传统和非传统的心血管风险因素关系冠状动脉钙在型2 糖尿病

RelationshipofTraditionalandNontraditionalCardiovascularRiskFactorstoCoronaryArteryCalciuminType2DiabetesTheodoreMazzone1,PeterM.Meyer2,GeorgeT.Kondos3,MichaelH.Davidson4,StevenB.Feinstein4,RalphB.D’Agostino,Sr.5,AlfonsoPerez6,andStevenM.Haffner71DepartmentofMedicine,SectionofEndocrinology,DiabetesandMetabolism,UniversityofIllinoisCollegeofMedicine,Chicago,Illinois2DepartmentofPreventiveMedicine,RushUniversityMedicalCenter,Chicago,Illinois3DepartmentofMedicine,SectionofCardiology,UniversityofIllinoisCollegeofMedicine,Chicago,Illinois4DepartmentofMedicine,SectionofCardiology,RushUniversityMedicalCenter,Chicago,Illinois5DepartmentofMathematics,StatisticsandConsultingUnit,BostonUniversity,Boston,Massachusetts6TakedaGlobalResearchandDevelopment,Lincolnshire,Illinois7DepartmentofMedicine,UniversityofTexasHealthScienceCenter,SanAntonio,TexasAddresscorrespondenceandreprintrequeststoTheodoreMazzone,MD,SectionofDiabetesandMetabolism(MC797),UniversityofIllinoisatChicago,1819W.PolkSt.,Chicago,IL60612.E-mail:[e-mail]:apo,apolipoprotein;CAC,coronaryarterycalcium;CACS,coronaryarterycalciumscore;sBP,systolicbloodpressure;TAT,totalabdominaladiposetissue;TRL,triglyceride-richlipoprotein;VAT,visceraladiposetissue;WHR,waist-to-hipratioABSTRACTWeevaluatedcorrelatesofcoronaryatherosclerosis,measuredbycoronaryarterycalcium,inaraciallydiversegroupofmaleandfemalesubjectswithtype2diabetes.Age,systolicbloodpressure,sex,andrace/ethnicityweresignificantdeterminantsofcoronaryarterycalcium.Amonglipoproteins,cholesterollevelcontainedinaparticleexcludedfromdirectmeasuresofLDLandHDLcholesterol(designatedtriglyceride-richlipoproteincholesterol)wasmoststronglylinkedtocoronaryarterycalcium.Neitherinflammatorymarkersnormetabolicfactorscorrelatedwithcoronaryarterycalciuminmodelsadjustedforageandsex,butmeasuresofadiposedistributiondid.Waist-to-hipratioandtheratioofvisceraltototalabdominaltissuewerepositivelyassociatedwithcoronaryarterycalcium.Infullyadjustedmultivariatemodels,therelationshipofadipositymeasurestocoronaryarterycalciumwasnolongersignificantafterinclusionofapolipoproteinBortriglyceride-richlipoproteincholesterol.Traditionalriskfactorsandrace/ethnicityremainimportantcorrelatesofcoronaryarterycalciuminacohortatelevatedriskofcardiovasculardiseasebecauseoftype2diabetes.Adipositymeasuresaresignificantlyassociatedwithcoronaryarterycalciumscore,buttheirimportancemaybelargelyexplainedbyapolipoproteinBortriglyceride-richlipoproteincholesterol.Patientswithdiabeteshaveamarkedlyincreasedriskofmyocardialinfarctionandcardiovasculardeathduetoacceleratedcoronaryatherosclerosis(1).Thepathophysiologyleadingtoacceleratedatherosclerosisinpatientswithdiabetesismultifactorialandincompletelydefined.Forexample,ithasbeensuggestedthattraditionalcardiovascularriskfactors(age,systolicbloodpressure[sBP],smoking,lipids)donotcompletelyaccountfortheincreasedcardiovascularmortalityinpatientswithdiabetes,andnovelapproachesarebeingsoughttoaddressadditionalfactorsthatcouldcontributetoacceleratedatherosclerosisindiabetes(2–4).Theincreasedatherosclerosisseeninpatientswithdiabetesisreflectedinincreasedcoronaryarterycalcium(CAC)measuredbyelectronbeamtomography(5,6).CACisameasureoftotalcoronaryatheroscleroticburdenthathasbeenvalidatedbyautopsyandcoronaryangiography(7,8).Inlargestudies,CAChasbeenfoundtobeasignificantpredictorofcardiovasculareventsinsymptomaticandasymptomaticsubjects(9,10).Insubjectswithtype1diabetes,CACisanindependentcorrelateofmyocardialinfarctionandobstructivecoronaryarterydisease(11).TheTOPABSTRACTRESEARCHDESIGNANDMETHODSRESULTSDISCUSSIONNOTEADDEDINPROOFREFERENCESamountofCAChasalsobeenshowntocorrelatewellwiththeamountofatheromatousplaqueinpatientswithtype2diabetes(12).Accordingtocurrentformulations,cardiovasculareventsrequireavesselwalldiseasedwithatheromatousplaquealongwithsuperimposedplaqueruptureandthrombosis.Thedetectionandquantitationofcoronaryatherosclerosisbyelectronbeamtomographyinpatientsbeforecardiovasculareventscanbeapowerfultoolforidentifyinggeneticandpathophysiologicalfactorsassociatedwithatheroscleroticvasculardiseaseseparatefromthosefactorsproducingplaqueruptureand/orthrombosis(13,14).Inthisstudy,weevaluatedlipoprotein,inflammatory,andmetaboliccorrelatesofCACinagroupofwell-characterizedsubjectswithtype2diabetesandasymptomaticforcoronaryarterydisease.Wefocusedonapaneloffactorsfoundtobepredictiveofcoronaryatherosclerosisorcoronaryeventsinnondiabeticcohorts.RESEARCHDESIGNANDMETHODSStudydescription.CHICAGO(CarotidIntima-MediaThicknessinAtherosclerosisUsingPioglitazone)isamulticenterrandomized18-monthclinicalstudycomparingtheeffectsofpioglitazoneversusglimepirideonmeasuresofatheroscleroticdiseaseandbiochemicalindexesofcardiovascularrisk.Asecondaryendpointofthistrialincludeschangeincoronaryarterycalciumscore(CACS).Theinformationreportedinthisarticlerepresentsacross-sectionalanalysisofbaselineinformation.Eligiblesubjectsweremenandwomen45–85yearsofage,withadiagnosisoftype2diabetes(basedonAmericanDiabetesAssociationdiagnosticcr