Comparison of the ACC/AHA and Framingham algorithms to assess cardiovascular risk in HIV-infected patients

brazjinfectdis2017;21(6):577–580

w w w . e l s e v i e r . c o m / l o c a t e / b j i d

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Original

article

Comparison

of

the

ACC/AHA

and

Framingham

algorithms

to

assess

cardiovascular

risk

in

HIV-infected

patients

Lauro

Ferreira

da

Silva

Pinto

Neto

_,

_Fernanda

_Rezende

_Dias

_,

_Flavia

_Feres

_Bressan

_,

Carolina

Rocio

Oliveira

Santos

a_{EscoladeCiênciasdaSantaCasadeVitória,UnidadedeDoenc¸asInfecciosas,Vitória,ES,Brazil} b_{SantaCasadeMisericórdiadeVitória,Vitória,ES,Brazil}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received6November2016

Accepted20June2017

Availableonline19July2017

Keywords: Cardiovasculardisease HIV Co-morbidities Non-AIDSevents

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TheaimofthisstudywastocomparethepredictionsofFraminghamcardiovascular(CV)risk

score(FRS)andtheAmericanCollegeofCardiology/AmericanHeartAssociation(ACC/AHA)

riskscoreinanHIVoutpatientclinicinthecityofVitoria,EspiritoSanto,Brazil.Ina

cross-sectionalstudy341HIVinfectedpatientsover40yearsoldconsecutivelyrecruitedwere

interviewed. Cohen’skappacoefficient wasused toassessagreementbetweenthetwo

algorithms.61.3%werestratifiedaslowriskbyFraminghamscore,comparedwith54%

byACC/AHAscore(Spearmancorrelation0.845;p<0.000).Only26.1%wereclassifiedas

car-diovascularhighriskbyFraminghamcomparedto46%byACC/AHAscore(Kappa=0.745;

p<0.039).OnlyoneoutofeightpatientshadcardiovascularhighriskbyFraminghamatthe

timeofamyocardialinfarctioneventregistereduptofiveyearsbeforethestudyperiod.Both

cardiovascularriskscoresbutespeciallyFraminghamunderestimatedhigh-riskpatientsin

thisHIV-infectedpopulation.

©2017SociedadeBrasileiradeInfectologia.PublishedbyElsevierEditoraLtda.Thisisan

openaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/

by-nc-nd/4.0/).

Introduction

The World Health Organization (WHO) estimates that the

numberofAIDSrelateddeathsreachedabout1.1millionat

theendof2015.1_{TheoverallincidenceofAIDSrelateddeaths}

duetoopportunisticinfectionsandAIDSdefiningcancershas

decreasedsignificantlywithwidespreadavailabilityof

effec-tiveantiretroviraltreatment.2_{PeoplelivingwithHIVareliving}

∗ _{Correspondingauthor.}

E-mailaddress:lauro.neto@emescam.br(L.F.PintoNeto).

longenoughtoexperiencenon-AIDSdefiningillnesses.These

eventsalsocalledchronicnoncommunicablediseasesinclude

diabetes,chronicobstructivepulmonarydisease,kidney

dis-eases,hypertension,cardiovasculardiseases,andcancer.3

Cardiovascular disease (CVD) isone ofthe most

impor-tantcausesofmortalityamongadultsindevelopedcountries.

Furthermore,amongHIV-infectedpatientstheestimatedCVD

riskis61%greatercomparedwithuninfectedcontrols,

accord-ingtoameta-analysis,4_{andtheriskforsuddencardiacdeath}

http://dx.doi.org/10.1016/j.bjid.2017.06.007

1413-8670/©2017SociedadeBrasileiradeInfectologia.PublishedbyElsevierEditoraLtda.ThisisanopenaccessarticleundertheCC

578

isabout4-foldgreater.5_{Immunedysfunctionandpersistent}

inflammationfeaturesofHIVinfection haveapossiblerole

in the pathogenesis of CVD risk in addition to traditional

riskfactorssuchascigarettesmoking,elevatedblood

pres-sureandtotalcholesterol.AlthoughfindingsfromtheSMART

study clearly demonstrated fewer CVD events in patients

treatedwithART comparedto thoseinterruptingtherapy,6

largeprospectivecohortstudiesasD.A.Dstudyhaveshown

excessCVDriskassociatedwithsomespecificARVdrugs.7,8

WHOrecommendsthatassessmentandmanagementof

cardiovascularriskshouldbeprovidedforallindividuals

liv-ing with HIVaccording to standard protocols used forthe

generalpopulation.9_{BrazilianHIVtreatmentguidelines}

rec-ommendscreeningallHIVadultpatientsforcardiovascular

riskusingFraminghamscorerisk,beforetherapyandatleast

yearly.10_{However,thebestalgorithmforpredictingCVDrisk}

remains controversial.TheAmerican College ofCardiology

andAmericanHeartAssociation(ACC/AHA)developedtheir

ownassessment ofcardiovascularrisk.11 _{Asnoneofthose}

riskscoreshasbeenvalidatedonHIVpopulations,itseems

importanttoassesshowthesetwoscoresagreeinreallife.

Methods

Thiswasacross-sectionalanalysisperformedatanAIDS

out-patientclinicfromJanuary2015toJuly2015.Thisclinicisone

ofthemostimportantspecializedreferralservices(SAS)inthe

cityofVitoria,insoutheastBrazil,andispartofthenational

public network providing care for HIV-infectedpatients in

thecountry.AllHIV-infectedpatientsover40yearsoldwere

invitedtoparticipateand those who agreedwere selected,

afterprovidingtheirwritteninformedconsent.

Individualinformationwascollectedeitherbythe

exam-iner during the interview,or abstracted from the patients’

medicalrecords ifobtainedin thelast three months.Data

includedage,sex,race,yearssinceHIVdiagnosis,probable

meansoftransmission,lastHIV-1viralloadandTCD4+

lym-phocytescount,systolicblood pressuremeasurement,total

cholesterol and high density lipoprotein cholesterol (HDL)

levels, antiretroviral therapy (ARV) used, anti-hypertensive

therapy, and associated conditions like cigarette smoking,

diabetes mellitus, systemic arterial hypertension (SAH),

and previous myocardial infarction. The few patients with

previousmyocardialinfarctionhadtheircardiovascularscore

risks measured using information of the medical records

atthe timethe eventhad occurred.These patientsaswell

asthose with diabeteswere further stratified ashigh risk.

TheFraminghamandACC/AHAscoresforallotherpatients

were calculated according to algorithms accessed

respec-tively at http://my.americanheart.org/cvriskcalculator and at

http://www.cardiosourse.org/science-and-quality/practice-guidelines-and-quality-standards/2013-prevention-guideline-tools.

aspx. IBMSPSSstatistics version 23(SPSS, Chicago,IL)was

used for statistical analysis. Continuous variables are

pre-sented as mediansand interquartile range and categorical

variablesaspercentages.Spearmancorrelationwasusedto

compare values of Framingham and ACC/AHA scores and

Kappa coefficient was used to assess agreement beyond

chancebetweenthesetwoscores.Thegoalofthisstudywas

toapplyandtocomparedifferentkindsofscoresforCVDrisk

inanHIV-infectedpopulation.Thestudywasconductedafter

approvalbytheInstitutionEthicalCommitteeforResearch.

Allparticipantsgavetheirwritteninformedconsent.

Results

Atotalof341HIV-infectedpatientswereincludedinthe

anal-ysis.Table1presentsbaselinecharacteristicsfortheincluded

patients.Mostofthem(62.2%)weremale;57.2%white,median

ageatenrollment51(IQR46–57)years.

According to patients’ self reports, unprotected

hetero-sexual activitywas themostfrequentmode(64.5%)ofHIV

acquisition,while29%reportedhomosexualsexandonly4.4%

reportedinjectingdruguse.

Patients who have been diagnosedwith HIVin the last

5–10yearsrepresented31.7%oftotal,while20.2%havebeen

diagnosedrecently(lessthefiveyearsago).Theproportionof

patientsdiagnosedinthelast11–15yearswas22.6%,similar

tothosewhoknewtheyhavethevirusfor16–20years(18.8%).

Only 6.7%had been diagnosed withHIV formore than 20

years.Almostallpatients(97.9%)wereonART.Thebackbone

ofnucleosidetranscriptaseinhibitorsofmostpatientsused

wasTDF+3TC(54.3%)followedbyAZT+3TC(37%).Thethird

drugmostcommonlyusedwasEfavirenz(39.9%)followedby

Lopinavir/r(26.7%),Atazanavir/r(16.4%),andNevirapine(7%).

TCD4 cell countwas above500cells/mL in66% ofpatients

and HIV viral loadwas bellow detection limitsin 76.2%of

patients.

Diabeteswasfoundin15.8%ofpatientsand30.8%wereon

currenttreatmentforSAH.MedianSBPwas130mmHg(IQR

120–140).Cigarettesmokingwasreportedby20.8%while5%

declaredtobeformersmokers.Mediantotalcholesterollevel

was 199(IQR167–231)mg%and levelsabove 200mg%were

detectedin49.9%ofthepatients.HDLlevelsbelow40mg%was

foundin41.3%ofthepatients,whilemedianHDLlevelwas42

(IQR36–50)mg%.Triglycerideswereabove150mg%in52.8%

oftheindividuals,medianlevelwas155(IQR105–229)mg%.

TheassessmentofcardiovascularriskbyFraminghamand

ACC/AHAscorerisksareshowninTable2.Among209patients

classifiedaslowriskbyFraminghamscore,184werealso

clas-sified aslow riskbyACC/AHA score(Spearmancorrelation

0.845;p<0.000).Among43patientsclassifiedasintermediate

riskbyFraminghamscore,37wereclassifiedashighriskby

ACC/AHA score.Therefore,lower concordanceforhighrisk

betweenthetwoscoreswasobserved,as26.1%were

classi-fiedashighriskbyFraminghamand46%byACC/AHAscore

(Kappa=0.745;p<0.039).

Acutemyocardialinfarctionwasrelatedbyninepatients

up tofive years before the study period, eightwere male,

eight were treating SAH, one had diabetes mellitus, and

four were previous smokers. Efavirenz was used by four

patients, Atazanavir/r bythreepatients, andLopinavir/rby

twopatients.MedianTCD4was540cells/mLandallbutone

ofthesepatientshadHIV-1viralloadbelowdetectionlimits.

Dataforestimationofscoreriskswereavailablefrommedical

recordsatthetimeoftheeventforeightpatients.Fiveoutof

eightpatientshadhighscoreriskbyACC/AHAcomparedto

brazj infect dis.2017;21(6):577–580

579

Table1–CharacteristicsofHIV-infectedpatientson treatmentatSantaCasaMisericórdia,Vitória,ES,Brazil, 2015. No. % Sex Male 212 62.2 Female 129 37.8 Skincolor White 195 57.2 NotWhite 146 42.8 Age 40–49 139 40.8 50–59 139 40.8 60–69 51 15 >70 12 3.6

RiskfactorforHIVinfection

Heterosexual 220 64.5

MSMa _{99 29}

IDUb _{15 4.4}

Bloodtransfusion 1 0.3 Notdetermined 6 1.8

TimesinceHIVdiagnosis(years)

<5 69 20.2 5–10 108 31.7 11–15 77 22.6 16–20 64 18.8 >20 23 6.7

HIV-1viralload

Undetectable 260 76.2 Detectable 81 23.6

TCD4+cellcount(cells/mL)

<200 11 4 200–500 100 20 >500 226 66 Smoking Not 253 74.2 Yes 71 20.8 Former 17 5.0 Diabetes Not 287 84.2 Yes 54 15.8 SBPc_(mmHg) <120 70 20.5 120–129 103 30.2 130–139 61 17.9 140–159 88 25.8 ≥160 19 5.6 Useofanti-hypertensive Not 236 69.2 Yes 105 30.8 Cholesterol <200mg% 171 50.1 >200mg% 170 49.9 HDLcholesterol <40mg% 141 41.3% >40mg% 200 58.7% Triglycerides <150mg% 161 47.2% –Table1(Continued) No. % >150mg% 180 52.8% Total 341 100

a _{Menwhohavesexwithmen.} b _{Injectiondrugusers.} c _{Systolicbloodpressure.}

Table2–Comparisonbetweencardiovascularrisk estimationusingFraminghamandACC/AHAalgorithms.

Lowrisk(N-%) Highrisk(N-%)

Framinghama _{209patients(61.3%) 89patients(26.1%)}

ACC/AHA 184patients(54%) 157patients(46%)

a _{43patients(12.6%)wereclassifiedasmoderateriskby}

Framing-hamscore.37patientsoutofthese43wereclassifiedashighrisk byACC/AHAscore.

Discussion

Inthiscross-sectionalanalysisofanHIV-infectedcohorton

treatmentweobservedanimportantprevalenceoftraditional

cardiovascularriskfactorssuchasdiabetes(15.8%),cigarette

smoking(20.8%),andSAH(30.8%).Theseratesarehigherthan

thoseobservedinthegeneralpopulationinBrazil,according

toaregular phone callsurveillanceconductedbythe

Min-istryofHealth,respectively8%fordiabetes,10.8%forcigarette

smoking,and24.8%forSAH.12_{Theaverageyearsoflifelost}

duetosmokingamongHIV-infectedpatientswasestimated

as12.3years,whichismorethantwicethatforthegeneral

population.13_{InBrazil,theprevalenceofsmokingreducedin}

thelastdecadesbutremainshighespeciallyincitiesinthe

southandsoutheastregions.14

In our study the agreement between Framingham and

ACC/AHAscoreswaslowerforidentifyinghigh-riskpatients.

Conflicting results havebeen reported comparing different

cardiovascularriskscoresamongHIV-infectedpopulationsin

differentcountries.15–19_{Curiously,theFraminghamriskscore}

overestimatedhearteventsinaMediterraneanHIV-infected

populationandaRegicorchart(anadaptionforthe

character-isticsoftheSpanishpopulation)workedbetterasapredictor

for ischemic CV events.20 _{Some intrinsic characteristics of}

thisSpanishpopulationmayexplainthisdifferentimpactof

FraminghamscoreasitusuallyunderestimatesCVriskin

HIV-infectedpopulations.Only26.1%ofourpatientswerestratified

ashigh-riskbyFraminghamcomparedto46%byACC/AHA.

Onlyoneout ofeightpatientswascategorizedashigh-risk

accordingtoFraminghamscoreatthetimeofamyocardial

infarction.

Dyslipidemiaremainsanimportantissueinouroutpatient

clinic. Wehaveshownbefore thatuse ofboosted protease

inhibitors, especially lopinavir/r, was associatedwith high

cholesterol levels.21 _{Friis-Moller et al. have demonstrated}

in the D:A:Dstudy that the additional riskof CVDamong

patientsreceivinglopinavir/rrangedfrom8to12%peryear,

580

statin therapy were using a weak statin, pravastatin, that

was not always available for all patients in need. Use of

atorvastatininHIV-infectedpatientsontherapywasreported

toreducethetotalcoronaryarteryplaquevolume.23_The

mul-ticenterREPRIEVEtrialaimedtoassessthepotentialbenefits

ofstatintherapy(pitavastatin)inpreventingCVDinpeople

withHIV.24

Ourstudyhasimportantlimitations.Itisacross-sectional

analysiscomparingtwodifferentCVriskscores.Certainly,the

best waytocompare those scoresshould bea prospective

studyobservinghowthesescoresworkasanHIVcohortgrows

older.However,aspatientswithHIVlivelongerontherapy,the

effectofCVDonmorbidityandmortalitywillprobablyworsen

unlesseffectivemanagementstrategiesaredeveloped.

Tradi-tionalscreeningmethodsforCVDmightunderestimatethe

riskofHIV-infectedpatientsasthesemethodsdonottakeinto

accountnon-traditionalriskfactorsinvolvedinthe

develop-mentofatherosclerosis.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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