高血壓代謝危險因素控制面臨的困惑與啟示祝之明

高血壓代謝危險因素控制面臨的困惑與啟示

祝之明第三軍醫(yī)大學全軍高血壓代謝病中心重慶大坪醫(yī)院高血壓內分泌科重慶市高血壓研究所DyslipidemiaAbdominalObesityDiabetesUricacidRenallesionEndotheliumdamage

HypertensiveSyndrome

-ConstellationsofCardiometabolicRiskFactorsHypertension80%高血壓危險因素CVD事件更強調危險因素的早期控制更關注血管和代謝因素的相互作用對高血壓的危險進行總體評估防治上既遵循循證醫(yī)學證據，也強調個體化治療Abdominalobesity

Waistcircumference>102cm(M),88cm(W)DyslipidaemiaTC>5.0mmol/l(原為6.1)orLDL-C>3.0mmol/l(原為4.0)orHDL-C:M<1.0mmol/l(40mg/dL),W<1.2mmol/l(46mg/dL)or:TG>1.7mmol/l(150mg/dL)IFG&IGTFastingplasmaglucose5.6-6.9mmol/L(102-125mg/dL)AbnormalglucosetolerancetestESC/ESH

2007高血壓指南Metabolic

syndrometheclusterofthreeoutof5riskfactorsamongabdominalobesity,alteredfastingplasmaglucose,BP≥130/85mmHg,low

HDL-cholesterolandhighTG(asdefinedabove)DiabetesMellitusFastingplasma≥7.0mmol/l(126mg/dL)onrepeatedmeasurements,orPostloadplasmaglucose>11.0mmol/l(198mg/dL)〔JHypertens2007,25：1105〕ESC/ESH

2007——關注高血壓伴發(fā)的代謝異?！睯Hypertens2007,25：1105〕如何評估高血壓的代謝危險性DiabetesVascDisRes2021;5:9–14心血管代謝危險性評估1.Framinghamscore(USA)

Age,Sex,SBP,TC,Smoking,HDL-c2.TheUKPDSriskengine(UK)

Age,Sex,SBP,Smoking,TC/HDL-c,HbA1c3.PROCAMscore(Germany)

Age,LDL-c,TC,smoking,HDL-c,SBP,FHofMI,DM,TG4.ICVD(China)

Age,Sex,SBP,BMI,TC,Smoking,DM危險分層：ESC/ESH靶器官損害的評價Otherriskfactors,ODordiseaseNormalSBP120-129orDBP80-84HighnormalSBP130-139orDBP85-89Grade1HTSBP140-159orDBP90-99Grade2HTSBP160-179orDBP100-109Grade3HTSBP≥180orDBP≥110NootherriskfactorsNoBPinterventionNoBPinterventionLifestylechangesforseveralmonthsthendrugtreatmentifBPuncontrolledLifestylechangesforseveralweeksthendrugtreatmentifBPuncontrolledLifestylechanges+immediatedrugtreatment1-2riskfactorsLifestylechangesLifestylechangesLifestylechangesforseveralweeksthendrugtreatmentifBPuncontrolledLifestylechangesforseveralweeksthendrugtreatmentifBPuncontrolledLifestylechanges+immediatedrugtreatment3ormoreriskfactors,MS,ODordiabetesLifestylechangesLifestylechangesandconsiderdrugtreatmentLifestylechanges+drugtreatmentLifestylechanges+drugtreatmentLifestylechanges+immediatedrugtreatmentDiabetesLifestylechangesLifestylechanges+drugtreatmentEstablishedCVorrenaldiseaseLifestylechanges+immediatedrugtreatmentLifestylechanges+immediatedrugtreatmentLifestylechanges+immediatedrugtreatmentLifestylechanges+immediatedrugtreatmentLifestylechanges+immediatedrugtreatment干預高血壓相關的代謝危險因素能顯著降低心腦血管事件嗎？LowerbloodpressureYes(30%-60%)LowerlipidsYes(17%-43%)LowerbodyweightParadoxLowerglucoseUncertainBMIandWCvsfatparameters肥胖與心血管危險存在U形關系GuDF,etal.JAMA.2006;295:776-783肥胖與心衰Paradoxprognosis:excessbodyweighthaveaparadoxicalprotectiverole?

EnchaiahS,etal.NEnglJMed2002;347:305-13.DIAMONDstudygroupGustafsson1F,EurHeartJ,2005,26:58–64肥胖與AMI

Obesityandtheriskofmyocardialinfarctionin27000participantsfrom52countries:acase-controlstudyYusufS,etal.Lancet2005;366:1640NicolettiI,etal.InterJCardiol,2006,107:395–399Paradoxprognosis:excessbodyweighthaveaparadoxicalprotectiverole?生活方式改變的局限BMI不能反映內臟脂肪的實際變化腹型肥胖的類型與代謝綜合征的關系腹型肥胖類型腰圍超標

(≥90/85cm)腹內脂肪面積

VA≥100cm2非肥胖組－－隱性內臟脂肪型肥胖組(MaskedVFO)－＋假性內臟脂肪型肥胖組(PseudoVFO)＋－內臟型腹型肥胖組(visceralfatobesity，VFO)＋＋MS43%MS78%MS89%中華醫(yī)學雜志2021Proposedmechanismsbywhichvisceralobesity,asthemostdangerousformofobesity,couldbelinkedtotheathero-thrombotic-inflammatoryabnormalitiesofinsulinresistance.

ATVB,2021微血管并發(fā)癥心肌梗死HbA1c37%14%強化降糖與減少CVD事件面臨的困惑糖尿病相關的死亡21%1%StrattonIM,etal.BMJ2000;321:405–412.糖尿病作為冠心病的等危癥是有條件的DiabetesandCoronaryRiskEquivalency糖尿病不合并其他危險因素，其心血管危險不高，也即單純高血糖至少在短期對心血管危害不大。糖尿病合并其他危險因素，其心血管危險性明顯增加，可視為冠心病等危癥。

GrandySM,DiabetesCare,2006理論假說

降壓和調脂的臨床試驗證實：血壓和血脂水平控制得越嚴格，獲得的益處更大。合理假設:強化血糖控制有益于減少CVD事件

控制血糖至一定范圍顯著減少心腦血管事件

ACCORD,ADVANCE,VADT強化血糖控制無益處在ACCORD試驗結果公布之前一個月，EurHeartJ連續(xù)刊登了2篇降糖治療增加心血管事件的臨床研究，編輯部予以評論。DIGAMI2trial

Theimpactofglucoseloweringtreatmentonlong-termprognosisinpatientswithtype2diabetesandmyocardialinfarction:areportfromtheDIGAMI2trial

1996DIGAMI1研究顯示予胰島素治療顯著減少糖尿病的急性心肌堵塞死亡率Circulation1999;99:2626–2632.2005DIGAMI2探討降糖治療對糖尿病心肌堵塞的影響入選1181例2型糖尿病，平均年齡68歲，67%為男性，平均隨訪2.1年37%口服降糖藥，58%用胰島素EuropeanHeartJournal(2021)與口服降糖藥相比，胰島素與全因死亡和心血管死亡無關，但可增加非致死心梗或腦卒中

(HR:1.95,95%CI:1.35–2.82;P=0.0004)EuroHeartSurveyonDiabetesandtheHeart

Glucoseloweringtreatmentinpatientswithcoronaryarterydiseaseisprognosticallyimportantnotonlyinestablishedbutalsoinnewlydetecteddiabetesmellitus:areportfromtheEuroHeartSurveyonDiabetesandtheHeart

本研究比較了目前的降糖治療對冠心病己合并糖尿病和新發(fā)糖尿病的作用。從110個中心，入選4676例冠心病患者，其中1425例既往有糖尿病，452例為新發(fā)糖尿病。探討不同的降糖治療對心血管事件(死亡、心梗、卒中)的影響。EuropeanHeartJournal(2021)與口服降糖藥相比，對合并糖尿病的冠心病，胰島素治療增加1年心血管死亡風險2.23(95%CI1.24–4.03;P=0.006)，但對新發(fā)糖尿病患者，與未降糖治療相比，降糖治療那么明顯減少其心血管事件最近的血糖控制試驗帶來的困惑

JessupM,etal.NEJM,2003,348:2007-18.BlaschkeF,etal.ATVB,2006,26:28-40VanGaalLF,etal.Lancet,2005,365:1389-97多靶點藥物降壓藥物的選擇降壓藥物的選擇EffectofInhibitionoftheRASonDevelopmentofType2DiabetesMellitus(Meta-AnalysisofRandomizedTrials)

AmJCardiol2007;99:1006–1012Irbesartanforthetreatmentofhypertensioninpatientswiththe

metabolicsyndrome:AsubanalysisoftheTreattoTargetpost

authorizationsurvey.Prospectiveobservational,twoarmedstudy

in14,200patients

CardiovascularDiabetology2007,6:12

降糖藥對心血管事件的影響

EuropeanHeartJournal(2021)

不同降糖藥組合對LDL-C和血壓影響不同

BolenSAnnInternMed.2007客觀評價β-blocker在糖尿病治療中的