ACCAHA胆固醇新指南IAS血脂异常管理的全球建议解读课件

ACC/AHA胆固醇新指南、

IAS血脂异常管理的全球建议解读

ACC/AHA胆固醇新指南要点完全依据RCT证据聚焦胆固醇---LDL-C四个需他汀治疗人群ASCVDLDL-C>190mg/dlII型糖尿病40-75岁（LDL-C70-189mg/dl）10年ASCVD风险≥7.5%（LDL-C70-189mg/dl）三个他汀剂量强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%比中等强度剂量更小不同人群他汀剂量推荐ASCVDLDL-C>190mg/dlII型糖尿病（40-75岁）10年ASCVD风险≥7.5%大剂量中-大剂量两个不建议使用他汀人群心功能不全（心功能II-IV级）慢性肾功能不全一个用他汀需谨慎人群年龄≥75岁指南不适宜人群亚裔指南仅适用美国黑人白人设置警戒线LDL-C<40mg/dl不推荐他汀以外的调脂药物依折麦布贝特烟酸血脂康植物甾醇IAS建议Panel(15人）Chair:ScottM.Grundy美国Member：HidenoriArai日本 PhilipBarter澳大利亚IAS主席 ThomasP.Bersot美国 D.JohnBetteridge英国 RafaelCarmena西班牙 AdaCuevas智利 MichaelH.Davidson美国 JacquesGenest加拿大 Y.AnteroKesäniemi芬兰 ShaukatSadikot印度 RaulD.Santos巴西 AndreyV.Susekov俄罗斯 RodyG.Sy菲律宾 S.LaleTokgözoglu土耳其 GeraldF.Watts澳大利亚 DongZhao中国建议的证据基础流行病学研究遗传学研究临床试验（RCT）病理学研究药理学研究代谢研究较小规模临床试验临床试验的荟萃分析动物实验/基础研究RCT的局限性主要为药物试验，生活方式干预试验很少主要在欧美国家人群，其他人群较少入选标准/排除标准，研究对象的代表性局限大多数由制药企业赞助，主要为药物注册上市而非回答临床干预中的临床问题动脉粥样硬化--生活方式病基于流行病学而非RCT完全依赖RCT的指南重视药物，忽略生活行为二级预防：药物重要一级预防：生活方式干预/改变不健康生活习惯优先坚持百年胆固醇学说不动摇血清胆固醇水平↑

→

CHD风险↑血清胆固醇水平低→

CHD风险低降低血清胆固醇→降低CHD风险-RCT流行病学坚持百年胆固醇学说不动摇致动脉粥样硬化脂蛋白LDL一定程度升高---动脉粥样硬化/ASCVD必要条件LDL占致动脉粥样硬化脂蛋白75%Cholesterol-enrichedremnants(富含甘油三酯脂蛋白,即VLDL）25%TG升高时起作用较大VLDL中致动脉粥样硬化的组分是胆固醇，不是TGLDL浸润动脉壁--启动/促进动脉粥样硬化LDL-C增高单一因素即可致ASCVD家族性高胆固醇血症（FH）

（即使无任何其他危险因素）早发动脉粥样硬化和临床ASCVD

--BrownandGoldstein1976LDL水平低的人群即使存在其他危险因素

（吸烟、高血压、HDL↓、糖尿病）无早发ASCVD---Grundy等1990LDL升高是“源”其他危险因素是“流”LDL升高

到足以启动动脉粥样硬化程度其他危险因素促进加快动脉粥样硬化ASCVD预防必须聚焦LDL↓并保持终生低水平ASCVD的危险因素MajorriskfactorsEmergingriskfactorsUnderlyingriskfactorsMajorRiskFactors吸烟高血压HDL-C↓糖尿病EmergingRiskFactors

促炎症/促血栓状态

某些类型的血脂异常※与动脉粥样硬化及其并发症相关

与ASCVD的机制联系尚未完全清楚UnderlyingRiskFactors

致动脉粥样硬化饮食

肥胖

缺少身体活动

遗传倾向※产生Major/Emergingriskfactors的

基础---不健康的生活方式/行为AdvancingAge通常列为Majorriskfactor年龄本身不是动脉粥样硬化原因年龄常反应动脉硬化负荷一定年龄的动脉粥样硬化负荷程度明显因人而异年龄不是个体风险的准确指标ASCVD一级预防

降胆固醇

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.如何评估ASCVD风险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]根据长期风险降脂治疗强调风险程度至80岁的风险水平低（小于15%）中（15%-24%）中高（25%-40%）高（>40%）治疗强度--中度中高度高度特殊治疗公众健康指导充分生活方式治疗+降胆固醇药物，首选他汀可选充分生活方式治疗+降胆固醇药物，首选他汀，可考虑充分生活方式治疗+降胆固醇药物，首选他汀，适应证基于非脂质危险因素（吸烟/高血压）的风险较高年青患者

一级预防不一定强调降LDL-C药物

重点戒烟，控制高血压

强调具体的危险因素，而非总体风险中度风险人群

生活方式治疗应足以控制风险！

如LDL-C