Cardiometabolic Syndrome

14/10/2015
www.medscape.com/viewarticle/583529_print
www.medscape.com
ManagementofCardiometabolicSyndromeinthePrimaryand
SecondaryPreventionofCardiovascularDisease
M.DominiqueAshen,PhD,CRNP
JournalforNursePractitioners.20084(9):673680.
AbstractandCaseStudies
Abstract
Cardiometabolicsyndrome(CMS)isaclusteringofinterrelatedriskfactorsthatpromotethedevelopmentof
atheroscleroticvasculardiseaseandtype2diabetesmellitus.Theseinterrelatedriskfactorshaveadirecteffecton
atherogenicdyslipidemia,elevatedbloodpressure,andelevatedplasmaglucose,andpromoteproinflammatoryand
prothrombicstates.MechanismsofthemajorunderlyingforcesofCMSabdominalobesityandinsulinresistance
arediscussedandincludereviewofobesityinducedinflammationwiththedevelopmentofabdominalobesity.
Twoclinicalcasestudiesarepresentedforprimaryandsecondarycardiovasculardiseasepatientswithdiscussionof
clinicalmanagementbasedonguidelinerecommendations.
CaseStudies
CaseStudy1.A52yearoldfemalewithdyslipidemiaandafamilyhistoryofprematurecoronaryarterydisease
(CAD)andtype2diabetesmellitus(DMmotherisdiabeticwithCABGat56andPCI/stentat70).Shedenies
cigarettesmoking,exercisesonlyoccasionally,anddoesnotpayattentiontoherdiet.Shedoesnottake
prescriptionmedications.Herbloodpressureis142/78mmHg,bodymassindex27,andwaistcircumference38
inches.Thefastingglucoselevelis98mg/dL.Thetotalcholesterollevelis220mg/dL,thelowdensitylipoprotein
cholesterol(LDLC)levelis168mg/dL,thehighdensitylipoproteincholesterol(HDLC)levelis38mg/dL,andthe
triglyceridelevelis68mg/dL.
CaseStudy2.A65yearoldmalewithdyslipidemia,hypertension,andahistoryofPCI/stent4yearspreviously.
Thereisnoknownfamilyhistoryofcoronaryheartdiseaseortype2DM.Hewasaformersmoker(1pack/dayquit
afterPCI).Hefollowsalowsaturatedfatdietbutneverexercises.Medicationsincludeastatin,abetablocker,an
angiotensinconvertingenzymeinhibitor,andaspirin.Hisbloodpressureis146/86mmHg,bodymassindexis29,
andwaistcircumferenceis43inches.Thefastingglucoselevelis99mg/dL.Thetotalcholesterollevelis191
mg/dL,theLDLClevelis125mg/d,theHDLClevelis32mg/dL,andthetriglyceridelevelis170mg/dL.
Casestudy1representsaprimarycardiovasculardisease(CVD)preventionpatientclassifiedaslowriskbythe
FraminghamRiskScore(FRS), [1]with4%riskofmyocardialinfarction(MI)in10years.ByATPIIIguidelinesfor
LDLCmanagement, [2]hergoalLDLCis<130mg/dL.Casestudy2representsasecondaryCVDprevention
patientclassifiedashighrisk(knowncoronaryarterydiseaseCAD)withoptimalgoalLDLCof<70mg/dL. [2]Both
patientshavebeenidentifiedwithcardiometabolicsyndrome(CMS).Whatstrategieswillreducetheirriskfor
atheroscleroticcardiovasculardisease(ASCVD)andtype2DM?
ClinicalProblem
Cardiometabolicsyndrome(CMS),alsoknownas"metabolicsyndrome,""SyndromeX,"and"prediabetes,"isa
clusteringofinterrelatedriskfactorsthatpromotethedevelopmentofASCVD[3,4]andtype2DM. [4,5,6,7]While
somereportsindicatethatCMSisassociatedwithagreaterriskforASCVD, [8]oncetype2DMemerges,therisk
ofASCVDmayfurtherincrease. [9]CMSisalsoariskfactorforcardiovascularevents.Arecentmetaanalysisof
almost175,000patientswithmetabolicsyndromeindicatesarelativeriskof2.2and1.9forcardiovascularevents
anddeath,respectively. [10]OveronequarteroftheU.S.populationhasCMS, [11,12]withabdominalobesity[13,14]
andinsulinresistance[15,16]asthedrivingforces.
EtiologyofCMS
InterrelatedRiskFactors
http://www.medscape.com/viewarticle/583529_print
1/11
14/10/2015
TheinterrelatedriskfactorsforCMS,withadirecteffectonatheroscleroticvasculardisease,includeatherogenic
dyslipidemia,elevatedbloodpressure,elevatedplasmaglucose,andtheproinflammatoryandprothrombicstates.
[7]ThelipoproteinabnormalitiesunderlyingASCVDconsistofelevatedtriglycerideandsmall,denseLDLC
particlesandreductioninHDLC.Bothtriglyceriderichlipoproteinsandsmall,denseLDLCparticlescarrythe
greatestriskforatherosclerosis. [3,17]HDLCplaysaprotectiveroleinatherogenesisviacytokineproduction,lipid
oxidation,cholesterolefflux,andreversecholesteroltransport,withlowlevelsofHDLCidentifiedasindependently
atherogenic. [3,18]Increasedreninangiotensinaldosteronesystemresultinginelevatedbloodpressureisa
metabolicabnormalityassociatedwithCMS. [19]Elevatedbloodpressure,awellknownriskfactorforASCVD, [20]
togetherwithatherogenicdyslipidemia,asdescribedabove,canincreaseriskforASCDV,evenwithonlymild
abnormalityofeachcomponent. [7]Elevatedplasmaglucosecanresultinglycosylatedproteinsthatcaninduce
oxidativestressandstimulateproinflammatoryresponses. [21]
CMShasalsobeenassociatedwiththepresenceofinflammatorymarkers.Finally,highcirculatinglevelsof
prothrombicfactorsmayplayanimportantroleinpredisposingtoprothrombicepisodes,whichunderlieASCVD
events.Hypofibrinolysis,duetoelevatedplasminogenactivatorinhibitor1(PAI1)levels,hasbeenimplicatedin
CMS. [22]
AbdominalObesityandInsulinResistance
AbdominalobesityandinsulinresistancearemajorunderlyingforcesinCMS.Eckeletal[23]definethelink
betweenabdominalobesityandinsulinresistance(Figure1A).Briefly,inexpandedadiposetissue,freefattyacids
(FFA)stimulateincreasedproductionofglucose,triglycerides,LDLC,andVLDLCfromtheliver,alongwith
reductionsinHDLC.FFAalsoinduceinsulinresistanceofskeletalmuscle,inhibitinginsulinmediatedglucose
uptakeandstorageasglycogen.TheresultingincreaseincirculatingglucoseandFFAstimulatepancreaticinsulin
secretion,whichenhancessodiumreabsorptionandsympatheticnervoussystemdrive,resultinginhighblood
pressure.
2/11
14/10/2015
Themetabolicsyndrome.Eckeletal.Lancet2005365:1415.Usedbypermission.
Superimposedonthisinsulinresistanceschemearetheproinflammatoryandprothrombicstates(Figure1B).
Adiposetissueadipocytesandmonocytederivedmacrophagesproducecytokines,includinginterleukin6(IL6)and
tumornecrosisfactor(TNF)amongothers,whichfurtherstimulateinsulinresistanceaswellaslypolysisofadipose
tissuetriglycerides.CytokinesalsoincreaseglucoseandVLDLCproductionbytheliverandinsulinresistanceinthe
skeletalmuscle.PAI1andplasminogenarealsoproducedbytheliverinresponsetocytokinesandFFA,resulting
inaprothrombicstate.Finally,adiponectin,whichplaysaroleasanantiinflammatorymoleculeandaninsulin
sensitizingagent,isreducedinexpandedadiposetissue.
Inreviewingthelinkbetweenadiposetissueandinsulinresistance,itisclearthatadiposetissueplaysanimportant
roleinCMS.AmoreindepthviewofadiposetissueinCMS(Figure2)revealsobesityinducedinfiltrationby
macrophagesandinflammationasobesitydevelops. [24]Withexpansionofadiposetissue,adipocytesbeginto
secreteTNF(whichstimulatesproductionofmonocytechemoattractantprotein1[MCP1]),andleptin(and/or
decreasesproductionofadiponectin),whichcontributetomacrophageaccumulationinadiposetissue.The
3/11
14/10/2015
presenceofmacrophagesinadiposetissuethenperpetuatesmorerecruitmentofmacrophagesandinflammation.
Inflammationischaracterizedbytheoverproductionofproinflammatorycytokines(IL6,resistinTNF,andCreactive
protein[CRP])andthedeficiencyofantinflammatorycytokines(adiponectin).Ofthemultiplesubstancesthatplaya
roleinobesityandinsulinresistance,CRP,Il6,MCP1,PAI1,andTNFalsoplayaroleinatherosclerosis,also
consideredaninflammatorydisease. [25]
Inflammationinobeseadiposetissue.WellenandHotamisligil.JClinInvestig.2003112:17851788.Usedby
permission.
GenesandEnvironment
ThereisevidenceforageneticcontributiontoCMSfromobservationsintwinsandfamilies. [26]Inaddition,single
genehumanmodelsandgeneticassociationstudieshaveidentifiedmultiplegenesassociatedwiththephenotypic
expressionofCMS.However,nogenomicDNAmarkershavebeenidentifiedandnogenetictestiscurrently
availableinthediagnosisortreatmentofCMS.Theinfluenceofethnicityandsexandtheinteractionofgeneswith
environmentalfactors(calorieexcess,physicalinactivity)willlikelyinfluencethephenotypicexpressionofCMSand
complicatethegeneticassociationsthatcanbemade.
ClinicalDiagnosis
MultipleclinicaldefinitionsforCMShavebeenestablishedinanattempttoprovidealistofclinicalmarkersthat
canbeusedtoidentifyindividualswithCMS. [26]ThreeofthesedefinitionsincludethoseproposedbytheWorld
HealthOrganization(WHO),theUSNationalCholesterolEducationProgramAdultTreatmentPanelIII(NCEP
ATPIII),andtheInternationalDiabetesFoundation(IDF)(Figure3). [1,27,28]Guidelinesforall3include
glucose/insulinabnormality,obesity/centraladiposity,dyslipidemia,andhypertension.OnlytheWHOguideline
includesmicroalbuminuria,whiletheIDFprioritizesabdominalobesity,makingonlyindividualswithincreasedwaist
circumferenceeligibleforassessment.
4/11
14/10/2015
ClinicaldefinitionsforCMS.
MinimumcriteriafordiagnosisbytheWHOisglucoseintolerance/insulinresistanceplus2otherfeatures,byNCEP
ATPIIIisany3features,andbyIDFiscentraladiposityplus2otherfeatures.Ofthe3,theNCEPATPIIIdefinition
hasempiricalclinicalvaluebecauseitismorepredictiveinlowerrisksubjectsandmorestronglyassociatedwith
incidenceofDM. [6,29]However,regardlessofthedefinitionused,adiagnosisofCMScanbepredictiveof
increasedlifetimeriskofcardiovasculardisease.
ClinicalManagementofCMSinPrimaryandSecondaryCVDPreventionPatients
UsingtheNCEPATPIIIguidelines,bothpatientshaveCMS.Incasestudy1,the52yearoldprimaryprevention
patientwithahistoryofdyslipidemiahas3riskfactorsforCMS,includinglowHDLC,hypertension,andabdominal
obesity.Incasestudy2,the65yearoldsecondarypreventionpatientwithdyslipidemia,hypertension,andcoronary
arterydiseasestatuspostPCI/stenthas4riskfactorsforCMSincludinglowHDLC,elevatedtriglycerides,
hypertension,andabdominalobesity.Inbothcases,theydonothavefastingbloodglucoselevelsabove100
mg/dL,althoughthelevelsareintheupperrangeofnormal(6099mg/dL).
TheidentificationofCMSplacesbothpatientsatincreasedriskforthedevelopmentoftype2DM,particularlyin
thecaseofthe52yearoldpatientwhohasafamilyhistoryoftype2DM.Thisisimportantinthattheidentification
ofCMSidentifiesadysmetabolicstatethatispredictiveofdiabetes. [30]
WithregardtoASCVD,theidentificationofCMSalsoplacesthe65yearoldmalewithCADatincreasedriskfor
progressionofatheroscleroticvasculardiseaseandsubsequentmyocardialinfarctionasCMSriskfactors
collectivelyaccentuateprogressionofASCVDandincreaseendpointssuchasstroke,congestiveheartfailure,
chronickidneydisease,andoverallmortality. [31]The52yearoldfemalewithdyslipidemiaandnoknownASCVD,
butafamilyhistoryofASCVD,isconsideredlowriskbyFRS.However,theFRS,whichprovidesashortterm10
yearassessmentofrisk,frequentlyclassifieswomenaslowriskeveninthepresenceofsignificantcoronaryartery
[32]
calcium(CAC). BecausetheadditionofCMStotheFRSaddslittletothis10yearriskprediction,itisprudent 5/11

14/10/2015
calcium(CAC). [32]BecausetheadditionofCMStotheFRSaddslittletothis10yearriskprediction,itisprudent
toapplyfurthermeasuresforriskstratificationforthisprimarypreventionpatient.
FurtherRiskStratification
Thereare2additionalteststhatmaybeusefulinfurtherassessingtheASCVDriskofthe52yearoldfemalewith
dyslipidemiaandnoknownASCVD,butafamilyhistoryofprematureASCVD:aCACscanandmeasurementof
highsensitivity(hs)CRP.CMSpredictsthepresenceofCACandthus,atheroscleroticvasculardisease,in
asymptomaticlowriskpatients. [33]Inaddition,thereisevidencethatincreasingCACimprovespredictionofevents
inasymptomaticadults. [34]WhileguidelinesfromtheACC/AHAandNCEPendorsethemeasurementofCACin
intermediateriskpatients(6%10%FRS),itmaybeprudenttomeasureCACinthislowriskpatient(4%FRS)
becauseofherfamilyhistoryofprematureCAD.Inaddition,inasituationwheretheuseofaspirinandstatin
therapyareunclear,asinthispatient,aCACscanmaybehelpfulinreclassifyingherasintermediateorhighrisk
andthusmovetowardapplyingthesetherapeuticoptions.
InCMS,obesityinducedinfiltrationbymacrophagesandinflammationwithexpandedadiposetissue(obesity)
resultsinoverproductionofproinflammatorycytokines,includingCRP.CRPisalsoasensitivemeasureof
subclinicalatherosclerosis[35]andasimplewaytoidentifyaproinflammatorystateinclinicalpractice.While
guidelinesfromtheAHA/CDCsupportmeasurementofhsCRPinintermediateriskpatients,itmayalsobe
prudenttomeasurehsCRPinthispatientasafurthermeansofriskstratificationforASCVD.
ClinicalManagement
Manypatientsatriskfor,orwithASCVD,presentwithCMS.TheclusteringofriskfactorsthatdefineCMS
promotesthedevelopmentofASCVD[3,4]andtype2DM. [4,5,6,7]Aggressiveriskreductionmanagementinboth
primaryandsecondaryCVDpreventionpatientscannotonlyreducetheriskfortype2DMbutminimizeprogression
toASCVDorworseningofdiseaseandincreasedriskofcardiacevent.Inreviewingthemechanismsthatunderlie
CMS,itisclearthatmanagementofobesity(adiposetissueexpansion)tominimizeinsulinresistanceand
inflammationisofimportance.Thus,theprimarytherapyofCMSinvolveslifestylemodificationsthatfocuson
weightreductionthroughincreasedphysicalactivity,withincreasedcaloriesexpended,andanonatherogenicdiet,
withreducedcalorieintake.Thetherapeuticgoalforweightreduction[7]isdefinedasreductioninbodyweightby
7%to10%duringoneyearoftherapy,withanultimategoalofabodymassindex(BMI)<25kg/m2andwaist
circumference<40inchesinmenand<35inchesinwomen.
Physicalactivitycontributestocardiorespiratoryfitness,whichisassociatedwithincreasedinsulinsensitivity[36]and
decreasedriskforCMS. [37]Thetherapeuticgoalforexercise[7]isdefinedasregularmoderateintensityphysical
activityatleast30minutes5days/week,preferablydaily.Anincreaseindailyactivityisalsorecommended,such
asgardeningandhousework.Resistancetraining2days/weekisalsoencouraged.
Dietsrichinfruits,vegetables,fiber,wholegrains,omega3fattyacids,andotherunsaturatedfatshavebeen
showntoreduceproinflammatorycytokinesandincreaseantiinflammatorycytokines. [38]TheMediterraneandiet,
showntoreduceinsulinresistanceandproinflammatorycytokines, [39]andalowglycemicindexdiet,shownto
optimizeHDLCandtriglyceridesandreduceweight, [40]haveshowntobebeneficialinpatientswithCMS.The
recommendedtherapeutic,nonatherogenicdiet [7]includessaturatedfat<7%oftotalcalories,cholesterol<200
mg/dL,andtotalfat25%to35%oftotalcalories.Itisalsorecommendedthatdietaryfatshouldbeunsaturated
andsugarsbelimited.
Changesinphysicalactivityanddiettoaffectweightlossandreductioninwaistcircumferenceandthus,abdominal
obesity,requirebehavioralchangethatisoftendifficultformanypatientstoinitiateandmaintain.Itisimportant
thathealthcareprovidersnotonlydefinegoalsforpatientsintheseareasbutdiscussstrategiestoattainthose
goals.Settingspecific,attainable,andforgivinggoalsisafirststepinthisprocess.Keepingajournal,rewarding
shorttermgoals,andlearningsocialorenvironmentalcuesthatresultinsetbacksarealsoimportant. [41]
DrugtherapyisalsousedtotargetindividualriskfactorsforCMS. [7]Drugtherapyincludeslipidloweringdrugs,
antihypertensiveagents,hypoglycemicdrugs,antiplateletdrugs,andweightlossagents.Itisrecommendedthat
theuseofthesedrugsfollowcurrenttreatmentguidelines. [1,3,20,42,43,44,45]Withtheexceptionofantiplatelet
6/11
14/10/2015
drugs,thecombinationofdrugtherapyandlifestylemodificationsisimportantinaffectingchangeinlipids,blood
pressure,glucose,andweight.
SpecificManagementGuidelinesforCaseStudies
PrimaryPreventionPatient
Inthe52yearoldprimarypreventionpatientidentifiedaslowriskforacardiaceventin10years,furtherrisk
stratificationisrecommendedinlightofherfamilyhistoryofprematureCADandpersonalhistoryofdyslipidemia
(elevatedLDLCandlowHDLC),newonsethypertension,andincreasedBMI/waistcircumference.Acoronary
calciumscanandmeasurementofhsCRParerecommended.Lifestylemodificationsandpossiblydrugtherapywill
beinitiatedtominimizeriskofCADandprogressiontotype2DM.
LifestyleModifications.Aggressiveriskfactormodificationthroughlifestylechangesistheprimarygoalof
therapy.Sheshouldbeencouragedtodeveloparegularaerobicexerciseprogramconsistingofbriskactivityfor30
minutes5days/week.Sheshouldalsobecounseledondietarychoicestomaintainalowsaturatedfat,low
cholesteroldiethighinfruits,vegetables,wholegrains,andfiberwithreducedservingsize.Thecombinationof
increasedcalorieexpenditureandreductionincaloricintakewilldriveweightlossandreductioninwaist
circumference.
DrugTherapy.EventhoughpatientswithCMSareatincreasedriskofthrombosisasaresultofdecreased
fibrinolysisviaincreasedPAI1,thebenefitsofaspirinmustbeweighedagainsttheriskofbleeding,whichare
greaterinwomenlessthan65yearsold. [46]Theuseofaspirinasanantiplateletagentwouldberecommendedif
aboveaveragelevelsofcoronarycalciumwereobservedand/orhsCRPwas>3mg/dL,movinghertoahighrisk
category.TheACC/AHAguidelineshaveoutlinedaclassIbrecommendation(BenefitRiskadditional
studies/registrydatawouldbehelpfulprocedureorRxmaybeconsidered)forintermediateriskwomen<65years
old. [47]Thus,unlessherriskstatusiselevatedthroughfurtherriskstratification,aspirinwouldnotbeprescribedfor
thispatient.
Severalstudiessupporttheuseofangiotensinconvertingenzymeinhibitors(ACEI)orangiotensinreceptor
blockers(ARB)inthepreventionofdiabetes[48,49,50]andarerecommendedasthefirstchoicefortreatingpatients
withCMS.TheadditionofanACEIorARB,inadditiontolifestylemodifications,wouldberecommendedinthis
patienttooptimizebloodpressuretotheJNC7targetof,140/90. [7,20]
ThispatientexhibitsanLDLCabovetheATPIIIguidelines(130mg/dL)forindividualswith21riskfactors. [2]While
theuseofalowdosestatinwouldbebeneficialinloweringherLDLCtogoal,withoutfurtherriskstratification,
lifestylemodificationswouldbetheinitialfocustooptimizeherLDLC.However,ifuponfurtherriskstratification,
sheisreclassifiedasintermediateorhighrisk,alowdosestatin,inadditiontolifestylemodifications,wouldbe
recommended,givenherfamilyhistoryofprematureCADandpersonalhistoryofdyslipidemiaandnewonset
hypertension.
SecondaryPreventionPatient
Inthe65yearoldsecondarypreventionpatientidentifiedashighriskwithknownCADandahistoryofdyslipidemia
andhypertension,aggressiveriskfactormodificationthroughlifestylechangesandoptimizationofdrugtherapyis
requiredforminimizingprogressionofatheroscleroticvasculardiseaseandprogressiontowardtype2DM.
LifestyleModifications.Aswiththeprimarypreventionpatient,lifestylechangesareanimportantpartoftherapy.
Hewillalsobeencouragedtodeveloparegularaerobicexerciseprogramandcounseledonincorporating
unsaturatedfats,fiber,wholegrains,andfruitsandvegetablesintohislowsaturatedfatdiet.Aswiththeprimary
preventionpatient,thecombinationofincreasedcalorieexpenditureandreductionincaloricintakewilldriveweight
lossandreductioninwaistcircumference.
DrugTherapy.Itisrecommendedthatheremainonaspirin,basedontheACC/AHAclassIrecommendation
(Benefit>>>RiskprocedureorRxshouldbeperformedoradministered)forsecondarypreventionpatientswith
knownCHD/ASVD.HeiscurrentlyonanACEIandastatin,asrecommendedbyJNC7andNCEPATPIII
7/11
14/10/2015
guidelines.However,hisbloodpressureandLDLCaresuboptimal.Modificationofhisantihypertensivetherapy,
followingJNC7guidelines,toreachoptimalbloodpressure,aswellastitrationofthestatintoreachtheoptimal
LDLCgoalof<70mg/dL,isrecommended.
Summary
PrimaryandsecondaryCVDpreventionpatientsoftenpresentwithclusteringofinterrelatedriskfactorsknownas
CMS.Theseinterrelatedriskfactorspromotethedevelopmentand/orprogressionofASCVDaswellasthe
developmentoftype2DM.Inpreventivecardiovascularmedicine,itisimportanttoidentifypatientswithCMSasa
meanstoreducetheriskforprogressionofatheroscleroticdiseaseanddevelopmentoftype2DM.Whileneitherof
thepatientspresentedhaveplasmaglucoselevelsabove100mg/dL,failuretooffsetpoorlifestylehabits,resulting
infurtherweightgain,willpromoteCMS.
BothprimaryandsecondaryCVDpatientscanbenefitfromthedevelopmentofaregularaerobicexerciseprogram,
dietarymodifications,andweightloss,whicharetheprimarytherapeuticgoalsofCMS.InCMS,expansionof
adiposetissue(abdominalobesity)drivesdyslipidemia,elevatedbloodpressure,elevatedplasmaglucose,
inflammation,insulinresistance,andtheprothrombicstate.Modificationsinlifestylethatresultinweightlossand
reductioninwaistcircumferenceareimportantinminimizingthisdrive.WorkingwithpatientstoidentifyCMSand
optimizetheirlifestyle,withthepossibleoptimizationofdrugtherapy,canminimizediseaseinthoseindividuals
withoutASCVDordiabetesandminimizeprogressionofASCVDanddevelopmentoftype2DMinthosewith
ASCVD.
References
1. ExpertPanelonDetection,EvaluationandTreatmentofHighBloodCholesterolinAdults.Executive
summaryofthethirdreportoftheNationalCholesterolEducationProgram(NCEP)expertpanelon
Detection,Evaluation,andTreatmentofHighBloodCholesterolinAdults(AdultTreatmentPanelIII).
JAMA.2001285:24862497.
2. GrundySM,CleemanJI,BaireyMerzCN,etal.ImplicationsofrecentclinicaltrialsfortheNational
CholesterolEducationProgramAdultTreatmentPanelIIIGuidelines.Circulation.2004110:227239
3. NationalCholesterolEducationProgram(NCEP)ExpertPanelonDetection,EvaluationandTreatmentof
HighBloodCholesterolinAdults(AdultTreatmentPanelIII).ThirdreportonDetection,Evaluation,and
TreatmentofHighBloodCholesterolinAdults(AdultTreatmentPanelIII)finalreport.Circulation.
2002106:31433421
4. WilsonPWF,D'AgostinoRB,PariseH,SullivanL,MeigsJB.Metabolicsyndromeasaprecursorof
cardiovasculardiseaseandtype2diabetesmellitus.Circulation.2005112(20):30663072.
5. HanleyAJG,FestaA,D'AgostinoRB,WagenknechtLE,SavagePJ,etal.Metabolicandinflammation
variableclustersandpredictionoftype2diabetes:factoranalysisusingdirectlymeasuredinsulinsensitivity.
Diabetes.200453:17731781.
6. FordES.Riskforallcausemortality,cardiovasculardiseaseanddiabetesassociatedwiththemetabolic
syndrome:asummaryoftheevidence.DiabetesCare.200528:17691778.
7. GrundySM,CleemanJI,DanielsSR,DonatoKA,EckelRH,etal.Diagnosisandmanagementofthe
metabolicsyndrome.AnAmericanHeartAssociation/NationalHeart,Lung,andBloodInstitutescientific
statement.Circulation.2005112:27352752.
8. AlexanderCM,LandsmanPB,TeutschSM,HaffnerSM.ThirdNationalHealthandNutritionExamination
Survey(NHANESIII)NationalCholesterolEducationProgram(NCEP).NCEPdefinedmetabolic
syndrome,diabetesandprevalenceofcoronaryheartdiseaseamongNHANESIIIparticipantsage50years
andolder.Diabetes.200352:12101214.
8/11
14/10/2015
9. NestoRW.Correlationbetweencardiovasculardiseaseanddiabetesmellitus:currentconcepts.AmJMed.
2004116(suppl5A):11s22s.
10. GamiAS,WittBJ,HowardDE,ErwinPJ,GamiLA,etal.Metabolicsyndromeandriskofincident
cardiovasculareventsanddeath:asystematicreviewandmetaanalysisoflongitudinalstudies.JAmColl
Cardiol.200749:403414.
11. FordES,GilesWH,DietzWH.PrevalenceofthemetabolicsyndromeamongUSadults:findingsfromthe
thirdNationalHealthandNutritionExaminationSurvey.JAMA.2002287:356359.
12. FordES,GilesWH,MokdadAH.IncreasingprevalenceofthemetabolicsyndromeamongUSAdults.
DiabetesCare.200427:24442449.
13. LemieuxI,PascotA,CouillardC,LamarcheB,TchernofA,etal.Hypertriglyceridemicwaist:amarkerof
theatherogenicmetabolictriad(hyperinsulinemiahyperapolipoproteinBsmalldenseLDLC)inmen?
Circulation.2000102:179184.
14. CarrDB,UtzschneiderKM,HullRL,KodamaK,RetzlaffBM,etal.Intraabdominalfatisamajor
determinantoftheNationalCholesterolEducationProgramAdultTreatmentPanelIIIcriteriaforthe
metabolicsyndrome.Diabetes.200453:20872094.
15. ReavenGM.Bantinglecture1988.Roleofinsulinresistanceinhumandisease.Diabetes.198837:1595
1607.
16. FerranniniE,HaffnerSM,MitchellBD,SternMP.Hyperinsulinemia:thekeyfeatureofacardiovascularand
metabolicsyndrome.Diabetologia.199134:416422.
17. BerneisKK,KraussRM.MetabolicoriginsandclinicalsignificanceofLDLCheterogeneity.JLipidRes.
200243:13631379.
18. vonEckardsteinA,HersbergerM,RohrerL.Currentunderstandingofthemetabolicandbiologicalactionsof
HDLC.CurrOpinClinNutrMetabCare.20058:147152.
19. JellingerPS.Metabolicconsequencesofhyperglycemiaandinsulinresistance.ClinCornerstone.
20078:S30S42.
20. ChobanianAV,BakrisGL,BlackHR,CushmanWC,GreenLA,etal.NationalHeart,Lung,andBlood
InstituteJointNationalCommitteeonPrevention,Detection,EvaluationandTreatmentofHighBlood
Pressure:NationalHighBloodPressureEducationProgramCoordinatingCommittee.TheSeventhReport
oftheJointNationalCommitteeonPrevention,Detection,EvaluationandTreatmentofHighBlood
Pressure:TheJNC7Report.JAMA.2003289:25602572
21. AronsonD,RayfieldEJ.Howhyperglycemiapromotesatherosclerosis:molecularmechanisms.Cardiovasc
Diabetol.20021:110.
22. JuhanVagueI,MorangePE,AlessiMC.Theinsulinresistancesyndrome:implicationsforthrombosisand
cardiovasculardisease.PathophysiolHaemostThromb.200232:269273.
23. EckelRH,GrundySM,ZimmetPZ.Themetabolicsyndrome.Lancet.2005365:14151420.
24. WellenKE,HotamisligilGS.Obesityinducedinflammatorychangesinadiposetissue.JClinInvestig.
2003112:17851788.
25. RossR.Atherosclerosisaninflammatorydisease.NEJM.1999340:115126.
26. PollexRL,HegeleRA.Geneticdeterminantsofthemetabolicsyndrome.NatClinPract.20063:482489.
9/11
14/10/2015
27. WHO.ReportofaWHOconsultation.Definition,diagnosisandclassificationofdiabetesmellitusandits
complications.Part1:diagnosisandclassificationofdiabetesmellitus.Availableat:
http://www.staff.newcastle.ac.uk/phillip.home/who_dmc.htmLastaccessedJune15,2008.
28. GeorgeK,AlbertiMM,ZimmetP,ShawJ.Themetabolicsyndromeanewworldwidedefinition.Lancet.
2005366:10591062.
29. HuntKJ,ResendezRG,WilliamsK,HaffnerSM,SternMP.NationalCholesterolEducationProgram
VersusWorldHealthOrganizationMetabolicSyndromeinRelationtoAllCauseandCardiovascular
MortalityintheSanAntonioHeartStudy.Circulation.2004110:12511257.
30. LorenzoL,WilliamsK,HuntKJ,HaffnerSM.TheNationalCholesterolEducationProgramAdultTreatment
PanelIII,InternationalDiabetesFoundationandWorldHealthOrganizationdefinitionsofthemetabolic
syndromeaspredictorsofincidentcardiovasculardiseaseanddiabetes.DiabetesCare.200730(1):813.
31. DavisS.Evolvingtreatmentsforcardiometabolicsyndrome.ManagCareMed.20069:1721.
32. MichosED,NasirK,BraunsteinJB,RumbergerJA,BudoffMJ,etal.Framinghamriskequation
underestimatessubclinicalatherosclerosisriskinasymptomaticwomen.Atherosclerosis.2006184:201206.
33. SantosRD,NasirK,TufailK,MenegheloRS,CarvalhoJAM,etal.Metabolicsyndromeisassociatedwith
coronaryarterycalciuminasymptomaticwhiteBrazilianmenconsideredlowriskbyFraminghamriskscore.
PrevCardiol.200710(3):141146.
34. ShawLJ,RaggiP,SchistermanE,BermanDS,CallisterTQ.Prognosticvalueofcardiacriskfactorsand
coronaryarterycalciumscreeningforallcausemortality.Radiology.2003228(3):826833.
35. WangTJ,LarsonMG,LevyD,BenjaminEJ,KupkaMK,etal.Creactiveproteinisassociatedwith
subclinicalepicardialcoronarycalcificationinmenandwomen:theFraminghamHeartStudy.Circulation.
2002106:11891191.
36. NassisGP,PapantakouK,SkenderiK,TriandafillopoulouM,KavourasSA,etal.Aerobicexercisetraining
improvesinsulinsensitivitywithoutchangesinbodyweight,bodyfat,adiponectinandinflammatorymarkers
inoverweightandobesegirls.Metabolism.200554:14721479.
37. LaMonteMJ,BarlowCE,JurcaR,KampertJB,ChurchTS,etal.Cardiorespiratoryfitnessisinversely
associatedwiththeincidenceofmetabolicsyndrome:aprospectivestudyofmenandwomen.Circulation.
2005112(4):505512.
38. LopezGarciaE,SchulzeMB,FungTT,MeigsJB,RifaiN,etal.Majordietarypatternsarerelatedto
plasmaconcentrationsofmarkersofinflammationandendothelialdysfunction.AmJClinNutr.
200480(4):10291035.
39. EspositoK,MarfellaR,CiotolaM,DiPaloC,GiuglianoF,etal.EffectofMediterraneanstyledieton
endothelialdysfunctionandmarkersofvascularinflammationinthemetabolicsyndrome:arandomizedtrial.
JAMA.2004292:14401446.
40. EbbelingCB,LeidigMM,FeldmanHA,LoveskyMM,LudwigDS.Effectsofalowglycemicloadvslowfat
dietinobeseyoungadults:arandomizedtrial.JAMA.2007297(19):20122092.
41. Availableat:www.nhlbi.nih.gov/health/public/heart/obesity/lose_wt/behavior.htmLastaccessedJune15,
2008.
42. AmericanDiabetesAssociation.Clinicalpracticerecommendations.DiabetesCare.200528(Suppl1):s1s9.
43. SmithSC,BlairSN,BonowRO,BrassLM,CerqueiraMD,etal.AHA/ACCguidelinesforpreventingheart
attackanddeathinpatientswithatheroscleroticvasculardisease:2001update:astatementforhealthcare
10/11
14/10/2015
professionalsfromtheAmericanHeartAssociationandtheAmericanCollegeofCardiology.Circulation.
2001104:15771579.
44. PearsonTA,BlairSN,DanielsSR,EckelRH,FairJM,etal.AHAguidelinesforprimarypreventionof
cardiovasculardiseaseandstroke:2002update:consensuspanelguidetocomprehensiveriskreductionfor
adultpatientswithoutcoronaryorotheratheroscleroticvasculardiseases.AmericanHeartAssociation
ScienceAdvisoryandCoordinatingCommittee.Circulation.2002106:388391.
45. NationalInstitutesofHealth.Clinicalguidelinesontheidentification,evaluationandtreatmentof
overweightandobesityinadultstheevidencereport.ObesRes.19986(Suppl2):51S209S.
46. RidkerPM,CookNR,LeeIM,GordonD,GazianoJM,etal.Arandomizedtrialoflowdoseaspirininthe
primarypreventionofcardiovasculardiseaseinwomen.NEnglJMed.2005352:12931304.
47. MoscaL,BankaCL,BenjaminEJ,BerraK,BushnellC,etal.Evidencebasedguidelinesforcardiovascular
diseasepreventioninwomen:2007update.Circulation.2007115:14811501.
48. YusufS,GersteinH,HoogwerfB,PogueJ,BoschJ,etal.Ramaprilandthedevelopmentofdiabetes.
JAMA.2001286:18821885.
49. LindholmLH,IbsenH,BorchJohnsenK,OlsenMH,WachtellK,etal.Riskofnewonsetdiabetesinthe
LosartanInterventionForEndpointReductioninHypertensionStudy.JHypertens.200220(9):18791886.
50. KjeldsenS,JuliusS,ManciaG,McInnesG,HuaT,etal.Effectsofvalsartancomparedtoamlodipineon
preventingtype2diabetesinhighriskhypertensivepatients:theVALUEtrial.JHypertens.200624(7):1045
1412.
ReprintAddress
M.DominiqueAshen,PhD,CRNP,JohnsHopkinsCiccaroneCenterforthePreventionofHeartDiseasein
Baltimore,MarylandEmail:mashen1@jhmi.edu
JournalforNursePractitioners.20084(9):673680.2008ElsevierScience,Inc.
ThiswebsiteusescookiestodeliveritsservicesasdescribedinourCookiePolicy.Byusingthiswebsite,youagreetothe
useofcookies.
close
11/11

Cardiometabolic Syndrome

Diunggah oleh

Informasi Dokumen

Hak Cipta

Format Tersedia

Bagikan dokumen Ini

Bagikan atau Tanam Dokumen

Opsi Berbagi

Apakah menurut Anda dokumen ini bermanfaat?

Apakah konten ini tidak pantas?

Hak Cipta:

Format Tersedia

Cardiometabolic Syndrome

Diunggah oleh

Hak Cipta:

Format Tersedia

14/10/2015

calcium(CAC). BecausetheadditionofCMStotheFRSaddslittletothis10yearriskprediction,itisprudent 5/11

Anda mungkin juga menyukai