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1、BackgroundHealth problems on aged people have been growing bigger in Japan because with advancing age, a variety of diseases especially on vascular diseases, such as cardio- and cerebro-vascular diseases have been increasing. And therefore, early detection of vascular diseases is a very important is

2、sue for vascular prevention and reduction of mortality.第1页/共25页Diagnostic Criteria for Metabolic Syndrome (8 Japanese Medical Associations Joint-Committee) Fat accumulation in the intra-abdominal cavityAbdominal Circumference at the WaistMale85cm, Female90cm( 80cm recommended by me)(Visceral fat are

3、aMale and Female 100 cm2)Hypertriglyceridemia 150 mg/dLLow HDL-cho 40 mg/dLSystolic Blood Pressure 130 mmHgDiastolic Blood Pressure 85 mmHgFasting Blood Sugar 110 mg/dL Lipoprotein abnormality High Blood Pressure High Blood Sugar At least, more than following 2 itemsand / orand / ormodified and tran

4、slated into English by Toshio ShimadaMajor CriteriaMinor Criteria第2页/共25页ObesityInsulin ResistanceDMDyslipidemiaHypertensionAtherosclerosisArteriosclerosisPathophysiology of Metabolic SyndrmeOver-eatingPoor ExerciseInheritance第3页/共25页LDLISynthesis of Cholesterol in the Liver and Absorption of Choles

5、terol in the Intestine- Two Important Supply Sources of Cholesterol in Vivo-BileFoodLiverVesselsCholesterolSmall IntestineBiliary8002000mg/dayDietary400500mg/day第4页/共25页AimOur purpose is to investigate the frequency of metabolic syndrome (MS) and life style related diseases and also to examinewhethe

6、r any difference in absorption of cholesterol from the digestive system is present in participants between with metabolic syndrome (MS) and non-MS randomly selected, using plant sterols in general population.第5页/共25页Subjects and method In 2007, 1980 participants for annual health check-up were subje

7、cted for this cohort study. Average age is 6610.8 years, and female is 1260(64%);male is 720(36%). All subjects underwent routine blood examinations, insulin, remnant like particle cholesterol (RemLC), hs-CRP, cystatin C, plasma brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) measu

8、rements. Blood pressure, abdominal circumference, and electrocardiography were measured at the same time. Abdominal circumference was measured at the navel level in the supine position like CT for visceral fat. Evaluation of cholesterol absorption was done by plant sterols in each 30 participants ch

9、osen randomly from the participants. BNP and NT-proBNP were measured for heart failure screening by immunoluminesence method. Plant sterols were measured by gas chromatography.第6页/共25页In 1964 participants, 218 participants(11%) were diagnosed as MS, using 80cm waist circumference in female and 85cm

10、in male as major criterion.From each group, 30 participants were randomly chosen to check plant sterol levels for the evaluation of absorption of cholesterol and lathosterol for the evaluation of cholesterol synthesis.Each sterol level was measured by gas chromatography.The Measurement of Serum Plan

11、t Sterols to Evaluate Cholesterol Absorptionin Okuizumo Cohort, 2007第7页/共25页Abnormal and Normal Proportion of Clinical Paramerers in General Population, JapanOkuizumo Cohort 20070%10%20%30%40%50%60%70%80%90%100%Syst BP(130mmHg)Diast BP(85mmHg)Gender(F/M)Waist Circum90-85Waist Circum80-85Metabo90-85M

12、etabo80-85CKDnormalabnormalN=1972N=1972N=1972N=1972N=1972N=1972N=1972N=1980N=1964N=1964N=1964N=1964N=1980DM (HbA1c 5.8% )(220mg/dL)TG (150mg/dL)LowHDL (40mg/dL)Obesity (BMI 25)第8页/共25页DifferenceFullReducedModel 190.26599 288.24139 478.50738-LogLikelihood 10DF 380.532ChiSquare ChiSqRSquare (U)Observa

13、tions (or Sum Wgts) 0.3976 1963Converged by GradientWhole Model TestWhole Model TestInterceptageBMIHbCystatinCBNPpg/mlInsulinhsCRPRemLCGGTTchoTerm-22.8051470.021023040.482891490.424063531.29025592-0.00157170.02058377-0.05252970.120160870.00117904-0.0074947Estimate2.29055890.01305390.04313070.0884903

14、0.55992250.0031283 0.0067180.06711130.01972250.00167760.0038915Std Error 99.12 2.59125.35 22.97 5.31 0.25 9.39 0.61 37.12 0.49 3.71ChiSquare.00010.1073.0001.00010.02120.61540.00220.4338ChiSq-27.458855-0.00405540.401298640.251751980.20551102-0.00875360.00772354-0.21378630.08321302-0.0027261-0.0152304

15、Lower 95%-18.4677920.047165930.570650550.599081832.40457893 0.0032556 0.03406730.033278730.160522370.004029270.00004675Upper 95% .4.83909518795859.059378.75497325.49652980.2377459360.10967020.00195908 2584.58234.304435430.19083836Odds Ratio .0.73774446 80128.69133.93774411.675032670.000335214.650543

16、229.5313e-12230.7418110.034219130.03453053Odds Lower .34.37896659402299.584390.26855418.004882 19.601818879.53493551.944975836190.7207146.6777721.01038549Odds UpperFor log odds of 0/1Parameter EstimatesParameter EstimatesageBMIHbCystatinCBNPpg/mlInsulinhsCRPRemLCGGTTchoSource 1 1 1 1 1 1 1 1 1 1Npar

17、m 1 1 1 1 1 1 1 1 1 1DF2.68235372178.17741223.54888125.45324054 0.2853525 10.0994580.83403457 41.867040.441615913.79336512L-R ChiSquare 0.1015 0.0000 0.0000 0.0195 0.5932 0.0015 0.3611 0.0000 0.5063 0.0515ProbChiSqEffect Likelihood Ratio TestsEffect Likelihood Ratio TestsNominal Logistic Fit for MSF

18、90M85-DxNominal Logistic Fit for MSF90M85-DxTrue PositiveSensitivity0.0000.400.500.600.700.800.901.00.00 .10 .20 .30 .40 .50 .60 .70 .80 .901-SpecificityFalse PositiveUsing MSF90M85-Dx=0 to be the positive levelArea Under Curve = 0.93304Receiver Operating CharacteristicReceiver Operating

19、CharacteristicMetabolic Syndrome and its Influential Factors Analyzedby Multivariate Logistic RegressionFemale Waist Circumference 90cm90cmInfluential ParametersBMIHbCystatin CInsulinRem LC Tcho第9页/共25页DifferenceFullReducedModel 550.5289 761.5187 1312.0476-LogLikelihood 10DF1101.058ChiSquare ChiSqRS

20、quare (U)Observations (or Sum Wgts) 0.4196 1963Converged by GradientWhole Model TestWhole Model TestInterceptageBMIHbCystatinCBNPpg/mlInsulinhsCRPRemLCGGTTchoTerm-18.6015930.009407250.83709624-0.1869676 -0.958875-0.00192810.00615102 -0.0044340.036492640.000503370.00580768Estimate1.26844290.00730960.

21、03993060.05363570.41153680.00171970.00584050.01256940.01481360.00145630.0022599Std Error215.06 1.66439.48 12.15 5.43 1.26 1.11 0.12 6.07 0.12 6.60ChiSquare.00010.1981ChiSq-21.142974 -0.0048660.76108626-0.2926968-1.7654754-0.0055659-0.0050259-0.03257220.00721438 -0.0024910.00139564Lower 95%-16.167686

22、0.023805080.91770739-0.0823535 -0.1522810.001173960.017786840.017756420.065700640.003069310.01026077Upper 95% .2.024947251.69491e10 0.0729817 0.09010530.171655033.400942920.5907795810.87268681.864833873.60924199Odds Ratio .0.6942320719967329170.01660992 0.01189850.006174970.367824390.020935151.60279

23、342 0.04578181.36129396Odds Lower .5.961850841.63756e110.315704220.68234132 2.924127634.45250458.2291869173.417666944.69229859.65649116Odds UpperFor log odds of 0/1Parameter EstimatesParameter EstimatesageBMIHbCystatinCBNPpg/mlInsulinhsCRPRemLCGGTTchoSource 1 1 1 1 1 1 1 1 1 1Nparm 1 1 1 1 1 1 1 1 1

24、 1DF1.66491762952.81688212.35061455.39280408 1.40145031.135766870.130256865.934509040.116323366.66824093L-R ChiSquare 0.1969 0.0000 0.0004 0.0202 0.2365 0.2865 0.7182 0.0148 0.7331 0.0098ProbChiSqEffect Likelihood Ratio TestsEffect Likelihood Ratio TestsNominal Logistic Fit for Abd-CF80M85Nominal Lo

25、gistic Fit for Abd-CF80M85True PositiveSensitivity0.0000.400.500.600.700.800.901.00.00 .10 .20 .30 .40 .50 .60 .70 .80 .901-SpecificityFalse PositiveUsing Abd-CF80M85=0 to be the positive levelArea Under Curve = 0.89483Receiver Operating CharacteristicReceiver Operating CharacteristicMeta

26、bolic Syndrome and its Influential Factors Analyzed by Multivariate Logistic Regression Female Waist Circumference 80cm80cmInfluential ParametersBMIHbCystatin CRem LC Tcho第10页/共25页DifferenceFullReducedModel 36.14842 442.42746 478.57588-LogLikelihood 1DF72.29684ChiSquare ChiSqRSquare (U)Observations

27、(or Sum Wgts) 0.0755 1964Converged by GradientWhole Model TestWhole Model TestLack Of FitSaturatedFittedSource 864 865 1DF 307.65972 134.76773 442.42746-LogLikelihood615.3194ChiSquare1.0000ProbChiSqLack Of FitLack Of FitInterceptRemLCTerm-3.56518450.13107891Estimate0.1593054 0.016439Std Error500.84

28、63.58ChiSquare.0001ChiSq-3.88732440.09953428Lower 95%-3.26243630.16394934Upper 95% . 5277.7231Odds Ratio .670.850599Odds Lower .45281.1913Odds UpperFor log odds of 0/1Parameter EstimatesParameter EstimatesRemLCSource 1Nparm 1DF63.5795227Wald ChiSquare 0.0000ProbChiSqEffect Wald TestsEffect Wald Test

29、sRemLCSource 1Nparm 1DF72.2968416L-R ChiSquare 0.0000ProbChiSqEffect Likelihood Ratio TestsEffect Likelihood Ratio TestsNominal Logistic Fit for MSF90M85-DxNominal Logistic Fit for MSF90M85-DxTrue PositiveSensitivity0.0000.400.500.600.700.800.901.00.00 .10 .20 .30 .40 .50 .60 .70 .80 .901

30、-SpecificityFalse PositiveSensitivity 0.81Specificity 0.65Odds Ratio 5278AUC 0.77p = 0.0000 Cut-Off Value7.34mg/dLCut-Off Value of Rem LC Based on ROC Curve for Screening Metabolic Syndrome(Abdominal Circumference of Women 90 cmand that of Men 85 cm)第11页/共25页Cut-Off Value of Rem LC Based on ROC Curv

31、e for Screening Metabolic Syndrome(Abdominal Circumference of Women 80 cmand that of Men 85 cm)DifferenceFullReducedModel 86.39771 598.24630 684.64401-LogLikelihood 1DF172.7954ChiSquare ChiSqRSquare (U)Observations (or Sum Wgts) 0.1262 1964Converged by GradientWhole Model TestWhole Model TestLack Of

32、 FitSaturatedFittedSource 864 865 1DF 392.34823 205.89806 598.24630-LogLikelihood784.6965ChiSquare0.9746ProbChiSqLack Of FitLack Of FitInterceptRemLCTerm-3.45451880.19834187Estimate0.14984460.0170002Std Error531.49136.12ChiSquare.0001ChiSq-3.75578580.16563887Lower 95%-3.16806380.23230396Upper 95% .4

33、29155.572Odds Ratio .50570.6136Odds Lower . 3954464.4Odds UpperFor log odds of 0/1Parameter EstimatesParameter EstimatesRemLCSource 1Nparm 1DF136.120162Wald ChiSquare 0.0000ProbChiSqEffect Wald TestsEffect Wald TestsRemLCSource 1Nparm 1DF172.795429L-R ChiSquare 0.0000ProbChiSqEffect Likelihood Ratio

34、 TestsEffect Likelihood Ratio TestsNominal Logistic Fit for MSF80M85-DxNominal Logistic Fit for MSF80M85-DxTrue PositiveSensitivity0.0000.400.500.600.700.800.901.00.00 .10 .20 .30 .40 .50 .60 .70 .80 .901-SpecificityFalse Positive7.26mg/dLCut-Off ValueSensitivity 0.82Specificity 0.67Odds

35、Ratio 429156AUC 0.79p = 0.0000 第12页/共25页Cut-Off Value of Rem LC Based on ROC Curve for Screening Metabolic Syndrome(Abdominal Circumference of Women 90 cm)DifferenceFullReducedModel 16.90222 149.87402 166.77624-LogLikelihood 1DF33.80444ChiSquare ChiSqRSquare (U)Observations (or Sum Wgts) 0.1013 1253

36、Converged by GradientWhole Model TestWhole Model TestLack Of FitSaturatedFittedSource 674 675 1DF 124.82440 25.04962 149.87402-LogLikelihood249.6488ChiSquare1.0000ProbChiSqLack Of FitLack Of FitInterceptRemLCTerm-4.73714260.16928943Estimate0.30152180.0270757Std Error246.83 39.09ChiSquare.0001ChiSq-5

37、.36145690.11619794Lower 95%-4.17452420.22315915Upper 95% .300.381681Odds Ratio .50.1927448Odds Lower .1845.42194Odds UpperFor log odds of 0/1Parameter EstimatesParameter EstimatesRemLCSource 1Nparm 1DF 39.093168Wald ChiSquare 0.0000ProbChiSqEffect Wald TestsEffect Wald TestsRemLCSource 1Nparm 1DF33.

38、8044417L-R ChiSquare 0.0000ProbChiSqEffect Likelihood Ratio TestsEffect Likelihood Ratio TestsNominal Logistic Fit for MSF90M85-DxNominal Logistic Fit for MSF90M85-DxSensitivity 0.89Specificity 0.70Odds Ratio 300AUC 0.83p = 0.0000 True PositiveSensitivity0.0000.400.500.600.700.800.901.00.

39、00 .10 .20 .30 .40 .50 .60 .70 .80 .901-SpecificityFalse Positive6.19mg/dLCut-Off Value第13页/共25页Sensitivity 0.80Specificity 0.72Odds Ratio 429156AUC 0.82p = 0.0000 DifferenceFullReducedModel 78.47062 328.19877 406.66940-LogLikelihood 1DF156.9412ChiSquare ChiSqRSquare (U)Observations (or Sum Wgts) 0.

40、1930 1253Converged by GradientWhole Model TestWhole Model TestLack Of FitSaturatedFittedSource 674 675 1DF 244.75924 83.43953 328.19877-LogLikelihood489.5185ChiSquare1.0000ProbChiSqLack Of FitLack Of FitInterceptRemLCTerm -4.1308570.27163009Estimate0.22042030.0243002Std Error351.22124.95ChiSquare.00

41、01ChiSq-4.57858840.22521655Lower 95%-3.71348570.32058974Upper 95% .9451.54891Odds Ratio .1977.91364Odds Lower .49211.0934Odds UpperFor log odds of 0/1Parameter EstimatesParameter EstimatesRemLCSource 1Nparm 1DF124.950051Wald ChiSquare 0.0000ProbChiSqEffect Wald TestsEffect Wald TestsRemLCSource 1Npa

42、rm 1DF156.941249L-R ChiSquare 0.0000ProbChiSqEffect Likelihood Ratio TestsEffect Likelihood Ratio TestsNominal Logistic Fit for MSF80M85-DxNominal Logistic Fit for MSF80M85-DxTrue PositiveSensitivity0.0000.400.500.600.700.800.901.00.00 .10 .20 .30 .40 .50 .60 .70 .80 .901-SpecificityFalse

43、 Positive6.88mg/dLCut-Off ValueCut-Off Value of Rem LC Based on ROC Curve for Screening Metabolic Syndrome(Abdominal Circumference of Women 80cm)第14页/共25页Sensitivity 0.81Specificity 0.63Odds Ratio 1647AUC 0.75p = 0.0000 DifferenceFullReducedModel 18.51012 257.29236 275.80248-LogLikelihood 1DF37.0202

44、4ChiSquare ChiSqRSquare (U)Observations (or Sum Wgts) 0.0671 711Converged by GradientWhole Model TestWhole Model TestLack Of FitSaturatedFittedSource 500 501 1DF 207.96904 49.32332 257.29236-LogLikelihood415.9381ChiSquare0.9975ProbChiSqLack Of FitLack Of FitInterceptRemLCTerm-2.67010310.11326969Esti

45、mate0.19397980.0218623Std Error189.47 26.84ChiSquare.0001ChiSq -3.0675730.07291559Lower 95%-2.30654810.15834166Upper 95% . 1646.9906Odds Ratio .117.677833Odds Lower .31381.1116Odds UpperFor log odds of 0/1Parameter EstimatesParameter EstimatesRemLCSource 1Nparm 1DF26.8433082Wald ChiSquare 0.0000Prob

46、ChiSqEffect Wald TestsEffect Wald TestsRemLCSource 1Nparm 1DF37.0202361L-R ChiSquare 0.0000ProbChiSqEffect Likelihood Ratio TestsEffect Likelihood Ratio TestsNominal Logistic Fit for MSF80M85-DxNominal Logistic Fit for MSF80M85-DxTrue PositiveSensitivity0.0000.400.500.600.700.800.901.00.0

47、0 .10 .20 .30 .40 .50 .60 .70 .80 .901-SpecificityFalse Positive7.27mg/dLCut-Off ValueCut-Off Value of Rem LC Based on ROC Curve for Screening Metabolic Syndrome(Abdominal Circumference of Men 85cm)第15页/共25页Abnormal and Normal Proportion of Plasma BNP Levels With Advancing Age in General Population,

48、 JapanOkuizumo Cohort 2007Cut-Off Value 20pg/mLN=145N=322N=721N=341N=269N=132N=48Years 第16页/共25页Abnormal and Normal Proportion of NT-proBNP Levels With Advancing Age in General Population, JapanOkuizumo Cohort 2007Cut-Off Value 55pg/mLN=145N=322N=721N=341N=269N=132N=48Years 第17页/共25页Campesterol12345

49、601丂MetaboEach PairStudents t 0.0501 2.00172t 0.05Alpha10-0.55586-0.15586-0.15586-0.55586Abs(Dif)-LSD10Positive values show pairs of means that are significantlydifferent.Comparisons for each pair using Students tComparisons for each pair using Students tMeans ComparisonsMeans ComparisonsOneway Anal

50、ysis of Campesterol By 丂MetaboOneway Analysis of Campesterol By 丂MetaboComparison of Campesterol Between Metabo(0) and Non-Metabo(1) in General Population, JapanOkuizumo Cohort 2007Campesterol(Absorption Marker of Cholesterol)MetaboNon-MetaboNS第18页/共25页Sitosterol00.511.522.533.501丂MetaboEach PairStu

51、dents t 0.0501 2.00172t 0.05Alpha10-0.23786 0.07547 0.07547-0.23786Abs(Dif)-LSD10Positive values show pairs of means that are significantlydifferent.Comparisons for each pair using Students tComparisons for each pair using Students tMeans ComparisonsMeans ComparisonsOneway Analysis of Sitosterol By

52、丂MetaboOneway Analysis of Sitosterol By 丂MetaboComparison of Sitosterol Between Metabo(0) and Non-Metabo(1) in General Population, JapanOkuizumo Cohort 2007Sitosterol(Absorption Marker of Cholesterol)MetaboNon-Metabop0.05第19页/共25页Lathosterol0.511.522.533.544.501丂MetaboEach PairStudents t 0.0501 2.00

53、172t 0.05Alpha01-0.32369-0.06369-0.06369-0.32369Abs(Dif)-LSD01Positive values show pairs of means that are significantlydifferent.Comparisons for each pair using Students tComparisons for each pair using Students tMeans ComparisonsMeans ComparisonsOneway Analysis of Lathosterol By 丂MetaboOneway Anal

54、ysis of Lathosterol By 丂MetaboComparison of Lathosterol Between Metabo(0) and Non-Metabo(1) in General Population, JapanOkuizumo Cohort 2007Lathosterol(Synthesis Marker of Cholesterol)MetaboNon-MetaboNS第20页/共25页Summary Results High blood pressure was 52%, high cholesterol 25%, low HDL-cholesterol 5%, high triglyceridemia 18%, high blood sugar 17% and in women, abdominal circumference 90cm 10% and 80cm 44%

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