ACCAHA膽固醇新指南IAS血脂異常管理的全球建議解讀課件

ACC/AHA膽固醇新指南、

IAS血脂異常管理的全球建議解讀

ACC/AHA膽固醇新指南要點(diǎn)完全依據(jù)RCT證據(jù)聚焦膽固醇---LDL-C四個(gè)需他汀治療人群ASCVDLDL-C>190mg/dlII型糖尿病40-75歲（LDL-C70-189mg/dl）10年ASCVD風(fēng)險(xiǎn)≥7.5%（LDL-C70-189mg/dl）三個(gè)他汀劑量強(qiáng)LDL-C↓≥50%阿托伐他汀80（40）；瑞舒伐他汀40,20中LDL-C↓30%-50%阿托伐他汀10（20），瑞舒伐他汀5，10；辛伐他汀20，40；普伐他汀40（80）；氟伐他汀80弱LDL-C↓<30%比中等強(qiáng)度劑量更小不同人群他汀劑量推薦ASCVDLDL-C>190mg/dlII型糖尿?。?0-75歲）10年ASCVD風(fēng)險(xiǎn)≥7.5%大劑量中-大劑量?jī)蓚€(gè)不建議使用他汀人群心功能不全（心功能II-IV級(jí)）慢性腎功能不全一個(gè)用他汀需謹(jǐn)慎人群年齡≥75歲指南不適宜人群亞裔指南僅適用美國(guó)黑人白人設(shè)置警戒線LDL-C<40mg/dl不推薦他汀以外的調(diào)脂藥物依折麥布貝特?zé)熕嵫抵参镧薮糏AS建議Panel(15人）Chair:ScottM.Grundy美國(guó)Member：HidenoriArai日本 PhilipBarter澳大利亞IAS主席 ThomasP.Bersot美國(guó) D.JohnBetteridge英國(guó) RafaelCarmena西班牙 AdaCuevas智利 MichaelH.Davidson美國(guó) JacquesGenest加拿大 Y.AnteroKes?niemi芬蘭 ShaukatSadikot印度 RaulD.Santos巴西 AndreyV.Susekov俄羅斯 RodyG.Sy菲律賓 S.LaleTokg?zoglu土耳其 GeraldF.Watts澳大利亞 DongZhao中國(guó)建議的證據(jù)基礎(chǔ)流行病學(xué)研究遺傳學(xué)研究臨床試驗(yàn)（RCT）病理學(xué)研究藥理學(xué)研究代謝研究較小規(guī)模臨床試驗(yàn)臨床試驗(yàn)的薈萃分析動(dòng)物實(shí)驗(yàn)/基礎(chǔ)研究RCT的局限性主要為藥物試驗(yàn)，生活方式干預(yù)試驗(yàn)很少主要在歐美國(guó)家人群，其他人群較少入選標(biāo)準(zhǔn)/排除標(biāo)準(zhǔn)，研究對(duì)象的代表性局限大多數(shù)由制藥企業(yè)贊助，主要為藥物注冊(cè)上市而非回答臨床干預(yù)中的臨床問題動(dòng)脈粥樣硬化--生活方式病基于流行病學(xué)而非RCT完全依賴RCT的指南重視藥物，忽略生活行為二級(jí)預(yù)防：藥物重要一級(jí)預(yù)防：生活方式干預(yù)/改變不健康生活習(xí)慣優(yōu)先堅(jiān)持百年膽固醇學(xué)說不動(dòng)搖血清膽固醇水平↑

→

CHD風(fēng)險(xiǎn)↑血清膽固醇水平低→

CHD風(fēng)險(xiǎn)低降低血清膽固醇→降低CHD風(fēng)險(xiǎn)-RCT流行病學(xué)堅(jiān)持百年膽固醇學(xué)說不動(dòng)搖致動(dòng)脈粥樣硬化脂蛋白LDL一定程度升高---動(dòng)脈粥樣硬化/ASCVD必要條件LDL占致動(dòng)脈粥樣硬化脂蛋白75%Cholesterol-enrichedremnants(富含甘油三酯脂蛋白,即VLDL）25%TG升高時(shí)起作用較大VLDL中致動(dòng)脈粥樣硬化的組分是膽固醇，不是TGLDL浸潤(rùn)動(dòng)脈壁--啟動(dòng)/促進(jìn)動(dòng)脈粥樣硬化LDL-C增高單一因素即可致ASCVD家族性高膽固醇血癥（FH）

（即使無任何其他危險(xiǎn)因素）早發(fā)動(dòng)脈粥樣硬化和臨床ASCVD

--BrownandGoldstein1976LDL水平低的人群即使存在其他危險(xiǎn)因素

（吸煙、高血壓、HDL↓、糖尿?。o早發(fā)ASCVD---Grundy等1990LDL升高是“源”其他危險(xiǎn)因素是“流”LDL升高

到足以啟動(dòng)動(dòng)脈粥樣硬化程度其他危險(xiǎn)因素促進(jìn)加快動(dòng)脈粥樣硬化ASCVD預(yù)防必須聚焦LDL↓并保持終生低水平ASCVD的危險(xiǎn)因素MajorriskfactorsEmergingriskfactorsUnderlyingriskfactorsMajorRiskFactors吸煙高血壓HDL-C↓糖尿病EmergingRiskFactors

促炎癥/促血栓狀態(tài)

某些類型的血脂異常※與動(dòng)脈粥樣硬化及其并發(fā)癥相關(guān)

與ASCVD的機(jī)制聯(lián)系尚未完全清楚UnderlyingRiskFactors

致動(dòng)脈粥樣硬化飲食

肥胖

缺少身體活動(dòng)

遺傳傾向※產(chǎn)生Major/Emergingriskfactors的

基礎(chǔ)---不健康的生活方式/行為AdvancingAge通常列為Majorriskfactor年齡本身不是動(dòng)脈粥樣硬化原因年齡常反應(yīng)動(dòng)脈硬化負(fù)荷一定年齡的動(dòng)脈粥樣硬化負(fù)荷程度明顯因人而異年齡不是個(gè)體風(fēng)險(xiǎn)的準(zhǔn)確指標(biāo)ASCVD一級(jí)預(yù)防

降膽固醇

控制accelatingriskfactorsMajorEmergingPublicHealthApproachestoPreventionPromotinglifestylebehaviorstopreventRiskfactorsIdentifying/treatingRiskFactorsSmokingHypertensionAtherogenicCholesterolLDL-Cornon-HDL-Cnon-HDL-C:morestronglyrelatedtoASCVDTC:lessreliableasatargetoftherapyoftenusedinriskassessmentalgorithHDLPowerfulindicatorofriskKeyroleinglobalriskassessmentHighHDL-CmayprotectagainstASCVDLowHDL-C--amajorriskpredictorofASCVDLifestyleInfluenceonLipoproteins/ASCVDPrevalenceofASCVDdiffersgreatlyindifferentregionsDueinparttogenetic/racialfactorsLifestyleinfluencespredominateLifestyleinfluencesDietTotalcaloricintakeBodyweightPhysicalactivitySmokingaffectLDLHealthylifehabitsadoption↓prevalenceofASCVD↓MajorTargetofTherapyMajorTarget:LDL-CAlternateTarget:non-HDL-CFuture:non-HDL-CwillreplaceLDL-CMajorTargetofTherapyWhynottotalapoB?CostLackofstandardizationLackofconsensusontreatingtargetAdvantageovernon-HDL-CissmallMajorTargetsofTherapyHDL-CUsefulasacomponentofglobalriskassessmentNotprimarytargetofdrugtherapyInterventionoflowHDL-CmainlythroughlifestyletherapiesOtherLipidRiskFactorsNotincorporatedintoriskassessmenttoolsUtility:limited/uncertainMeasurementsaddexpenseNotrecommendedforroutinetestingLp(a)atmoderatelyhigh/highASCVDriskOtherLipidRiskFactorsFastingTGUsefulforcalculatingLDL-ClevelsTG↑furthersupportuseofnon-HDL-CasatreatmenttargetOtherLipidRiskFactorsSmallDenseLipoproteinsDeterminationisanoptionButusefulnessinpredictionortherapyislargelysubsumedbynon-HDL-COtherLipidRiskFactorsTC/LDL-CratioAddsnothingtoglobalriskassessmentRatioisalreadypartofthelatterTG/HDL-CratioContainedinthemetabolicsyndromeOtherLipidRiskFactorsLp(a)↑SignifiesagreaterriskNeedformoreintensivemanagementofotherriskfactors,notablyatherogeniccholesterolHighLp-PLA2AppearstobepredictiveofASCVD;Butatpresent,testnotwidelyavailable.Non-LipidEmergingRiskFactorsC-reactiveprotein(CRP)Anoptioninpatientsatmoderatelifetimerisk.Reynoldsriskscore.如何評(píng)估ASCVD風(fēng)險(xiǎn)Short-term(10-years)riskassessmentwithmajorriskFactorsASCVD--1/3higherthanCHD2.Riskassessmentwithmajor+emergingriskfactorsMetabolicsyndromeTG(PROCAM)SmallLDLParticlesCRP(Reynoldsriskscore)RiskAssessmentbyAsImagingCoronaryarterycalcium-CACstronglycorrelatedwithcoronaryarteryplaqueburdenAddspredictivepowerwhencombinedwithFraminghamriskscoringCarotidarterysonographynotasmuchpredictivepowerforCHDusefulforidntificationforstrokeriskRiskAssessmentbyAsImagingCACCanbeusedasanadjuncttoriskfactorscoringinintermediaterisk(moderate-to-moderatelyhighpatientsCouldbeaguidetointensityofstatintherapyinthesePtsNotwidelyavailableandisrelativelyexpensiveAppropriateapplicationnotwellunderstoodbymostphysicians※NOTapartofROUTINETESTLimitationof10-yearriskassessment1.Purposeofprimarypreventionistoreducelifetimerisk,not10-yearrisk.2.Estimatesof10-yearriskunderestimatelifetimeriskexceptintheelderlyLong-termriskassessment

lifetimeriskEstimationLloyd-Jones/FraminghamRiskAlgorithmRiskFactorMinor*Moderate*MajorCholesterol(mg/dL)180-199200-239>240SystolicBP(mmHg)120-139140-159>160Cigarettesmoking00+++Diabetes00+++TotalCVDmorbiditybyage80fromage50(Lloyd-Jones）RiskforCVDMorbiditybyAge80RiskFactorMenWomenNone5%8%≥1minor25%10%≥1moderate38%22%1major45%25%≥2major60%45%Long-termRiskforASCVDbyage80(fromage50)Long-RiskCategoryAbsoluteRiskforASCVDLow<15%Moderate15-30%Moderatelyhigh30-44%High>45%RiskassessmentcalibrationRiskfactorsaffecttotalriskdifferentlyinvariouspopulations.DifferencesinbaselinepopulationriskInherentriskofapopulationbeyondtraditionalriskfactorsAdjustriskscoringfordifferentpopulationsRecalibrateFraminghamscoringforseveralpopulationsFraminghamscoringSimilarlypredictedCHDriskinwhitesandblacksOver-predictedriskinseveralEuropeancountriesandinChinaCorrectlyestimatedriskinruralIndiansbutunder-predictedriskinurbanIndiansItaly,China,andJapanBaselinepopulationriskappearstobeunusuallylowLifetimeofrelativelylowLDL-ClevelsHypertension--dominantriskfactorStrokeincidence>CHDFHSRecalibrationCoefficientsforCHDChina0.36JapaneseAmerican0.50Germany0.43France0.41Italy0.37Germany0.43Korean1.02(male)0.96(female)UrbanIndia1.81(male)1.54(female)PrimaryPrevention(lifetime)LDL-C/non-HDL-C理想水平LDL-C<100mg/dL(2.6mmol/L)non-HDL-C<130mg/dL(3.4mmol/L)PopulationEpidemiologicalstudiesGeneticstudiesClinicaltrialsPrimaryPrevention(lifetime)OptimallevelsofLDL-C--especiallydesirableinhigh-riskpopulations.Near-optimallevels--acceptableinlow-riskpopulationsorinindividualswithapaucityofotherriskfactors.LDL-C<100-129mg/dL[2.6-3.3mmol/L]

或non-HDL-C<130-159mg/dL[3.4-4.1mmol/L]根據(jù)長(zhǎng)期風(fēng)險(xiǎn)降脂治療強(qiáng)調(diào)風(fēng)險(xiǎn)程度至80歲的風(fēng)險(xiǎn)水平低（小于15%）中（15%-24%）中高（25%-40%）高（>40%）治療強(qiáng)度--中度中高度高度特殊治療公眾健康指導(dǎo)充分生活方式治療+降膽固醇藥物，首選他汀可選充分生活方式治療+降膽固醇藥物，首選他汀，可考慮充分生活方式治療+降膽固醇藥物，首選他汀，適應(yīng)證基于非脂質(zhì)危險(xiǎn)因素（吸煙/高血壓）的風(fēng)險(xiǎn)較高年青患者

一級(jí)預(yù)防不一定強(qiáng)調(diào)降LDL-C藥物

重點(diǎn)戒煙，控制高血壓

強(qiáng)調(diào)具體的危險(xiǎn)因素，而非總體風(fēng)險(xiǎn)中度風(fēng)險(xiǎn)人群

生活方式治療應(yīng)足以控制風(fēng)險(xiǎn)！

如LDL-C