流行和临床症状不显的心血管疾病的预断冲击在个体以新陈代谢的综合症状和糖尿病.docx

流行和临床症状不显的心血管疾病的预断冲击在个体以新陈代谢的综合症状和糖尿病.docx

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流行和临床症状不显的心血管疾病的预断冲击在个体以新陈代谢的综合症状和糖尿病

PrevalenceandPrognosticImpactofSubclinicalCardiovascularDiseaseinIndividualsWiththeMetabolicSyndromeandDiabetes

ErikIngelsson1,LisaM.Sullivan2,JoanneM.Murabito1,3,CarolineS.Fox1,4,EmeliaJ.Benjamin1,5,6,JosephF.Polak7,JamesB.Meigs8,MichelleJ.Keyes1,9,ChristopherJ.O'Donnell1,10,11,ThomasJ.Wang1,10,RalphB.D'Agostino,Sr.1,9,PhilipA.Wolf1,12,andRamachandranS.Vasan1,5,6

1NationalHeart,Lung,andBloodInstitute'sFraminghamStudy,Framingham,Massachusetts

2DepartmentofBiostatistics,BostonUniversity,Boston,Massachusetts

3SectionofGeneralInternalMedicine,BostonUniversitySchoolofMedicine,Boston,Massachusetts

4DivisionofEndocrinology,Diabetes,andHypertension,BrighamandWomen'sHospital,HarvardMedicalSchool,Boston,Massachusetts

5DepartmentofPreventiveMedicine,BostonUniversitySchoolofMedicine,Boston,Massachusetts

6CardiologySection,BostonUniversitySchoolofMedicine,Boston,Massachusetts

7NewEnglandMedicalCenter,Tuft'sUniversity,Boston,Massachusetts

8GeneralMedicineDivision,DepartmentofMedicine,MassachusettsGeneralHospitalandHarvardMedicalSchool,Boston,Massachusetts

9DepartmentofMathematicsandStatistics,BostonUniversity,Boston,Massachusetts

10CardiologyDivision,MassachusettsGeneralHospitalandHarvardMedicalSchool,Boston,Massachusetts

11NationalHeart,Lung,andBloodInstitute,CenterforPopulationStudies,Bethesda,Maryland

12DepartmentsofNeurologyandPreventiveMedicineandEpidemiology,BostonUniversitySchoolofMedicine,Boston,Massachusetts

AddresscorrespondenceandreprintrequeststoRamachandranS.Vasan,MD,FACC,FraminghamHeartStudy,73MountWayteAve.,Suite2,Framingham,MA01702-5803.E-mail:

vasan@bu.edu

Abbreviations:

CVD,cardiovasculardisease;IMT,intima-mediathickness;LVH,leftventricularhypertrophy;MetS,metabolicsyndrome

  ABSTRACT

TOP

ABSTRACT

RESEARCHDESIGNANDMETHODS

RESULTS

DISCUSSION

REFERENCES

Dataarelimitedregardingprevalenceandprognosticsignificanceofsubclinicalcardiovasculardisease（CVD）inindividualswithmetabolicsyndrome（MetS）.WeinvestigatedprevalenceofsubclinicalCVDin1,945FraminghamOffspringStudyparticipants（meanage58years;59%women）usingelectrocardiography,echocardiography,carotidultrasound,ankle-brachialbloodpressure,andurinaryalbuminexcretion.WeprospectivelyevaluatedtheincidenceofCVDassociatedwithMetSanddiabetesaccordingtopresenceversusabsenceofsubclinicaldisease.Cross-sectionally,51%of581participantswithMetShadsubclinicaldiseaseinatleastonetest,afrequencyhigherthanindividualswithoutMetS（multivariable-adjustedoddsratio2.06[95%CI1.67–2.55];P<0.0001）.Onfollow-up（mean7.2years）,139individualsdevelopedovertCVD,including59withMetS（10.2%）.Overall,MetSwasassociatedwithincreasedCVDrisk（multivariable-adjustedhazardsratio[HR]1.61[95%CI1.12–2.33]）.ParticipantswithMetSandsubclinicaldiseaseexperiencedincreasedriskofovertCVD（2.67[1.62–4.41]comparedwiththosewithoutMetS,diabetes,orsubclinicaldisease）,whereastheassociationofMetSwithCVDriskwasattenuatedinabsenceofsubclinicaldisease（HR1.59[95%CI0.87–2.90]）.AsimilarattenuationofCVDriskinabsenceofsubclinicaldiseasewasobservedalsofordiabetes.SubclinicaldiseasewasasignificantpredictorofovertCVDinparticipantswithoutMetSordiabetes（1.93[1.15–3.24]）.Inourcommunity-basedsample,individualswithMetShaveahighprevalenceofsubclinicalatherosclerosisthatlikelycontributestotheincreasedriskofovertCVDassociatedwiththecondition.

Presenceofsubclinicaldiseaseinmultiplevascularbedshasbeensuggestedasanindicatorofoverallatheroscleroticburden

（1）.Consistentwiththisconcept,investigatorshavereportedanincreasedriskofovertcardiovasculardisease（CVD）eventsinindividualswithsubclinicaldisease（2–4）ortargetorgandamage（asevidencedbyleftventricularhypertrophy[LVH][5,6]ormicroalbuminuria[7–9]）.ItisalsowidelyacknowledgedthatestablishedriskfactorsforovertCVDpromotethedevelopmentofsubclinicalCVD（10）.

Inthiscontext,themetabolicsyndrome（MetS）isaconditionthatisassociatedwiththeclusteringofriskfactorsincludinghighbloodpressure,abdominalobesity,glucoseintolerance,anddyslipidemia.WhereasthedefinitionandclinicalutilityofMetShasbeenthesubjectofrecentdebate（11,12）,itisacceptedthatMetScarriesanincreasedriskofCVD（13,14）.GiventheclusteringofriskfactorsthatcharacterizesMetS,itislikelythatindividualswithMetShaveahighburdenofsubclinicaldisease（atermusedhereintorefertobothsubclinicalatherosclerosisandtargetorgandamage）.ItisalsolikelythatsubclinicaldiseasewouldcontributetotheincreasedriskofCVDassociatedwithMetS.Yet,dataexaminingthispremisecomprehensivelyarelackinginthepublishedliterature.Ofnote,whereasseveralstudies（15–25）havedocumentedtheincreasedprevalenceofsubclinicaldiseaseinMetS,theyhavenotinvestigatedthepotentialroleofsuchdiseaseinmediatingthevascularriskassociatedwiththecondition.Additionally,previousstudies（15–25）assessingsubclinicaldiseaseinMetShavetypicallyfocusedonsinglemeasuresofsubclinicaldisease.

Accordingly,wecharacterizedcomprehensivelythecross-sectionalprevalenceofsubclinicaldiseaseinindividualswithprevalentMetSinthecommunity.Additionally,wetestedthehypothesisthatthepresenceofsubclinicaldiseasecontributestotheincreasedriskofovertCVDassociatedwithMetSprospectively.

  RESEARCHDESIGNANDMETHODS

TOP

ABSTRACT

RESEARCHDESIGNANDMETHODS

RESULTS

DISCUSSION

REFERENCES

ThedesignandselectioncriteriaoftheFraminghamOffspringStudyhavebeendescribedpreviously（26）.Participantswhoattendedthesixthexaminationcycle（1995–1998）wereeligibleforthepresentstudy（n=3,532）.Theparticipantsunderwentroutinemedicalhistory,physicalexaminationincludingbloodpressuremeasurement,anthropometry,laboratoryassessmentofCVDriskfactors,andtestingforthepresenceofsubclinicalCVD（seesectionbelow）.TheinstitutionalreviewboardatBostonMedicalCenterapprovedthestudy,andallparticipantsgavewritteninformedconsent.

Participantswereexcludedfromthepresentinvestigationforthefollowingreasons:

prevalentCVDatbaseline（n=415）,unavailableelectrocardiographydata（n=6）,unavailablemeasurementofurinaryalbumin（n=460）,unavailableankle-brachialbloodpressuredata（n=49）,unavailableorinadequatecarotidultrasonographydata（n=70）,andunavailableorinadequateechocardiographicleftventricularmassdata（n=587）.Aftertheseexclusions,1,945individuals（meanage58years;59%women）wereeligibleandconstitutedthestudysample.

DefinitionofriskfactorsandMetS.

Cigarettesmokingwasdefinedbyself-reportofcigaretteusewithintheyearprecedingtheheartstudybaselineexamination.Diabeteswasdefinedasafastingplasmaglucose

126mg/dloruseofinsulinororalhypoglycemicagents（27）.TheMetSwasdefinedaccordingtothemodifiedNationalCholesterolEducationProgramAdultTreatmentPanelIIIcriteria（28）bythepresenceofthreeormoreofthefollowing:

increasedwaistcircumference（

102cmformen,

88cmforwomen）,elevatedbloodpressure（

130mmHgsystolicor

85mmHgdiastolicortreatmentforhypertension）,hyperglycemia（fastingbloodglucose

100mg/dlortreatmentforelevatedglucose）,hypertriglyceridemia（

150mg/dlortreatmentwithnicotinicacidorfibrates）,orlowHDLcholesterol（<40mg/dlinmen,<50mg/dlinwomen）.

Subclinicaldiseasemeasuresandscore.

Measuresofsubclinicalvasculardiseaseandtargetorgandamagewerechosenbasedonareviewofthepublishedliterature.ThefivetestsusedtocharacterizetheprevalenceofsubclinicaldiseasearedetailedinTable1anddescribedbrieflybelow.Astandard12-leadcomputerizedrestingelectrocardiogramwasobtainedwiththeparticipantsinasupineposition.Thesex-specificCornellvoltagecriteriawereusedtoassessthepresenceofelectrocardiographicLVH（29）.Allparticipantsunderwentroutinetransthoracicechocardiographicexamination.M-modemeasurementsofleftventriculardimensionswereobtainedbytheleading-edge-to-leading-edgetechnique（30）.Leftventricularejectionfractionwasestimatedbyexperiencedobserversbasedonthevisualassessmentofleftventricularcontractileperformanceandwallmotioninmultipletwo-dimensionalviews.Carotidultrasoundreadingswereacquiredandimagesanalyzedaccordingtoastandardprotocol（31）.Imagingwasconductedusingahigh-resolution7.5-MHztransducerforthecommoncarotidarteryanda5.0-MHztransducerforthecarotidbulbandinternalcarotidartery（ToshibaMedicalSystems）,asdescribedpreviously（32）.Carotidintima-mediathickness（IMT）measurementsweremadefromgateddiastolicimagesoftheleftandrightcarotidarteryatthelevelofthedistalcommoncarotidartery,thecarotidarterybulb,andtheproximal2cmoftheinternalcarotidartery.ThemaximalIMTateachsitewasdefinedasthemeanofthemaximalIMTmeasuredatthenearandfarwallsofthevessel.TheinternalcarotidarteryIMTwasdefinedasthemeanofthemaximalIMTmeasurementsforthecarotidarterybulbandtheinternalcarotidarteryonboththerightandleftside.Ankle-brachialsystolicbloodpressuremeasurementswereobtainedbytrainedtechniciansaccordingtoastandardprotocol,usingan8-MHzDopplerpenprobeandanultrasonicDopplerflowdetector