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

byPlantSterolsinGeneralPopulation,JapanToshioShimada,YoMurakami,NobuyukiOyake,HiroyukiYoshitomi,Nobuhiro

Kodani,AkiraMatsumori*DivisionofCardiovascularMedicine,DepartmentofInternalMedicine,ShimaneUniversityFacultyofMedicin

e,DepartmentofCardiovascularMedicine,KyotoUniversity,GraduateSchoolofMedicine*The4thShino-JapanCardiovascularForumonOctober23-

24,2008inBeijing编辑课件BackgroundHealthproblemsonagedpeoplehavebeengrowingbiggerinJapanbecausewithadvancingage,a

varietyofdiseasesespeciallyonvasculardiseases,suchascardio-andcerebro-vasculardiseaseshavebeenincreasing.Andtheref

ore,earlydetectionofvasculardiseasesisaveryimportantissueforvascularpreventionandreductionofmortality.T

he4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件DiagnosticCriteriaforMetabolicSyndrome(8JapaneseMedicalAssociationsJoin

t-Committee)Fataccumulationintheintra-abdominalcavityAbdominalCircumferenceattheWaistMale≧85cm,Female≧90cm(≧80c

mrecommendedbyme)（VisceralfatareaMaleandFemale≧100cm2)•Hypertriglyceridemia≧150mg/dL•LowHDL-cho＜40mg/dL•SystolicBloodPressure≧130mm

Hg•DiastolicBloodPressure≧85mmHg•FastingBloodSugar≧110mg/dL•Lipoproteinabnormality•HighBloodPressure•HighBloodSugar＋Atleast,more

thanfollowing2itemsand/orand/ormodifiedandtranslatedintoEnglishbyToshioShimada•MajorCriteria•MinorCr

iteriaThe4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件ObesityInsulinResistanceDMDyslipidemiaHypertensionAtherosclerosisArteri

osclerosisPathophysiologyofMetabolicSyndrmeOver-eatingPoorExerciseInheritanceThe4thShino-JapanCardiovascularForumonOctobe

r23-24,2008inBeijing编辑课件LDLレセプタISynthesisofCholesterolintheLiverandAbsorptionofCholesterolintheIntes

tine-TwoImportantSupplySourcesofCholesterolinVivo-BileFoodLiverVesselsCholesterolSmallIntestineBiliary800~2000mg/dayDietary400

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

frequencyofmetabolicsyndrome(MS)andlifestylerelateddiseasesandalsotoexaminewhetheranydifferenceinabsorptionofcholesterolfromth

edigestivesystemispresentinparticipantsbetweenwithmetabolicsyndrome(MS)andnon-MSrandomlyselected,usingplantsterolsingeneralpopula

tion.The4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件SubjectsandmethodIn2007,1980participantsforannualhealthchec

k-upweresubjectedforthiscohortstudy.Averageageis66±10.8years,andfemaleis1260(64%)；maleis720(36%).Allsubjectsunderwentroutinebloodexaminations,insul

in,remnantlikeparticlecholesterol(RemLC),hs-CRP,cystatinC,plasmabrainnatriureticpeptide(BNP)andN-terminalproBNP(NT-proBNP

)measurements.Bloodpressure,abdominalcircumference,andelectrocardiographyweremeasuredatthesametime.Abdominalc

ircumferencewasmeasuredatthenavellevelinthesupinepositionlikeCTforvisceralfat.Evaluationofcholesterolabs

orptionwasdonebyplantsterolsineach30participantschosenrandomlyfromtheparticipants.BNPandNT-proBNPweremeasuredforh

eartfailurescreeningbyimmunoluminesencemethod.Plantsterolsweremeasuredbygaschromatography.The4thShino-JapanCardiovascularForu

monOctober23-24,2008inBeijing编辑课件✓In1964participants,218participants(11%)werediagnosedasMS,using≥80cmwaistcircumferencei

nfemaleand≥85cminmaleasmajorcriterion.✓Fromeachgroup,30participantswererandomlychosentocheckplantsterollevelsfortheeval

uationofabsorptionofcholesterolandlathosterolfortheevaluationofcholesterolsynthesis.✓Eachsterollevelwasmeasur

edbygaschromatography.TheMeasurementofSerumPlantSterolstoEvaluateCholesterolAbsorptioninOkuizumoCohort,2007The4thShino-J

apanCardiovascularForumonOctober23-24,2008inBeijing编辑课件AbnormalandNormalProportionofClinicalParamerersinGeneralPopulation,Japan[OkuizumoCoho

rt2007]0%10%20%30%40%50%60%70%80%90%100%normalabnormalThe4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件DifferenceFull

ReducedModel190.26599288.24139478.50738-LogLikelihood10DF380.532ChiSquare<.0001Prob>ChiSqRSquare(U)Observations(orSumWgts)0.39761963Conver

gedbyGradientWholeModelTestInterceptageBMIHbCystatinCBNPpg/mlInsulinhsCRPRemLCGGTTchoTerm-22.8051470.021023040.

482891490.424063531.29025592-0.00157170.02058377-0.05252970.120160870.00117904-0.0074947Estimate2.29055890.01305390.04313070.08849030.55992250

.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-27.458855-0.00405540.401298640.251751980.20551102-0.00875

360.00772354-0.21378630.08321302-0.0027261-0.0152304Lower95%-18.4677920.047165930.570650550.599081832.40457893

0.00325560.03406730.033278730.160522370.004029270.00004675Upper95%.4.83909518795859.059378.75497325.49652980.2377459360.10967020.001959

082584.58234.304435430.19083836OddsRatio.0.7377444680128.69133.93774411.675032670.000335214.650543229.5313

e-12230.7418110.034219130.03453053OddsLower.34.37896659402299.584390.26855418.00488219.601818879.53493551.944975836190.7207146.677772

1.01038549OddsUpperForlogoddsof0/1ParameterEstimatesageBMIHbCystatinCBNPpg/mlInsulinhsCRPRemLCGGTTchoSourc

e1111111111Nparm1111111111DF2.68235372178.17741223.54888125.453240540.285352510.0994580.8340345741.867040.441615913.79336512L-RChiSquare0.10150

.00000.00000.01950.59320.00150.36110.00000.50630.0515Prob>ChiSqEffectLikelihoodRatioTestsNominalLogisticFitforMSF90M85-DxTruePositiveSensiti

vity0.000.100.200.300.400.500.600.700.800.901.00.00.10.20.30.40.50.60.70.80.901-SpecificityFalsePositiveU

singMSF90M85-Dx='0'tobethepositivelevelAreaUnderCurve=0.93304ReceiverOperatingCharacteristicMetabolicSyndromeanditsInfluentialFactor

sAnalyzedbyMultivariateLogisticRegressionFemaleWaistCircumference≥90cmInfluentialParameters✓BMI✓Hb✓Cys

tatinC✓Insulin✓RemLC✓TchoThe4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件DifferenceFullReducedM

odel550.5289761.51871312.0476-LogLikelihood10DF1101.058ChiSquare<.0001Prob>ChiSqRSquare(U)Observations(orSumWgts)0.41961963Convergedby

GradientWholeModelTestInterceptageBMIHbCystatinCBNPpg/mlInsulinhsCRPRemLCGGTTchoTerm-18.6015930.009407250.837

09624-0.1869676-0.958875-0.00192810.00615102-0.0044340.036492640.000503370.00580768Estimate1.26844290.00730960.03993060.05363570.41153680.00171970.0

0584050.01256940.01481360.00145630.0022599StdError215.061.66439.4812.155.431.261.110.126.070.126.60ChiSquare<.00010.1981<.00010.00050.01980.

26220.29230.72430.01380.72960.0102Prob>ChiSq-21.142974-0.0048660.76108626-0.2926968-1.7654754-0.0055659-0.0050259-0.0325722

0.00721438-0.0024910.00139564Lower95%-16.1676860.023805080.91770739-0.0823535-0.1522810.001173960.017786840.0177564

20.065700640.003069310.01026077Upper95%.2.024947251.69491e100.07298170.09010530.171655033.400942920.59

07795810.87268681.864833873.60924199OddsRatio.0.6942320719967329170.016609920.01189850.006174970.367824390.020935151.602793420.

04578181.36129396OddsLower.5.961850841.63756e110.315704220.682341322.924127634.45250458.2291869173.417666944.69229859.65649116OddsUpperForlogoddsof0

/1ParameterEstimatesageBMIHbCystatinCBNPpg/mlInsulinhsCRPRemLCGGTTchoSource1111111111Nparm1111111111DF1.6649

1762952.81688212.35061455.392804081.40145031.135766870.130256865.934509040.116323366.66824093L-RChiSquare0.19690.00000.0004

0.02020.23650.28650.71820.01480.73310.0098Prob>ChiSqEffectLikelihoodRatioTestsNominalLogisticFitforAbd-CF80M85Tr

uePositiveSensitivity0.000.100.200.300.400.500.600.700.800.901.00.00.10.20.30.40.50.60.70.80.901-SpecificityFalsePositiveUsing

Abd-CF80M85='0'tobethepositivelevelAreaUnderCurve=0.89483ReceiverOperatingCharacteristicMetabolicSyndromeanditsInfluentialFactorsAnalyzedbyMultivar

iateLogisticRegressionFemaleWaistCircumference≥80cmInfluentialParameters✓BMI✓Hb✓CystatinC✓RemLC✓TchoThe4thShino-JapanCardiovascularForumonOctober2

3-24,2008inBeijing编辑课件DifferenceFullReducedModel36.14842442.42746478.57588-LogLikelihood1DF72.29684ChiSquare<.0001Pro

b>ChiSqRSquare(U)Observations(orSumWgts)0.07551964ConvergedbyGradientWholeModelTestLackOfFitSaturatedFitt

edSource8648651DF307.65972134.76773442.42746-LogLikelihood615.3194ChiSquare1.0000Prob>ChiSqLackOfFitInterceptRemLCTerm-3.56518450.13107891Estimate0.1

5930540.016439StdError500.8463.58ChiSquare<.0001<.0001Prob>ChiSq-3.88732440.09953428Lower95%-3.26243630.16394934Upper95%.5277.7231OddsRatio.670.850

599OddsLower.45281.1913OddsUpperForlogoddsof0/1ParameterEstimatesRemLCSource1Nparm1DF63.5795227WaldChiSquare0.0000Prob>ChiSqEff

ectWaldTestsRemLCSource1Nparm1DF72.2968416L-RChiSquare0.0000Prob>ChiSqEffectLikelihoodRatioTestsNominalLog

isticFitforMSF90M85-DxTruePositiveSensitivity0.000.100.200.300.400.500.600.700.800.901.00.00.10.20.30.40.50.60.70.80.901-Specifici

tyFalsePositiveSensitivity0.81Specificity0.65OddsRatio5278AUC0.77p=0.0000Cut-OffValue7.34mg/dLCut-OffValueofRemLCBasedonROCCurveforScreen

ingMetabolicSyndrome(AbdominalCircumferenceofWomen≥90cmandthatofMen≥85cm)The4thShino-JapanCardiovascularForumonO

ctober23-24,2008inBeijing编辑课件Cut-OffValueofRemLCBasedonROCCurveforScreeningMetabolicSyndrome(AbdominalCircumferenceofWomen≥80cmandthatof

Men≥85cm)DifferenceFullReducedModel86.39771598.24630684.64401-LogLikelihood1DF172.7954ChiSquare<.0001Prob>ChiSqRSquare(U)Observations(orSumWgts)0.

12621964ConvergedbyGradientWholeModelTestLackOfFitSaturatedFittedSource8648651DF392.34823205.89806598.24630-LogLikelihood784.6965ChiSquar

e0.9746Prob>ChiSqLackOfFitInterceptRemLCTerm-3.45451880.19834187Estimate0.14984460.0170002StdError531.49136

.12ChiSquare<.0001<.0001Prob>ChiSq-3.75578580.16563887Lower95%-3.16806380.23230396Upper95%.429155.572OddsRatio.505

70.6136OddsLower.3954464.4OddsUpperForlogoddsof0/1ParameterEstimatesRemLCSource1Nparm1DF136.120162WaldChiSquare0.0000Prob>ChiS

qEffectWaldTestsRemLCSource1Nparm1DF172.795429L-RChiSquare0.0000Prob>ChiSqEffectLikelihoodRatioTestsNominalLogisticFitforMSF80M85-DxTruePositiveSe

nsitivity0.000.100.200.300.400.500.600.700.800.901.00.00.10.20.30.40.50.60.70.80.901-SpecificityFalsePositive7.26mg/dLCut-OffValueSensitivity

0.82Specificity0.67OddsRatio429156AUC0.79p=0.0000The4thShino-JapanCardiovascularForumonOctober23-24,2008inBe

ijing编辑课件Cut-OffValueofRemLCBasedonROCCurveforScreeningMetabolicSyndrome(AbdominalCircumferenceofWomen≥90cm)DifferenceFullReducedModel16.90222149.8

7402166.77624-LogLikelihood1DF33.80444ChiSquare<.0001Prob>ChiSqRSquare(U)Observations(orSumWgts)0.10131253ConvergedbyGradientWholeModelTestLackOfF

itSaturatedFittedSource6746751DF124.8244025.04962149.87402-LogLikelihood249.6488ChiSquare1.0000Prob>ChiSqLackOfFitInterceptRemLCTerm-4.73714

260.16928943Estimate0.30152180.0270757StdError246.8339.09ChiSquare<.0001<.0001Prob>ChiSq-5.36145690.11619794Lower95%-4.17452420.

22315915Upper95%.300.381681OddsRatio.50.1927448OddsLower.1845.42194OddsUpperForlogoddsof0/1ParameterEstimatesRemLCSource1Npa

rm1DF39.093168WaldChiSquare0.0000Prob>ChiSqEffectWaldTestsRemLCSource1Nparm1DF33.8044417L-RChiSquare0.0000Prob>ChiSqEffectLikeli

hoodRatioTestsNominalLogisticFitforMSF90M85-DxSensitivity0.89Specificity0.70OddsRatio300AUC0.83p=0.0000Tru

ePositiveSensitivity0.000.100.200.300.400.500.600.700.800.901.00.00.10.20.30.40.50.60.70.80.901-SpecificityFalsePositive6.19m

g/dLCut-OffValueThe4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件Sensitivity0.80Specificity0.72OddsRatio4

29156AUC0.82p=0.0000DifferenceFullReducedModel78.47062328.19877406.66940-LogLikelihood1DF156.9412ChiSquare<.0001Prob>ChiSqRSquare(U)Observati

ons(orSumWgts)0.19301253ConvergedbyGradientWholeModelTestLackOfFitSaturatedFittedSource6746751DF244.7592

483.43953328.19877-LogLikelihood489.5185ChiSquare1.0000Prob>ChiSqLackOfFitInterceptRemLCTerm-4.1308570.27163009Estimate0.22042030.024300

2StdError351.22124.95ChiSquare<.0001<.0001Prob>ChiSq-4.57858840.22521655Lower95%-3.71348570.32058974Upper95%.9451.54891OddsRatio.1977.913

64OddsLower.49211.0934OddsUpperForlogoddsof0/1ParameterEstimatesRemLCSource1Nparm1DF124.950051WaldChiSquare0.0000Prob>ChiSqEf

fectWaldTestsRemLCSource1Nparm1DF156.941249L-RChiSquare0.0000Prob>ChiSqEffectLikelihoodRatioTestsNom

inalLogisticFitforMSF80M85-DxTruePositiveSensitivity0.000.100.200.300.400.500.600.700.800.901.00.00.10.20.30.40.50.60.70.80.901-Specificit

yFalsePositive6.88mg/dLCut-OffValueCut-OffValueofRemLCBasedonROCCurveforScreeningMetabolicSyndrome(AbdominalCircumferenceof

Women≥80cm)The4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件Sensitivity0.81Specificity0.63OddsRatio1647AUC

0.75p=0.0000DifferenceFullReducedModel18.51012257.29236275.80248-LogLikelihood1DF37.02024ChiSquare<.0001Prob>ChiSqRSquare(U)Observations(orS

umWgts)0.0671711ConvergedbyGradientWholeModelTestLackOfFitSaturatedFittedSource5005011DF207.9690449.32332257.29236-LogLikel

ihood415.9381ChiSquare0.9975Prob>ChiSqLackOfFitInterceptRemLCTerm-2.67010310.11326969Estimate0.19397980.0218623StdError189.47

26.84ChiSquare<.0001<.0001Prob>ChiSq-3.0675730.07291559Lower95%-2.30654810.15834166Upper95%.1646.990

6OddsRatio.117.677833OddsLower.31381.1116OddsUpperForlogoddsof0/1ParameterEstimatesRemLCSource1Nparm1DF26.8433082WaldChiSqu

are0.0000Prob>ChiSqEffectWaldTestsRemLCSource1Nparm1DF37.0202361L-RChiSquare0.0000Prob>ChiSqEffectLikelihoodRatioTestsNominalLogisticFi

tforMSF80M85-DxTruePositiveSensitivity0.000.100.200.300.400.500.600.700.800.901.00.00.10.20.30.40.50.60.70.80.901-SpecificityFalsePositi

ve7.27mg/dLCut-OffValueCut-OffValueofRemLCBasedonROCCurveforScreeningMetabolicSyndrome(AbdominalCircumferenceofMen≥85cm)The4thSh

ino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件0%10%20%30%40%50%60%70%80%90%100%<5050-6060-7070-7575-8080-85≥85abnormalnormalAbnormala

ndNormalProportionofPlasmaBNPLevelsWithAdvancingAgeinGeneralPopulation,Japan[OkuizumoCohort2007]Cut-Of

fValue20pg/mLN=145N=322N=721N=341N=269N=132N=48YearsThe4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件0%10%20%30%40%50%60%70%80%

90%100%<5050-6060-7070-7575-8080-85≥85abnormalnormalAbnormalandNormalProportionofNT-proBNPLevelsWithAdvancingAgeinGeneralPo

pulation,Japan[OkuizumoCohort2007]Cut-OffValue55pg/mLN=145N=322N=721N=341N=269N=132N=48YearsThe4thShino

-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件Campesterol12345601丂MetaboEachPairStudent'st0.05012.00172t0.05Alpha10-0.55586-0.

15586-0.15586-0.55586Abs(Dif)-LSD10Positivevaluesshowpairsofmeansthataresignificantlydifferent.ComparisonsforeachpairusingStudent'stMeans

ComparisonsOnewayAnalysisofCampesterolBy丂MetaboComparisonofCampesterolBetweenMetabo(0)andNon-Metabo(1)inGeneralPop

ulation,Japan[OkuizumoCohort2007]Campesterol(AbsorptionMarkerofCholesterol)MetaboNon-MetaboNSThe4thShino-JapanCardiovascularForumo

nOctober23-24,2008inBeijing编辑课件Sitosterol00.511.522.533.501丂MetaboEachPairStudent'st0.05012.00172t0.05Alpha

10-0.237860.075470.07547-0.23786Abs(Dif)-LSD10Positivevaluesshowpairsofmeansthataresignificantlydifferent.ComparisonsforeachpairusingStudent'stMe

ansComparisonsOnewayAnalysisofSitosterolBy丂MetaboComparisonofSitosterolBetweenMetabo(0)andNon-Metabo(1)inGeneralPopulation,Japan[OkuizumoCohort2

007]Sitosterol(AbsorptionMarkerofCholesterol)MetaboNon-Metabop<0.05The4thShino-JapanCardiovascularForumonOctober23-24,2008

inBeijing编辑课件Lathosterol0.511.522.533.544.501丂MetaboEachPairStudent'st0.05012.00172t0.05Alpha01-0.32369-0.063

69-0.06369-0.32369Abs(Dif)-LSD01Positivevaluesshowpairsofmeansthataresignificantlydifferent.ComparisonsforeachpairusingStudent'stMeansCom

parisonsOnewayAnalysisofLathosterolBy丂MetaboComparisonofLathosterolBetweenMetabo(0)andNon-Metabo(1)inGeneralPopulation,Japan[OkuizumoCoho

rt2007]Lathosterol(SynthesisMarkerofCholesterol)MetaboNon-MetaboNSThe4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件SummaryRes

ultsHighbloodpressurewas52%,highcholesterol25%,lowHDL-cholesterol5%,hightriglyceridemia18%,highbloodsugar17%andinw

omen,abdominalcircumference≥90cm10%and≥80cm44%,respectively.AccordingtoJapaneseabdominalcircumferencecriteriaforMSinwomen,only3%of

womenwerediagnosedasMS.Using≥80cmascriteriaforabdominalcircumference,10%werediagnosedasMS.Inmen(≥85cm),13%wereMS.Participantswithpossiblecardiac

dysfunctionwere46%inBNPand52%inNT-proBNP,respectively.RemLCwasverycloselyrelatedtoMS.Receiveroperatingcharacteristic(ROC)curveanalysisfo

rdiagnosingMSdemonstratedthatcut-offvalueofLemLCwas7.26mg/dlusingfemalewaistcircumference≥80cmandmalewaistcircumfere

nce≥85cm,7.28mg/dlonlyusingmalewaistcircumference≥85cmand6.88mg/dlonlyusingfemalewaistcircumference≥80cm.The4thShino-Jap

anCardiovascularForumonOctober23-24,2008inBeijing编辑课件SummaryResults（Continued)AbsorptionofcholesterolmarkerlevelswereparadoxicallylowerinMSthanin

nonMS.Lathosterol,amarkerofcholesterolsynthesiswas2.4μg/mLinMSand2.8μg/mLinnonMS(p=0.1133),sitosterol,amarkerofcholesterolabs

orption1.5μg/mLinMSand1.8μg/mLinnonMS(p=0.0107),campesterol,amarkerofcholesterolabsorption,2.4μg/mLinMSand2.8μg/mLinnonMS(p=0

.1551).CKDwasfoundin9.5%oftheparticipantsusingMDRD.The4thShino-JapanCardiovascularForumonOctober23-24,2

008inBeijing编辑课件ConclusionMSwasfoundinabout10%ingeneralpopulationofJapan.Absorptioncholesterolmarker,plant

sterolswereparadoxicallylowerinMSthaninnonMSandthenabnormalabsorptionwasstronglysuspectedinMS.Inotherwords,lowp

lantsterollevelsmayimplicateincreasedcholesterolabsorptioninthesmallintestine.RemLCmaybeausefulsinglemark

erforscreeningofMS.PresentJapanesecriteriaforMSshouldbemodifiedcorrectlyasearlyaspossible.Weneedmoredetailinvestigationformore

clarificationonMS.The4thShino-JapanCardiovascularForumonOctober23-24,2008inBeijing编辑课件Thankyouverymuchforyourattention(BeijingOlympicYea

r)TheLakeShinji,Shimane