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7 low density lipoprotein cholesterol LDL-C NHANES III Munster PROCAM high density lipoprotein cholesterol, HDL-C NHANES PROCAM 1.2~ PROCAM PROCAM NHANES III NHANES III 20 mg/dl 240 mg/dl NHANES III PROCAM 1/2 1/ mg/dl 198 mg/dl 201 mg/dl 205 mg/dl 30% 250 mg/dl NHANES III mg/dl 217 mg/dl 7

8 19 192mg/dl 195mg/dl 186mg/dl 188mg/dl 196mg/dl 181mg/dl % 13.1% 6.3% % 13.5% 7.4% NHANES III PROCAM NHANES III mg/dl 107mg/dl % 12.1% 5.0% % 10.7% 3.7% NHANES III PROCAM 19 55mg/dl 57mg/dl 50mg/dl, 61mg/dl 68mg/dl 56mg/dl % 17.3% 8.4% 19 8

9 7.7% 12.2% 2.1% A-I B-100 A-I B-100 B-100 PROCAM A-I PROCAM mg/dl 17.2% 5% PROCAM NHANES III PROCAM 12% 7% mg/dl 165mg/dl 107mg/dl 97mg/dl 154mg/dl 91mg/dl % 23.4% 6.8% % 23.7% 4.5% 1.9~1.12 9

10 A-I B-100 metabolic syndrome mg/dl Lp a A-I B-100 Lp a Lp a Woo Lp a 30 mg/dl Sandholzer Lp a 10

11 Apo a isoforms B, S1, S2 15.9% 8.5% X X VLDL Kylin 1920 Reaven Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation 1998 NCEP-ATP III NCEP-ATP III 11

12 III 1.13 NCEP- ATP III % 30 % 34.5% 30% P/S % mg/dl 13.6% mg/dl 3.3% mg/dl 3.6 % 12

13 mg/dl P/S P/S P/S P/S % P/S

14 plasma lipids cholesterol triacylglycerol ; TG phospholipids apolipoprotein lipoprotein chylomicrons very low-density lipoprotein VLDL intermediate-density lipoprotein low-density lipoprotein LDL high-density lipoprotein HDL a lipoprotein a 60-70% atherosclerosis LDL-C % HDL-C 10% free fatty acids FFA 14

15 2.1 fatty liver mg/dl 2 insulin resistance X Syndrome X small, dense-ldl 2.1 chylomicron 15

16 lipoprotein lipase chylomicron remnants VLDL IDL VLDL IDL LDL 50% LDL LDL receptor ApoB/E receptor HMG-CoA reductase HMG-CoA reductase 16

17 HDL 20-30% a Lp a a a a a ApoB-100 Apo a a Apo a a Apo a plasminogen a a a 17

18 apolipoproteins B-48 C-II E C-II C-II E C-II E VLDL IDL LDL HDL 18

19 2.1 g/ml <0.96 B-48, E, A-I, A-IV, Chylomicrons C-1, C-II, C-III <1.006 B-100, E, C-1, Very low density C-II, C-III lipoprotein VLDL B-100, E, Intermediate- C-II, C-III density lipoprotein VLDL B-100 Low-density lipoprotein / / A-I, A-II, E, C-I, High-density C-II, C-III lipoprotein a B-100, Apo a Lipoprotein a Lp a 2 HDL g/ml 3 HDL g/ml Thompson GR, Handbook of Hyperlipidemia,

20 2.3 mg/dl kda ApoA-I 130 ~29 HDL LCAT cofactor HDL ApoA-II 40 ~17 ApoA-I HDL ApoB ~550 IDL LDL LDL LDL ApoB-48 ~250 ApoC-I LCAT activator ; ApoC-II LPL ApoC-III ApoE 5 34 VLDL IDL VLDL IDL VLDL IDL LDL HDL ApoE4 Apo a Lp a LDL LCAT lecithin cholesterol acyltransferase LPL lipoprotein lipase 20

21 第二章 脂蛋白的代謝與檢測 圖2.1 外源性脂質 以三酸甘油酯為主 經小腸吸收成為乳糜微粒 chylomicrons 經脂蛋白脂 解瓷 LPL 分解成乳糜微粒殘體 chylomicron remnants 後者再由肝細胞攝取 內源性脂質 代謝起始於肝細胞釋放出極低密度脂蛋白 VLDL 經脂蛋白脂解瓷分解成中密度脂蛋白 IDL 後者一部份由肝細胞攝取 另一部份則進而代謝成低密度脂蛋白 LDL 至於高密度脂蛋白 HDL 主要亦由肝細胞釋出 可自血漿與周邊組織清除運送膽固醇回肝臟 血漿是上述脂蛋白代 謝過程中各脂質交換之場所 21

22 Adult Treatment Panel III ATP III of NCEP ~ ~1.8 22

23 EDTA 30 3%

24 1. bias CV 5% 3% Centers for Disease Control CDC Abell Sperry Brand chromotrotic acid 2 1 C 24

25 3. 40 mg/dl B / / / / 4. mg/dl mmol/l mm 0.97 mg/dl mmol/l mg/dl mmol/l mm mmol/l mm mg/dl 38.7 mg/dl mmol/l mm mmol/l mm mg/dl 88.2 Friedewald 400mg/dl 25

26 Friedewald /A mg/dl A=5 mm A=

27 TSH 160 mg/dl glycated hemoglobin 27

28 70% atherosclerosis small vessel disease Kawasaki's disease Takayasu anomalous origin of coronary artery dyslipidemia emerging risk factors a homocysteine fibrinogen VII factor VII plasminogen activator inhibitor-1 PAI-1 chlamydia pneumoniae herpesviruses insulin resistance microalbumin 30 mg/dl psychosocial influences 28

29 10 % 10% mg/dl 1000 mg/dl 12 Coronary Primary Prevention Trial Cholestyramine The Coronary Drug Project National Health and Nutrition Examination Surveys, NHANES mg/dl 56 mg/dl 29

30 47 mg/dl Lp a HDL2 Framingham Framingham Study TC/HDL-C 5 7% % 7 20% The Prospective Established Populations for Epidemiologic Studies of the Elderly EPESE TC/HDL-C 1 17% HDL-C 35 mg/dl 60 mg/dl HDL-C 35 mg/dl Lp a LDL disulfide bond apoprotein B-100 fibrinolytic proenzyme plasminogen plasminogen atherosclerotic plaque foam cells macrophages Lp a 40 mg/dl coronary equivalent

31 C- high-sensitivity C-reactive protein hs-crp hs-crp statin hs-crp statin 25% IIb/IIIa thrombus acute coronary syndrome Statin C- metabolic syndrome 1 hyperglycemia 2 dyslipidemia 3 160/90 mmhg 4 5 abdominal/central obesity 6 ACE gene polymorphism homocysteine 1969 McCully homocysteinuria homocysteine 10.6 nmol/ml cystathionine beta-synthase CBS 12% 31

32 methylene tetrahydrofolate reductase MTHFR methionine synthase MS homocysteine folate psychosocial influences Framingham A type A behaviour nephrotic syndrome VLDL LDL apob 60% Lp a homocysteine lipoprotein a 30 mg/dl fibrinogen von Willebrand factor homocysteine 32

33 down-regulation 1000 mg/dl lipoprotein lipase triglyceride lipase fibrate heparin 33

34 % 29% 44.8% 14% 37.5% 3.7% 200mg/dl VI VII A-I -B a % 150mg/dl 200mg/dl 49.8% 45.8% 29.3% 34

35 578 30% protein C protein S Antithrombin III statin pravastatin simvastatin atorvastatin CARE LIPID 4S MIRACLE GREACE 19% 50% 35

36 HPS 2 Simvastatin 24% VA-HIT fibrate statin C statin nitric oxide statin nitric oxide cytokine astrocytes macrophages

37 statin

38 European Atherosclerosis Society >200 mg/dl 2. >200 mg/dl >200 mg/dl 3 >200 mg/dl National Cholesterol Education Program optimal near optimal boderline high very high

39 4.2 mg/dl < mg/dl < mg/dl < mg/dl < Fredrickson I IV 39

40 II IIa IIb III C-I apo-cii B / B IIa ++++ IIa IIb ++? III? ++ IV II +++ I V V ++ IIa IIb III 40

41 TC/HDL-C 5 40mg/dl 4.7 mg/dl TC 200 TC 200 TG 200 TG 200 TC/HDL-C Thiazide phenytoin phenobarbital cimetidine rifampin 41

42 4.8 42

43 Adult Treatment Panel III ATP III of NCEP 1. Framingham Risk Prediction Score % 100mg/dl 130 mg/dl mg/dl mg/dl 20 % 100 mg/dl % > 140/90 mmhg <40 mg/dl <55 <65 >45 >55 43

44 2 2 20% 130 mg/dl % 160 mg/dl 3-6 NCEP ATP III International Lipid Information Bureau ILIB mg/dl mg/dl 5 40 mg/dl mg/dl 40 mg/dl mg/dl 40 mg/dl mg/dl 44

45 a. 130 mg/dl 5 b mg/dl 2 c. 200 mg/dl 5 40 mg/dl d. a mg/dl 2 b 200 mg/dl 5 40 mg/dl c 160 mg/dl 3-6 e. a 190 mg/dl b 160 mg/dl 2 45

46 c 200 mg/dl 5 40 mg/dl a. 130 mg/dl b. 200 mg/dl 5 40 mg/dl 2 a. 130 mg/dl b. 200 mg/dl 5 40 mg/dl mg/dl 200 mg/dl

47 1 160 mg/dl mg/dl mg/dl 5 40 mg/dl 190 mg/dl 160 mg/dl 200 mg/dl mg/dl 200 mg/dl 5 40 mg/dl 100 mg/dl 150 mg/dl 2 47

48 % 48

49 5.2 BMI BMI=BW kg/bh BMI kg/ % 1 mg/dl 3.5%

50 3-6 50

51 51

52 52

53 第五章 圖 血脂異常 中華民國成人冠心病之次段預防血脂異常之處理流程 以空腹至少 小時後測量為宜 * 需同時合併有 TC/HDL-C 5 或是 HDL-C 40 mg/dl 註 1 做脂蛋白測定時 個案不可處於急性冠心病或是其他疾病的恢復期 否則可能導致 LDL-C 濃度低於平常 2 若二次所得之 LDL-C 濃度相差達 30 mg/dl 以上 則應再間隔 1-8 週 再測定一次 取 三次平均值 53

54 * mg/dl 160 mg/dl 130 mg/dl 130 mg/dl 200 mg/dl 200 mg/dl 130 mg/dl 130 mg/dl * 200 mg/dl 200 mg/dl 2 2 * mg/dl 160 mg/dl 160 mg/dl 130 mg/dl 200 mg/dl 200 mg/dl 130 mg/dl 130 mg/dl * 200 mg/dl 200 mg/dl * 5 TC/HDL-C 5 40 mg/dl HDL-C 40 mg/dl Bezafibrate 200mg tid Ciprofibrate 100mg qd Clofibrate 1000mg bid Fenofibrate 100mg tid Gemfibrozil 600mg bid 54

55 NCEP Adult Treatment Panel III ATP III of NCEP ATP III ATP III Therapeutic Lifestyle Changes TLC TLC therapeutic lifestyle changes TLC ATP III TLC

56 6 200 TLC Diet TLC TLC % 7% 200 / 2 / 10% 20% 25 35% 50 60% / / 15% 200 saturated fatty acids SFA 1980 Keys dose response relationship 56

57 1% 2% 1% 2% apoa-i apoa-i HDL-C LDL- CNCEP 7% 1. 7% % stearic acid palmitic acid myristic acid lauric acid oleic acid 57

58 butter margarine canola oil H H -C=C- cis trans H -C=C- H linoleic acid stearic acid oleic acid elaidic acid trans fatty acids hydrogenated oil shortening margarine 58

59 7% Anitschkon The Nurses Health Study / mg/dl 213 lutein macular degeneration 59

60 % ~20% APOA4 APOE 200 polyunsaturated fatty acids PUFA PUFA linoleic acid 18 2n-6 arachidonic acid 20 4n-6 -linolenic acid 18 3n-3 eicosapentaenoic acid EPA 20 5n-3 docosahexaenoic acid DHA 22 6n-3 -linoleic acid linolenic acid 5% 1% n-3 4% n-6 n-6 linoleic acid arachidonic acid 60

61 n-3 platelet aggregatiion triacylglycerol population 10% monounsaturated fatty acids MUFA oleic acid cis 20% 35% 61

62 30% 60% 25-35% 30-35% 1. carbohydrate HDL-C HDL-C AHA NCEP 62

63 Five a day 40 FDA oats guar gum pectin psyllian % ATP 5-10 plant sterols 2-3 / 6~15% LDL-C HDL-C 2 63

64 / plum / / glycemic index 1981 Jenkins

65 WHO FAO 1997 ATP III 60% 50% 15% 65

66 n-3 n-3 -linolenic acid canola oil EPA DHA 50% n-3 ATP III n-3 n B6 B12 methionine homocysteine B6 B12 collagen 10 nmol/ml 31~100 nmol/ml 100 nmol/ml B B6 B12 66

67 400 B B B6 6 B12 2. C E C E - ubiquinone coenzyme Q10 ployphenol catechin lycopene E E E ATP III C E

68 J 2 drink The Dietary Approaches to Stopping Hypertension, DASH 68

69 NCEP

70 BMI BMI ATP III BMI 10% BMI ATP III 70

71 1. TLC TLC TLC 71

72 1. 72

73 Lp a V0 2 max 7. adrenergic drive 73

74 down regulation

75 A-I LCAT

76 maximal oxygen intake 5-30% 76

77 77

78 40-85% 55-90% = - x55%+ = - x75%+ Karvonen Target heart rate THR = - x 65 % + = x = x

79 ~

80 >240mmHg >ll0mmhg 5. ST lmm

81 6. 7. warm-up cool-down

82 85~ ~40%

83 %THR

84 ~85% 84

85 55~80% 3~5 30~40 85

86 bile acid sequestrant resin 15-30% 3-5% Warfarin Probucol fibrates 400mg/dl Cholestyramine 4 Colestipol 5 Colesevelam fibric acid derivatives % 5-20 % 86

87 10-35% Clofibrate 2-4 IV IIb IV Clofibrate Atromid S Cholenal Gemfibrozil Lopid Fenofibrate Lipanthyl % Bezafibrate Ciprofibrate Etofibrate Gemfibrozil 600mg mg Fenofibrate 200mg 1 Micronized 200mg; clofibrate 1000mg mg ALT Clofibrate Clofibrate creatine phosphokinase Gemfibrozil Lovastatin Clofibrate Gemfibrozil Fenofibrate Warfarin 3. nicotinic acid B % 5-25 % % 87

88 7-14 Aspirin Acipimox 0.25 gm 0.1 gm 4 1 gm 4 Niaspan 2g 4. HMG-CoA reductase inhibitor Statin HMG-CoA reductase homogenous heterogenous Lovastatin Pravastatin Simvastatin Fluvastatin Atorvastatin Rosuvastatin Lovastatin Simvastatin Lactones hydroxy acid Pravastatin hydroxy acid % % 7-30% 5-15% ALT 5 % 0.5 % 88

89 Cyclosporin Lovastatin mg 80mg Pravastatin 2 20 mg 40mg Simvastatin mg 80mg Fluvastatin 2 40mg 80mg Atorvastatin 10-20mg 80mg 5. 1 Probucol Probucol 5-15 % 25 % QT Probucol Omega-3 Omega-3 Omega-3 EPA DHA B 89

90 3 Estrogen % 15 % HERS II trial WHI Women's Health Initiative Study Group resin nicotinic acid fibrate Probucol HMG-CoA reductase inhibitor statins 50 % Statin fibrate Statin nicotinic acid fibrate nicotinic acid

91 a. HMG-CoA reductase inhibitor Statin b. c. d. 2 a. b. c. HMG-CoA reductase inhibitor Statin 3 a. b. c. Omega Colestipol 5 Cholestyramine HMG-CoA reductase inhibitor 2 91

92 2 HMG-CoA reductase inhibitor HMG-CoA reductase inhibitor 3 HMG-CoA reductase inhibitor % Gemfibrozil Bezafibrate Fenofibrate mg/dl Omega-3 92

93 5 10 % 500 mg/dl % medium chain triglyceride MCT 6 HMG-CoA reductase inhibitor 2. 93

94 5-4.1 parameters schedule bile acid sequestrant nicotinic acid statins CK CK fibrates peptic ulcer FBS UA ALT AST ALT AST cholelithiasis 6~8 1500mg 6~8 6~

95 50% triglyceride-rich lipoprotein particle VLDL LPL B 85%-95% 400 mg/dl Lp 95

96 a American Diabetes Association ADA 100 mg/dl 130 mg/dl mg/dl 45 mg/dl 35 mg/dl mg/dl 200 mg/dl 400 mg/dl mg/dl 100 mg/dl non-hdl cholesterol 130 mg/dl NCEP ATP III secondary prevention 4S, CARE, LIPID 100mg/dl 130 mg/dl statin 200mg/dl 96

97 40mg/dl 150mg/dl 10%- 15% Thiazolidinedione I. HMG CoA reductase inhibitor statin Bile acid binding resin resin fenofibrate II. nicotinic acid fibrate III. fibric acid derivative gemfibrozil, fenofibrate statin IV. statin statin fibric acid derivative 97

98 gemfibrozil, fenofibrate resin fibric acid derivative gemfibrozil, fenofibrate statin nicotinic acid 130 mg/dl TLC stanols/sterols mg/dl statins bile acid sequestrant fibrate statins fibrate statins VLDL remnants 100 mg/dl 100 mg/dl 200 mg/dl 130 mg/dl fibrate nicotinic acid < 3 g/day 130 mg/dl Statins Bile acid sequestrant statins Fibrate statins Nicotinic acd 98

99 1. HMG CoA reductase inhibitors statins HMG CoA reductase 18%-55% 7%-30% 5%-15% cyclosporine macrolide antibiotics various anti-fungal agents cytochrome P450 inhibitors fibrate nicotinic acid lovastatin 20 mg pravastatin 20 mg simvastatin 20 mg fluvastatin 20 mg atorvastatin 10 mg FDA lovastiatin 80 mg pravastatin 40 mg simvastatin 80 mg fluvastain 80 mg atorvastatin 80 mg 0.5%-2.0% myopathy 2. Bile acid sequestrants 15%- 30% 3%-5% cholestyramine 4-16 g colestipol 5-20 g colesevelam g cholestyramine 24 g colestipol 30 g colesevelam 4.4 g 3. Nicotinic acid 5%-25% 15%-35% 20%-50% 99

100 Crystalline nicotinic acid g Sustained-release nicotinic acid 1-2 g Extended-release nicotinic acid 1-2 g Crystalline nicotinic acid 4.5 g Sustained release nicotinic acid 2 g Extended-release nicotinic acid 2 g 4. Fibric acid derivatives fibrates peroxisome proliferative activated receptor PPAR -alpha 5%-20% 10%-35% 20%-50% gemfibrozil 600 mg bid fenofibrate 200 mg clofibrate 1000 mg bid gemfibrozil 1200 mg fenofibrate 200 mg clofibrate 2000 mg 5. statin bile acid sequestrant statin fibrate statin nicotinic acid fibrate nicotinic acid 100

101 metabolic syndrome insulin resistance syndrome risk enhancer 1. abdominal obesity * cm 88 cm >150 mg/dl <40 mg/dl <50 mg/dl >130/85 mmhg mg/dl *

102 Component Dyslipidemia Obesity Hypertension Microalbuminuria Description of Criteria Elevated plasma triglyceride 1.7 mmol/l and/or Low HDL cholesterol concentrations <0.9 mmol/l for men; <1.0 mmol/l for women BMI 30kg/m 2 and/or High waist-to-hip ratio >0.9 for men; >0.85 for women Antihypertensive treatment or High blood pressure >160/90 mmhg Overnight urinary albumin excretion rate 20 g/min BMI aspirin Metformin Thiazolidinedione 102

103 NCEP APTIII very high low-density lipoprotein cholesterol therapeutic lifestyle change, TLC 190 mg/dl heterozygous homozygous familial hypercholesterolemia B-100 familial defective apolipoprotein B-100, FDB polygenic hypercholesterolemia receptor 1/2 2. 1/ mg/dl 4. xanthoma Statins 4. bile acid sequestrant resin Statins 5. Statins 103

104 B /1,000, mg/dl atherosclerosis B /700-1/1, mg/dl polymorphism 2. 1/10-1/ mg/dl Statins 4. ileal exclusion operation pheresis Statins mg/dl

105 mg/dl mg/dl mg/dl 500 mg/dl 1. * * * * * 60% 2. lipodystrophy corticosteroids, - blockers, retinoids, oral estrogens, tomoxifen, protease inhibitors for AIDS * * * * C II atherogenic * * 2. * * * prothrombotic state * proinflammatory state

106 mg/dl 3. chylomicronemia syndrome 2000 mg/dl * * hepatic steatosis * Lipemia retinalis * * mg/dl 1. B- 100 B mg/dl 2/ mg/dl 2. chylomicron 3. remnant lipoproteins III 106

107 E E isoform E2 E3 E4 E2 E2 E2 E E2 1/

108 * * 30 mg/dl 30 mg/dl mg/dl 130 mg/dl 100 mg/dl 190 mg/dl 160 mg/dl 130 mg/dl * * * * * * Statins * * 5. * Statins * Statins * myopathy 108

109 1. * * 2. * mg/dl 15% * 1000 mg/dl * * * * Statins Statins * 3. * 40 mg/dl blockers anabolic steroids progestational agents 8. postulated factors 1. * reverse * oxidation * aggregation * 2. * * * 3. * * * * * *

110 Statin % 5-30% 5% Statins 5-10% 5-15% 15-30% 160 mg/dl Statin Statin myopathy 110

111 protease-inhibitor HIV ACEI hydralazine minoxidil K-sparing diuretics Reserpine 5-10 mg/dl -1-adrenergic blockers - 2-receptor agonist -blocker 111

112 uncomplicated -blocker ACEI -blocker -blocker adherence -blocker 1 4 myopathy compliance 50% 60% 112

113 >20% % 2 10 <10% <10% 1. LDL-C <100 mg/dl 2. LDL-C LDL-C <100 mg/dl LDL-C <130 mg/dl LDL-C <130 mg/dl LDL-C <130 mg/dl 2. LDL-C 160 mg/dl 3. LDL-C mg/dl 1. LDL-C <160 mg/dl LDL-C 190 mg/dl 4. LDL-C mg/dl /3 1/

114 >20% % 2 10 <10% <10% 1. LDL-C <100 mg/dl 2. Statin LDL 3. HDL-C TG fibrate nicotinic acid LDL-C <130 mg/dl 2. Statin LDL WOSCOPS/AFCAPS 3. LDL-C>160 mg/dl 4. LDL mg/dl LDL-C <100 mg/dl 2. LDL-C>160 mg/dl 3. LDL-C mg/dl LDL-C <160 mg/dl 2. LDL-C>190 mg/dl 3. LDL-C mg/dl >20% 1. LDL-C <100 mg/dl 2. Statin Aspirin -blocker

115 % 2 10 <10% <10% 1. LDL-C <130 mg/dl LDL-C 160 mg/dl 4. LDL-C mg/dl LDL-C <130 mg/dl 2. LDL-C 160 mg/dl 3. LDL-C mg/dl LDL-C 190 mg/dl 2. LDL-C mg/dl >20% % 2 10 <10% <10% 1. LDL-C <100 mg/dl LDL-C <130 mg/dl LDL-C 130 mg/dl LDL-C <130 mg/dl 2. LDL-C 160 mg/dl LDL-C <160 mg/dl LDL-C 190 mg/dl 4. LDL-C mg/dl 115

116 附錄一 國人血脂狀況及動脈粥樣硬化疾病 流行病學附圖及附表 附圖1.1台灣地區 年男性心臟血管疾病年齡標準化死亡率變化 註明 1.資料來源 行政院衛生署統計資料 2.以1976年 WHO世界標準化人口數為準 附圖1.2 台灣地區 年女性心臟血管疾病年齡標準化死亡率變化 註明 1.資料來源 行政院衛生署統計資料 2.以1976年 WHO世界標準化人口數為準 116

117 A-I B-100 (mg/dl) 1% 5% 10% 25% 50% 75% 90% 95% 99% A-I B Wen-Harn Pan, Benjamin N, Chiang. Plasma lipid profiles and epidemiology of atherosclerotic disease in Taiwan-a unique experience. Atheroslerosis ,

118

119

120

121

122

123 P/S 123

124 附圖1.3 不同人群年齡別及性別血總膽固醇濃度 資料來源 Wen-Harn Pan, Benjamin N, Chiang. Plasma lipid profiles and epidemiology of atherosclerotic disease in Taiwan-a unique experience. Atheroslerosis ,1995. 附圖1.4 不同人群年齡別及性別高血總膽固醇盛行率 資料來源 Wen-Harn Pan, Benjamin N, Chiang. Plasma lipid profiles and epidemiology of atherosclerotic disease in Taiwan-a unique experience. Atheroslerosis ,

125 附錄一 國人血脂狀況及動脈粥樣硬化疾病流行病學附圖及附表 附圖1.5 不同人群年齡別及性別血低密度脂蛋白膽固醇濃度 資料來源 Wen-Harn Pan, Benjamin N, Chiang. Plasma lipid profiles and epidemiology of atherosclerotic disease in Taiwan-a unique experience. Atheroslerosis ,1995. 附圖1.6 不同人群年齡別及性別血高密度脂蛋白膽固醇濃度 資料來源 Wen-Harn Pan, Benjamin N, Chiang. Plasma lipid profiles and epidemiology of atherosclerotic disease in Taiwan-a unique experience. Atheroslerosis ,

126 附圖1.7 不同人群年齡別及性別三酸甘油酯濃度 資料來源 Wen-Harn Pan, Benjamin N, Chiang. Plasma lipid profiles and epidemiology of atherosclerotic disease in Taiwan-a unique experience. Atheroslerosis ,1995. 附圖1.8 不同人群年齡別及性別高三酸甘油酯盛行率 資料來源 Wen-Harn Pan, Benjamin N, Chiang. Plasma lipid profiles and epidemiology of atherosclerotic diseasein Taiwan-a unique experience. Atheroslerosis ,

127 附錄一 國人血脂狀況及動脈粥樣硬化疾病流行病學附圖及附表 附圖1.9 動脈硬化患者與健康對照組的三酸甘油酯值之比較 註 1. *P<0.05 **P<0.001? 沒有檢定 2. MI 心肌梗塞 AMI 急性心肌梗塞 CAD 冠狀動脈疾病 CVA 腦血管疾病 ICD 缺血性腦血管疾病 DM 糖尿病 HT 高血壓 m 男性 f 女性 資料來源 Wen-Harn Pan, Benjamin N, Chiang. Plasma lipid profiles and epidemiology of atherosclerotic disease in Taiwan-a unique experience. Atheroslerosis ,1995. 附圖1.10 動脈硬化患者與健康對照組的血總膽固醇值之比較 註 1. *P<0.05 **P<0.001? 沒有檢定 2. MI 心肌梗塞 AMI 急性心肌梗塞 CAD 冠狀動脈疾病 CVA 腦血管疾病 ICD 缺血性腦血管疾病 DM 糖尿病 HT 高血壓 m 男性 f 女性 資料來源 Wen-Harn Pan, Benjamin N, Chiang. Plasma lipid profiles and epidemiology of atherosclerotic disease in Taiwan-a unique experience. Atheroslerosis ,

128 附圖1.11 動脈硬化患者與健康對照組的低密度脂蛋白膽固醇值之比較 註 1. *P<0.05 **P<0.001? 沒有檢定 2. MI 心肌梗塞 AMI 急性心肌梗塞 CAD 冠狀動脈疾病 CVA 腦血管疾病 ICD 缺血性腦血管疾病 DM 糖尿病 HT 高血壓 m 男性 f 女性 資料來源 Wen-Harn Pan, Benjamin N, Chiang. Plasma lipid profiles and epidemiology of atherosclerotic disease in Taiwan-a unique experience. Atheroslerosis ,1995. 附圖1.12 動脈硬化患者與健康對照組的高密度脂蛋白膽固醇值之比較 註 1. *P<0.05 **P<0.001? 沒有檢定 2. MI 心肌梗塞 AMI 急性心肌梗塞 CAD 冠狀動脈疾病 CVA 腦血管疾病 ICD 缺血性腦血管疾病 DM 糖尿病 HT 高血壓 m 男性 f 女性 資料來源 Wen-Harn Pan, Benjamin N, Chiang. Plasma lipid profiles and epidemiology of atherosclerotic disease in Taiwan-a unique experience. Atheroslerosis ,

129 1.13 TG HDL BP OB 129

130 The Lipid Research Clinics Coronary Primary Prevention Trial National Exercise and Heart Disease Program Lifestyle Heart Trial n=22 n= % 34 % p Program on the Surgical Control of the Hyperlipidemia POSCH 28 % 38 % 4 % 130

131 10 % 13 6 % 1. The European Collaborative Trial 74 % 2. The Oslo Heart Study mg/dl % 20 % 45 % 47 % 3. The American Multiple Risk Factors Intervention Trial % 7 % Diet and Reinfarction Trial DART

132 3-4% 29% 5. GISSI GISSI-Prevenzione trial E -Tocopherol n-3 n- 3 polyunsaturated fatty ( E ~5 n-3 10% E n-3 E n-3 10 % 16 3 % secondary prevention primary prevention 132

133 1. The Coronary Drug Project CDP 8000 Estrogen Clofibrate Dextrothyroxine Niacin Estrogen Clofibrate Niacin The World Health Organization Trial Clofibrate 9 % 3. The Stockholm Heart Study 555 Clofibrate 2 Niacin % 20 % 28 % 30 % 60 % 4. Scandinavian Simvastatin Surival Study 4S 4, mg/dl % 25 % 8 % 133

134 30 % 9 % 5 % 42 % 8.5 % 5.0 % 34 % 28 % 19 % 5. Cholesterol and Recurrent Events Trails CARE CARE mg/dl LDL-C mg/dl pravastatin 40 5 pravastatin 20% 28% TG 14% HDL-C 5% 24% 31% pravastatin 6 Veterans Affairs High-Density Lopoprotein cholesterol Intervention Trial VA-HIT mg/dl 140 mg/dl 1200 Lopid 5.1 6% 31% 4% 24% 134

135 7. Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering MIRACL Lipitor 3086 Q mg Heart Protection Study HPS MRC Medical Research Council BHF British Heart Foundation Simvastatin Vitamin E, C, - Carotene mg/dl 2x2 40mg mg/dl 42-46mg/dl % 18% 24% myopathy 0.01% 9. Lescol Intervention 135

136 Prevention Study LIPS Primary Coronary Intervention Lescol or Fluvastsatin mg/dl 40mg 3.9 MACE Major Adverse Cardiac Event 22% p= The Helsinki Heart Study Gemfibrozil 34 % 70 % 2. The Lipid Research Clinics Coronary Primary Prevention Trial

137 Cholestyramine 13% 20 % 24 % 39 % 3. West of Scotland Coronary Prevention Study WOS WOSCOPS WOS HMG-CoA pravastatin mg/dl 272 mg/dl 4.9 pravastatin 20% LDL-C 26% TG 12% HDL-C 5% 31% 22% pravastatin 4. / AioForce / Texas Coronary Atherosclerosis Prevention Study AFCAPS / TexCAPS mg/dl 151mg/dl 36.5mg/dl lovastatin 20-40mg 5.2 lovastatin LDL-C 25% 114.3mg/dl HDL-C 6% 40mg/dl 18% lovastatin 137

138 37% % POSCH POSCH 138

139 Familial Atherosclerosis Treatment Study FATS B 120 Lovastatin Colestipol Niacin Colestipol 7 % Lovastatin-Colest ipol 46 % Niacin-Colestipol 32 % Lovastatin-Colestipol 0.7 % Niacin-Colestiopl 0.9 % 2.1 % Cholesterol Lowering and Atherosclerosis Study CLAS 162 Colestipol Niacin 39 % 61 % % 15 % p % 2 % 139

140 The Monitored Atherosclerosis Regression Study 270 Lovas- tatin Lovastatin 32 % 38 % 26 % 8.5 % 50 % 0.9 % 4.1 % Lovastatin The Canadian Coronary Atherosclerosis Intervention Trial 331 Lovastatin 21 % Lovastatin -0.05mm mm Lovastatin Lovastatin Asymptomatic Carotid Artery Progression Study NIH 919 Lovastatin Lovastatin 140

141 The Pravastatin, Lopids and Ather osclerosis in the Carotid Arteries trial, PLAC- II Pravastatin mg/dl P ravastatin 75 10~40mg Pravastatin 3 22% 28% 7% 14% pravastatin 54% / Pravastatin ( ) / ( ) Pravastatin 60% / Pravastatin (10/76) / (4/75) Pravastatin The Regression Growth Evaluation Statin Study, REGRESS Pravastatin mg/dl 400 Pravastatin 2 20% 29% 10% 7% 0.06 mm % Pravastatin 89% pravastatin 141

142 % 10%

143 6 A B C - s-glucan pectin

144 kg/m 2 Body Mass Index BMI kg/m 2 BMI 30 40kg/m 2 BMI 40 kg/m 2 BMI 30 kg/m 2 BMI 27 kg/m 2 BMI 27 kg/m 2 85% BMI 24 kg/m 2 27 kg/m 2 BMI BMI<18.5 kg/m 2 Body 18.5<= BMI <24 kg/m 2 Mass Index BMI 24<= BMI <27 kg/m 2 27<= BMI <30 kg/m 2 30<= BMI <35 kg/m 2 BMI >=35 kg/m 2 90 > % 10% 144

145 10% % 55% 15% 0.5 glycemic index, GI 145

146 40 mg/dl -3 A saturated fatty acid 146

147 10% 7% 3-3 B trans-fatty acids % 147

148 53% % 2-4% B

149 ND ND ND not detected S.M.Innis.J Am Coll Nutr 1999; C

150 *** 20 ** 10 * 5~10 ~ A *** 1220 * 2075 ~ 359 *** 1131 ~ 267 ~ 196 ** 870 ~ 260 ** 144 ** 741 * 199 ** 143 ** 600 *** 143 ** 114 * 599 ~ 134 ** 102 ** 514 ~ 130 ~ 93 * 433 ** 127 * 88 * 329 *** 112 ~ 72 * 303 ** 112 ** 71 *** 103 * 54 *** 94 ~ 49 ** 68 *** 67 ~ 66 *** 66 *** 65 ~ 65 *** 65 *** 55 ~ 54 ** 52 *** 49 * 44 ~ 33 ** 24 ~

151 3-5 B *** 103 ~ 669 *** 577 *** 91 ~ 645 ~ 277 *** 83 * 632 ** 246 ** 56 ~ 330 *** 146 ** 44 ~ 316 *** 146 * 31 ~ 296 *** 136 ~ 21 * 240 ** 124 ~ 15 ~ 203 *** 109 * 14 ~ 183 *** 103 ~ 14 ~ 157 *** 100 ~ 10 ~ 112 ** 100 * 8 ~ 102 * 82 ~ 7 ** 88 ~ 80 *** 0 ~ 84 ~ 78 ~ 0 ** 80 * 76 *** 0 ~ 77 ** 73 ~ 72 * 67 ~ 69 *** 65 ~ 68 ** 65 ~ 66 * 62 * 66 * 61 ~ 65 * 63 ~ 63 *** 60 ** 60 ~ 60 ~ 56 ~ 55 ~

152 D 12% 21% 25% 34% 10% 14% 25% 16% 20% 12% 5% 19% 5% 42% cholesteryl oleate 152

153 30% > > >70% >70% Cashews Macadamia nuts Pecans

154 E % 45% % - -3 docosahexaenoic acid DHA eicosapentaenoic acid EPA - linolenic acid n-3 n-3 n-3 B - IIb (glutathione peroxidase) 154

155 n-3 B n-3 n-3 - n mmol 2.2 mg/dl 5 6.4% 10.5% 3 3% 155

156 % 8.5% 9.4% ~17% % - 5 4~5% 6~7% 8.9% 13.2% 15 17% 26% Food and Drug Administration FDA

157 25% B AI - 4.2% 60% /100 95% /100 AI 8.82 /100 95% / /100 95% / % 24 53% 73%

158 23 11% % 46 46% / Pennington JAT Bowes&Church's Food Values of portions commonly used. 16 th ed.j.b.lippincott Co. (1994). 158

159 A Stevinson /100 Warshafsky /100 9% B / % 21.7 / % 13.3 / % aglycon aglycon Genistein Daidzein Estradiol-17 Genistein Daidzein Estradiol Phytoestrogen Genistein Daidzein Estradiol Estradiol Estradiol Genistein Daidzein 159

160 estradiol Genistein Daidzein estradiol C monascus purpureus monacolins X L K J M HMG-CoA reductase inhibitor statin D C E - 160

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176 GPN ISBN