The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing Frequency of Metabolic Syndrome and its Absorption Abnormality by Plant Sterols in General Population, JapanToshio Shimada, Yo Murakami, Nobuyuki Oyake, Hiroyuki Yoshitomi, Nobuhiro Kodani, Akira Matsumori*Division of Cardiovascular Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine, Department of Cardiovascular Medicine, Kyoto University, Graduate School of Medicine*The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing 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 issue for vascular prevention and reduction of mortality.The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing 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 areaMale 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 translated into English by Toshio ShimadaMajor CriteriaMinor CriteriaThe 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing ObesityInsulin ResistanceDMDyslipidemiaHypertensionAtherosclerosisArteriosclerosisPathophysiology of Metabolic SyndrmeOver-eatingPoor ExerciseInheritanceThe 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing LDL ISynthesis of Cholesterol in the Liver and Absorption of Cholesterol in the Intestine- Two Important Supply Sources of Cholesterol in Vivo-BileFoodLiverVesselsCholesterolSmall IntestineBiliary8002000mg/dayDietary400500mg/dayThe 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing AimOur purpose is to investigate the frequency of metabolic syndrome (MS) and life style related diseases and also to examinewhether 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.The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing Subjects and method In 2007, 1980 participants for annual health check-up were subjected 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) measurements. 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 chosen randomly from the participants. BNP and NT-proBNP were measured for heart failure screening by immunoluminesence method. Plant sterols were measured by gas chromatography.The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing In 1964 participants, 218 participants(11%) were diagnosed as MS, using 80cm waist circumference in female and 85cm 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 Plant Sterols to Evaluate Cholesterol Absorptionin Okuizumo Cohort, 2007The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing Abnormal and Normal Proportion of Clinical Paramerers in General Population, JapanOkuizumo Cohort 20070%10%20%30%40%50%60%70%80%90%100%SystBP(130mmHg)DiastBP(85mmHg)Gender(F/M)WaistCircum90-85WaistCircum80-85Metabo90-85Metabo80-85CKDnormalabnormalN=1972N=1972N=1972N=1972N=1972N=1972N=1972N=1980N=1964N=1964N=1964N=1964N=1980DM(HbA1c5.8%）（220mg/dL）TG(150mg/dL）LowHDL(40mg/dL）Obesity(BMI25）The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing TruePositiveSensitivity0.000.100.200.300.400.500.600.700.800.901.00.00 .10 .20 .30 .40 .50 .60 .70 .80 .901-SpecificityFalsePositiveUsingMSF90M85-Dx=0tobethepositivelevelAreaUnderCurve= 0.93304ReceiverOperatingCharacteristicReceiverOperatingCharacteristicMetabolic Syndrome and its Influential Factors Analyzedby Multivariate Logistic RegressionFemale Waist Circumference 90cm90cmInfluential ParametersBMIHbCystatin CInsulinRem LC TchoThe 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing TruePositiveSensitivity0.000.100.200.300.400.500.600.700.800.901.00.00 .10 .20 .30 .40 .50 .60 .70 .80 .901-SpecificityFalsePositiveUsingAbd-CF80M85=0tobethepositivelevelAreaUnderCurve= 0.89483ReceiverOperatingCharacteristicReceiverOperatingCharacteristicMetabolic Syndrome and its Influential Factors Analyzed by Multivariate Logistic Regression Female Waist Circumference 80cm80cmInfluential ParametersBMIHbCystatin CRem LC TchoThe 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing TruePositiveSensitivity0.000.100.200.300.400.500.600.700.800.901.00.00 .10 .20 .30 .40 .50 .60 .70 .80 .901-SpecificityFalsePositiveSensitivity 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)The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing Cut-Off Value of Rem LC Based on ROC Curve for Screening Metabolic Syndrome(Abdominal Circumference of Women 80 cmand that of Men 85 cm)TruePositiveSensitivity0.000.100.200.300.400.500.600.700.800.901.00.00 .10 .20 .30 .40 .50 .60 .70 .80 .901-SpecificityFalsePositive7.26mg/dLCut-Off ValueSensitivity 0.82Specificity 0.67Odds Ratio 429156AUC 0.79p = 0.0000 The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing Cut-Off Value of Rem LC Based on ROC Curve for Screening Metabolic Syndrome(Abdominal Circumference of Women 90 cm)Sensitivity 0.89Specificity 0.70Odds Ratio 300AUC 0.83p = 0.0000 TruePositiveSensitivity0.000.100.200.300.400.500.600.700.800.901.00.00 .10 .20 .30 .40 .50 .60 .70 .80 .901-SpecificityFalsePositive6.19mg/dLCut-Off ValueThe 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing Sensitivity 0.80Specificity 0.72Odds Ratio 429156AUC 0.82p = 0.0000 TruePositiveSensitivity0.000.100.200.300.400.500.600.700.800.901.00.00 .10 .20 .30 .40 .50 .60 .70 .80 .901-SpecificityFalsePositive6.88mg/dLCut-Off ValueCut-Off Value of Rem LC Based on ROC Curve for Screening Metabolic Syndrome(Abdominal Circumference of Women 80cm)The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing Sensitivity 0.81Specificity 0.63Odds Ratio 1647AUC 0.75p = 0.0000 TruePositiveSensitivity0.000.100.200.300.400.500.600.700.800.901.00.00 .10 .20 .30 .40 .50 .60 .70 .80 .901-SpecificityFalsePositive7.27mg/dLCut-Off ValueCut-Off Value of Rem LC Based on ROC Curve for Screening Metabolic Syndrome(Abdominal Circumference of Men 85cm)The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing Abnormal and Normal Proportion of Plasma BNP Levels With Advancing Age in General Population, JapanOkuizumo Cohort 2007Cut-Off Value 20pg/mLN=145N=322N=721N=341N=269N=132N=48Years The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing 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 The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing Comparison of Campesterol Between Metabo(0) and Non-Metabo(1) in General Population, JapanOkuizumo Cohort 2007Campesterol(Absorption Marker of Cholesterol)MetaboNon-MetaboNSThe 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing Comparison of Sitosterol Between Metabo(0) and Non-Metabo(1) in General Population, JapanOkuizumo Cohort 2007Sitosterol(Absorption Marker of Cholesterol)MetaboNon-Metabop0.05The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing Comparison of Lathosterol Between Metabo(0) and Non-Metabo(1) in General Population, JapanOkuizumo Cohort 2007Lathosterol(Synthesis Marker of Cholesterol)MetaboNon-MetaboNSThe 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing 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%, respectively. According to Japanese abdominal circumference criteria for MS in women, only 3% of women were diagnosed as MS. Using 80cm as criteria for abdominal circumference, 10% were diagnosed as MS. In men (85cm), 13% were MS. Participants with possible cardiac dysfunction were 46% in BNP and 52% in NT-proBNP, respectively. RemLC was very closely related to MS. Receiver operating characteristic (ROC) curve analysis for diagnosing MS demonstrated that cut-off value of LemLC was 7.26mg/dl using female waist circumference 80cm and male waist circumference 85cm , 7.28mg/dl only using male waist circumference 85cm and 6.88mg/dl only using female waist circumference 80cm. The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing Summary Results（Continued)Absorption of cholesterol marker levels were paradoxically lower in MS than in non MS. Lathosterol, a marker of cholesterol synthesis was 2.4g/mL in MS and 2.8 g/mL in non MS (p=0.1133), sitosterol, a marker of cholesterol absorption 1.5 g/mL in MS and 1.8 g/mL in non MS (p=0.0107), campesterol, a marker of cholesterol absorption, 2.4 g/mL in MS and 2.8 g/mL in non MS (p=0.1551). CKD was found in 9.5% of the participants using MDRD.The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing ConclusionMS was found in about 10% in general population of Japan. Absorption cholesterol marker, plant sterols were paradoxically lower in MS than in non MS and then abnormal absorption was strongly suspected in MS. In other words, low plant sterol levels may implicate increased cholesterol absorption in the small intestine. RemLC may be a useful single marker for screening of MS. Present Japanese criteria for MS should be modified correctly as early as possible. We need more detail investigation for more clarification on MS.The 4th Shino-Japan Cardiovascular Forum on October 23-24, 2008 in Beijing Thank you very much for your attention(Beijing Olympic Year)The Lake Shinji, Shimane