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控制糖尿病患者心血管危险
的干预治疗策略糖尿病与心血管危险影响心血管危险的因素综合控制的理论与实践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:177million366MILLIONBY2030Type2diabetesandCHD
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<0.001Type2diabetesandStroke
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<0.001PrevalenceofCHDbytheMetabolicSyndromeandDiabetesintheNHANESPopulationAge50+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%CHDPrevalence1.00.90.80.70.60.00246810Follow-up,years#atrisk174214099062828935NometabolicsyndromeMetabolicsyndromelog-rank=45.4p<0.001Event-freesurvivalSchillaciG.JACC.2004;43:1817-1822代谢综合征与心血管危险MlandMicrovascularEndPoints:IncidencebyMeanSystolicBPandHbA1cConcentrationMlMicrovascularandpointsMlMicrovascularandpoints50403020100806040200Adjustedincidenceper1000person-yr(%)110120130140150160170567891011UpdatedmeansystolicBP(mmHg)UpdatedmeanHbA1cconcentration(%)Adjustedincidenceper1000person-yr(%)AdlerAletal.BMJ2000;321:412-419StrationIMetal.BMJ2000;321:405-412MetS和DM患者血脂异常特征游离脂肪酸TGHDL-C
VLDL-C
小而密LDL颗粒氧化LDL-C餐后高脂血症MaleGender-adjustedFemaleReducedriskwithsmall,denseLDL0.1Relativeriskformyocardialinfarction110Increasedriskwithsmall,denseLDLSmall,denseLDLincreases
cardiovascularriskUKPDS
StepwiseSelectionofRiskFactors*inPatientswithType2Diabetes
VariableLDL-CHDL-CHemoglobinA1cSystolicBloodPressureSmokingPValue<0.00010.00010.00220.00650.056CoronaryArteryDisease(n=280)PositioninModelFirstSecondThirdFourthFifth*Adjustedforageandsex.TurnerRCetal.BMJ1998;316:823-828.Mangagingoverweightintype2diabeticsEffectiveweightmanagementisthefirststepintreatingtype2diabetesWeightloss(kg)infirst12monthsLeanMEJetal.,DiabetMed,1990;7:228-233Lifeexpectancy(years)95%confidenceinterval1816141210800481216Weightlossisdifficulttomaintainbydietandexercisealoneintype2diabetesUKPDS34.Lancet1998;352:354InsulinChlorpropamideGllbenclamideDietaloneMetforminWeightchange(kg)76543210-10246810YearsfromrandomisationGoodglycemiccontrolisnotenoughUKPDSGOODGLYCEMICCONTROLMICROVASCULARCOMPLICATIONSSignificantreductionsMACROVASCULARCOMPLICATIONSNosignificanteffectPROACTIVEStudySept.2005,
欧洲糖尿病会议
Pioglitazone
vsPlaceboACCORDStudyActiontoControlCardiovascularriskinDiabetesPrisantLM.JClin
Pharmacol2004;44(4):423-430HbA1c:≤6.0%vs7.0-7.9%
糖尿病患者降压治疗临床试验SHEPALLHATSYST-EURHOPECAPPPHOTNORDILRENAALSTOP-2PRIMEINSIGHTLIFEUKPDS
Majorcardiovascularevents(per100patients-years)inalltreatedhypertensiveandinhypertensivepatientswithdiabetesinrelationtotargetbloodpressuresof90.85,and80mmHg.302520151050808590908580P=0.50fortrendP=0.005fortrendAllhypertensivepatients(n=18790)Hypertensivewithdiabetes(n=1501)TargetbloodpressuregroupsMajorcardiovascularevents/1000patients-yearsHOTStudy:ResultsinPatientswithDMEffectofIntensivevsModerateAntihypertensiveTreatmentonStrokeIncidenceinDiabeticNormotensives Intensive ModerateAchievedBP(mmHg) 128/75 137/81Stroke(%) 1.7 5.4P=0.03Schrieretal.,KidneyInt2002;61:1086CHDPreventionTrialswithStatinsinDiabeticSubjects
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;PyöräläKetal.DiabetesCare1997;20:614-620;TheLong-TermInterventionwithPravastatininIschaemicDisease(LIPID)StudyGroup.NEnglJMed1998;339:1349-1357;HaffnerSMetal.ArchInternMed1999;159:2661-2667.CARDS:主要终点年安慰剂组事件数127立普妥®组事件数83累积危险(%)051015012344.75P=0.001ColhounHM,BetteridgeDJ,DurringtonPN,etal.Lancet.2004;364:685-696.
37%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;angiostudyFIELDStudyFenofibrateInterventionandEventLoweringinDiabetesMazzoneT.AmJCardiol2004;93:27C-31C糖尿病患者心血管危险因素的控制目标★减轻体重★降糖:HbA1c≤7.0%★降压:130/80★调脂:LDL-C1.81mmol/LSteno-2StudyMultifactorialInterventionandCardiovascularDiseaseinPatientswithType2DiabetesGradeP,etal.NENGLJMED2003;348:383-393Steno-2:IntensiveTherapyNEJM2000;342:905-912BasicIntervention脂肪摄入30%饱和脂肪酸摄入10%运动30’35次/wACEIorARB多种维生素AspirinPharmacologyIntervention降糖
metformin
gliclazide
metformin+gliclazide降压
thiazideACEIorARB+CCB
-blocker降脂
statinsSteno-2:TreatmentGoalsVariable ConventionalIntensive Therapy TherapySBP(mmHg) 140130
DBP(mmHg) 8580
Hba1c(%)6.56.5TC(mg/dl)190175
TG(mg/dl)
150150Steno-2ChangeinClinicalVariablesattheEndoftheStudyVariableConventionalIntensivepTherapy TherapySBP(mmHg) -33-1420.001DBP(mmHg)-82-1220.006
Carbohydrates(%)4.80.99.30.9
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