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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health ProfessionalsACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
CardiovascularRiskManagementinHIV
JudithA.Aberg,MDGeorgeBaehr ProfessorMedicine
IcahnSchoolofMedicineatMountSinaiHealthSystem
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
LearningObjectivesUponcompletionofthispresentation,learnersshouldbebetterableto:
• AbilitytoeducateandcounselpersonswithHIVonrisk factormodificationtoreducetherisk ofcardiovascular disease.
• Abilitytodetectandmanagecardiovascularrisk factorsamongpersonswithHIVaccordingtoevidence-basedguidelines
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
FacultyandPlanningCommitteeDisclosuresPleaseconsultyourprogrambookortheConferenceApp.
Therewillbenooff-label/investigationalusesdiscussedinthispresentation.
Off-LabelDisclosure
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
MultifactorialetiologyofCVDinHIV
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Tobacco
Mdodo R et al. Ann Intern Med. 2015;162(5):335-344. doi:10.7326/M14-0954
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HIVandMultimorbidity 2000-2009
NAACORD Clin. Infect Dis 2017 Nov 15. doi: 10.1093/cid/cix998
28% 27% 30% 31% 32% 32% 33% 33% 32% 32%
7% 7% 9% 10% 11% 13% 14% 14% 15% 15%
2% 2% 2%
3% 3% 4%
4% 5% 6% 6%
0%
10%
20%
30%
40%
50%
60%
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
6 conditions
5 conditions
4 conditions
3 conditions
2 conditions
1 condition
Perc
enta
ge o
f Ind
ivid
uals
in H
IV
Car
e w
ith A
ge-A
ssoc
iate
d C
ondi
tions
N= 4172 6325 8365 9121 9733 10861 11166 12277 9074 3705No of conditions
1 1162 1705 2512 2833 3137 3517 3687 4004 2892 11952 287 452 727 923 1108 1375 1601 1756 1363 5623 73 126 179 234 296 405 499 592 530 2144 2 8 16 30 39 69 96 111 120 525 0 1 1 1 1 1 8 10 8 36 0 0 0 0 0 0 0 0 1 0
HLDandHTNRemainMostCommon
NAACORD Clin. Infect Dis 2017 Nov 15. doi: 10.1093/cid/cix998
Hypercholesterolemia18.2%
Hypercholesterolemia19.8%3.6% 8.9% Hypertension 8.7%
0.8%0.8%1.0%
Diabetes 1.5% CKD1.3%
1.6%1.6%
1.3%
Hypertension 5.9%
2000N=4172
2009N=3705
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CardiovascularDiseaseMortalityAmongHIV-Infected
§ In HIV+ individuals, CVD deaths increased from 6% to 15% of all deaths (p<0.001)– Decreased in the general population: 47% →
39%
§ HIV associated with a 56% increased rate of CVD death
§ Both viremic and virologically suppressed HIV+ individuals had higher CVD mortality rates than uninfected individuals until age 65.
Hanna DB, et al. CID 2016;63:1122-9.
New York City HIV Surveillance Registry
Evaluation of age-adjusted mortality rates due to CVD inNew York City from 2001-2012; N=29,588 deaths
*Adjusted for sex, race/ethnicity, borough of residence, and calendar year
Adjusted relative rate* (95% CI) of CVD death for HIV-diagnosed New Yorkers, by age
0.27 (0.18-0.41)
0.65 (0.54-0.80)
1.10 (0.99-1.23)
1.31 (1.20-1.42)
1.75 (1.60-1.92)
2.66 (2.35-3.01)
3.02 (2.21-4.13)
2.81 (1.04-7.53)
85+
75-84
65-74
55-64
45-54
35-44
25-34
13-24
0.1 1 10
Age
CVD mortality was lower among HIV-diagnosed individuals with a suppressed HIV RNA level (<40 copies/mL) versus an unsuppressed level (age-standardized rate 3.9 vs. 7.7/1,000, p<0.001)
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Treatment—PrimaryPrevention
• ThinkaboutASCVDriskandassessmentinHIVpatients*1st stepistoapplyGenpopguidelines
• Smokingcessationresources-Bupropion,varenicline andnon-pharmacologictherapies
• ARTforHIVVLSuppression• Manageco-morbidities:Glucose,HTN,Lipids,Obesity
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health ProfessionalsAberg J, et al. Clin Infect Dis. 2014 Jan;58(1): 1-10 and e1-34http://www.eacsociety.org/guidelines/eacs-guidelines/eacs-guidelines.html
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Question1:WhoisRecommendedtobeprescribedastatin?
• 1.PWHwithLDL>130mg/dL• 2.PWHwithLDL>190mg/dL• 3.PWHaged40-75withLDL160-190mg/dL andCACscorezero• 4.PWHaged40-75withACC/AHAriskscore5%
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
TwoDifferentPreventionApproacheswithTwoDifferentPerspectives
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
SimilaritiesbetweentheACC/AHAandNLA• Lipidscreeningforprimarypreventionevery5years• Lifestyleadvocacyisrecommendedfirst• ASCVDriskreductionisprimarygoal• Moderate-HighStatinIntensityforprimarypharmacotherapy• Patient-providerdiscussionofrisk-to-benefitprecedesallprescribing• “Regular”lipidprofilestoassessadherence
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
LipidManagement• 2013 AHA guidelines for general
population age >21 for ASCVD and aged 40-75 for other categories
– LDL-C >190, DM, ≥7.5%risk of atherosclerotic CV disease àstatins
– No lipid targets• Risk calculator controversy• How to apply to HIV+ pts
is uncertain
Stone NJ et al, Circulation, 2013
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
FourStatinBenefitGroups
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
DefiningCVDriskamongPWH
• Riskscoresfluctuateasweage,changebehaviorsandtreatconditions• Atwhattimeistheriskscoreaccurate?• WhendoesHVIVcontributetorisk?
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
HIVasRiskEnhancingFactor
• Inadults40to75yearsofagewithoutdiabetesmellitusand10-yearriskof7.5%to19.9% (intermediaterisk),risk-enhancingfactorsfavorinitiationofstatintherapy
• Risk-enhancingfactorsmay favorstatintherapyinpatientsat10-yearriskof5-7.5%(borderlinerisk).
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6. Inadults40to75yearsofageevaluatedforprimaryASCVDprevention,haveaclinician–patientriskdiscussionbeforestartingstatintherapy.
Riskdiscussionshouldincludeareviewofmajorriskfactors(e.g.,cigarettesmoking,elevatedbloodpressure,(LDL-C),hemoglobinA1C[ifindicated],andcalculated10-yearriskofASCVD);
•thepresenceofrisk-enhancingfactors(seeNo.8);•thepotentialbenefitsoflifestyleandstatintherapies;•thepotentialforadverseeffectsanddrug–druginteractions;•theconsiderationofcostsofstatintherapy;and•thepatientpreferences&valuesinshareddecision-making.
Top10TakeHomeMessages
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Imaging• Inadults40to75yearsofagewithoutdiabetesmellitusandwithLDL-Clevels≥70mg/dl-89mg/dl(≥1.8-4.9mmol/L),ata10-yearASCVDriskof≥7.5%-19.9%,ifadecisionaboutstatintherapyisuncertain,considermeasuringCAC.– IftheCACscoreiszero,treatmentwithstatintherapymaybewithheldordelayed,exceptincigarettesmokers,thosewithdiabetesmellitus,andthosewithastrongfamilyhistoryofprematureASCVD.
– ACACscoreof1-99favorsstatintherapy,especiallyinthose>55yearsofage.
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Aberg J, et al. CID 2014
Cardiovascular Disease Prevention:Lipid Management• Screening: fasting lipids
– At HIV diagnosis– Start of ART– Change of ART– Every 6-12 months
• Lipid management– Beware of drug interactions
between statins and ART
Safe (Prava caution with DRV/r)
Statin Levelwith PI/cobi
Use
Pitavastatin --Pravastatin --Atorvastatin ↑Rosuvastatin ↑Simvastatin ↑↑↑Lovastatin ↑↑↑
Contraindicated
Use with caution/low dose
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
INTREPID:StatinsWorkinPWHwithDyslipidemia
. Aberg J et al. Lancet HIV 2017
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REPRIEVEStudy Design
REPRIEVEBaseline Demographics
39
Characteris'cs Total (n=7530)
Sexat Birth
Age (years)
Male 5135 (68%)
Female 2395 (32%)
Median(Q1, Q3) 50 (45--55)
EverBeenona StatinNo 6927 (94%)
Yes 467 (6%)
10--yearASCVDRisk (%) Median(Q1,Q3) 4.3 (2.1--6.9)
Race
White 2349 (32%)
Black or African 3309 (44%)American
Asian 1136 (15%)
Ethnicity Hispanicor Latino 1890 (25%)
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BaselineCVDHistoryandRisk Factors
40
Characteris'cs Total (n=7530)
Totalcholesterol (mg/dL) Median(Q1, Q3) 184 (162--208)
LDL calculated (mg/dL) Median(Q1,Q3) 108 (87--127)
HDL--C (mg/dL) Median(Q1,Q3) 48 (39--59)
SystolicBP(mmHg) Median(Q1,Q3) 122 (113--132)
BMI(kg/m2) Median(Q1,Q3) 25.8 (22.8--29.4)
Smoking Status
Current 1746 (24%)
Former 1811 (25%)
Never 3821 (52%)
FamilyHistoryof CVDNo 5812 (79%)
Yes 1333 (18%)
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
PCSK-9inhibitors??• LeuckerTM.JAmHeartAssoc2018
48PWHonART,noknownCADvs.15age/LDLmatchedHIVnegativePCSK-9levels65%higherPWHv.controlPWHwithmorecoronaryendothelialdysfunction(%changeincoronaryacrosssectionalareaduringisometrichandgriponMRI)
• ZanniMV.OpenForumInfectDis.2017149PWHv.69matchedHIVnegativePWHhigherPCSK-9;PCKS-9assoc.withsCD14andsCD163(monocyteactivation)LDL-candFraminghamscorebutnotsubclinicalcoronaryatheroscleroticplaque
• BoccaraF.AIDS2017103PWHbeforeandafterstartingPIbasedARTv.90HIVnegativePWHhigherPCSK-9,nochangepre/postPIbasedARTPCSK-9assoc.withdetectableVLandCD4<200
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Question2:WhoisRecommendedtobeprescribedaspirin?
• 1.PWHonstatins• 2.PWHwithknownASCVD• 3.PWHaged40-75asprimaryprevention• 4.PWHaged40-75withACC/AHAriskscore5%
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
HypercoaguabilityinHIV
BibasMMediterrJHematolInfectDis2011
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
BackgroundASA• PWHonARThaveanincreasedriskofischemiccardiovascularevents• Activatedplateletshavebeenimplicatedinthromboticcardiovascularevents
becauseoftheirproinflammatoryandthrombogenic effects• PWHhaveincreasedcirculatingplatelet-monocytecomplexesandtheirplatelets
expresshighlevelsofP-selectin• Aspirinisalow-risk andlow-costplateletinhibitorthathasimmunomodulatory
properties• Aspirindecreasesriskofmortalityandcardiovasculareventsinindividualswith
knownCVDandmayplayanimportantroleincardiovascularandcancerpreventioninthoseatrisk
Refs:Triant etal.JID2012;205Suppl 3:5255-361.,Singhetal.2012;JVirol MethodsMay;181(2):170-6.,Mayneetal.JAIDS2012;59:340-346.,Berger,etal.AmJMed2012;12143-49.,Thunetal.NatRevClinOnc2012;9,259-267.,Hussainetal.Int Immunopharmacol 2012;12,10-20.
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
AspirinBenefits• Aspirinhasprovenbenefitsinsecondaryprevention• QuestionabletonobenefitsasprimarypreventionexceptinDM
– ARRIVE:over12,000ptsRCTasa 100mgvsplb over5years(Lancet2018;392:1036-1046)• Nosignificantdifferencesintheratesofdeaths,heartattacks,orstrokes• SignificantincreaseinGIB
– ASCEND:over15,000ptswithDMRCTover7.4years(NEnglJMed2018;379:1529-1539)
• Seriousvascularevents658participants[8.5%]vs.743[9.6%];rateratio,0.88;95%confidenceinterval[CI],0.79to0.97;P=0.01)
• Majorbleedingeventsoccurredin314participants(4.1%)intheaspiringroup,ascomparedwith245(3.2%)intheplacebogroup(rateratio,1.29;95%CI,1.09to1.52;P=0.003)
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
TakeHomePoints• ExcessCVDriskinHIV+population(1.5x)• Individualsagingwith HIVvs.IndividualsnewlydiagnosedwithdifferentCVDrisk
• LargestmodifiableRFissmoking• Etiologymultifactorial:chronicinflammation,directviraleffect,ARVsetc.
• TreatHIVandmanageco-morbiditiesaggressively• NeedforimprovedCVDriskassessment• Anydiabeticw/LDL>70shouldbeonastatinandpossibleaspirin(oftenoverlookedpopulationinHIVclinicalpractice)
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health ProfessionalsACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals