控制糖尿病患者心血管危險(xiǎn)的干預(yù)治療策略

控制糖尿病患者心血管危險(xiǎn)的干預(yù)治療策略第1頁/共29頁糖尿病與心血管危險(xiǎn)影響心血管危險(xiǎn)的因素綜合控制的理論與實(shí)踐第2頁/共29頁CountriesWithHighestNumbersofEstimatedCasesofDiabetesfor2000and2030RankingCountryPeoplewithdiabetes(millions)CountryPeoplewithdiabetes(millions)200020301 India 31.7 India 79.42 China 20.8 China 42.33 U.S. 17.7 U.S. 30.34 Indonesia 8.4 Indonesia 21.35 Japan 6.8 Pakistan 13.96 Pakistan 5.2 Brazil 11.37 RussianFederation 4.6 Bangladesh 11.18 Brazil 4.6 Japan 8.99 Italy 4.3 Pinecones 7.810 Bangladesh 3.2 Egypt1 6.7Total:177million366MILLIONBY2030第3頁/共29頁Type2diabetesandCHD

7-YearIncidenceofFatal/NonfatalMI(EastWestStudy)

IncidenceDuringFollow-up(%)(n=69)NondiabeticswithpriorMINondiabeticswithnopriorMIDiabeticswithpriorMIDiabeticswithnopriorMI18.8HaffnerSMetal.NEnglJMed1998;339:229-234.(n=1304)(n=169)(n=890)3.00.57.83.23.545.020.2Eventsper

100person-yr:P<0.001p<0.001第4頁/共29頁Type2diabetesandStroke

7-YearIncidenceofFatal/NonfatalStroke(EastWestStudy)IncidenceDuringFollow-up(%)(n=69)NondiabeticswithpriorMINondiabeticswithnopriorMIDiabeticswithpriorMIDiabeticswithnopriorMI7.2HaffnerSMetal.NEnglJMed1998;339:229-234.(n=1304)(n=169)(n=890)1.20.33.41.61.919.510.3Eventsper

100person-yr:P=0.01p<0.001第5頁/共29頁P(yáng)revalenceofCHDbytheMetabolicSyndromeandDiabetesintheNHANESPopulationAge50+AlexanderCetal.Diabetes2003;52:1210-121425%20%15%10%5%0%NoMS/NoDM8.7%13.9%7.5%19.2%MS/NoDMDM/NoMSDM/MS%ofpopulation= 54.2% 28.7% 2.3% 14.8%CHDPrevalence第6頁/共29頁1.00.90.80.70.60.00246810Follow-up,years#atrisk174214099062828935NometabolicsyndromeMetabolicsyndromelog-rank=45.4p<0.001Event-freesurvivalSchillaciG.JACC.2004;43:1817-1822代謝綜合征與心血管危險(xiǎn)第7頁/共29頁MlandMicrovascularEndPoints:IncidencebyMeanSystolicBPandHbA1cConcentrationMlMicrovascularandpointsMlMicrovascularandpoints50403020100806040200Adjustedincidenceper1000person-yr(%)110120130140150160170567891011UpdatedmeansystolicBP(mmHg)UpdatedmeanHbA1cconcentration(%)Adjustedincidenceper1000person-yr(%)AdlerAletal.BMJ2000;321:412-419StrationIMetal.BMJ2000;321:405-412第8頁/共29頁MetS和DM患者血脂異常特征游離脂肪酸TGHDL-C

VLDL-C

小而密LDL顆粒氧化LDL-C餐后高脂血癥第9頁/共29頁MaleGender-adjustedFemaleReducedriskwithsmall,denseLDL0.1Relativeriskformyocardialinfarction110Increasedriskwithsmall,denseLDLSmall,denseLDLincreases

cardiovascularrisk第10頁/共29頁UKPDS

StepwiseSelectionofRiskFactors*inPatientswithType2Diabetes

VariableLDL-CHDL-CHemoglobinA1cSystolicBloodPressureSmokingPValue<0.00010.00010.00220.00650.056CoronaryArteryDisease(n=280)PositioninModelFirstSecondThirdFourthFifth*Adjustedforageandsex.TurnerRCetal.BMJ1998;316:823-828.第11頁/共29頁Mangagingoverweightintype2diabeticsEffectiveweightmanagementisthefirststepintreatingtype2diabetesWeightloss(kg)infirst12monthsLeanMEJetal.,DiabetMed,1990;7:228-233Lifeexpectancy(years)95%confidenceinterval1816141210800481216第12頁/共29頁GoodglycemiccontrolisnotenoughUKPDSGOODGLYCEMICCONTROLMICROVASCULARCOMPLICATIONSSignificantreductionsMACROVASCULARCOMPLICATIONSNosignificanteffect第13頁/共29頁P(yáng)ROACTIVEStudySept.2005,

歐洲糖尿病會議

PioglitazonevsPlacebo第14頁/共29頁ACCORDStudyActiontoControlCardiovascularriskinDiabetesPrisantLM.JClinPharmacol2004;44(4):423-430HbA1c:≤6.0%vs7.0-7.9%第15頁/共29頁

糖尿病患者降壓治療臨床試驗(yàn)SHEPALLHATSYST-EURHOPECAPPPHOTNORDILRENAALSTOP-2PRIMEINSIGHTLIFEUKPDS

第16頁/共29頁Majorcardiovascularevents(per100patients-years)inalltreatedhypertensiveandinhypertensivepatientswithdiabetesinrelationtotargetbloodpressuresof90.85,and80mmHg.302520151050808590908580P=0.50fortrendP=0.005fortrendAllhypertensivepatients(n=18790)Hypertensivewithdiabetes(n=1501)TargetbloodpressuregroupsMajorcardiovascularevents/1000patients-yearsHOTStudy:ResultsinPatientswithDM第17頁/共29頁EffectofIntensivevsModerateAntihypertensiveTreatmentonStrokeIncidenceinDiabeticNormotensives Intensive ModerateAchievedBP(mmHg) 128/75 137/81Stroke(%) 1.7 5.4P=0.03Schrieretal.,KidneyInt2002;61:1086第18頁/共29頁CHDPreventionTrialswithStatinsinDiabeticSubjects

SubgroupAnalyses

PrimaryPreventionAFCAPS/TexCAPSSecondaryPreventionCARE4SLIPID4S-ExtendedCHDRisk

Reduction

(overall)DrugNo.LovastatinPravastatinSimvastatinPravastatinSimvastatin43%25%(p=0.05)55%(p=0.002)19%42%(p=0.001)37%23%32%25%32%239586202782483CHDRisk

Reduction

(diabetes)StudyAdaptedfromDownsJRetal.JAMA1998;279:1615-1622;GoldbergRBetal.Circulation1998;98:2513-2519;Py?r?l?Ketal.DiabetesCare1997;20:614-620;TheLong-TermInterventionwithPravastatininIschaemicDisease(LIPID)StudyGroup.NEnglJMed1998;339:1349-1357;HaffnerSMetal.ArchInternMed1999;159:2661-2667.第19頁/共29頁TrialswithFibratesinPatientswithDiabetesStudyEffectp-valueCommentHelsinkiHeartStudy(gemfibrozil)75%eventsnsPrimaryprevention;

post-hocsubgroupanalysisSENDCAP(bezafibrate)65%events0.01SpecificallyconductedinType2diabetes;post-hocanalysisforIHDVA-HIT(gemfibrozil)24%events0.05Secondaryintervention;pre-plannedsubgroupanalysisDAIS(fenofibrate)40-42%focalangiochanges0.02SpecificallyconductedinType2diabetes;mixedprimaryandsecondaryintervention;angiostudy第20頁/共29頁FIELDStudyFenofibrateInterventionandEventLoweringinDiabetesMazzoneT.AmJCardiol2004;93:27C-31C第21頁/共29頁糖尿病患者心血管危險(xiǎn)因素的控制目標(biāo)★減輕體重★降糖:HbA1c≤7.0%★降壓:130/80★調(diào)脂:LDL-C1.81mmol/L第22頁/共29頁Steno-2StudyMultifactorialInterventionandCardiovascularDiseaseinPatientswithType2DiabetesGradeP,etal.NENGLJMED2003;348:383-393第23頁/共29頁Steno-2:IntensiveTherapyNEJM2000;342:905-912BasicIntervention脂肪攝入30%飽和脂肪酸攝入10%運(yùn)動30’35次/wACEIorARB多種維生素AspirinPharmacologyIntervention降糖

metformingliclazide

metformin+gliclazide降壓

thiazideACEIorARB+CCB

-blocker降脂

statins第24頁/共29頁Steno-2:TreatmentGoalsVariable ConventionalIntensive Therapy TherapySBP(mmHg) 140130

DBP(mmHg) 8580

Hba1c(%)6.56.5TC(mg/dl)190175

TG(mg/dl)

150150第25頁/共29頁Steno-2ChangeinClinicalVariablesattheEndoftheStudyVariableConventionalIntensivepTherapy TherapySBP(mmHg) -33-1420.001DBP(mmHg)-82-1220.006

Carbohydrates(%)4.80.99.30.9

0.001FPG(mg/dl)-1811