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The4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件FrequencyofMetabolicSyndromeanditsAbsorptionAbnormalitybyPlantSterolsi

nGeneralPopulation,JapanToshioShimada,YoMurakami,NobuyukiOyake,HiroyukiYoshitomi,NobuhiroKodani,AkiraMatsumori*DivisionofCa

rdiovascularMedicine,DepartmentofInternalMedicine,ShimaneUniversityFacultyofMedicine,DepartmentofCardi

ovascularMedicine,KyotoUniversity,GraduateSchoolofMedicine*The4thShino-JapanCardiovascularForumonOctober23-24,2008i

nBeijing编辑课件BackgroundHealthproblemsonagedpeoplehavebeengrowingbiggerinJapanbecausewithadvancingage,avarietyofdiseasesespeciallyonvascul

ardiseases,suchascardio-andcerebro-vasculardiseaseshavebeenincreasing.Andtherefore,earlydetectionofvasculardiseasesisaveryimportantissueforvascularpr

eventionandreductionofmortality.The4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件Di

agnosticCriteriaforMetabolicSyndrome(8JapaneseMedicalAssociationsJoint-Committee)Fataccumulationintheintra-abdominalcavityAbdominalCircumfere

nceattheWaistMale≧85cm,Female≧90cm(≧80cmrecommendedbyme)（VisceralfatareaMaleandFemale≧100cm2)•Hypertriglyceridemia≧150mg/dL•Lo

wHDL-cho＜40mg/dL•SystolicBloodPressure≧130mmHg•DiastolicBloodPressure≧85mmHg•FastingBloodSugar≧110mg/dL•Lipoproteinabnormality•H

ighBloodPressure•HighBloodSugar＋Atleast,morethanfollowing2itemsand/orand/ormodifiedandtranslatedintoEnglishbyToshioShi

mada•MajorCriteria•MinorCriteriaThe4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件ObesityI

nsulinResistanceDMDyslipidemiaHypertensionAtherosclerosisArteriosclerosisPathophysiologyofMetabolicSyndrmeOver-eatingPoorExerciseInheritanceThe

4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件LDLレセプタISynthesisofCholesterolintheLiverandAbsorptionof

CholesterolintheIntestine-TwoImportantSupplySourcesofCholesterolinVivo-BileFoodLiverVesselsCholesterolSmallIntestineBiliary800~2000mg/

dayDietary400~500mg/dayThe4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件AimOurpurposeistoinvestigatethefreque

ncyofmetabolicsyndrome(MS)andlifestylerelateddiseasesandalsotoexaminewhetheranydifferenceinabsorptionofcholester

olfromthedigestivesystemispresentinparticipantsbetweenwithmetabolicsyndrome(MS)andnon-MSrandomlyselected,usingplantsterolsin

generalpopulation.The4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件SubjectsandmethodIn2007,1980participantsforann

ualhealthcheck-upweresubjectedforthiscohortstudy.Averageageis66±10.8years,andfemaleis1260(64%)；maleis720(36%).Allsub

jectsunderwentroutinebloodexaminations,insulin,remnantlikeparticlecholesterol(RemLC),hs-CRP,cystatinC,plasmabrainnatri

ureticpeptide(BNP)andN-terminalproBNP(NT-proBNP)measurements.Bloodpressure,abdominalcircumference,andelectrocardiographywe

remeasuredatthesametime.AbdominalcircumferencewasmeasuredatthenavellevelinthesupinepositionlikeCTforvisceral

fat.Evaluationofcholesterolabsorptionwasdonebyplantsterolsineach30participantschosenrandomlyfromtheparticipants.BNPandNT-proBNPwer

emeasuredforheartfailurescreeningbyimmunoluminesencemethod.Plantsterolsweremeasuredbygaschromatography.

The4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件✓In1964participants,218participants(11%)werediagnosedasMS,using≥80cmwaistcirc

umferenceinfemaleand≥85cminmaleasmajorcriterion.✓Fromeachgroup,30participantswererandomlychosentocheckp

lantsterollevelsfortheevaluationofabsorptionofcholesterolandlathosterolfortheevaluationofcholesterolsynthesis.✓

Eachsterollevelwasmeasuredbygaschromatography.TheMeasurementofSerumPlantSterolstoEvaluateCholesterolAbsorptioninOkuizumoCohort,

2007The4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件AbnormalandNormalProportionofClinicalParamerersinGeneralPopulation,Japan[Ok

uizumoCohort2007]0%10%20%30%40%50%60%70%80%90%100%normalabnormalThe4thShino-JapanCardiovascularForumonOctober23-24,2008in

Beijing编辑课件DifferenceFullReducedModel190.26599288.24139478.50738-LogLikelihood10DF380.532ChiSquare<.0001Prob>ChiSqRSquare(U)Observati

ons(orSumWgts)0.39761963ConvergedbyGradientWholeModelTestInterceptageBMIHbCystatinCBNPpg/mlInsulinhsCRPRemLCGGTTchoTerm-22.8051470.021023040.4828

91490.424063531.29025592-0.00157170.02058377-0.05252970.120160870.00117904-0.0074947Estimate2.29055890.01305390.04313070.08849030.55

992250.00312830.0067180.06711130.01972250.00167760.0038915StdError99.122.59125.3522.975.310.259.390.6137.

120.493.71ChiSquare<.00010.1073<.0001<.00010.02120.61540.00220.4338<.00010.48220.0541Prob>ChiSq-27.458855-0.00405540.401298640.251751980.20551102

-0.00875360.00772354-0.21378630.08321302-0.0027261-0.0152304Lower95%-18.4677920.047165930.570650550.599081832.404578930.00325560.03406730.033278

730.160522370.004029270.00004675Upper95%.4.83909518795859.059378.75497325.49652980.2377459360.10967020.001959

082584.58234.304435430.19083836OddsRatio.0.7377444680128.69133.93774411.675032670.000335214.650543229.5313e-12230.7418110.034219130

.03453053OddsLower.34.37896659402299.584390.26855418.00488219.601818879.53493551.944975836190.7207146.6777721.01038549OddsUpperFo

rlogoddsof0/1ParameterEstimatesageBMIHbCystatinCBNPpg/mlInsulinhsCRPRemLCGGTTchoSource1111111111Nparm1111111111DF2.68235372178.17741223.54888125.453

240540.285352510.0994580.8340345741.867040.441615913.79336512L-RChiSquare0.10150.00000.00000.01950.59320.00150.36

110.00000.50630.0515Prob>ChiSqEffectLikelihoodRatioTestsNominalLogisticFitforMSF90M85-DxTruePositiveSensitivity0.000.100.200.300.400.500.600.7

00.800.901.00.00.10.20.30.40.50.60.70.80.901-SpecificityFalsePositiveUsingMSF90M85-Dx='0'tobethepositivelevelAreaU

nderCurve=0.93304ReceiverOperatingCharacteristicMetabolicSyndromeanditsInfluentialFactorsAnalyzedbyMultivariateLogisticRegressionFemaleWaistCircu

mference≥90cmInfluentialParameters✓BMI✓Hb✓CystatinC✓Insulin✓RemLC✓TchoThe4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing

编辑课件DifferenceFullReducedModel550.5289761.51871312.0476-LogLikelihood10DF1101.058ChiSquare<.0001Prob

>ChiSqRSquare(U)Observations(orSumWgts)0.41961963ConvergedbyGradientWholeModelTestInterceptageBMIHbCystatinCBNPpg/mlInsulinhsCRPRemLCGGTTchoTerm-18

.6015930.009407250.83709624-0.1869676-0.958875-0.00192810.00615102-0.0044340.036492640.000503370.00580768Estimate1.26844290.

00730960.03993060.05363570.41153680.00171970.00584050.01256940.01481360.00145630.0022599StdError215.061.66439.

4812.155.431.261.110.126.070.126.60ChiSquare<.00010.1981<.00010.00050.01980.26220.29230.72430.01380.72960.0102Prob>ChiSq-21.142974-0.0048660.76

108626-0.2926968-1.7654754-0.0055659-0.0050259-0.03257220.00721438-0.0024910.00139564Lower95%-16.1676860.023805080.91770739-0.082353

5-0.1522810.001173960.017786840.017756420.065700640.003069310.01026077Upper95%.2.024947251.69491e100.07298170.09010530.171655033.4

00942920.5907795810.87268681.864833873.60924199OddsRatio.0.6942320719967329170.016609920.01189850.006174970.367824390

.020935151.602793420.04578181.36129396OddsLower.5.961850841.63756e110.315704220.682341322.924127634.45250458.2291869173.417666944.69

229859.65649116OddsUpperForlogoddsof0/1ParameterEstimatesageBMIHbCystatinCBNPpg/mlInsulinhsCRPRemLCGGTTchoSource1111111111Nparm1111111111DF1.66491

762952.81688212.35061455.392804081.40145031.135766870.130256865.934509040.116323366.66824093L-RChiSqua

re0.19690.00000.00040.02020.23650.28650.71820.01480.73310.0098Prob>ChiSqEffectLikelihoodRatioTestsNominalLogisticFitforAbd-CF80M85TruePositive

Sensitivity0.000.100.200.300.400.500.600.700.800.901.00.00.10.20.30.40.50.60.70.80.901-SpecificityFalsePositiveUsingAbd-CF80M85='0'

tobethepositivelevelAreaUnderCurve=0.89483ReceiverOperatingCharacteristicMetabolicSyndromeanditsInfluentialFactorsAnalyzedbyMultivariateLogis

ticRegressionFemaleWaistCircumference≥80cmInfluentialParameters✓BMI✓Hb✓CystatinC✓RemLC✓TchoThe4thShino-JapanCardiovascularForum

onOctober23-24,2008inBeijing编辑课件DifferenceFullReducedModel36.14842442.42746478.57588-LogLikelihood1DF72.29684ChiSquare<.0001Prob>ChiSqRSquare(U)Obse

rvations(orSumWgts)0.07551964ConvergedbyGradientWholeModelTestLackOfFitSaturatedFittedSource8648651DF307.65972134.76773442.42746-LogLike

lihood615.3194ChiSquare1.0000Prob>ChiSqLackOfFitInterceptRemLCTerm-3.56518450.13107891Estimate0.15930540.016439StdError500.8463

.58ChiSquare<.0001<.0001Prob>ChiSq-3.88732440.09953428Lower95%-3.26243630.16394934Upper95%.5277.7231OddsRatio.670.850599OddsLower

.45281.1913OddsUpperForlogoddsof0/1ParameterEstimatesRemLCSource1Nparm1DF63.5795227WaldChiSquare0.0000Prob>ChiSqEffectWaldTestsRemLCSource1Npar

m1DF72.2968416L-RChiSquare0.0000Prob>ChiSqEffectLikelihoodRatioTestsNominalLogisticFitforMSF90M85-DxTruePositiveSensitivity0.000.

100.200.300.400.500.600.700.800.901.00.00.10.20.30.40.50.60.70.80.901-SpecificityFalsePositiveSensitivity0.81Specificity0.65OddsR

atio5278AUC0.77p=0.0000Cut-OffValue7.34mg/dLCut-OffValueofRemLCBasedonROCCurveforScreeningMetabolicSyndrome(AbdominalCircu

mferenceofWomen≥90cmandthatofMen≥85cm)The4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件Cut-OffValueofRemLC

BasedonROCCurveforScreeningMetabolicSyndrome(AbdominalCircumferenceofWomen≥80cmandthatofMen≥85cm)DifferenceFullReducedModel86.39771598

.24630684.64401-LogLikelihood1DF172.7954ChiSquare<.0001Prob>ChiSqRSquare(U)Observations(orSumWgts)0.12621964ConvergedbyGradientWholeModelTestLackOfFi

tSaturatedFittedSource8648651DF392.34823205.89806598.24630-LogLikelihood784.6965ChiSquare0.9746Prob>ChiSqLa

ckOfFitInterceptRemLCTerm-3.45451880.19834187Estimate0.14984460.0170002StdError531.49136.12ChiSquare<.00

01<.0001Prob>ChiSq-3.75578580.16563887Lower95%-3.16806380.23230396Upper95%.429155.572OddsRatio.50570.6136O

ddsLower.3954464.4OddsUpperForlogoddsof0/1ParameterEstimatesRemLCSource1Nparm1DF136.120162WaldChiSquare0.0000Prob>ChiSqEffectW

aldTestsRemLCSource1Nparm1DF172.795429L-RChiSquare0.0000Prob>ChiSqEffectLikelihoodRatioTestsNominalLogisticFitforMSF80M85-DxTruePositiveSensitivity0.

000.100.200.300.400.500.600.700.800.901.00.00.10.20.30.40.50.60.70.80.901-SpecificityFalsePositive7.26mg/dL

Cut-OffValueSensitivity0.82Specificity0.67OddsRatio429156AUC0.79p=0.0000The4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件Cut-

OffValueofRemLCBasedonROCCurveforScreeningMetabolicSyndrome(AbdominalCircumferenceofWomen≥90cm)Differenc

eFullReducedModel16.90222149.87402166.77624-LogLikelihood1DF33.80444ChiSquare<.0001Prob>ChiSqRSquare(U)Observati

ons(orSumWgts)0.10131253ConvergedbyGradientWholeModelTestLackOfFitSaturatedFittedSource6746751DF124.8244025.04962149

.87402-LogLikelihood249.6488ChiSquare1.0000Prob>ChiSqLackOfFitInterceptRemLCTerm-4.73714260.16928943Est

imate0.30152180.0270757StdError246.8339.09ChiSquare<.0001<.0001Prob>ChiSq-5.36145690.11619794Lower95%-4.17452420.22315915Upper95%.300.

381681OddsRatio.50.1927448OddsLower.1845.42194OddsUpperForlogoddsof0/1ParameterEstimatesRemLCSource1Nparm1DF39.093168WaldChiSquare0.0000Prob>ChiS

qEffectWaldTestsRemLCSource1Nparm1DF33.8044417L-RChiSquare0.0000Prob>ChiSqEffectLikelihoodRatioTestsNominalLogisticFitforMSF90M85-DxSensitivity0.89Sp

ecificity0.70OddsRatio300AUC0.83p=0.0000TruePositiveSensitivity0.000.100.200.300.400.500.600.700.800.901.00.00.10.20.30.40.50.60.70.80.901-S

pecificityFalsePositive6.19mg/dLCut-OffValueThe4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件Sensitivity0.80Specificity0.72O

ddsRatio429156AUC0.82p=0.0000DifferenceFullReducedModel78.47062328.19877406.66940-LogLikelihood1DF156.9412ChiSquare<.0001Prob>ChiS

qRSquare(U)Observations(orSumWgts)0.19301253ConvergedbyGradientWholeModelTestLackOfFitSaturatedFittedSource6746751DF2

44.7592483.43953328.19877-LogLikelihood489.5185ChiSquare1.0000Prob>ChiSqLackOfFitInterceptRemLCTerm-4.

1308570.27163009Estimate0.22042030.0243002StdError351.22124.95ChiSquare<.0001<.0001Prob>ChiSq-4.57858840.22521655Lower95%-3.7134

8570.32058974Upper95%.9451.54891OddsRatio.1977.91364OddsLower.49211.0934OddsUpperForlogoddsof0/1ParameterEstimatesRemLCSourc

e1Nparm1DF124.950051WaldChiSquare0.0000Prob>ChiSqEffectWaldTestsRemLCSource1Nparm1DF156.941249L-RChiSquare0.0000Prob>ChiSqEffectL

ikelihoodRatioTestsNominalLogisticFitforMSF80M85-DxTruePositiveSensitivity0.000.100.200.300.400.500.600.700.800.901.00.00.10.20.

30.40.50.60.70.80.901-SpecificityFalsePositive6.88mg/dLCut-OffValueCut-OffValueofRemLCBasedonROCCurveforScreeningMetabo

licSyndrome(AbdominalCircumferenceofWomen≥80cm)The4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件Sensitivity0.81Specificity0.63Odd

sRatio1647AUC0.75p=0.0000DifferenceFullReducedModel18.51012257.29236275.80248-LogLikelihood1DF37.02024ChiSquare<.0001Prob>ChiSqRSquare(U)Observations

(orSumWgts)0.0671711ConvergedbyGradientWholeModelTestLackOfFitSaturatedFittedSource5005011DF207.969044

9.32332257.29236-LogLikelihood415.9381ChiSquare0.9975Prob>ChiSqLackOfFitInterceptRemLCTerm-2.67010310.11326969Estimate0.19397980.02

18623StdError189.4726.84ChiSquare<.0001<.0001Prob>ChiSq-3.0675730.07291559Lower95%-2.30654810.15834166Upp

er95%.1646.9906OddsRatio.117.677833OddsLower.31381.1116OddsUpperForlogoddsof0/1ParameterEstimatesRemLCSource1Nparm1DF2

6.8433082WaldChiSquare0.0000Prob>ChiSqEffectWaldTestsRemLCSource1Nparm1DF37.0202361L-RChiSquare0.0000Prob>ChiSqEffect

LikelihoodRatioTestsNominalLogisticFitforMSF80M85-DxTruePositiveSensitivity0.000.100.200.300.400.500.600.700.800.901.00.00.10.20.30.4

0.50.60.70.80.901-SpecificityFalsePositive7.27mg/dLCut-OffValueCut-OffValueofRemLCBasedonROCCurveforScreeningMetabolicSyndrome(A

bdominalCircumferenceofMen≥85cm)The4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件0%10%20%30%40%50%60%70%

80%90%100%<5050-6060-7070-7575-8080-85≥85abnormalnormalAbnormalandNormalProportionofPlasmaBNPLevelsWithAdvancingAge

inGeneralPopulation,Japan[OkuizumoCohort2007]Cut-OffValue20pg/mLN=145N=322N=721N=341N=269N=132N=48YearsThe4thShino-JapanCardiovasc

ularForumonOctober23-24,2008inBeijing编辑课件0%10%20%30%40%50%60%70%80%90%100%<5050-6060-7070-7575-8080-85≥85a

bnormalnormalAbnormalandNormalProportionofNT-proBNPLevelsWithAdvancingAgeinGeneralPopulation,Japan[OkuizumoCohort2007]Cut-OffValue55pg/mLN=145N=322N

=721N=341N=269N=132N=48YearsThe4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件Campes

terol12345601丂MetaboEachPairStudent'st0.05012.00172t0.05Alpha10-0.55586-0.15586-0.15586-0.55586Abs(Dif)-LSD10Positivevaluessho

wpairsofmeansthataresignificantlydifferent.ComparisonsforeachpairusingStudent'stMeansComparisonsOnewayAnalysisofCampesterolBy丂Meta

boComparisonofCampesterolBetweenMetabo(0)andNon-Metabo(1)inGeneralPopulation,Japan[OkuizumoCohort2007]Campesterol(Absorp

tionMarkerofCholesterol)MetaboNon-MetaboNSThe4thShino-JapanCardiovascularForumonOctober23-24,2008inBeiji

ng编辑课件Sitosterol00.511.522.533.501丂MetaboEachPairStudent'st0.05012.00172t0.05Alpha10-0.237860.075470.07547-0.23786Abs(Dif)-LSD10Posi

tivevaluesshowpairsofmeansthataresignificantlydifferent.ComparisonsforeachpairusingStudent'stMeansComparisonsOnewayAnalysisofSitoste

rolBy丂MetaboComparisonofSitosterolBetweenMetabo(0)andNon-Metabo(1)inGeneralPopulation,Japan[OkuizumoCohort2007]Sitosterol(Absorptio

nMarkerofCholesterol)MetaboNon-Metabop<0.05The4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件Lathosterol0.511.522.533.544

.501丂MetaboEachPairStudent'st0.05012.00172t0.05Alpha01-0.32369-0.06369-0.06369-0.32369Abs(Dif)-LSD01Positivevaluesshowpairsofmeansthatar

esignificantlydifferent.ComparisonsforeachpairusingStudent'stMeansComparisonsOnewayAnalysisofLathosterolBy丂MetaboComparisonofLatho

sterolBetweenMetabo(0)andNon-Metabo(1)inGeneralPopulation,Japan[OkuizumoCohort2007]Lathosterol(Synthes

isMarkerofCholesterol)MetaboNon-MetaboNSThe4thShino-JapanCardiovascularForumonOctober23-24,2008inBeij

ing编辑课件SummaryResultsHighbloodpressurewas52%,highcholesterol25%,lowHDL-cholesterol5%,hightriglyceridemia18%,highbloo

dsugar17%andinwomen,abdominalcircumference≥90cm10%and≥80cm44%,respectively.AccordingtoJapaneseabdomin

alcircumferencecriteriaforMSinwomen,only3%ofwomenwerediagnosedasMS.Using≥80cmascriteriaforabdominalcircumference,10%werediagnose

dasMS.Inmen(≥85cm),13%wereMS.Participantswithpossiblecardiacdysfunctionwere46%inBNPand52%inNT-proBNP,respectively.Rem

LCwasverycloselyrelatedtoMS.Receiveroperatingcharacteristic(ROC)curveanalysisfordiagnosingMSdemonstratedthatcut-offvalueofLemLCwas7.26mg/dlu

singfemalewaistcircumference≥80cmandmalewaistcircumference≥85cm,7.28mg/dlonlyusingmalewaistcircumference≥85cmand

6.88mg/dlonlyusingfemalewaistcircumference≥80cm.The4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件SummaryResults（

Continued)AbsorptionofcholesterolmarkerlevelswereparadoxicallylowerinMSthaninnonMS.Lathosterol,amarke

rofcholesterolsynthesiswas2.4μg/mLinMSand2.8μg/mLinnonMS(p=0.1133),sitosterol,amarkerofcholesterolabsorption1.5μg/mLinMSand1.8μg/mLinnonMS(p=0.0107)

,campesterol,amarkerofcholesterolabsorption,2.4μg/mLinMSand2.8μg/mLinnonMS(p=0.1551).CKDwasfoundin9.5%oftheparticipants

usingMDRD.The4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件ConclusionMSwasfoundinabout10%ingeneralpopulationofJapan

.Absorptioncholesterolmarker,plantsterolswereparadoxicallylowerinMSthaninnonMSandthenabnormalabsorptionwasstronglysuspectedinMS.Inoth

erwords,lowplantsterollevelsmayimplicateincreasedcholesterolabsorptioninthesmallintestine.RemLCmaybeausefulsinglemarkerforscreeningof

MS.PresentJapanesecriteriaforMSshouldbemodifiedcorrectlyasearlyaspossible.WeneedmoredetailinvestigationformoreclarificationonMS.The4thS

hino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件Thankyouverymuchforyourattention(BeijingOlympicYear)TheLakeShinji,Shi

mane