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ATPIII:NewApproachesinIdentifyingandTreatingHigh-RiskPatientsStevenHaffner,MD0.01.02.03.04.05.06.0Hospi

talizationforMIHasNotDeclinedHospitalizationforMI(per1,000)**Age-adjusted19871989199019921988199319941991Rosamon

dWDetal.NEnglJMed1998;339:861-867.©1998MassachusettsMedicalSociety.Allrightsreserved.MenWomenCriteriaforAcceptingC

ardiovascularRiskFactorManagementasSimilarinCHDEquivalentsasinCHDPatients1.TheriskofvasculardiseaseissimilarinCHDequivalentsandinpatient

swithCHD.2.LipidinterventionstoreduceCHDcanbeequallyeffectiveinCHDequivalentandCHDpatients.3.Indiabeticpatients,glycemiaalonewillnotcompl

etelyeliminatetheexcessCHDrisk.NewCHDRiskEquivalents◼>20%10-yearriskofCHD(Framinghamprojections)◼Diabetes◼Otherformsofclinicalatheroscleroticdiseas

e:–Peripheralarterialdisease–Abdominalaorticaneurysm–CarotidarterydiseaseExpertPanelonDetection,Evaluation,andTreatme

ntofHighBloodCholesterolinAdults.JAMA2001;285:2486-2497.NoncoronaryAtherosclerosis:Overview◼Atheroscleroticdiseaseinoneregionofthearterialtreei

sassociatedwithandpredictsdiseaseinotherarterialregions–Pathobiologyandpredisposingriskfactorsaresimilarfora

therosclerosisincoronary,peripheral,andcarotidarteries◼Thus,clinicalatheroscleroticdiseaseinnoncoronaryarteriesisapowerfulpredictorofCHDPeri

pheralArterialDisease(PAD)◼StudiesofpatientswithatheroscleroticPADsupporttheconceptthatPAD,regardlessofdiagnosi

sbyABI,lowerlimbbloodflowstudies,orclinicalsymptoms,isaCHDriskequivalentEdinburghArteryStudy◼Ankle/brachialbloodpress

ureindex(ABI)inrandomlyselectedpopulation,5-yearfollow-up◼1592menandwomen,614withCHD,aged55–74◼137fatalandnonfatalCHDeventsduringfollow-up>1.11.1

–1.011.0–0.910.9–0.71<0.7ABICHDEventOutcomesperYear(%)LengGCetal.BMJ1996;313:1440-1444.1.4%3.8%01234AbdominalAor

ticAneurysm(AAA)◼Studypopulation:300menand43women(aged45–89)operatedonforAAA,separatedinto4groupsbasedonpreoperativeCHDhisto

ryandECG◼Follow-up:6–11years◼Results:annualCHDmortality–1.9%inpersonswithnosymptoms,nopriorhistoryofCHD,andnormalECG(31%)–2.0%in

personswithnosymptoms,butpreviousMIbyECG(33%)–3.9%inpersonswithangina/priorMI(30%)◼BecausetherateofCHDevent

sisatleasttwicethatofCHDmortality,patientswithnoprevioushistoryofCHDeventswouldfallintotheCHDriskequivalentcategoryHertzerNR.Ann

Surg1980;192:667-673.CarotidArteryDisease:Symptomatic◼NorthAmericanSymptomaticCarotidEndarterectomyTrial(NASCET)–Symptomaticpatientsundergoingcaro

tidendarterectomyhadanaverage10-yearCHDmortalityof19%◼EuropeanCarotidSurgeryTrial(ECST)–Symptomaticpatientshadver

yhighdeathratesfromnonstrokevasculardiseaseregardlessofthepercentofcarotidarterystenosisattheonset–72%ofdeathswereduetononstrokevasculardiseaseandthu

s10-yearCHDdeathisestimatedat30%FergusonGGetal.Stroke1999;30:1751-1758.|BarnettHJetal.NEnglJMed1998;339:1415-1425.|ECSTCollab

orativeGroup.Lancet1998;351:1379-1387.◼MayoAsymptomaticCarotidAtherosclerosisStudy–Subjects—158patients,40%withhistoryofCAD,15%di

abetic–Diseaseseverity—Asymptomaticstenosis50%—TrialstoppedbecauseofhighMIandTIAeventrateinsurgicalarmsecondarytoc

essationofmedicaltherapy(aspirin)–CHDevents—After2.5-yearfollow-up:12CHDevents—Estimated10-yearCHDeventrate=30%Exe

cutiveCommitteefortheAsymptomaticCarotidAtherosclerosisStudy.JAMA1995;273:1421-1428.CarotidArteryDisease:AsymptomaticHeartProtectionStudy:Vascula

rEventsbyBaselineDiseaseBaselinefeatureSimvastatin(n=10,269)Placebo(n=10,267)PreviousMI10071255OtherCHD(notMI)9141234No

priorCHDCVD182215PVD332427Diabetes279369Allpatients2042(19.9%)2606(25.4%)CollinsR.PresentedatAHA,Anaheim,California,13November2001

.Riskratioand95%CIStatinbetterStatinworse24±2.6%(2P<0.00001)0.40.60.81.01.21.4-50-40-30-20-1001020*Innationals

ampleofadultsinNHANESI(1971–75)andNHANESII(1982–84).GuKetal.JAMA1999;281:1291-1297.ChangesinCHDMortalityRatesinPatientswithandwithoutDiabetes*%C

hangeinMortality–16.610.7–43.8–20.4NondiabeticsDiabeticsP=0.46P=0.76P=0.001P=0.12MenWomenMenWomenCVDDeathRate/10,000PersonYears

(Age-Adjusted)StamlerJetal.DiabetesCare1993;16:434-444.MRFIT:DiabetesAmplifiesRiskfromOtherRiskFactorsNo.ofAdditio

nalRFs*NoDiabetesDiabetes01236311259229147125*TC>200mg/dLSBP>120mmHgCurrentsmoker020406080100120%Mor

talityMenMiettinenHetal.DiabetesCare1998;21:69-75.1-YearMortalityinDiabeticandNondiabeticSubjectsafteraFirst

MIWomenDiabetesNoDiabetesDiabetesNoDiabetes01020304050Hospitalization–28d28d–1yOutofhospital28.611.05.522.17.53.010.920.07.611.97.92.20

1020304050HaffnerSMetal.NEnglJMed1998;339:229-234.IncidenceofMIduringa7-YearFollow-upinaFinnishPopulationFatalo

rNonfatalMI(%)PriorMI18.83.545.020.2P<0.001P<0.001PriorMINopriorMINopriorMINondiabeticsubjectsDiabeticsubjects(n=1373)(n=1059)0.000.

050.100.150.200.25OASISStudy:TotalMortalityEventRateMonths69153182112RR=2.88(2.37–3.49)MalmbergKetal.Circulat

ion2000;102:1014-1019.©2000LippincottWilliams&Wilkins.24RR=1.99(1.52–2.60)RR=1.71(1.44–2.04)RR=1.00Diabetes/CVD(n=1148)NoDi

abetes/CVD(n=3503)Diabetes/NoCVD(n=569)NoDiabetes/NoCVD(n=2796)StudyDrugNo.BaselineLDL-C,mg/dl(mmol/L)LDL

-CLoweringPrimaryPreventionAFCAPS/TexCAPSLovastatin155150(3.9)25%HPSSimvastatin3985127(3.3)30%SecondaryPrevent

ionCAREPravastatin586136(3.6)28%4SSimvastatin202186(4.8)36%LIPID*Pravastatin782150(3.9)25%HPSSimvastatin197812

7(3.3)30%CHDPreventionTrialswithStatinsinDiabeticSubjects:SubgroupAnalyses*LDL-CvaluesforoverallgroupDownsJRetal.JAMA

1998;279:1615-1622.|HPSInvestigators.PresentedatAHA,2001.|GoldbergRBetal.Circulation1998;98:2513-2519.|PyoralaK

etal.DiabetesCare1997;20:614-620.|HaffnerSMetal.ArchInternMed1999;159:2661-2667.|LIPIDStudyGroup.NEnglJMed1998;339:1349

-1357.StudyDrugNo.CHDRiskReduction(overall)CHDRiskReduction(diabetics)PrimaryPreventionAFCAPS/TexCAPSLovastatin15537%43%(

NS)HPSSimvastatin398524%26%(p<.00001)SecondaryPreventionCAREPravastatin58623%25%(p=.05)4SSimvastatin20232%55%(p=.002)LIPIDPravastat

in78225%19%4SReanalysisSimvastatin48332%42%(p=.001)HPSSimvastatin197824%unreportedCHDPreventionTrialswithStatinsinDiabeti

cSubjects:SubgroupAnalyses(cont’d)DownsJRetal.JAMA1998;279:1615-1622.|HPSInvestigators.PresentedatAHA,2001.|GoldbergRBeta

l.Circulation1998;98:2513-2519.|PyoralaKetal.DiabetesCare1997;20:614-620.|LIPIDStudyGroup.NEnglJMed1998;339:1349-1357.|HaffnerSMetal.Arc

hInternMed1999;159:2661-2667.StudyDrug(dose)No.BaselineLDL-C,mg/dl(mmol/L)LDL-CLoweringCHDReductionPrimaryPreventionHe

lsinkiHeartStudyGemfibrozil(1200mg/d)135203(5.2)6%68%NSSecondaryPreventionVA-HITGemfibrozil(1200mg/d)627112*(2.9*)–24%P=.05DAISFenofibr

ate(200mg/d)4181306%23%NSCHDPreventionTrialswithFibratesinDiabeticSubjects:SubgroupAnalyses*MedianvalueKoskinenPetal.DiabetesCare1992;15:820-825.|

RubinsHBetal.NEnglJMed1999;341:410-418.|DAISInvestigators.Lancet2001;357:905-910.AdlerAIetal.BMJ2000;321:412-419.|StrattonIMetal.BMJ2000;321:405

-412.ReprintedwithpermissionfromtheBMJPublishingGroup.Adjustedincidenceper1000person-years(%)UpdatedmeanHbA1cconcentration(%)UpdatedmeansystolicBP(

mmHg)02040608001020304050Adjustedincidenceper1000person-years(%)567891011110120130140150160170MIMicrovascularendpointsMi

crovascularendpointsMIMIandMicrovascularEndPoints:IncidencebyMeanSystolicBPandHbA1cConcentrationinUKPDSSumma

ry:DiabetesasaCHDRiskEquivalent◼ImpliesthatenhancedbenefitwillbeachievedfromaggressiveLDL-loweringtherapy◼Post-hocanalys

isofallstatintrialsshowedatrendforbenefitofLDLloweringinpersonswithdiabetesATPIII:ManagementofDiabeticDyslipidemia◼Primarytargetoftherapy

:LDL-C◼Diabetes:CHDriskequivalent◼Therefore,goalforpersonswithdiabetes:<100mg/dL◼Therapeuticoptions:–LDL-C100–129mg

/dL:increaseintensityofTLC;adddrugtomodifyatherogenicdyslipidemia(fibrateornicotinicacid);intensifystatintherapy–LDL-C1

30mg/dL:simultaneouslyinitiateTLCandLDL-C–loweringdrugs◼AfterLDL-Cgoalismet,ifTG200mg/dL:non–HDL-C(<130mg/dl)becomessecondarytargetExpertPan

elonDetection,Evaluation,andTreatmentofHighBloodCholesterolinAdults.JAMA2001;285:2486-2497.TheMetabolicSyndrome

◼MetabolicsyndromeisasecondarytargetoftherapyinATPIII.◼Primaryinterventionsarebehavioral,withpharmacologicalagentssuggestedtotreatcomponentssucha

shypertensionanddyslipidemia.◼Componentsofthemetabolicsyndromehavebeenshowntobestronglypredictiveofcardiovasculardi

sease.1◼Althoughinsulinconcentrationsstronglypredictthedevelopmentofmultiplemetabolicdisorders2andcardiovasculardisease,3insu

linresistanceispresentinonlyoneortwocomponentsintheFraminghamStudy.4,51IsomaaBetal.DiabetesCare2001;24:683-689.2

HaffnerSMetal.Diabetes1992;41:715-722.3PyoralaMetal.Circulation1998;98:398-404.4MeigsJB.AmJEpidemiol2000;152:908-911.5MeigsJB

etal.Diabetes1997;46:1594-1600.ATPIII:TheMetabolicSyndromeDiagnosisisestablishedwhen3oftheseriskfactorsarepresent.ExpertPanelonDetection,Evalua

tion,andTreatmentofHighBloodCholesterolinAdults.JAMA2001;285:2486-2497.RiskFactorDefiningLevelAbdominalobesity(Waist

circumference)MenWomen>102cm(>40in)>88cm(>35in)TG150mg/dLHDL-CMenWomen<40mg/dL<50mg/dLBloodpressure130/85mmHgFastingglucose110mg/dLComparisonof

ATPIIIRiskFactorCountingandtheMetabolicSyndromeRiskFactorRiskFactorCountingMetabolicSyndromeAbdominalobesityMe

nWomenNotincluded>102cm>88cmTGNotincluded*150mg/dLHDL-CMenWomen<40mg/dL<40mg/dL<40mg/dL<50mg/dLBloodpressure140/90m

mHg130/85mmHgFastingglucoseNotincluded†110mg/dL‡*TG200mg/dLpartofcriteriatodeterminewhethernon-HDL-Cshouldbetargeted.†Diabe

tesisaCHDriskequivalent.‡DiabetesplusIFG.ExpertPanelonDetection,Evaluation,andTreatmentofHighBloodCholester

olinAdults.JAMA2001;285:2486-2497.ComparisonofATPIIIRiskFactorCountingandtheMetabolicSyndrome(cont'd)RiskFactorRiskFactorC

ountingMetabolicSyndromeCigarettesmokingIncludedNotincludedFamilyhistoryofCHDIncludedNotincludedAgeMen(45)Women(55)IncludedIncludedNotincluded

NotincludedNegativeriskfactorHDL60mg/dLIncludedNotincludedExpertPanelonDetection,Evaluation,andTreatmentofHighBloodC

holesterolinAdults.JAMA2001;285:2486-2497.BaselineInsulinDisorderLow(%)High(%)RelativeRiskPValueHypertension5.5

11.42.040.21Hypertriglyceridemia2.68.93.46<.001LowHDL-C16.226.31.630.012HighLDL-C16.420.11.230.223Type2dia

betes2.212.35.62<.001RelationshipofFastingInsulinLevelstoRelativeRiskforMultipleMetabolicDisorders:SanAntonioHeartStudyHaffnerSMetal.Diabetes1

992;41:715-722.RiskofMajorCHDEventAssociatedwithInsulinQuintilesinNondiabeticSubjects:HelsinkiPolicemenStudy0

.700.750.800.850.900.951.00Years5102001525PyoralaMetal.Circulation1998;98:398-404.©1998LippincottWilliams&Wilkins.Logrank:OverallP=.001Q5vs

.Q1P<.001Q1Q2Q3Q4Q5ProportionwithoutMajorCHDEvent0ClinicalManagementofMetabolicSyndrome◼Managementofunderlyingcauses–WeightcontrolenhancesLDL

loweringandreducesallriskfactors–PhysicalactivityreducesVLDLandLDLandincreasesHDL◼Treatlipidandnonlipidriskfactors–Hypertension–AspirininCHDpatient

s–Elevatedtriglycerides–LowHDLExpertPanelonDetection,Evaluation,andTreatmentofHighBloodCholesterolinAdults.JAMA2001;285:2486-2497.MultipleRiskFactor

s:AdditiveRiskThetotalseverityofmultiplelow-levelriskfactorsoftenexceedsthatofasingleseverelyelevatedriskfactor.8%GrundySMetal.JAmCollCardiol1999;34

:1348-1359.BP165/95mmHgBP165/95mmHgAge56yearsBP165/95mmHgAge56yearsLDL-C155mg/dLBP165/95mmHgAge56yearsLDL-C155mg/dLSmoker13%19%27%051015202530MeanAbs

oluteRisk(%)CHDRiskEquivalentSummary◼PatientswithestablishedCHDhaveariskforrecurrentMIandCHDdeaththatexceeds20%per10years.Clinicallyevidentnonco

ronaryatherosclerosis,aswellastype2diabetesmellitus,imposeanapproximatelyequalriskfordevelopingCHDinp

atientswithoutclinicalCHD.◼CHDriskequivalents:–Multipleriskfactors(>20%10-yearCHDrisk)–Type2diabetesmellitus–Peripheralarterialdisea

se–Abdominalaorticaneurysm–CarotidarterydiseaseExpertPanelonDetection,Evaluation,andTreatmentofHighBloodCholestero

linAdults.JAMA2001;285:2486-2497.ClassificationofSerumTriglyceridesTriglycerideCategoryATPIILevelsATPIIILevelsNormal<200mg/dL<150mg/dLBorde

rline-high200–399mg/dL150–199mg/dLHigh400–1000mg/dL200–499mg/dLVeryhigh>1000mg/dL500mg/dLExpertPanelonDetection,Evaluation,andTreatmentofHighBlood

CholesterolinAdults.JAMA1993;269:3015-3023.|ExpertPanelonDetection,Evaluation,andTreatmentofHighBloodCholesterolinAdults.JA

MA2001;285:2486-2497.RationaleforChangeintheCategorizationofTriglycerideLevelsinATPIII◼ATPIIIgivesadditionalemphasist

omoderateelevationsoftriglycerides(150–200mg/dL)forthefollowingreasons:–Newmeta-analysissuggeststhatraisedtr

iglyceridelevelsmaybeanindependentriskfactorforCHD.1–2–Elevatedtriglyceridesareassociatedwithcomponentsofthemetabolicsyndromesuchasglu

coseintolerance,lowHDL,inflammation,andprothromboticstate.3–Subjectswithmodestlyelevatedtriglyceridelevelshaveatherogenicremnantlipoproteins.3◼In

creasedtriglyceridesarenotaspecifictargetforinterventioninATPIIIbutenterintothedeterminationofwhethertot

argetnon-HDL-C.1AustinMA.CanJCardiol1998;14:14B-17B.2AssmannGetal.EurHeartJ1998;19:M8-M14.3GrundySM.AmJCardiol1998;81:18B-25B.Cla

ssificationofSerumHDL-CLevelsHDL-CCategoryATPIILevelsATPIIILevelsLowHDL-C<35mg/dL<40mg/dLHighHDL-C60mg/dL60mg/dLExpertPane

lonDetection,Evaluation,andTreatmentofHighBloodCholesterolinAdults.JAMA1993;269:3015-3023.|ExpertPanelonDetection,Evaluation,andTreatme

ntofHighBloodCholesterolinAdults.JAMA2001;285:2486-2497.RationaleforChangeintheLowHDL-CCategoryintheATP

IIIGuidelines◼TheinverseassociationbetweenHDL-CconcentrationsandCHDriskiscontinuous;nothresholdrelationshiphasbeenidenti

fied.Clearly,lowHDL-ClevelspredictCHDatlevelsabove35mg/dL.1◼WomentypicallyhavehigherHDL-Clevelsthanmen,andacutpointof<40mg/dLwil

lidentifymorementhanwomenwithlowHDL-C,i.e.,approximatelyone-thirdofmenandone-fifthofwomeninthegeneralpopulation.1Wi

lsonPWetal.Circulation1998;97:1837-1847.AtherogenicParticlesApolipoproteinBNon-HDL-CMEASUREMENTS:TG-richlipoproteins

VLDLVLDLRIDLLDLSmall,denseLDLAtherogenicLipoproteins◼Non-HDL-C=TC–HDL-C◼Canbeaccuratelymeasuredinnonfastingstate◼ApoBconcentrationrepresentst

otalnumberoflipoproteinparticles(LDL+IDL+VLDL)◼Thismaybecalled“non-HDL”cholesterolor“atherogeniccholesterol”GrundySM.Circulation1997;95:1-

4.CuiYetal.ArchInternMed2001;161:1413-1419.LRCFollow-upStudy:CVDMortalitybyNon-HDL-CandLDL-CinMenLRC=LipidRe

searchClinics;RR=Relativerisk;CI=confidenceinterval.00.250.500.751.001.251.501.752.002.252.502.753.00RRwith95%CINon-HDL-C(mg/dL)Rate/10,000<16

038.0160to<19043.0190to<22053.922080.6LDL-C(mg/dL)<13040.2130to<16048.2160to<19054.919071.3CuiYetal.ArchInternMed2

001;161:1413-1419.LRCFollow-upStudy:CVDMortalitybyNon-HDL-CandLDL-CinWomenLRC=LipidResearchClinics;RR=Relativerisk;CI=

confidenceinterval.00.501.001.502.002.503.003.504.00RRwith95%CINon-HDL-C(mg/dL)Rate/10,000<16017.6160to<19026.5190to<22029.

222051.3LDL-C(mg/dL)<13025.4130to<16022.8160to<19027.719040.1CorrelationCoefficientsbetweenApoBandLD

L-CorNon-HDL-CatWeek54:ACCESSBallantyneCMetal.AmJCardiol2001;88:265–269.©2001,Reprintedwithpermission

fromExcerptaMedicaInc.Non-HDL-CandapoBLDL-CandapoBAllpatients0.9380.849BaselineTGstratumTG<150mg/dLTG150–250mg/dLTG>250mg/dL0.9460.9440.90

00.9220.8850.805ATPIIriskcategory<2RFwithoutCHD2RFwithoutCHDCHD0.9080.9360.9290.8550.8350.810Allpvalues<0.0001.Non-H

DL-CGoalsinPatientswithTG200mg/dLRiskcategoryNon-HDL-Cgoal(mg/dL)CHDorCHDriskequivalents(10-yrrisk>20%)<1302+riskfactors(10-yrrisk20%)<1600–1r

iskfactor<190ExpertPanelonDetection,Evaluation,andTreatmentofHighBloodCholesterolinAdults.JAMA2001;285:2486-2497.Summary:IdentifyingandTreatingHigh-

RiskIndividuals◼Increasednumberofpatientswith"CHDequivalent"withLDL-Cgoal<100mg/dL◼NewcriteriaforHDL-C,TG,andthemetabolicsy

ndrome◼Newtargetsfornon-HDL-CinpatientswithTG200mg/dL谢谢您的聆听与观看THANKYOUFORYOURGUIDANCE.感谢阅读！为了方便学习和使用，本文档的内容可以在下载后随意修改，调整和打印。欢迎下载

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