6/14/2016 Clinicalfeaturesanddiagnosisofcoronaryheartdiseaseinwomen

OfficialreprintfromUpToDate
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Clinicalfeaturesanddiagnosisofcoronaryheartdiseaseinwomen

Author SectionEditors DeputyEditor

PamelaSDouglas,MD JuanCarlosKaski,DSc,MD,DM GordonMSaperia,MD,FACC
(Hons),FRCP,FESC,FACC,FAHA
PatriciaAPellikka,MD,FACC,FAHA,
FASE

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:May2016.|Thistopiclastupdated:Aug19,2014.
INTRODUCTIONCardiovasculardiseasesarethemostcommoncauseofdeathanddisabilityinwomenintheUnited
States[1,2].Althoughtherehasbeenareductioninthedeathratefromcoronaryheartdisease(CHD)since1980[3],
CHDaccountedfor35percentofallcausemortalityinwomenin1995[2]and23percentin2004[4].Betweentheagesof
45to64,oneinninewomendevelopssymptomsofsomeformofcardiovasculardisease.Afterage65,theratioclimbsto
oneinthreewomen,accordingtotheNationalCenterforHealthStatistics[5].

Therearesignificantdifferencesbetweenmenandwomenintheepidemiology,diagnosis,treatment,andprognosisof
CHDthatshouldbetakenintoaccountinthecareofwomenwithknownorsuspecteddisease.Furthermore,most
availabledatasuggestthatwomenarenotreferredasoftenasmenforappropriatediagnosticand/ortherapeutic
procedures,despitesimilarclinicalconditions[612].(See'DiagnostictestingforsuspectedCHD'below.)

TheclinicalfeaturesanddiagnosisofCHDinwomenwillbereviewedhere.TheepidemiologyandprognosisofCHD,
managementofCHDinwomen,andtheproblemofCHDinyoungwomenarediscussedseparately.(See"Epidemiology
ofcoronaryheartdisease"and"Managementofcoronaryheartdiseaseinwomen"and"Coronaryheartdiseaseand
myocardialinfarctioninyoungmenandwomen".)

CLINICALPRESENTATIONWomenwithcoronaryheartdisease(CHD)aregenerallyabout10yearsolderthanmen
atthetimeofpresentationandcarryagreaterburdenofriskfactors[1315].Womenmaynotidentifytheirinitial
symptomsasanexpressionofheartdiseaseandthereforemaynotseekmedicaladvicepromptlyandpractitionersmay
notevaluatesymptomsthatrepresentmyocardialischemiaasearlyinwomen[4,16].(See"Overviewofcardiovascular
riskfactorsinwomen".)

Althoughwomenaregenerallyolderthanmenatpresentation,womenyoungerthanage45yearsalsodevelopCHD[17]
andhaveaworseprognosisthanmen[18].ThefirstpresentationofCHDmaybechestpain,myocardialinfarction(MI),
heartfailure(HF),orsuddencardiacdeath(SCD).(See"Coronaryheartdiseaseandmyocardialinfarctioninyoungmen
andwomen".)

Ofimportance,theFraminghamRiskEstimationunderestimatesriskinwomenwithafamilyhistoryofearlyheartdisease
andforthisreasonalternativescores,suchastheReynoldsRiskScore,havebeendevelopedspecificallyforusein
women[19].(See"Estimationofcardiovascularriskinanindividualpatientwithoutknowncardiovasculardisease",
sectionon'ReynoldsCVDriskscoreforwomen(2007)'.)

ChestpainWhiledifferencesbetweenwomenandmeninthedescriptionofischemicsymptomshavebeenidentified
[20],webelievethattherearemoresimilaritiesthandifferences.Chestpainisthemostcommonanginalsymptominboth
sexesandisdescribedsimilarlywithregardtoqualityofpain(heaviness,pressure),patternofradiation,andmany
associatedsymptoms(fatigue,nausea,etc).Further,asinmen,thequalityofchestpain(typicalversusatypical)isan
importantpredictorofangiographicdiseaseinwomen(table1AB)[21,22].

Inastudyof109womenand128menwithsuspectedcoronaryarterydisease(CAD)withorwithoutanginaandatleast
onepriorabnormalcardiactestresultwhounderwentcoronaryarteriography,theratesoftheuseofthefollowing
descriptorsofchestpainweresimilarbetweenwomenandmenwhowerefoundtohaveobstructiveCAD:chestpain(84
versus82percent),pressure(58versus54percent),andtightness(58versus43percent)[20].Similarfindingshave
beennotedinotherstudies[23,24],whileolderstudiesbasedonpatientsundergoingtestingsuggestthatwomenmay
havemoreatypicalpain[25].

Onepotentialfactorimportantintheinterpretationofsymptomsinwomenisthegreaterlikelihoodoftheirbeinginducedby
rest,sleep,andmentalstress,inadditiontoorinsteadofphysicalexertion[26].Asanexample,aprevioushistoryofan
anxietydisorderisassociatedwithalowerriskofsignificantangiographicCHDinwomen(oddsratio2.74)[27].
Psychosocialfactorsarealsoimportant,aswomendrasticallyunderestimatetheirownriskofCHD,andphysicians'
estimatesarecoloredbypatientaffect[28].

MIMIinwomenmaygounrecognized,particularlyatyoungeragesandwhencomparedtomen:

ThefrequencyofunrecognizedMIwasillustratedinareportfromIcelandinwhich13,000womenwerefollowedfor
29years[29,30].TheincidenceofMIontheelectrocardiogram(ECG)increasedfrom1.3per1000atage35to60
per1000atage75theproportionthatwereunrecognizedwashigherintheyoungerwomen(41versus24percent).

AhigherproportionofsilentQwaveinfarctionsinolderwomenwasnotedinareportfromtheHERStrial,which
evaluatedtheefficacyofhormonereplacementtherapyin2763postmenopausalwomenwithknownCHD[30].
Duringafouryearfollowup,9.3percenthadECGevidenceofanMIthatwasunrecognizedclinicallyin46percent.
(See"Epidemiologyofcoronaryheartdisease",sectionon'Silentmyocardialischemiaandinfarction'.)

Similartothebroadpopulationofpatientswithchestpain(see'Chestpain'above),webelievethattherearemore

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similaritiesthandifferencesbetweenwomenandmeninthepresentationofMI.Most[3133],butnotall[34],studies
supportthispoint.However,womenwhopresentwithMImaymorefrequentlypresentwithoutchestpain.Thefollowing
studiesillustratethesetwopoints:

Aprospectivecohortstudyevaluated796womenand1679menwhopresentedtoanemergencydepartmentwithin
12hoursoftheonsetofacutechestpain(adiagnosisofMIwasgiveninabout20percent)[33].Thewomenwere
older(medianage70versus59years)andfewerhadaprioracuteMI(15versus28percent).Thirtyfourpredefined
chestpaincharacteristicswererecordedforeachpatient,includinglocationandsizeoftheareaofpain,painquality,
radiation,onset,duration,dynamics,severity,andtheaggravatingandrelievingfactorsincludingresponseto
nitrates.Mostofthesecharacteristicswerereportedwithsimilarfrequencyinwomenandmen,includingthe
subpopulationofindividualswhowerediagnosedwithMI.Ofnote,theaccuracyofmostofthesecharacteristicsfor
thediagnosisofMIwaslowinbothsexes.

Inasecondprospectivecohortstudyof1015patients(30percentwomen)55yearsofageoryoungerwhowere
evaluatedforanacutecoronarysyndrome(ACS),thepercentofpatientswhopresentedwithoutchestpainwas
significantlygreaterinwomen(19.0versus13.7)[35].Patientswithoutchestpainreportedfewersymptomsoverall.

Inareportof515womenwithanacuteMI,acutechestpainwasabsentin43percentandonly30percent
experiencedprodromalchestpain[31].

Inastudyofover1,000,000womenandmenintheNationalRegistryofMyocardialInfarction(UnitedStates),the
proportionofMIpatientswhopresentedwithoutchestpainwassignificantlyhigherforwomenthanmen(42.0versus
30.7percent)[32].

SeveralstudieshavespecificallyevaluatedtheoutcomesinwomenwithanonSTelevationACS(unstableanginaornon
STelevationMI).IntheGUSTOIIbtrial,whichevaluated12,142patientspresentingwithanACS,womenwereless
likelytohaveSTsegmentelevation(27versus37percentformen)and,amongthosewithoutSTsegmentelevation,
womenwerelesslikelytohaveanMI(37versus48percent).

TheoptimalapproachtoaccurateassessmentofriskinwomenwithanonSTelevationACSmaydifferfromthatinmen.
ThiswassuggestedbyananalysisfromTACTICSTIMI18,whichfoundthatwomenweremorelikelytohaveelevations
ofhighsensitivityCreactiveprotein(hsCRP)andbrainnatriureticpeptide(BNP),andlesslikelytohaveelevationsof
troponinsandcreatinekinaseMBfraction,thanmen,despitesimilarlevelsofrisk[36].Further,whenamultimarker
approachincorporatinghsCRP,BNP,andtroponinswasused,womenwithanypositivemarkerbenefitedfroman
invasivestrategy,whilethosewithnopositivemarkersbenefitedfromaconservativestrategy.Incontrast,menbenefited
fromaninvasivestrategywhentherewasbiomarkerpositivity,buttherewasnodifferenceinbenefitaccordingtostrategy
ifbiomarkerswerenegative.Thus,womenwithunstableanginawithoutpositivebiomarkersshouldbetreated
conservatively,withoutearlycatheterizationoruseofglycoproteinIIb/IIIainhibitors.

HeartfailureWomenwithCHDmorefrequentlyhaveordevelopsymptomaticHFthanmen[37,38].Thisappearsto
bedueatleastinparttoagreaterfrequencyofdiastolicdysfunction[38].Whythismightoccurisnotknown,butis
postulatedtoberelatedtoagreaterprevalenceofhypertensiveheartdiseaseandhypertrophyinwomen.

RiskfactorsforHFinwomenwithCHDwereexaminedinananalysisfromtheHERStrialof2391womenwith
establishedcoronarydiseasewhohadnoHFatbaseline[39].Atameanofsixyears,237women(10percent)developed
HF.Significantriskfactorsincludedthefollowing:

Diabetesmellitus
Atrialfibrillation
MI
Renaldysfunction(creatinineclearance<40mL/min)
Hypertension(systolicbloodpressure>120mmHg)
Currentsmoking
Obesity(bodymassindex>35kg/m2)
Leftbundlebranchblockonelectrocardiogram
Leftventricularhypertrophyonelectrocardiogram

DiabeteswasthevariableassociatedwiththegreatestincreaseinHFrisk(adjustedhazardratio3.1).Womenwith
diabetesandatleastthreeotherriskfactorshadanannualHFincidenceof8.2percent.

SuddencardiacdeathA38yearfollowupfromtheFraminghamHeartstudyevaluatedtheincidenceofSCDin
womencomparedtomen[40].Thefollowingfindingswerenoted:

WomenhadalowerSCDratethanmenatallagesandatanylevelofmultivariaterisk(figure1)theriskofsudden
deathamongwomenwithCHDwasonehalfthatofmenwithCHDandaccountedforasmallerproportionof
coronarydeaths(37versus56percent).

AhigherfractionofsuddendeathsinwomenoccurredintheabsenceofpriorovertCHD(63versus44percentin
men).(See"Pathophysiologyandetiologyofsuddencardiacarrest".)

ThepresenceofHFincreasedoverallmortalityandtheincidenceofSCDhowever,amongpatientswithHF,the
absoluteriskinwomenwasonlyonethirdthatofmen(figure2).

PhobicanxietyisassociatedwithanincreasedriskofSCDinwomen[41].Some,butnotall,ofthisriskcanbeascribed
toCHDriskfactorsassociatedwithphobicanxietysuchasdiabetes,hypertension,andelevatedserumcholesterol.

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DIAGNOSTICTESTINGFORSUSPECTEDCHDTheinitialevaluationofawomanpresentingwithsymptomsof
chestpainandsuspectedcoronaryheartdisease(CHD)issimilartothatformenandoftenincludessomeformof
noninvasivetesting.(See"Stresstestingforthediagnosisofobstructivecoronaryheartdisease".)

NoninvasivetestingThefollowingtestsareavailable:

Treadmillexercisetesting.(See"Stresstestingforthediagnosisofobstructivecoronaryheartdisease".)

Radionuclidemyocardialperfusionimagingwitheitherexerciseorpharmacologicstress.

Stressechocardiographywitheitherexerciseorpharmacologicstress.

Coronaryangiographywithcardiaccomputedtomography.(See"Noninvasivecoronaryimagingwithcardiac
computedtomographyandcardiovascularmagneticresonance".)

Coronaryarterycalciumscoring(CCTA).(See"Diagnosticandprognosticimplicationsofcoronaryarterycalcification
detectedbycomputedtomography".)

Cardiacmagneticresonanceimagingforeitherwallmotionorperfusion.(See"Noninvasivecoronaryimagingwith
cardiaccomputedtomographyandcardiovascularmagneticresonance",sectionon'Cardiovascularmagnetic
resonance'and"Teststoevaluateleftventricularsystolicfunction"and"Clinicalutilityofcardiovascularmagnetic
resonanceimaging".)

EachofthesetestsisimperfectinitsabilitytoaccuratelydiagnoseCHD(seeindividualtopicreviews).Thefollowing
pointsneedtobekeptinmindwhenconsideringanoninvasivetestinwomen:

Treadmillexercisetestinghasahigherfalsepositiverateinwomen[42].Thisisinpartduetoalowerprevalenceof
CHDinwomeninthepopulationsstudied(Bayesianfactors).Thediagnosticaccuracyinwomenisalsolowerdueto
olderageatpresentationwiththeattendanthigherfrequencyofcomorbiditiesandlowerexercisecapacity[4].Other
explanationsforthesexrelateddifferenceshaveincludedhormonalmedicationandautonomicinfluences[4].
Nevertheless,exercisestressprovidesvaluableinformationregardingreproducibilityofsymptoms,exercisecapacity
andlongevity,andisthepreferredmodeofstressinwomen,withorwithoutimaging.Ofnote,womenhavealower
functionalcapacitythanmen,usuallyachievingamaximalworkloadthatis2METslessthanformen.

Thesensitivityandspecificityofthesetestsaresuboptimal.Inametaanalysisthatevaluated19studiesofwomen
whounderwentexerciseelectrocardiogram(ECG)testing(fiveexercisethalliumandthreeofexercise
echocardiography)andcoronaryangiography,thesensitivityandspecificityforCHDofexerciseECGstresstesting,
exercisethallium,andexerciseechocardiographywere61and70percent,78and64percent,and86and79percent,
respectively[43].Thesevaluesaresimilartothoseinmenforstressechoandnuclear,butlowerforstressECG.

Noneofthestresstestsiswithoutsourcesofartifact.Allrequireadequatestressforoptimalaccuracy,whether
pharmacologicorexercise.Thus,anegativeexercisetestinapatientwithpoorexercisetolerancemaybe
inconclusive.

RadiationexposurefromCCTAandradionuclidetestshavenotbeenconvincinglyshowntobeharmful,butarebest
avoidedinyoungwomen,asbreasttissueisincludedintheradiationfield.(See"Radiationdoseandriskof
malignancyfromcardiovascularimaging".)

ForepisodicchestpainWomenwhopresentwithepisodicchestpainneedtobeevaluatedforCHD.The
likelihoodofCHDisbasedinpartuponthecharacterofthepresentingsymptoms(eg,typicalversusatypicalangina)and
thepresenceorabsenceofcoronaryriskfactors.Theriskassessmentmustbesexspecificbecausetheriskfactors
themselves,aswellastheirrelativeimportance,maydifferbetweenwomenandmen.Inparticular,hormonalstatus,
diabetes,smoking,andafamilyhistoryofprematureCHDappeartobemoreimportantinwomen.Ofnote,theAmerican
HeartAssociationguidelinesforprimarypreventioninwomensuggestthatusingalifetimelikelihoodofcoronaryartery
diseaseispreferredinwomen,ratherthanamoreconventional10yearFraminghamriskcalculation,asthelatteroften
underestimatesrisk[44].(See"Overviewofcardiovascularriskfactorsinwomen".)

Atpresent,localexpertiseandtestavailabilityshoulddictatenoninvasivetestselection,giventhelackofclearly
identifiabledifferencesinaccuracy.Onesequentialapproachisasfollowsanditisgenerallyinaccordwiththatinthe
2012AmericanCollegeofCardiology/AmericanHeartAssociationguidelineforthediagnosisandmanagementofpatients
withstableischemicheartdiseasethisapproachwasnotchangedinthe2014focusedupdate[4547].This2012
guidelinedoesnotspecifyseparatediagnosticapproachesforwomenandmen.

TheevaluationofawomanwithsuspectedCHDbeginswithacarefulhistoryandphysicalexamination,laboratory
work,andassessmentofrisk.Ifthepatientisdeterminedtobeatintermediaterisk,astresstestmaybeordered.
Theexactchoiceoftestwilldependonavarietyofclinicalfactorssuchaspatientrisk,abilitytoexercise,body
habitus,priortestinformationforcomparison,andnonclinicalfactorssuchaslocaltestavailabilityandexpertise.If
anexercisetreadmillischosen,thestressisadequate(maximal),theECGinterpretable,andthetestnegative,no
furtherevaluationisnecessary.

Womenwithapositivetestoranegativesubmaximaltestshouldundergoadditionaltesting,whichmayinclude
stressechocardiographyorstressnuclearimaging(ideallywithatechnetiumperfusionradiotracer),cardiac
computedtomographyangiography,ordiagnosticcath.Inparticular,patientswithahighprobabilitypositivetest
shouldgoontocoronaryangiographyiftheyarecandidatesforrevascularization.Suchwomenhaveaworse
outcomeiftheyarenotfurtherevaluated[48].

Theoptimalroleofcoronarycalciumscoringormeasurementofcarotidintimalmedialthicknessintheevaluationofstable

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symptomsisunclearatthistime[49].(See"Diagnosticandprognosticimplicationsofcoronaryarterycalcification
detectedbycomputedtomography"and"Noninvasivecoronaryimagingwithcardiaccomputedtomographyand
cardiovascularmagneticresonance"and"Overviewofthepossibleriskfactorsforcardiovasculardisease",sectionon
'Arterialintimamediathickness'.)

AfternonSTelevationACSEarlyexercisetestinginwomenafteranonSTelevationacutecoronarysyndrome
(ACS)canbeusefulinthosewhohavenothadacoronaryangiogramforestablishingthepresenceofcoronarydisease
andforriskstratificationandprognosis.Themajorityofpatientswhohaveundergonecoronaryangiographydonotneed
furtherriskassessment,althoughtestingmaybeindicatedoncetheacutephaseofACSisresolvedtoevaluatethe
possiblesignificanceoflesionsinvesselsotherthantheinfarctrelatedartery.

Iftestingisindicated,findingsontheexercisetestthatindependentlypredictfuturecardiaceventsarelowmaximal
workload,thenumberofleadswith0.1mVSTsegmentdepression,andmaximalratepressureproduct[5052].(See
"RiskfactorsforadverseoutcomesafternonSTelevationacutecoronarysyndromes".)

Highriskpatientshaveatleasttwoofthesethreecriteria,intermediateriskpatientshaveonecriterion,andlowrisk
patientslackallthreecriteria[52].However,asnotedabove,womenhaveahighpercentageoffalsepositiveexercise
tests,whichmightmakethetestlessreliable[42].Thisissuewasaddressedinastudyof395womenwithunstable
anginaenteredintotheFRISCtrialwhowerefollowedforsixmonths[52].Basedupontheexercisetestresults,low,
intermediate,andhighriskgroupswereidentifiedwitheventratesofcardiacdeathormyocardialinfarction(MI)of1,9,
and19percent,respectively.Theresultswerethesameasthoseobservedfor778meninthetrial.

AfterSTelevationMIWerecommendthattheuseofnoninvasivetestingbesimilarformenandwomen.

CoronaryangiographyTheindicationsfordiagnosticcardiaccatheterizationandcoronaryangiographyaresimilarfor
womenandmen.Recommendationsforinvasivetestingarefoundelsewhere.(See"Coronaryangiographyand
revascularizationforunstableanginaornonSTelevationacutemyocardialinfarction"and"Overviewoftheacute
managementofSTelevationmyocardialinfarction"and"Stableischemicheartdisease:Overviewofcare",sectionon
'Coronaryangiographyandrevascularization'.)

Theprevalenceofsignificantcoronarydiseasefoundatthetimeofangiographyislowerinwomenthanmenpresenting
withchestpain[37,53,54].Themagnitudeofthisdifferencewasillustratedinareportof886patientsreferredfor
angiographicevaluationofpresumedangina,23percentofwhomwerewomen[53].Normalcoronaryarteriesweremuch
morecommoninwomen(41versus8percentinmen).

AhigherrateofabsenceofsignificantcoronarystenoseshasalsobeennotedinwomenwithanonSTelevationACS
(unstableanginaornonSTelevationMI).Indifferentclinicaltrials,12to14percentofsuchpatientshave,oncoronary
angiography,eithernormalvesselsornovesselwith50to60percentstenosis.Thisappearstobemorecommonin
women(17versus9percentinmeninonetrial)[55,56].Possiblemechanismsfortheabsenceofsignificantcoronary
diseaseinthesepatientsincluderapidclotlysis,vasospasm,andcoronarymicrovasculardisease.(See"Classificationof
unstableanginaandnonSTelevationmyocardialinfarction",sectionon'Absenceofsignificantcoronarydisease'.)

GenderbiasAnumberofstudieshavedocumentedgenderbaseddifferencesinutilizationratesofcoronary
angiographyandrevascularization,evenamongthosewithanacuteMI[7,48,5763].Thesedifferencesreflectphysicians'
failuretoreferwomenwithpositiveexercisetestsforsubsequenttesting[62],leadingtoapooreroutcome[48].Inone
report,forexample,womenwithapositiveexercisetestweremorelikelytohavenofurthercardiacevaluationthanmen
(62versus38percent),adifferencethat,atthreeyearfollowup,wasassociatedwithahigherincidenceofMIordeathin
women(14.3versus6percentperyearinmen)[48].Alleventsoccurredinnonrevascularizedindividuals.

Otherstudieshavenotfoundadifferenceincatheterizationratesbetweenmenandwomen[6467].However,closer
examinationofthesereportsrevealsanoverreferraloflowriskmen(baseduponclinicalriskstratification)[64],anda
nearequalrateofcatheterizationfollowingMIwhentheprocedurewasperformedforthetreatment,notdiagnosis,ofCHD
[65].Inareviewofover3000patients(33percentwomen)whounderwentexerciseradionuclideimaging,referralratesfor
menandwomenwerecomparablewhenstratifiedbytheamountofabnormallyperfusedmyocardiumdetected[67].
However,amongpatientswithanabnormalscan,thesubsequentcardiaceventratewashigherforwomenthanmen(17.5
versus6.3percent),indicatingthatwomenwereunderreferredforcomparabledegreesofrisk.

Aseparateissueiswhethergenderbiasaffectsthelikelihoodofrevascularizationaftercardiaccatheterization.Inareview
ofover21,000patients,womenhadequalaccesstorevascularizationafteradjustmentforclinicalvariables(eg,age,
diabetes,heartfailure,renalinsufficiency)andcoronaryvariables(eg,extentofdisease,leftventricularejectionfraction)
[68].(See"Managementofcoronaryheartdiseaseinwomen".)

NonCHDcausesofchestpainThreenonCHDcausesofchestpainmaybefoundatthetimeofcatheterization:
cardiacsyndromeX,stressinducedcardiomyopathy,andspontaneouscoronaryarterydissection.

CardiacsyndromeXorcoronarymicrovasculardiseaseMyocardialischemiaand/orcoronarymicrovascular
dysfunctionispresentin20to50percentofwomenwithchestpainandnormalcoronaryarteries[6973].(See"Cardiac
syndromeX:Anginapectoriswithnormalcoronaryarteries".)

StressinducedcardiomyopathyAnuncommonbutincreasinglyreportedcauseofanacute,usuallySTelevation
coronarysyndromeoccurringintheabsenceofcriticalcoronaryarterydiseaseisstressinducedcardiomyopathy,also
calledtransientleftventricularapicalballooning,takotsubocardiomyopathy,andbrokenheartsyndrome.Thisdisorderis
typicallyprecipitatedbyintensepsychologicstressandprimarilyoccursinpostmenopausalwomen.Thistopicis
discussedindetailelsewhere.(See"Clinicalmanifestationsanddiagnosisofstress(takotsubo)cardiomyopathy".)

SpontaneouscoronaryarterydissectionSpontaneouscoronaryarterydissectionisararecauseofacuteMIthat

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ismorecommoninyoungerpatientsandinwomen[74].Theunderlyingmechanismisunknown,butanintimaltearor
bleedingofvasavasorumwithintramedialhemorrhagehavebeenproposed[75].Inpregnantwomen,dissectionmaybea
consequenceofincreasedhemodynamicstressorofhormonaleffectsonthearterialwall[76].(See"Acquiredheart
diseaseandpregnancy",sectionon'Myocardialinfarction'.)

MostpatientspresentingwiththisentitytypicallydonothaveriskfactorsforCHD.Histologically,aninflammatory
reactionintheadventitiahasbeendescribed,suggestiveofperiarteritis.However,thisinflammatoryresponsemaybe
reactiveratherthancausative[76].

A2012singlecenterreport(MayoClinic)containsthelargestseriesofpatients(87individualsfromoverthreedecades)
withspontaneouscoronaryarterydissectionandnoassociatedcoronaryarteryatherosclerosis[77].Thediagnosiswas
madebythefindingofadissectionplaneonangiography.Thisregistryreportnotedthefollowing:

Themeanagewas43yearsand82percentwerewomen.

Extremeexertionprecededtheeventin7of16menand2of71womenpostpartumstatuswaspresentin13of71
women(meanpostpartumperiod38days).

STelevationMI(STEMI)waspresentin49percentandnonSTelevationin44percentofpatientsonpresentation.
Chestpainwaspresentin91percentandlifethreateningventriculararrhythmiasin14percent.

Theleftanteriordescendingcoronaryarterywasthemostfrequentlyaffectedvesselandmultivesseldissectionwas
foundin23percent.

Theinhospitalprognosiswasgenerallygoodforthosemanagedeitherconservativelyorwithcoronaryarterybypass
grafting(CABG),whiletheshorttermoutcomewaslessfavorableinthosemanagedwithpercutaneouscoronary
intervention(PCI).TheauthorsspeculatedthatthispooreroutcomewithPCImighthavebeenattributabletotheuse
ofballoonangioplastywithoutstentinginpatientspresentingbeforetheuseofstentswascommon.

The10yearrecurrenceratewas29.4percent.Theestimated10yearrateofdeath,heartfailure,MI,ordissection
recurrencewas47percent(medianfollowupof47months).

Fibromusculardysplasiaoftherenalarterieswasfoundin8of16femoralangiograms.Twopatientswerenotedto
havecarotidarterydissection.

Thesefindingsaregenerallyconsistentwithearlierreports[76,7880].However,manyoftheseincludedpatientswith
associatedsignificantatheroscleroticcoronaryarterydisease,whichcouldpotentiallyinfluenceepidemiology,clinical
presentation,orprognosis.

Spontaneouscoronarydissectionshouldbeconsideredinanyyoungpatient,especiallyanyyoungwomanwithouta
previouscardiachistoryorCHDriskfactors,whopresentswithcardiacarrestoranacutecoronarysyndrome.The
optimalmanagementofspontaneouscoronaryarterydissectionisuncertain,inpartbecauseofthelimitedclinical
experience.

EmergentcoronaryangiographyfollowedbyPCIorCABGislikelytoofferthebestprospectofsurvival.Fibrinolytic
therapymayalsobesuccessfulforpatientswithSTEMI[74],butextensionofthedissectionispossible[81,82].

INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasicsandBeyond
theBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgradereadinglevel,and
theyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.Thesearticlesarebestfor
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Basicstopics(see"Patientinformation:Coronaryheartdiseaseinwomen(TheBasics)")

SUMMARYCardiovasculardiseasesarethemostcommoncauseofdeathanddisabilityinwomenintheUnited
States.Importantdifferencesbetweenwomenandmeninthepresentationofcoronaryheartdisease(CHD)maymakeit
moredifficulttoestablishthediagnosisinwomen(see'Clinicalpresentation'above):

Womengenerallypresentabout10yearslaterthanmenandwithagreaterriskfactorburden.

Womenarelesslikelythanmentohavetypicalangina.

Womenwhopresenttotheemergencydepartmentwithnewonsetchestpainareapproachedanddiagnosedless
aggressivelythanmen.

Womenaremorelikelytoinitiallypresentwithchestpainthanamoreclearlydefinedeventsuchasamyocardial
infarction(MI).

ThesymptomsofMIinwomenmaydifferslightlyfromthoseinmen.ManycasesofMIinwomengounrecognized,
particularlyatyoungeragesorinpatientswithdiabetes.(See'MI'above.)

TheprocessofestablishingthediagnosisofCHDinwomenissimilartothatinmen,butseveralpointsneedtobekeptin
mind:

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Treadmillexercisetestinghasahigherfalsepositiverateinwomen,whilestressimagingappearstohavesimilar
accuracy.(See'Noninvasivetesting'above.)

Theprevalenceofsignificantcoronarydiseasefoundatthetimeofangiographyislowerinwomenthanmen
presentingwithchestpain.

Womenwithchestpainandnoevidenceofatheroscleroticcoronaryarterydiseaseoncoronaryangiographymay
havecardiacsyndromeXormicrovasculardisease,orfarmorerarely,takotsubocardiomyopathyorcoronary
dissection.(See'NonCHDcausesofchestpain'above.)

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GRAPHICS

Pretestprobabilityofcoronaryheartdisease(CHD)inpatientswithchest
painaccordingtoage,gender,andsymptoms

Nonanginalpain Atypicalangina Typicalangina

Age
Men Women Men Women Men Women

30to39 4 2 34 12 76 26

40to49 13 3 51 22 87 55

50to59 20 7 65 31 93 73

60to69 27 14 72 51 94 86

Theprobabilityvaluesareexpressedasthepercentofpatientswithsignificantcoronaryarterydiseaseon
angiography.

CombineddatafromDiamondGA,ForresterJS.NEnglJMed1979300:1350andfromWeinerDA,RyanTJ,
McCabeCH,etal.NEnglJMed1979301:230.

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Pretestprobabilityofcoronaryheartdisease(CHD)andaccuracyof
exercisetestintheCASSpopulation

Clinical Prevalenceof Falsepositive, Falsenegative,

Gender
history CHD,percent percent percent
Definiteangina Male 89 4 65

Definiteangina Female 63 27 23

Probableangina Male 70 13 44

Probableangina Female 40 46 22

Nonischemic Male 22 91 14
chestpain

Nonischemic Female 5 94 5
chestpain

TheCoronaryArterySurgeryStudy(CASS)examinedinpartthepretestprobabilityofcoronaryheart
disease(CHD)andtheaccuracyofexercisetestingamongpatientspresentingwithcomplaintsof
chestpain.Theexercisetestwasconsideredpositivewhentherewas1mmSTsegmentdepression
orelevationforatleast0.08seccomparedtothebaselineECG.Whenpatientsweredividedinto
subgroupsbasedupongenderandthequalityoftheirchestpaincomplaints,thepretestprobability
ofCHD(asdeterminedbycoronaryangiography)variedbetween5and89percentandthefalse
positiveandnegativeratesofexercisetestingvariedbetween4and94and5and65percent,
respectively.Thehigherfalsepositiverateinwomencomparedtomencouldbeexplainedbythe
lowerprevalenceofCHDinwomen.

DatafromWeinerDA,RyanTJ,McCabeCH,etal.NEnglJMed1979301:230.

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Incidenceofsuddendeathinmenandwomen
increaseswithage

Duringa38yearfollowupofsubjectsintheFraminghamHeart
Study,theannualincidenceofsuddendeathincreasedwithagein
bothmenandwomen.However,ateachage,theincidenceofsudden
deathishigherinmenthanwomen.

DatafromKannelWB,WilsonPWF,D'AgostinoRB,etal.AmHeartJ1998
136:205.

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Heartfailurepredictsincreasedsuddencardiac
deathandoverallmortality

Duringa38yearoldfollowupofsubjectsintheFraminghamHeart
Study,thepresenceofheartfailure(HF)significantlyincreased
suddendeathandoverallmortalityinbothmenandwomen.

*p<0.01.
p<0.001.

Datafrom:KannelWB,WilsonPWF,D'AgostinoRB,etal.AmHeartJ1998
136:205.

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ContributorDisclosures
PamelaSDouglas,MDGrant/Research/ClinicalTrialSupport:NationalInstitutesofHealth(NIH)NHLBI,NCI,NIAID
UniversityofSouthFlorida[Cancer]ColumbiaUniversity[Diagnostictesting]MassachusettsGeneralHospital
[Diagnostictesting(FFRCT)]BristolMeyersSquibb[HepatitisC]EdwardsLifesciences[Valvularheartdisease(Sapien
valves)]GEHealthCare[Diagnostictesting(Optison)]Gilead[HepatitisC(Sofosbuvir)]HeartFlow[CADdiagnosis
(FFRCT)]Ikaria/Bellerophon[Heartfailure(IK5001)]ResMed[HeartFailure(ASVventilation)]Roche[Heartfailure]
Stealthpeptides[Heartfailure(Bendavia)].Consultant/AdvisoryBoards:PatientAdvocateFoundationGeneralElectric
HealthcareDSMB[Heartfailure(AdreScan)]Alere,IncGenomeMagazineOmiciaTGENHealthVenturesThirdPoint
LLCUSDiagnosticStandardsCardioDxInterleukinGeneticsPappasVenturesQCROC/PMPC/PreThera
TheHeart.orgMedscape/WebMDMedscape,LLC,GenomicMedicineInstituteUSDefenseAdvancedResearch
ProjectsAgencyNationalInstitutesofHealthNHGRI,NIAID,NHLBI,NIGMSGatesFoundationUnitedStatesAir
ForceHenryJacksonFoundationNovartisMerck.EquityOwnership/StockOptions:CardioDXOmicia.JuanCarlos
Kaski,DSc,MD,DM(Hons),FRCP,FESC,FACC,FAHASpeakersBureau:Menarini[Anginapectoris(Ranolazine)]
ServierUKSanofi[Anginapectoris(Ivabradine)].PatriciaAPellikka,MD,FACC,FAHA,FASENothingtodisclose.
GordonMSaperia,MD,FACCNothingtodisclose.

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