland.
KardiolPol63:614–68521.
NationalCholesterolEducationProgram(NCEP)ExpertPanelonDetection,Evaluation,andTreatmentofHighBloodCholesterolinAdults(AdultTreatmentPanelIII)(2002)Thirdreportofthenationalcholesteroleducationprogram(NCEP)expertpanelondetectionandtreatmentofhighbloodcholesterolinadults(adulttreatmentpanelIII)nalreport.
Circulation106:3143–342122.
KaynakD,G}oksanB,KaynakHetal(2003)Istherealinkbetweentheseverityofsleep-disorderedbreathingandathero-scleroticdiseaseofthecarotidarteriesEurJNeurol10:487–49323.
SavranskyV,NanayakkaraA,LiJetal(2007)Chronicinter-mittenthypoxiainducesatherosclerosis.
AmJRespirCritCareMed175:1290–129724.
DragerLF,BortolottoLA,LorenziMCetal(2005)Earlysignsofatherosclerosisinobstructivesleepapnea.
AmJRespirCritCareMed172:613–61825.
AltinR,O¨zdemirH,MahmutyaziciogluKetal(2005)Evaluationofcarotidarterywallthicknesswithhigh-resolutionsonographyinobstructivesleepapneasyndrome.
JClinUltrasound33:80–8626.
CuspidiC,ManciaG,ZanchettiAetal(2004)Leftventricularandcarotidstructureinuntreated,uncomplicatedessentialhypertension:resultsfromtheassessmentprognosticriskobser-vationalsurvey(APROS).
JHumHypertens18:891–89627.
GariepyJ,SalomonJ,DenarieNetal(1998)Sexandtopographicdifferencesinassociationsbetweenlarge-arterywallthicknessandcoronaryriskproleinaFrenchworkingcohort:theAXAstudy.
ArteriosclerThrombVascBiol18:584–59028.
AndoF,TakekumaK,NiinoNetal(2000)Ultrasonicevaluationofcommoncarotidintima-mediathickness(IMT)—inuenceoflocalplaqueontherelationshipbetweenIMTandage.
JEpi-demiol10(Suppl1):10–1729.
TanriverdiH,EvrengulH,KaraCOetal(2006)Aorticstiffness,ow-mediateddilatationandcarotidintima-mediathicknessinobstructivesleepapnea.
Respiration73:741–75030.
VanPopeleNM,GrobbeeDE,BotsMLetal(2001)Associationbetweenarterialstiffnessandatherosclerosis:theRotterdamstudy.
Stroke32:454–46031.
NarkiewiczK,vandeBornePJ,PesekCAetal(1999)Selectivepotentiationofperipheralchemoreexsensitivityinobstructivesleepapnea.
Circulation99:1183–118932.
WilsonAM,O'NealD,NelsonCLetal(2004)Comparisonofarterialassessmentsinlowandhighvasculardiseaseriskgroups.
AmJHypertens17:285–29133.
KobayashiK,AkishitaM,YuWetal(2005)Interrelationshipbetweennon-invasivemeasurementsofatherosclerosis:ow-mediateddilatationofbrachialartery,carotidintima-mediathicknessandpulsewavevelocity.
Atherosclerosis173:13–1834.
DyerAR,ElliotP,ShipleyMetal(1990)Bodymassindexversusheightandweightinrelationtobloodpressure.
Findingsforthe10,079personsintheintersaltstudy.
AmJEpidemiol131:589–59635.
ZanchettiA,ManciaG,BondMGetal(1998)Riskfactorsassociatedwithalterationsincarotidintima-mediathicknessinhypertension:baselinedatafromtheEuropeanlacidipinestudyonatherosclerosis.
JHypertens16:949–96136.
GiuseppeM,DeBackerG,DominiczakAetal(2007)Guidelinesformanagementofarterialhypertension.
ThetaskforceforthemanagementofarterialhypertensionoftheEuropeansocietyofhypertension(ESH)andtheEuropeansocietyofcardiology(ESC).
EurHeartJ28:1462–153637.
ClowardT,WalkerJ,FarneyRetal(2003)Leftventricularhypertrophyisacommonechocardiographicabnormalityinsevereobstructivesleepapneaandreverseswithnasalcontinuouspositiveairwaypressure.
Chest124:594–60138.
DursunogluD,DursunogluN,EvrengulHetal(2005)Impactofobstructivesleepapnoeaonleftventricularmassandglobalfunction.
EurRespirJ26:283–28839.
HoffmanP,JanuszewiczM,JanuszewiczAetal(2006)Atlasofarterialhypertension.
MedycynaPraktyczna,Cracow,pp45–4940.
KasprzakJD,Wierzbowska-DrabikK,Dro_zd_zJ(2004)Echo-kardiograapraktyczna,volI.
MedycynaPraktyczna,Cracow,pp135–14741.
LaabanJP,Pascal-SebaounS,BlochEetal(2002)Leftven-tricularsystolicdysfunctioninpatientswithobstructivesleepapneasyndrome.
Chest122:1133–113842.
GardinJM,SiscovickD,Anton-CulverHetal(1995)Sex,ageanddiseaseaffectechocardiographicleftventricularmassandsystolicfunctioninthefree-livingelderly.
Thecardiovascularhealthstudy.
Circulation91:1739–194843.
TanriverdiH,EvrengulH,KaftanAetal(2006)Effectofobstructivesleepapneaonaorticelasticparameters—relationshiptoleftventricularmassandfunction.
CircJ70:737–74344.
ParinelloG,CoulombaD,BolognaPetal(2004)Earlycarotidatherosclerosisandcardiacdiastolicabnormalitiesinhyperten-sivesubjects.
JHumHypertens18:201–205404Lung(2013)191:397–404123