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October2004URICACIDANDCARDIOVASCULARPROGNOSISANDTHEACTIONOFCARDIOVASCULARDRUGSONURICACIDArielJ.ReyesInstituteofC

ardiovascularTheory,Montevideo,Uruguay尿酸与心血管预后及心血管药物对尿酸的作用1ThesynthesisofuricacidTheantioxidantaction/functionofuricacidDoesuricaciddamaget

heheartandvesselsinman?TherenalexcretionofuricacidTheeffectsofcardiovasculardrugsonuricacidAllopurinolDiureticsAcet

ylsalicylicacidThepurportoftheincreasesinserumuricacidthatarecausedbycardiovasculardrugsinman尿酸与心血管预后及心血管药物对尿酸的作用2Uricacidisproducedinthepurinec

atabolicchainguanosineinosinehypoxanthinexanthineoxidoreductasexanthinexanthineoxidoreductaseuricacid尿酸与心血管预后及心血管药物对尿酸的作用3Xan

thineoxidoreductasesystemxanthinedehydrogenaselowoxygentensioninflammatorycytokineshormonesxanthineoxi

dase•XantinedehydrogenaseusesNAD+asanelectronacceptor•XanthineoxidaseusesO2asanelectronacceptorBerryCE,HareJM.JPhysiol2004;555:589

–606.尿酸与心血管预后及心血管药物对尿酸的作用4Reactiveoxygenspeciesareco-generatedwithxanthineandwithuricacidinreactionsmediatedbyxanthineoxidaseHypoxanthineXa

nthine+2O2+H2O+2O2+H2OxanthinexanthineoxidaseoxidaseXanthineUricacid+2O•-+2H++2O•-+2H+Four/twosuperoxideanionradica

ls(O•-)areformedpereachunitofinosine/guanosinecatabolisedthroughtheactionofxanthineoxidase尿酸与心血管预后及心血管药物对尿酸的作用5Thesynthesisofuri

cacidTheantioxidantaction/functionofuricacidDoesuricaciddamagetheheartandvesselsinman?TherenalexcretionofuricacidTheeffectsofcardiovasculardrugsonu

ricacidAllopurinolDiureticsAcetylsalicylicacidThepurportoftheincreasesinserumuricacidthatarecausedbycardiovasculardru

gsinman尿酸与心血管预后及心血管药物对尿酸的作用6Uricacidisanantioxidant:itcan/appearstobeabletoscavengeseveralreactiveoxygenspeci

es:•peroxynitriteandperoxylradicals•hydroxylradical•hypochlorousacid•nitrogendioxide,carbonateion–SquadritoGL,CuetoR,

SplenserAE,etal.ArchBiochemBiophys2000;376:333–7.–RegoliF,WinstonGW.ToxicolApplPharmacol1999;156:96–105.–WhitemanM,

KetsawatsakulU,HalliwellB.AnnNYAcadSci2002;962:242–259.–AugustoO,BoniniMG,AmansoAM,etal.FreeRadicBiolM

ed2001;32:841–859.尿酸与心血管预后及心血管药物对尿酸的作用7Elevationsinserumuricacidentailincreasesinplasmaantioxidantca

pacityinman–WaringWS,WebbDJ,MaxwellSR.JCardiovascPharmacol2001;38:365–371.–WaringWS,ConveryA,MishraV,etal.ClinSci(Lond)2003;1

05:425-430.尿酸与心血管预后及心血管药物对尿酸的作用8ThesynthesisofuricacidTheantioxidantaction/functionofuricacidDoesuricaciddamagethe

heartandvesselsinman?TherenalexcretionofuricacidTheeffectsofcardiovasculardrugsonuricacidAllopurinolDiureticsAcetylsalicylicacidThepurpo

rtoftheincreasesinserumuricacidthatarecausedbycardiovasculardrugsinman尿酸与心血管预后及心血管药物对尿酸的作用9Acutehyper

uricaemiadoesnotimpaircardiovascularfunctioninhealthymanLocalforearmandsystemichyperuricaemiawereproducedbyinfusionofuricacid•Basalforearmblood

flowwasnotaffected•Theresponsesofforearmbloodflowtoacetylcholine,sodiumnitroprussideandL-NMMAwerenotaffected•Centralh

aemodynamicvariables,baroreflexsensitivityandanindexoflargearterystiffnesswerenotaffectedWaringWS,AdwaniSH,BreukelsO,

etal.Heart2004;90:155–159.尿酸与心血管预后及心血管药物对尿酸的作用10ThesynthesisofuricacidTheantioxidantaction/functionofuricacidDoesuric

aciddamagetheheartandvesselsinman?TherenalexcretionofuricacidTheeffectsofcardiovasculardrugsonuricacidAllopurinolDiureticsAcetylsalicyl

icacidThepurportoftheincreasesinserumuricacidthatarecausedbycardiovasculardrugsinman尿酸与心血管预后及心血管药物对尿酸的作用112/3ofalltheuricacidthatisp

roducedisexcretedbythekidneysinnormalmanRenalhandlingofuricacid•Totalamountfiltered:100%•Amountsecretedintothenephronalproximaltubule:

40%•Amountreabsorbedfromthenephronalproximaltubule:130%•Netproximaltubularreabsorption:88–94%Renalfractionalexcretionofuricacid(%ofthefilteredamou

ntthatisexcretedinurine):6–12%尿酸与心血管预后及心血管药物对尿酸的作用12Eventhemoderatereductionsinsodiumintakeprescribedtopatientsw

ithhypertensionorheartfailureresultinsignificantincreasesinserumuricacidconcentration•Randomised,placebo-

controlled,anddouble-blindcrossoverstudy•Seventeenhypertensivepatientsaged65–79Mean24-hnatriuresis(mmol)30495Mea

nserumuricacid(mol.L-1)277174FotherbyMD,PotterJF.JHumHypertens1997;11:361–366.尿酸与心血管预后及心血管药物对尿酸的作用13ThesynthesisofuricacidTheantioxidanta

ction/functionofuricacidDoesuricaciddamagetheheartandvesselsinman?TherenalexcretionofuricacidTheeffectsofcardiovasculardrugsonuricacidAllopuri

nolDiureticsAcetylsalicylicacidThepurportoftheincreasesinserumuricacidthatarecausedbycardiovasculardru

gsinman尿酸与心血管预后及心血管药物对尿酸的作用14ThesynthesisofuricacidTheantioxidantaction/functionofuricacidDoesuricaciddamagetheheartandvesselsinman?

TherenalexcretionofuricacidTheeffectsofcardiovasculardrugsonuricacidAllopurinolDiureticsAcetylsalicylicacidThepurportoftheincreases

inserumuricacidthatarecausedbycardiovasculardrugsinman尿酸与心血管预后及心血管药物对尿酸的作用15Allopurinolanditsmetaboliteoxypurinolareinhibitorsofxanthineoxi

dasehypoxanthineorxanthine+2O2+H2Oallopurinolxanthineoxidaseoxypurinolxanthineoruricacid+2O2•-+2H+尿酸与心血管预后及心血管药物对尿酸的作用16Inadditionto

theiractiononxanthineoxidase,allopurinolanditsmetaboliteoxypurinolscavengefreeradicalsdirectly–MoorhousePC,GrootveldM,HalliwellB,etal.FEBSLett1

987;213:23–28.–DasDK,EngelmanRM,ClementR,etal.BiochemBiophysResCommun1987;148:314–319.–HoeyBM,ButlerJ,Hall

iwellB.FreeRadicResCommun1988;4:259–263.–RicardoSD,BertramJF,RyanGB.ExpNephrol1995;3:270–279.尿酸与心血管预后及心血管药物对尿酸的作用17Rel

evantactionsofallopurinol•Itimprovedperipheralvasodilationcapacityinheartfailure–DoehnerW,etal.Circulation2002;105:2619

–2624.–FarquharsonCA,etal.Circulation2002;106:221–226.•ItdecreasedtheserumconcentrationofoxidisedLDLautoantibodiesinpatientswithgout,wh

ereastheuricosuricbenzbromaronedidnot–TsutsumiZ,MoriwakiY,TakahashiS,etal.ClinChimActa2004;339:117–122.尿酸与心

血管预后及心血管药物对尿酸的作用18ThesynthesisofuricacidTheantioxidantaction/functionofuricacidDoesuricaciddamagetheh

eartandvesselsinman?TherenalexcretionofuricacidTheeffectsofcardiovasculardrugsonuricacidAllopurinolDiureticsAcetylsalicylicacidThepurportoft

heincreasesinserumuricacidthatarecausedbycardiovasculardrugsinman尿酸与心血管预后及心血管药物对尿酸的作用19Allloopdiuretics,mostthiazide-typediuret

icsandallpotassium-retainingdiuretics•enhancethereabsorptionofuricacidintheproximaltubuleofthenephron•reducetherenalexcretionofuricacid•elevat

eserumuricacidconcentration尿酸与心血管预后及心血管药物对尿酸的作用20ThesynthesisofuricacidTheantioxidantaction/functionofuricacidDoesuricaciddamagetheheartandves

selsinman?TherenalexcretionofuricacidTheeffectsofcardiovasculardrugsonuricacidAllopurinolDiureticsAcetylsalicylicacidThepurportoftheincrea

sesinserumuricacidthatarecausedbycardiovasculardrugsinman尿酸与心血管预后及心血管药物对尿酸的作用21•Acetylsalicylicacidat

adailydoseof500mgorhigherraisesuricosuriaandreducesserumuricacid•Acetylsalicylicacidat60or325mgoncedailyreduce

dtherenalfractionalexcretionofuricacidinhealthysubjectsLouthrenooW,KasitanonN,WichainunR,etal.JClinRheumatol2002;8:299–304.•Acetylsalicylicac

idat75or100mgoncedailyreducedtherenalclearanceofuricacidandincreaseduricaemia–CaspiD,LubartE,GraffE,etal.ArthritisRheum2000;43:103–

108.–SegalR,LubartE,LeibovitzA,etal.AmJMed2003;115:462–466.尿酸与心血管预后及心血管药物对尿酸的作用22Acetylsalicylicacid100mgoncedailywasfound

toincreaseserumantioxidantcapacityinhealthysubjectsRistimaeT,etal.CardiovascDrugsTher1999;13:485–490.尿酸与心血

管预后及心血管药物对尿酸的作用23ThesynthesisofuricacidTheantioxidantaction/functionofuricacidDoesuricaciddamagetheheartandvesselsinman?Therenalexc

retionofuricacidTheeffectsofcardiovasculardrugsonuricacidAllopurinolDiureticsAcetylsalicylicacidThepurportoftheincreases

inserumuricacidthatarecausedbycardiovasculardrugsinman尿酸与心血管预后及心血管药物对尿酸的作用24Increasesinserumuricacidperse•entailincrease

sintotalplasmaantioxidantcapacityandtherefore•arebeneficialtotheheartandvesselsHowever,thepurportoftheincreasesinserum

uricacidthatoccurinmandependsupondefiniteprocess(s)andontheircombinations尿酸与心血管预后及心血管药物对尿酸的作用251.Whenthesynthesisofuricacidmediat

edbyxanthineoxidaseaugments,theconsequentincreaseinserumuricaciddenotes:•anelevationinplasmaantioxidant

capacity•theoccurrenceoflocal(e.g.endothelial)oxidativestress(likely)Xanthineoxidaseinhibitionwithallopurinoloroxypurinolmaybeofvalueincar

diovascularprophylaxisandtherapyCont.尿酸与心血管预后及心血管药物对尿酸的作用26Cont.2.Whentherenalexcretionofuricaciddiminishes,t

heaccompanyingincreaseinserumuricaciddenotes:•anelevationinplasmaantioxidantcapacity•thatoxidativest

ressmightcoexist(?)compensatorymechanismhypothesis*Increasesinserumuricacidduetodiminishedrenalexcretion,ascausedby•low-

sodiumdiets•diuretics•low-doseacetylsalicylicacidaretobeconstruedasbeneficialtocardiovascularprognosis*

KirschbaumB.MedHypotheses2001;56:625–629.尿酸与心血管预后及心血管药物对尿酸的作用27AhypothesisTheincreaseinserumuricacidcausedbydiureticsisnotaccompaniedbyari

seinreactiveoxygenspeciesandthereforeconveysareductioninoxidativestress;hence,itshouldbeconstruedasbeneficialThiscouldpartlyexplainthepos

itiveactionofdiureticsoncardiovascularprognosisfoundintheALLHATandotherstudies–ReyesAJ,LearyWP.CardiovascD

rugsTher2002;16:485–487.–ReyesAJ,LearyWP.Hypertension2003;21:1775–1777.尿酸与心血管预后及心血管药物对尿酸的作用28InstituteofCardiovascularTheoryMontevideo,U

ruguay尿酸与心血管预后及心血管药物对尿酸的作用29ThepublishedsubanalysisoftheSHEPresultsdealingwithuricacidlackscogency尿酸与心血管预后及心血

管药物对尿酸的作用30Introduction•Uricacidisanantioxidant.Thus,theincreaseinserumuricacidcausedbydiureticsislikelytobenefittheheartandthevessels[1,2]

.•Chlorthalidone-inducedelevationsinserumuricacidhigherthan0.06mmol/L(about1mg/dL)werefoundtobluntthepositiveactionofbloodpressurereductionwithchlor

thalidoneontheriskofcoronaryheartdiseaseinacommerciallysponsoredsubanalysisoftheSHEPresultsthatwaspublishedin2000[3].尿酸与心血管预后

及心血管药物对尿酸的作用31ObjectiveofthepresentundertakingToreappraisethequestionofwhetherthechangesinserumuricacidthatwereinducedbychlorthal

idoneHadabearingoncardiovascularprognosisintheSHEP.尿酸与心血管预后及心血管药物对尿酸的作用32TheSystolicHypertensionintheElderlyPr

ogram(SHEP)4327patientswithisolatedsystolichypertensionwererandomlyallocatedtotreatmentwith•placebo•chlorthalidone12.5–25m

g/day,plusanotheragentifnecessaryandobservedfor5years.Chlorthalidonetreatment•reducedserumpotassium[4];•elevatedserumuricacid

[4].TwosubanalysesoftheSHEPresultswerepublishedin2003:•asubanalysisoftherelationshipbetweenserumuricacidandcardiovascularoutcomes[3];•asubanalysi

softherelationshipbetweenhypokalaemiaandcardiovascularoutcomes[5].尿酸与心血管预后及心血管药物对尿酸的作用33Firstofthetwoyear-2000papersontheSHEP:Uricacidandcardiovas

cularprognosis[3].•Therisksofcardiovascularevents,strokeorcoronaryheartdisease(myocardialinfarction,coronaryproceduresandcardiacde

ath)werelowerinchlorthalidone-treatedpatients.•Despitetheprecedinggeneralfinding,elevationsinserumuricacidof0.06mmol/L(about1mg/dL)

orhighernullifiedthedecreaseinriskofcoronaryheartdiseaseassociatedwithchlorthalidonetreatment.Thelatterconclusionresultedfromamultivariateana

lysisinwhichthedatawereadjustedforseverallikelyconfounders,butnotforserumpotassium(Table1).尿酸与心血管预后及心血管药物对尿酸的作用34Secondof

thetwoyear-2000papersontheSHEP:Serumpotassiumandcardiovascularprognosis[5]Patientswhopresentedhypokal

aemiaduringactivetreatment•presentedameanserumuricacidof0.41mmol/Lat1year(itwas0.37mmol/Linpatientswithouthypokalaemia,P<0.001);•hadasimilarrisko

fanycardiovascularevent,strokeorcoronaryheartdiseaseasthoseintheplacebogroup.Thelatterconclusionresulted

fromamultivariateanalysisinwhichthedatawereadjustedforseverallikelyconfounders,includingserumuricacid(Table1).尿酸与心血管预后及心血管药物对尿酸的作

用35Table1.LikelyconfoundersincludedinthesubanalysesPossibleconfounderK[5]UA[3]•AgeYesYes•SexYesYes•RaceYesYes•BodymassindexYesYes•Alc

oholconsumptionYesNo•SmokingYesNo•Historyofheartattack,strokeordiabetesYesYes•BaselineserumpotassiumYesNo•Year-1serumpotassiumIgnored•B

aselineserumuricacidNoYes•Year-1serumuricacidYes•Year-1serumcreatinineYesYes•Year-1serumglucoseYesYes•Year-1serumcholesterolYesYes•Year-1ser

umtriglyceridesYesYes•Year-1HDL-cholesterolYesYes•StudydrugdoseYesYes尿酸与心血管预后及心血管药物对尿酸的作用36Discussionandconc

lusions.I.•Theunfavourableeffectattributedtomarkedincreasesinserumuricacidcouldhavebeenduetoassociatedlowserumpota

ssiumlevels,whichdefinitelyimpaircardiovascularprognosis[6].•Diuretic-inducedincreasesinserumuricacidareunlikelytodamagetheheartor

vesselssince•nomechanismwherebythiscouldhappenhasbeendescribedinman;•uricacidinfusionshavebeenfoundnottoaffectendothelialfun

ction,arterialcomplianceorcentralhaemodynamicvariablesinhealthysubjects[7].尿酸与心血管预后及心血管药物对尿酸的作用37Discussionandconclusions.II.•O

xidativestressseeminglyhasabearingonthepathogenesisandprogressofhypertensionandassociatedcardiovascularconditions;thus

,theriseintheserumleveloftheantioxidanturicacidcausedbydiureticscouldbebeneficialtocardiovascularprognosis.

Diureticsincreaseserumuricacidbyloweringtherenalexcretionofthisetabolite;iftherisesinserumuricacidexceeding0.06mmol/Linthechlorthalidonegroupwerepart

lyduetoincreasedsynthesismediatedbyxanthineoxidase,theywoulddenotetheexistenceofoxidativedamagethatcouldaddto

thehypokalaemia-relatedbluntingofsomeofthebenefitofactivetreatment[8].尿酸与心血管预后及心血管药物对尿酸的作用38References[1]ReyesAJ,LearyWP.Cardio

vascDrugsTher2002;16:485–487.[2]ReyesAJ,LearyWP.JHypertens2003;21:1775–1777.[3]FranseLV,PahorM,DiBariM,etal.JHype

rtens2000;18:1149–1154.[4]SavagePJ,PresselSL,CurbJD,etal.ArchInternMed1998;158:741–751.[5]FranseLV,PahorM,DiB

ariM,etal.Hypertension2000;35:1025–1030.[6]SiscovickDS,RaghunathanTE,PsatyBM,etal.NEnglJMed1994;330:1852–1857.[7]War

ingWS,AdwaniSH,BreukelsO,etal.Heart2004;90:155–159.[8]ReyesAJ.CardiovascDrugsTher2003;17:397–414.尿酸与心血管预后及心血管药物对尿酸的作用39Table2.Serumuricacid(m

mol/L)accordingtothestateofserumpotassium(K)atyear1(mmol/L)–Mean(SD)[5]ActivePlacebotreatmentBaselineK>=3.5n=1951n=

20030.32(0.08)0.32(0.08)K<3.5n=151n=210.32(0.08)0.33(0.08)NSvsK>=3.5NSvsK>=3.51yearK>=3.5n=1951n=20030.37(0.10)0.3

3(0.09)K<3.5n=151n=210.41(0.11)0.42(0.09)P<0.001vsK>=3.5P<0.001vsK>=3.5尿酸与心血管预后及心血管药物对尿酸的作用40Losartan,serumuricacidandserump

otassiuminLIFEstudy:anindependentundertaking尿酸与心血管预后及心血管药物对尿酸的作用41IntroductionUricacidisanantioxidant;thus,theuricosuriceffectoflosartan

andtheattendantfallinserumuricacidaretobeconsidereddetrimentaltotheheartandvessels.TheauthorsoftheLIFEstudy[1]analysedthecontributi

onoftheactionoflosartanonserumuricacidtothetherapeuticeffectofthisagentandconcludedthatitwasbeneficial[2].TheLIFE

Study[1]•Patients:high-riskhypertensivesaged55–80.•Design:double-masked,randomised,parallel-groupstudy.•Patientswere

assignedtolosartan-oratenolol-basedanti-hypertensivetherapyfor4yearsoruntil1040patientshadacardiovascularevent(death,myoca

rdialinfarctionorstroke).尿酸与心血管预后及心血管药物对尿酸的作用42ResultsoftheLIFEstudy•Theprimaryendpoint(cardiovasculardeath,strokeandmyocardialinfarction)was•11.

0%inthelosartangroup,•12.8%intheatenololgroup(P=0.021)[1].•Meanserumuricacidincreasedduringtreatment•17.0μmol.L-1inthelosartangroup,

•44.4μmol.L-1intheatenololgroup(P<0.001)[2].•85and86%ofpatientsinthelosartanandatenololgroupswerealsotakinghydrochlorothiazideate

ndofstudy[2].•Theauthorsaffirmthatserumpotassiumdidnotchangesubstantiallyduringtreatmentineithergroup[2].尿酸与心血管预后及心血管药物对尿

酸的作用43Endofstudybiochemicalvariablesasreportedin[1]and[2].Meanvalues(SD).Losartan(n=4605)Atenolol(n=4588)Ref.BaselineYear4,5ChangeBaselineYear

4,5ChangePotassium(mmol/L)4.2(0.4)4.1(0.4)0.0(0.4)4.2(0.4)4.1(0.4)-0.1(0.5)[1]4.1414.109-0.0324.1434.025-0.118[2]Uricacid(μmol/L)328.2(76.9)3

47.7(90.0)19.5(72.2)328.8(77.1)375.9(93.1)47.2(76.8)[1]17.0(69.8)44.4(72.5)[2]尿酸与心血管预后及心血管药物对尿酸的作用44Conclusionb

ytheauthorsoftheLIFEstudy“Theincreaseinserumuricacidwasattenuatedbylosartancomparedwithatenololtreatme

nt,appearingtoexplain29%ofthetreatmenteffectontheprimarycompositeendpoint”[2].OurmainobjectiontotheconclusionbytheauthorsoftheLIFEstudy

:Serumpotassiumwasdisregardedasapotentialconfoundingfactorinthemultivariateanalysisthatgroundsthisconclusion,despitethefactthatpatientswithd

iuretic-inducedhypokalaemiatendtohavehigherserumuricacidlevelsthansubjectswhodonotpresenthypokalaemia[3].尿酸与心血管预后及心血管药物对尿酸的作用45Objectivesofthep

resentundertaking•toevaluatewhethertheresponsesofserumpotassiumtolosartanandtoatenololintheLIFEstudydiffered;•todiscussthepossiblebearing

ofserumuricacidonthedifferentialeffectoflosartanontheprimaryoutcome.MethodsofthepresentundertakingTocomparetheresponsesofserumpotass

iumtolosartanandtoatenolol,weusedthenumberofpatientswhotookeachmedicationquotedbytheauthorsaccordingtot

heirintent-to-treatanalysis,themeanvaluesreportedinthesubanalysisonuricacid[2]sincetheyaremoreprecisethanth

osereportedin[1](seethetableabove),andtheSDvaluesquotedintheprimereport[1]sincenoscatterestimatesarereportedin[2](seethetable

above).尿酸与心血管预后及心血管药物对尿酸的作用46ResultsofthepresentundertakingSerumpotassiumwashigherinthelosartanthanintheatenololgroupa

tendofstudyandtheincidenceofhypokalaemiawashigherintheatenololgroup•Meanserumpotassiumwashigherinthelosartan(4.109mmol.L-1)thanintheatenololgroup(4

.025mmol.L-1)atendofstudy(P<0.0001)–evaluatedbytheunpairedttest.•6.4%and9.4%ofpatientsinthelosartanandatenololgroupsrespectivelypres

entedhypokalaemiaatendofstudy(P<0.0001)–thesepercentageswereevaluatedbytheintegralofthestandardisednormalcurvebetwe

enminusinfinityand3.499,mmol/L,whileusingtheSDvaluesquotedin[1]andassumingthatserumpotassiumatendofstudyconformedtoaGaussiandistribu

tioninbothgroups.尿酸与心血管预后及心血管药物对尿酸的作用47ConclusionsLosartan,uricacidandcardiovascularriskintheLIFEstudy•TheLIFEstudyauthorsignore

dserumpotassiumintheirmultivariateanalysis;thisvariable,whichisknowntoassociatenegativelywithserumuricacidindiur

etic-treatedpatients,waslowerintheatenololthaninthelosartangroupatendofstudy.•TheLIFEstudyauthorsmaintainth

atthelowerlevelsofserumuricacidinthelosartangroupentailedanimprovedcardiovascularprognosis;thiscontentionisunscientific.Losartan-induce

dfallsinserumuricacidmaywelldetractfromthepositivecardiovascularactionsofthisagent,giventhaturicacidisapowerfulantioxidantinman[5].Intheabsen

ceoffurtheranalysesrefutingourobjections,theLIFEstudyauthors’analysisandconclusion[2]lackcogency.尿酸与心血管预后及心血管药物对尿酸的作用48Basisoftheoldstanceondiuretics

,uricacidandcardiovascularrisk•Selectedepidemiologicalstudieshavedisclosedthathighlevelsofserumuricacidimpaircardiovascularprognosis•Theco

ntrolofhighbloodpressurewithdiureticsfailstoimprovecardiovascularprognosiswhenitelevatesserumuricacidmarkedly•Theincreaseinuricosur

iaandreductioninuricaemiacausedbylosartanimprovecardiovascularprognosis•Raisedlevelsofserumuricacidcauserenaldamageandt

riggerthedevelopmentofhypertensionintheratSrinivasTR,Herrera-AcostaJ,FeigGIetal.JHypertens2004;22:inpress.尿酸与心血管预后及心

血管药物对尿酸的作用49