混合型血脂异常与糖尿病他汀治疗

混合型血脂异常与糖尿病他汀治疗关注糖尿病患者LDL-C,HDL-C和TG的全面控制内容血脂异常与心血管风险2型糖尿病混合型血脂异常与心血管预后2型糖尿病混合型血脂异常他汀干预的终点证据2型糖尿病患者他汀治疗的安全性LDL-C:他汀临床研究关注的主要血脂指标AdaptedfromBallantyneCM.AmJCardiol.1998;82:3Q-12Q.二级预防-安慰剂二级预防-他汀一级预防-安慰剂一级预防-他汀0510152025308090100110120130140150160170180190200LDL-CAchieved(mg/dL)AFCAPSAFCAPSWOSCOPSWOSCOPSCARECARELIPIDLIPID4S4SEventRate(%)HPSHPS辛伐他汀降低糖尿病合并冠心病且血脂异常三联症患者的心血管事件风险4S研究(LDL+LowHDL+HighTG)LDL=low-densitylipoprotein;HDL=high-densitylipoprotein;TG=triglycerides.CVEventRate(%)4037.524.235.5血脂异常三联症,糖尿病血脂异常三联症,非糖尿病非血脂异常三联症,糖尿病非血脂异常三联症,非糖尿病3319718819221817941782n18.137.523.425.919.001020304050安慰剂辛伐他汀BallantyneCM.Circulation.2001;140:3046-3051BallantyneCM.Circulation.2001;104:3046-3051.LipidTriadGroup:Baseline:LDL-C=195mg/dL,TG=191mg/dL,HDL-C=33mg/dL;LipidTriadGroup:n=424;Sim:n=206;Placebo:n=218.35.7%simvastatinpatientsweretitratedfrom20to40mgat1year.辛伐他汀显著改善糖尿病合并冠心病患者血脂异常三联症4S研究低HDL-C：高冠心病危险TheindependenteffectofraisingHDL-Candloweringtriglyceridesontheriskofcoronaryandcardiovascularmorbidityandmortalityhasnotbeendetermined.Systolicbloodpressure=135mmHgLDL-CCHDrelativerisk2.6mmol/L4.1mmol/L2.2mmol/L00.51.01.52.03.02.51.7mmol/L1.2mmol/L0.6mmol/L5.7mmol/LHDL-CFraminghamHeartStudyKannelWB.AmJCardiol.1987;59:80A–90A.TG与冠心病风险显著相关：29个研究荟萃分析*Individualsintopvsbottomthirdofusuallog-TGvalues,adjustedforatleastage,sex,smokingstatus,lipidconcentrations,andbloodpressure(most).N=262,52512CHDRiskRatio*(95%CI)1.72(1.56–1.90)AdjustedforHDLFastingstatusDurationoffollow-up5689No4469Yes2674Nonfasting7484Fasting1994Female7728Male425610years590210yearsCHDCasesGroupsSexSarwarNetal.Circulation.2007;115:450-458,内容血脂异常与心血管风险2型糖尿病混合型血脂异常与心血管预后2型糖尿病混合型血脂异常他汀干预的终点证据2型糖尿病患者他汀治疗的安全性2型糖尿病：高TG和低HDL-C的常见共同病因低HDL-C血症的常见原因ElevatedtriglyceridesOverweightandobesityPhysicalinactivityCigarettesmokingVeryhighcarbohydrateintakesType2diabetesCertaindrugs(beta-blockers,anabolicsteroids,progestationalagents)高甘油三酯血症的常见原因ObesityandoverweightPhysicalinactivityCigarettesmokingExcessalcoholintakeHighcarbohydratedietsType2diabetesSeveraldiseases（chronicrenalfailure,nephroticsyndrome)Certaindrugs(corticosteroids,estrogens,retinoids,higherdosesofbeta-blockers)Variousgeneticdyslipidemias•familialcombinedhyperlipidemiaand家族性低alpha球蛋白血症eachaffectabout1%ofthegeneralpopulation,andtype2diabetesaffectsmorethan5%.•Together,thesethreedisordershavebeenpurportedtoaccountforupto50%ofprematurecoronaryarterydiseaseevents.NEnglJMed2007;357:1009-17.亚洲各国面临2型糖尿病的巨大挑战(2003-2025)01000020000300004000050000600007000080000AustraliaChinaIndonesiaJapanKoreaMalaysiaPhilippinesSingaporeTaiwanThailandIndia20252003NumberofPeoplewithDiabetes(000)Source:(accessed10/7/2005)糖尿病显著增加心血管疾病风险BellDSH.DiabetesCare.2003;26:2433-41.CentersforDiseaseControl(CDC).型糖尿病的心血管并发症~65%的患者死于CV冠心病死亡2-4倍中风2-4倍心衰2-5倍心血管医生面临处理糖尿病患者的两大问题冠心病患者普遍合并2型糖尿病或存在未明确诊断的糖代谢异常对于合并糖尿病的急性冠脉综合症或稳定性冠心病的介入操作临床疗效不理想冠心病患者的糖代谢状况欧洲心脏研究0204060InpatientsOutpatients包括2107急性冠心病住院患者和2854例稳定性冠心病门诊患者BartnikMetal.EurHeartJ.2004;25:1880-90.Totalpatients(%)OGTT**n=1920withoutknowndiabetesOGTT=oralglucosetolerancetest;IGT=impairedglucosetolerance;IFG=impairedfastingglucose32300204060InpatientsOutpatients糖尿病病史5851IGTIFGNewDMPatients*(%)无论是冠心病住院患者还是门诊患者，2个中约1个是糖尿病.中国冠心病住院患者的糖代谢异常•冠心病住院患者中糖尿病检出率为52.9%•糖调节受损检出率为24.0%•总的糖代谢异常检出率为76.9%•单纯FPG检测的漏诊率:糖尿病80.5%,IGT:87.4%中华内分泌和代谢杂志.2006,22(1)7-10调查包括中国7大城市共52所三级医院3513例冠心病患者全体3513例：过去确诊糖尿病1153例；入院后2次FPG确诊糖尿病97例；其余2263例中通过OGTT发现糖尿病609例；所有糖尿病患者为1859例。血管再通术操作糖尿病患者获益并不理想JAMA.2005;293:1501-1508CABG围手术期和长期存活率PCI患者长期存活率PCI患者再狭窄与重复血运重建需要糖尿病合并冠心病患者的冠脉斑块特征：尸检资料显示糖尿病冠脉病变多累计左冠状动脉主干血管病变多呈现弥漫性分布，多血管受累动脉斑块脂质含量丰富，稳定性较差糖尿病患者血管病变缺乏良好的侧支循环糖尿病患者多存在冠脉阴性血管重构，斑块再狭窄发生率高与糖尿病相关的心血管危险因子小而密LDL颗粒ApoB低HDL-CApoA-1降低高TGCRP和其他炎症标志物升高纤维蛋白原升高高血压高血糖PAI-1升高血流变异常微量白蛋白尿高胰岛素血症内皮功能紊乱Apo=apolipoprotein;PAI-1=plasminogenactivatorinhibitor-1.McFarlaneSI,etal.JClinEndocrinolMetab.2001;86:713-718.ReuschJEB.AmJCardiol.2002;90(5A):19G-26G.胰岛素抵抗和糖尿病增加小而致密LDL颗粒的数量0102030405060708090100ISIRType2DMLDL=low-densitylipoprotein;SD=standarddeviation;IS=insulin-sensitive;IR=insulinresistance.GarveyWT,etal.Diabetes.2003;52:453-462.ConcentrationofSmallDenseLDL,mg/dL(mean±SD)糖尿病患者混合型血脂异常与心血管危险显著相关TG水平上升LDL-C在平均水平至中度上升低水平HDL-C小而密的颗粒UKPDS心血管危险因素回归分析CHD危险％LDL-C1mmol/L57HDL-C0.1mmol/L–15SBP10mmHg15HbA1c1%11“Triglycerideconcentrationwasariskfactorforcoronaryarterydiseaseafteradjustmentforageandsex,butitwasnotanindependentriskfactorwhentheothervariableswereincludedinthemodel.”TurnerRCetalBMJ1998;316:823-828.内容血脂异常与心血管风险2型糖尿病混合型血脂异常与心血管预后2型糖尿病混合型血脂异常他汀干预的终点证据2型糖尿病患者他汀治疗的安全性糖尿病患者冠心病一级预防临床试验（主要为他汀研究）*根据病史;†在糖尿病患者中的前瞻性研究;其他为亚群分析;‡均值30mg/d;§1或2型糖尿病–44(NS)5,80410,30520,5366,6056232,5322,912155+27(NS)普伐他汀40PROSPER–16(NS)阿托伐他汀10ASCOT–33(p=0.0003)辛伐他汀40HPS§洛伐他汀20–40‡AFCAPS4,081135–68(NS)吉非罗齐1200HHS2,4101,905–4(NS)阿托伐他汀10ASPEN9,7957,664–19(p=0.004)非诺贝特200FIELD††研究总例数2,8382,838糖尿病例数,*与安慰剂相比，事件发生率的变化%降脂药物,mg/d试验–37(p=0.001)阿托伐他汀10CARDS†舒降之显著降低糖尿病患者心血管事件风险,阿托伐他汀自相矛盾的结果糖尿病患者冠心病二级预防的临床试验