AssessmentandPrimaryPreventionofCAD

TuanD.Nguyen,M.D.Non-InvasiveCardiologySetonHeartInstitute

Objectives

•  IdentifyriskfactorsforCVdisease•  Identifypopulationsthatlikelybenefitfromcholesterolloweringmedicationsandassesstreatmentgoals

•  Selectappropriatetherapiesforlipidlowering•  Identifyadditionalriskstratificationtools•  “Powerslide”

BMI<25

<130/80

1-800-QUIT-NOW

40”,3-4x/weekWeighttraining

PLANT-basedLowsugar,saltLowsaturatedfat

HbA1c<6.5-7%

21+yo

ScreenCVriskfactors,checklipids(LDL)

ClinicalCVD(SecondaryPrevention)

Highintensitystatin(<75y.o.)

LDL190+(+FH)

Highintensitystatin

Age40-75,LDL70-189

Non-DM(PRIMARYPREVENTION)

10-yrRiskcalculation

7.5-20%:Shareddecision-making;Modintensitystatin(IIb)

>20%:Highintensitystatin(I)

5-7.5%:Shareddecision-making;*Consideradd’ltesting

DM-1/2

Mod-highintensityStatin

*LDL>160mg/dL*hs-CRP>2mg/L,HighLp(a),ApoB>130mg/dL*ABI<0.9*+FHx(M<65,F<55)*SouthernAsianancestry*Comorbidities(Metabolicsx,CKD,HIV,Rheumatologicd/o,prematuremenopause**CAC>100or75th%tile

2018ACC/AHAGuideline

Otherpopulations

•  Noformalrecommendations:– ESRD(maintenanceHD)– Non-IschemicCHF(NYHAII-IV)– Primarypreventionpatientsage>75(noclinicalASCVD)

Lipidmanagement

•  Focusonheart-healthyhabitsacrosslife-course

•  Shareddecision-makingprocess

Lipidmanagement

•  SecondarycausesofelevatedLDL•  Diet:Saturatedortransfats•  Drugs:Thiazidediuretics,BBl,cyclosporine,Amiodarone,Gluco-andandrogenicsteroids,proteaseinhibitors•  Diseases:Nephroticsyndrome,Biliaryobstruction,hypothyroidism,obesity,pregnancy

Lipidmanagement

•  ContinuedfocusonuseofHMGCo-Areductaseinhibitors(aka–statins)

•  Highintensity:LowersLDL50%+–  Rosuvastatin(Crestor)20-40mg–  Atorvastatin(Lipitor)40-80mg

•  Moderateintensitystatin:LowersLDL30-50%–  Simvastatin20-40mg–  Pravastatin40-80mg

Caveats•  Ifunabletotoleratehighintensity

•  Examples–  Previousstatinintolerance–  Severecomorbidities:Severehepaticorrenalimpairment–  Asianpopulation–  UnexplainedLFTS>3xULN–  Concomitantuseofdrugs(CytP450)effectingstatinmetabolism

–  >75y.o.•  Defaulttomoderateintensityorlowesttolerabledose

Non-statinmedications•  Lowerisbetter:CTTdata

–  Ezetimibe[Zetia]•  Additional20%reductioninLDL(-16mgdL)•  *Within30daysofACS

–  ModestbenefitinCVeventreduction(MI,CVA)–  Nochangein10yrall-causemortality

•  Usedincombinationwith–statins(unclearutilityasmono-therapy)•  PCSK-9MonoclonalAbs

*IMPROVE-IT

PCSK-9Inhibitors•  MonoclonalAbsagainstPCSK-9protein

–  Alirocumab[Praluent]orEvolocumab[Repatha]:SCinjection•  Nodoseadjustmentinmild-moderaterenal/hepaticimpairment

–  Adversereactions:Localinjectionsitereaction•  Nomuscleorhepatictoxicity(ie:myalgias)

–  Clinicalbenefit•  PCSK-9inhibitor+statin:Additional60%reductioninLDLvs.statinalone

•  StatisticallysignificantreductioninMIandCVA•  Mortalitybenefitsuggestedbymeta-analysis

Non-statinmedications•  Completestatinintolerance•  CombinationRxinpatientswithinadequateresponse– Highrisk(secondaryprevention):IfLDL>70mg/dL–  +FH:IfLDL>100

•  Notclinicallybeneficial–  ^Niacin:NoCVeventriskreduction

•  TrendtowardMSK/GIevents,infection,ischemicCVA,bleeding

–  *Fibrates:Nomortalitybenefit

^AIM-HIGH,HPS-2-THRIVE

*VA-HIT,HelsinkiHeart,FIELD,ACCORD-Lipid

BeyondLDL•  Hypertriglyceridemia

–  SecondarytargetinCVriskprevention•  Treatsecondarycauses

–  DM/metabolicsyndrome–  EtOHabuse–  CKD/ESRD/nephroticsyndrome–  Hypothyroid–  Meds(similartoLDLmedicationculprits)

•  Primaryprevention–  500+mg/dLèTreattopreventPancreatitisbeforeuseofLDLlowering

medication(Ic)–  *>150-199:O-3Fishoil

•  *Secondaryprevention–  >150-199èO-3Fishoil(PureEPA;Vascepa)–  ReductionofMACE

*REDUCE-IT

BeyondLDL

•  LowHDL:M<40mg/dL,F<50mg/dL– Stronglydeterminedbygenetics– *NoclinicalbenefittoraisingHDLwithexistingpharmacotherapies•  Cholesterylestertransferprotein(CETP)inhibitors•  Niacin

*Heartwire(Medscape),7/2014

BeyondLDL•  LowHDLè*LifestyleRx!

–  Diet•  Oliveoil(polyphenolshigherinEVOO)•  Coconutoil(2Tdaily;incorporatedindiet)•  Red/purplevegetables(anthocyaninsandanti-oxidantsineggplant,red

cabbage,blueberries/blackberries)•  Fattyfish(Omega-3fawith4x/wkconsumption:Salmon,herring,sardines,

mackerel)•  Lowercarbohydratediet(“Ketogenic”particularlyinpre-existingDM,Obese,

andMetabolicsyndrome)•  AVOIDartificialtrans-fats(“partiallyhydrogenated”)

–  Exercise(particularlyhighintensityexercise)–  Quittobacco(potentialbenefitofsimplyswitchingtovaporcigarettes)–  Weightloss(viaseveralmethodsofwtloss)

*Heartwire(Medscape),7/2014

Follow-up•  RecheckFLP4-12weeksfollowinginitiation– Routineq3-12monthreassessment

•  Follow-upvisits– Assesseffectivenessoftreatment

–  Assesscompliance/adherence–  Reinforcementtool–  Up-titrationifnecessary–  Assess/addressothersecondarycauses/lifestylechanges

– Assesssideeffects

Follow-up

•  CheckLFT’satbaseline– Noroutinecheckthereafter(unlesssignsofhepaticdysfunction)

•  CKnotroutinelychecked(unlessmusclesymptoms)

Statinsafety•  MAINconcern:Drug-druginteractions

–  NOTmetabolizedbyCytP450•  Pravastatin•  Pitavastatin[Livalo]

–  Simva,Atorva,Lova-statin:CYP3A4•  Avoidwith:

–  Trytoavoid/LOWdosewithDiltiazem,Verapamil(non-DHP)–  HIVPI–  -azole(antifungals)–  -mycin(MacrolideAbx)–  Gemfibrozil–  Grapefruitjuice

–  Simvastatin–  Maxdose10mg:Non-DHPCCB(Diltiazem,Verapamil)–  Maxdose20mg:Amiodarone,Ranolazine

Statinsafety•  Safetyinpregnancy

–  CategoryX:Recommenddiscontinuationpriortoconception–  Notrecommendedduringbreast-feeding

•  Myopathy*–  Myalgiasreported:5-29%%–  Myositis0.5%–  Rhabdomyolysis<0.1%–  Highestrisk:Renaldysfunction,hypothyroidism,liverdysfunction,concomitantmeds–  MeasurementofCK(ifmusclesymptoms)

•  Hepaticdysfunction–  0.5%-3%–  Dosedependent,andusuallywithinfirst4months–  Hepaticfailure:Incidencenodifferentfromgeneralpopulation–  2012FDAlabeling:BaselineLFTs,withrepeatmonitoringonlyifclinicallyindicated(notroutine)–  IfALT>3ULN,decreasedoseorchangestatin

•  DM–  AcceleratesdevelopmentofDMinpre-diabetics–  Assessrisk:benefit(althoughoverallbenefitofvasculareventreductionlikelyoutweighsrisk)

•  Cognition–  Datanotdefinitive–  Higherratesofconcernwithlipophilicstatins(atorva,simva)comparedtohydrophilic(prava,rosuva)

•  CA–  Nodatatosupportanincreasedrisk

*Pravastatinandfluvastatinlessintrinsicmuscletoxicity

Source:Uptodate

Pravastatin:DiminishedDMrisk

Statinsafety•  -StatinsassociatedwithLOWriskofadverseeffects

–  Seriousmuscleinjury<0.1%•  Myalgias5-29%•  10%willdiscontinue•  Incidenceofmusclesymptomsinstatinv.placebo-treated:<1%

–  >50%ptsalsohadsxw/placebo*

–  Serioushepatotoxicity<0.001–  Newlydx’dDM0.2%/year–  PotentialincreaseinhemorrhagicCVA–  NOcausalrelationship:

•  Cancer•  Cognitivedysfxn•  Cataracts,peripheralneuropathy,ED

•  “…benefitofreducingCVriskwithstatintherapyfaroutweighsanysafetyconcerns.”

AHAScientificStatement,12/2018,Arteriosclerosis,Thrombosis,andVascularBiology*GAUSS-3trial

CVRiskstratification

•  Asymptomaticadultscreeningexams•  ForCAD(CHDriskstratification)

–  Resting12-leadECG–  CalciumarteryscoreCT(“HeartHealthy”CT)–  ABIstudy(2ndline)–  Hs-CRP(2ndline)

•  ForAAA–  AbdominalaorticU/S

*Stresstesting(ETT,stress-echo,stress-Nuclear)NOTrecommendedscreeningtoolinasymptomaticadults

CoronaryarterycalciumCT(“HeartHealthy”CT)

•  M>40orF>45yo– 1Framinghamrisk(HTN,HLD,*FHx)– 5-20%CVeventriskbycalculator

•  Cashpaystudy– Widelyavailable/accessible

*Familyhxnotincludedinriskcalculators

ManagementofCVdisease:YesorNo?

Treatment/Test1.  Diet,exercise2.   Lipidmgmt.3.  HTNmgmt.4.  DMmgmt.5.  Tobaccocess6.  Carotiddoppler7.  AAAscreen8.  PADscreen(ABI)9.  Calciumscore10.  Lp(a),hs-CRP,apo-B11.  Stresstesting12.  Aspirin

•  PrimaryPrevention•  ABSOLUTELYYES•  YES*•  YES•  YES•  ABSOLUTELYYES•  NO•  YES(>65y.o.^)•  YES(riskstrat)•  YES(riskstrat)•  YES(riskstrat)•  NO•  ??

•  SecondaryPrevention•  ABSOLUTELYYES•  ABSOLUTELYYES*•  YES;ACEi,+/-BBl•  YES#•  ABSOLUTELYYES•  Symptom-driven•  YES/symptom-driven•  Symptom-driven•  NO•  NO•  Symptom-driven•  YES;Rivaroxaban

^Males>65yo+smoked100+cigarettesMalesorfemales>65yowitha+FHxofAAA

*Ezetimibe,PCSK-9,O-3fishoil(TG) #SGLT-2-I,GLP-1R-A

Summary•  ModifiableCVriskfactorsandhearthealthyhabits

–  Assessearly,often,andencourage/treataggressivelythroughoutlife

•  Identifythe4patientgroupsthatwouldbenefitfromlipidmanagement

•  Stillfocuson–statinsasworkhorsemedicationinlipidRx–  Ezetimibe,PCSK-9inhibitors,O-3fishoil

•  ConsideradditionalCVriskstratificationtoolsinmoreambiguousclinicalscenarios(ie:CACCT)

•  LipidmanagementandCVriskmanagement(similartoalltherapeuticdecisions)isneveranabsolutismè“shareddecision-makingprocess”