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Chapter01:EpidemiologyandRiskFactors
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EpidemiologyandRiskFactors

Overview
IntheUnitedStates,themortalityratefromcardiovasculardisease(CVD),includingheartdisease,
stroke,peripheralvasculardisease,hypertension,andheartfailurehassteadilydeclinedoverthepast
decade33%from1999to2009,likelyasaresultofbetterpreventionandacutecareefforts.
Nonetheless,CVDistheleadingkillerofbothmenandwomen,andalthoughmortalityofCVDis
decreasing,CVDprevalenceisincreasing.By2030,accordingtotheAmericanHeartAssociation's
HeartDiseaseandStrokeStatistics,morethan40%oftheU.S.populationisprojectedtohavesome
formofCVD.MorethanoneinthreeAmericanadultscurrentlyhavesomeformofCVD,andthe
prevalenceincreasesfrommorethan10%inthoseaged20to39yearstomorethan70%inthose
aged60to79years.BasedondatafromtheFraminghamHeartStudy,twooutofthreemenandone
outoftwowomenwilldevelopCVDintheirlifetime.Despitethedecreasingmortality,
hospitalizationsforcardiovascularrelateddiseaseshavesteadilycontinuedtorise.Therewerenearly
6millionhospitaldischargesforcardiovascularrelateddiseasesin2009,withanestimatedcostof
$312.6billion.
Theprevalenceofheartfailurecontinuestorise,withapredictedprevalenceintheUnitedStatesof
25%by2030.Itisestimatedthat5.1millionAmericansolderthan20yearshaveadiagnosisofheart
failure.Currently,theincidenceis1/100annuallyinthoseolderthan65years.Mostofthesepatients
haveahistoryofhypertension.Bothsystolicdysfunctionanddiastolicdysfunctionareassociatedwith
thedevelopmentofsymptomaticheartfailure,andtheprevalenceofheartfailurewithpreserved
ejectionfraction(diastolicdysfunction)isincreasing.Mortalityinheartfailureisquitehighnearly
50%mortalityat5years.

CardiovascularDiseaseinWomen
Since1984,thenumberofdeathsfromCVDhasbeengreaterforwomenthanmenandhighestamong
blackwomen.Morethan400,000womendiedofCVDin2009,51%ofallCVDdeaths.Womenhave
ahighermortalityrateaftermyocardialinfarction:26%inwomenversus19%inmenolderthan45
years.Thedeathrateforwomenwithheartfailureishigherthanamongmen,althoughwomenare
oftenolder.Incidenceofandmortalityfromstrokeishighestamongwomen,withthehighestamong
blackwomen.
WomenhaveahigherprevalenceofriskfactorsforCVD,includingelevatedcholesterollevels,
diabetesmellitus,hypertension,andinactivity.Onlytobaccouseishigheramongmen.
Morewomenpresentwithanginathanmen,butwomenoftenhaveothersymptomsinadditionto
chestpain.Womenhaveatypicalsymptomsmorefrequentlythanmen,includingnausea,shortness
ofbreath,andunusualfatigue.Morethantwothirdsofwomenwhodiesuddenlyfromcoronaryheart

diseaseeitherdidnotrecognizethesymptomsorhadnoprevioussymptoms.Womenundergofewer
revascularizationproceduresthanmen,with25%ofcoronaryarterybypasssurgeriesandnearly33%
ofpercutaneouscoronaryinterventionsoccurringinwomen.

EthnicityandCardiovascularDisease
TheprevalenceofCVDandriskfactorsintheUnitedStatesvarybyethnicity.AmericanIndiansand
AlaskaNativeshavethehighestrateofheartdisease(12.7%),followedbywhites(11.1%),blacksor
AfricanAmericans(10.7%),HispanicsorLatinos(8.6%),andAsians(7.4%).Peripheralarterial
diseaseaffectsnearly8.5%ofAmericansolderthan40years,andprevalenceishighestamongolder
persons,nonHispanicblacks,andwomen.ThepopulationmostaffectedbyheartfailureisAfrican
Americans,atarateof4.6/1000personyears,followedbyHispanic,white,andChineseAmericans.
Cardiovascularriskfactorsalsovaryamongethnicities.Blackshavethehighestrateofhypertension,
at33.4%(higherinblackwomen),followedbyAmericanIndiansorAlaskaNatives(25.8%),whites
(23.3%),HispanicsorLatinos(22.2%),andAsians(18.7%).Blackshavethehighestprevalenceof
twoormorecardiovascularriskfactors(48.7%).Theprevalenceofriskfactorsisincreasedwith
decreasinglevelsofeducationandincome.Obesityandlackofphysicalactivityarehighestamong
Hispanic/LatinoadultsandnonHispanicblacks.
EnvironmentalinfluencesoncardiovascularriskfactorsarechangingtheprevalenceofCVDin
certainpopulations.IncountrieswithpreviouslylowratesofCVD,ratesofdiseaseareincreasing
withtheadoptionofWesterneatinghabitsandincreasingtobaccouse.Withdecliningratesofinfant
mortalityanddeathfrominfectiousdiseases,theinfluenceofurbanizationandchangeintraditional
lifestylesareresultinginincreasingratesofCVD.

GeneticsinCardiovascularDisease
Familyhistoryofpremature(male<45yearsfemale<55years)coronaryarterydisease(CAD)
significantlyincreasesriskofCVD.HavingaparentwithprematureCADdoublesriskofmyocardial
infarctioninmenandincreasesriskinwomenby70%.CADinasiblingincreasesriskby50%.
Geneticpredispositionaswellassharedenvironmentmaycontributetoincreasedriskinfamily
members.AlthoughpredictionmodelsbasedonthegeneticsofCVDarenotyetavailable,research
continuesatarapidpace.

LifestyleRiskFactors
RelatedQuestion
Question17
Asmuchas90%oftheriskformyocardialinfarctionhasbeenattributedtomodifiableriskfactors,
withelevatedcholesterollevels,smoking,andpsychosocialstressorsaccountingforasignificant
portionoftheattributablerisk.Theattributableriskformyocardialinfarctionishighestforcholesterol
levels,followedbycurrentsmoking,psychosocialstressors,diabetes,hypertension,abdominal
obesity,noalcoholintake,inadequateexercise,andirregularconsumptionoffruitsandvegetables.
ElevatedcholesterollevelsincreasetheriskofCVD,andmultiplestudieshaveshownthatreductions
incholesterollevels,particularlyLDLcholesterol,reducerisk.Nearly14%ofadultsolderthan20
yearshavetotalcholesterollevelsgreaterthan240mg/dL(6.21mmol/L)approximately6%ofadults
areestimatedtohaveundiagnosedhypercholesterolemia.ElevatedLDLcholesterolandlowHDL
cholesterollevelsareindependentriskfactorsforCVD.Forevery1%decreaseinLDLcholesterol

level,thereisacorresponding1%decreaseinriskforcoronaryarterydisease.Theriskreductionis
evengreaterwithchangesinHDLcholesterol,withariskreductionof2%to3%forevery1%
increaseinHDLcholesterollevel.However,randomizedclinicaltrialsevaluatingpharmacologic
therapiesthatraiseHDLcholesterollevelsinpatientswithwelltreatedLDLcholesterollevelshave
notshownreductioninclinicalendpoints.Longstandingguidelines(AdultTreatmentPanelIII[ATP
III])haveprovidedtreatmentgoalsforLDLandnonHDLcholesterollevelsbasedoncardiovascular
riskfactorsandFraminghamriskscore.In2013,theAmericanCollegeofCardiologyandthe
AmericanHeartAssociation(ACC/AHA)publishedrevisedguidelinesthattreatlipidbloodlevels
accordingtocardiovascularrisk,ratherthanLDLcholesteroltargets(seeMKSAP17GeneralInternal
Medicine,Dyslipidemia).
Theuseoftobaccohasdeclinedoverthepastfewdecades,butdespitethisdecline,in2011,more
than21.3%ofmen,16.7%ofwomen,and18%ofhighschoolstudentsweresmokers.Therateswere
highestamongAmericanIndian/AlaskaNativesandnonHispanicblackmalesandlowestamong
Hispanicfemales.TobaccouseincreasestheriskofCVD,includingcoronaryheartdisease,stroke,
andperipheralvasculardisease,forwhichsmokingisamajorriskfactor,andincreasesCVD
mortalityby2to3times.Theriskofcoronaryarterydiseaseisincreasedby25%inwomenwho
smoke.Smokingincreasestheriskofstrokeby2to4times.Secondhandsmokeisalsoariskfactor
forCVD,increasingtheriskby25%to30%.Smokingcessationsubstantiallyreducescardiovascular
riskwithin2years,andthisriskreturnstothelevelofanonsmokerwithin5years.Effortstoassess
smokingstatusandprovideassistancewithcessationshouldbemadeateveryencounter(see
MKSAP17GeneralInternalMedicine,RoutineCareoftheHealthyPatient).
NearlyoneinthreeadultsintheUnitedStatesolderthan20yearshashypertension,andtheratesare
equalamongmenandwomen.Nearly30%ofadultsolderthan20yearshaveprehypertension
(systolicbloodpressure120139mmHgdiastolicbloodpressure8089mmHg).Theratesincrease
withage,withaprevalencegreaterthan70%inpersonsolderthan65years.Treatmentof
hypertensionreducesriskforcardiovascularevents,includingstroke,andreducesendorgandamage
suchasheartfailureandkidneydisease.Althoughtheprevalenceofbloodpressurecontrol(thatis,
bloodpressurewithinrecommendedranges)hasimprovedintheUnitedStatesfromlessthan30%
twodecadesago(19881994),itstillisonly50%(20072008).
Sedentarylifestyle,poordiet,andobesitycontributetoincreasedcardiovascularriskandincreased
riskfordiabetes.NearlyonethirdofallU.S.adultsreportnoleisuretimeactivity,andlessthan30%
ofhighschoolstudentsengagedin60minutesofdailyphysicalactivitythisratewaslowestamong
girls.Between1971and2004,totalenergyconsumptionincreasedby22%inwomenand10%in
men.Averagefruitandvegetableconsumptionwas2.4to4servingsdaily(recommended,>5daily)
andwaslowestamongblacks.Theincreasedcaloricintakecoupledwithdecreasedphysicalactivity
hasledtoanincreasedincidenceofobesity.MorethantwothirdsoftheAmericanpopulationolder
than20yearsareoverweight(BMI2529.9)withmorethanonethirdobese(BMI>30).Inchildren
andadolescentsbetweentheagesof2and19years,nearly33%areobeseoroverweightand17%of
thesechildrenareobese.
Psychosocialstressorsareanimportantcontributortocardiovascularrisk.Theseincludedepression,
anger,andanxiety,andareassociatedwithworseoutcomes.Depressionhasbeenassociatedwith
higherriskforcardiovascularevents,andpsychosocialstressorsalsoaffectthecourseoftreatment
andadherencetohealthylifestylesafteranevent.Awarenessofthesefactorsandappropriate
therapiesmayimproveoutcomesintheseindividuals.
Impairedglucosecontrolisasignificantcomponentofthemetabolicsyndrome,whichis
characterizedbyelevatedglucose,centralobesity,lowHDLcholesterol,elevatedtriglycerides,and
highbloodpressure.Morethan34%ofadultsolderthan20yearsmeetthecriteriaformetabolic
syndrome(threeofthefivecomponents).Thepresenceofmetabolicsyndromeisassociatedwithan
increasedriskofCVD.Thisriskincreaseswithanincreasednumberofcomponentsandalsoappears
tobehigheramongwomen.TheNationalDiabetesPreventionProgramfoundthatinpersonsathigh

riskfordiabetes,improvedfoodchoicesandatleast150minutesofexerciseweeklyledto5%to7%
weightlossandreducedtheriskofdevelopingdiabetesby58%,butnointerventionshaveshowna
reductioninCVDeventstodate.

KeyPoint
Elevatedcholesterollevels,smoking,andpsychosocialstressorsarethegreatestmodifiablerisk
factorsforcardiovasculardisease.

SpecificRiskGroups
DiabetesMellitus
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Question8
Question40
Thepresenceofdiabetesmellitusisassociatedwithincreasedcardiovascularrisk,particularlyamong
women.Personswithdiabeteshavea2to4timesincreasedriskofCVD,withmorethantwothirdsof
thosewithdiabeteseventuallydyingofheartdisease.Theriskofstrokeisincreased1.8to6foldin
personswithdiabetes.Thepresenceofdiabetesinthoseolderthan65yearsisnearly27%.Inthose
aged1219years,theprevalenceofdiabetesandprediabetesisincreasing,from9%to23%from
19992007.Diabetesisoftenundiagnosed,andisfrequentlydiagnosedatthetimeofanacuteevent
suchasmyocardialinfarction.Appropriatetreatmentofcardiovascularriskfactorsinpersonswith
diabetesisassociatedwithreducedcardiovascularrisk.Themostrecentcholesterolguidelines
recommendmoderateorhighintensitystatintherapyinpatientsaged40to75yearswithdiabetes.
Patientswithdiabetesaged40to75yearswitha10yearatheroscleroticcardiovasculardisease
(ASCVD)riskgreaterthanorequalto7.5%shouldreceivehighintensitystatintherapybecauseof
theirincreasedrisk.Inpatientswithdiabetesinthisagegroupwitha10yearriskbelow7.5%,
moderateintensitystatintherapyisrecommended.

ChronicKidneyDisease
Chronickidneydisease(CKD)isassociatedwithhighercardiovascularmortality,andmorepatients
withkidneydiseasewilldieofCVDthanwillgoontohaveendstagekidneydiseaserequiring
dialysis.ChronickidneydiseasesharesmanyofthesameriskfactorsforCVDsuchashypertension,
diabetes,andsmoking.TheexactetiologyofthehighdeathrateinpatientswithCKDisuncertainand
mayberelatedtoahigherincidenceoffatalarrhythmias,lackofadequatetherapiesatthetimeofan
acutecardiovascularevent,ormultiorganchangesrelatedtokidneyfailure.

SystemicInflammatoryConditions
Patientswithsystemicinflammatoryconditions,suchassystemiclupuserythematosus(SLE)and
rheumatoidarthritis,haveanincreasedriskofCVD.MostdeathsinpersonswithSLEandnearly40%
ofdeathsinthosewithrheumatoidarthritisarecardiovascularand,inparticular,heartfailurerelated.
TheriskofCVDincreaseswiththedurationoftheunderlyinginflammatorycondition.Theriskof
CVDincreasesfromtwotimesthatofthegeneralpopulationtothreetimesafter10years'durationof
rheumatoidarthritis.Theincreasedatheroscleroticburdenislikelyaresultofboththeinflammatory
processofthesystemicdisease,includingaprothromboticstate,aswellasthepresenceoftraditional
cardiovascularriskfactors.

CalculatingCardiovascularRisk
Cardiovascularriskscoresshouldbeutilizedtostratifypatientsforappropriatepreventiontargets.
Traditionally,theFraminghamriskscorehasbeenusedtoestimatethe10yearriskofamajor
cardiovascularevent(myocardialinfarctionorcoronarydeath).AnonlineFraminghamriskcalculator
isavailableathttp://cvdrisk.nhlbi.nih.gov/calculator.asp.Usingthismethod,a10yearriskofASCVD
oflessthan10%isconsideredlowrisk,10%to20%isclassifiedasintermediaterisk,andabove20%
isdesignatedashighrisk.Ageisthecomponentthatdrivesmostoftherisk,withincreasingage
reflectedinincreasedrisk.TheFraminghamriskscoreunderestimatesriskinwomenandminority
populations.Inanefforttoaccountfortheunderestimationinwomen,theReynoldsriskscorewas
developed,whichisasexspecificscoreforbothmenandwomenthatincludesfamilyhistoryand
highsensitivityCreactiveprotein(hsCRP)levels(www.reynoldsriskscore.org).
ThePooledCohortEquationsareanewriskassessmentinstrumentdevelopedfrommultiple
communitybasedcohorts(includingtheFraminghamstudy)thatincludesabroaderrangeofvariables
thantheFraminghamscorewhenevaluating10yearASCVDrisk.Itsuseasaprimaryrisk
assessmenttoolwasrecommendedinthe2013ACC/AHAGuidelineonAssessmentof
CardiovascularRisk.TheACC/AHACVriskcalculatorincludesage,sex,race,totalandHDL
cholesterollevels,systolicbloodpressure,bloodpressureloweringmedicationuse,diabetesstatus,
andsmokingstatus.Usingthismethod,a10yearriskofASCVDofbelow5%isconsideredlowrisk,
5%tobelow7.5%isclassifiedasintermediaterisk,and7.5%oraboveisdesignatedashighrisk.The
newriskcalculatorcanbeaccessedat
http://my.americanheart.org/professional/StatementsGuidelines/PreventionGuidelines/Prevention
Guidelines_UCM_457698_SubHomePage.jsp.

KeyPoint
Cardiovascularriskscoresshouldbeutilizedtostratifypatientsforappropriateprevention
targetsriskassessmenttoolsincludetheFraminghamriskscore,theReynoldsriskscore,and
theAmericanCollegeofCardiology/AmericanHeartAssociation'scardiovascularrisk
calculatorbasedonthePooledCohortEquations.

EmergingRiskFactors
RelatedQuestions
Question2
Question83
Becauseatheroscleroticdiseaseisthoughttobeinpartaninflammatoryprocess,hsCRPmeasurement
hasbeeninvestigatedforenhancingriskprediction.Currentguidelinesdonotsupporttheuseof
hsCRPevaluationinthegeneralpopulation.However,hsCRPtestingmaybeusedinintermediate
riskpatients(Framingham10yearriskscoreof10%20%)inwhomchoiceoftherapymaybe
affectedbyreclassificationofrisk.ElevatedhsCRPlevelsshouldberecheckedwithin2weeks,and
otherpotentialcausesofinfectionorinflammationshouldberuledout.Althoughstatintherapyhas
beenshowntolowerhsCRPlevels,therapytargetinghsCRPaloneisnotappropriateaspatients
shouldbetreatedaccordingtocardiovascularrisk.
AlthoughelevatedlevelsofLp(a)lipoproteinandhomocysteinehavebeenassociatedwithelevated
cardiovascularrisk,thesetestsshouldnotberoutinelyperformed.Interventionstoreduce
homocysteinelevelswithfolicacidsupplementationhavenotbeenshowntoreducecardiovascular
events.AlthoughepidemiologicevidencesupportstheassociationbetweenelevatedlevelsofLp(a)

lipoproteinandcardiovascularevents,todatenotrialshaveshownthattreatmenttolowerLp(a)
lipoproteinlevelslowersrisk.Thereiscurrentlynorolefortheevaluationoflipidparticlesizeand
number.Nostudiestodatehaveshownthattreatmenttargetedtoparticlesizeandnumberaffects
outcomes.
Theevaluationofsubclinicaldiseasewithcoronaryarterycalcium(CAC)scoringmaybeappropriate
tofurtherriskstratifyintermediateriskpatientsbutisnotacomponentofroutineriskassessment.
Evidenceofcalcificationofcoronaryvesselsisindicativeofatheroscleroticdisease,buttheabsence
ofcalcificationdoesnotruleoutthepresenceofsoftplaque.

KeyPoints
CurrentguidelinesdonotsupporttheuseofhighsensitivityCreactiveprotein(hsCRP)
evaluationinthegeneralpopulation,buthsCRPtestingmaybeusedinintermediaterisk
patientsinwhomchoiceoftherapymaybeaffectedbyreclassificationofrisk.
ThereiscurrentlynorolefortheroutinemeasurementofLp(a)lipoproteinlevelsor
homocysteinelevelsorevaluationoflipidparticlesizeasthesetestsareexpensiveandno
studiestodatehaveshownthattreatmenttargetedtotheselevelsaffectsoutcomes.
Theevaluationofsubclinicaldiseasewithcoronaryarterycalciumscoringmaybeappropriate
tofurtherriskstratifyintermediateriskpatientsbutisnotacomponentofroutinerisk
assessment.

AspirinforPrimaryPrevention
RelatedQuestion
Question88
Aspirinisapowerfulagentforbothprimaryandsecondarypreventionofcoronaryarterydisease.
AspirinforsecondarypreventionisdiscussedunderCoronaryArteryDisease.Forprimaryprevention
ofmyocardialinfarction,datasuggestthatthereisgreaterbenefitinmen,particularlythoseolderthan
45years.Forwomen,benefitoutweighsriskofaspirintherapyaftertheageof65years.Betweenthe
agesof55and65years,theriskofstrokeisreducedinwomenonaspirintherapy.Guidanceforusing
aspirinforprimarypreventionofmyocardialinfarctionandstrokeisprovidedinTable1andTable2.
Itisimportanttobalancethebenefitsofaspirintherapywiththerisksofgastrointestinal(GI)
bleeding.TheriskofseriousbleedingisgreatlyincreasedinpatientswithahistoryofGIulcersand
whouseNSAIDs,andthesefactorsshouldbeconsideredwhenassessingthebenefitsandharmsof
usingaspirinintheindividualpatient.
AspirinshouldnotberoutinelygiventopatientswithdiabeteswhoareatlowriskforCVD(men<50
yearsandwomen<60yearswithnomajoradditionalCVDriskfactors10yearCVDrisk<5%).Itis
reasonabletogivelowdoseaspirintoadultswithdiabetesandnoprevioushistoryofvasculardisease
whoareatincreasedCVDrisk(10yearFraminghamrisk>10%)andwithoutincreasedriskfor
bleeding.

KeyPoints
Inmenages45to79years,aspirinforprimarypreventionofmyocardialinfarctionis
recommendedifthebenefitoftreatmentoutweighstheriskofgastrointestinalbleeding.
Inwomenages55to79years,aspirinforprimarypreventionofstrokeisrecommendedifthe
benefitoftreatmentoutweighstheriskofgastrointestinalbleeding.

Aspirinshouldnotberoutinelygiventopatientswithdiabeteswhoareatlowriskthatis,men
youngerthan50yearsandwomenyoungerthan60yearswithnomajoradditional
cardiovascularriskfactors.

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EpidemiologyandRiskFactors
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