膽固醇的再回收機制及 HDL 的角色 Apo A-1 ABCA1 (lipid-poor particle) ABCA1 nascent prebeta HDL Phospholipid transfer protein (PLTP) nascent HDL cholester

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1 家庭醫業前言 lipid profile (Total Cholesterol, TC) 200mg/dL (LDL-C) (HDL-C) 60mg/ dl 100 mg/dl 高密度脂蛋白 (high density lipoprotein, HDL) 簡介 1 高雄榮總家庭醫學部住院醫師 2 高雄榮總家庭醫學部主治醫師 3 高雄榮總內科部新陳代謝科主治醫師 high density lipoprotein (HDL), Hyperalphalipoproteinemia (HALP), reverse cholesterol transport triglycerides (TG), phospholipid, cholesterol ( 14%) cholesteryl ester ( 36%) free fatty acid ( 4%) phospholipid( ) apolipoprotein ( ) lipoprotein ( ) Lipoprotein chylomicrons ( ) VLDL ( ) IDL, LDL, HDL HDL ( ) apolipoprotein HDL apolipoprotein A ( Apo A-I, ApoA -II) LDL apolipoprotein apolipoprotein B ( ApoB-100) Apolipoprotein HDL, LDL HDL-C, LDL-C HDL LDL 94 家庭醫學與基層醫療第四期

phospholipid, cholesterol ( 14%) cholesteryl ester ( 36%) free fatty acid ( 4%) phospholipid( ) apolipoprotein ( ) lipoprotein ( ) Lipoprotein chylomicrons ( ) VLDL ( ) IDL, LDL,

2 膽固醇的再回收機制及 HDL 的角色 Apo A-1 ABCA1 (lipid-poor particle) ABCA1 nascent prebeta HDL Phospholipid transfer protein (PLTP) nascent HDL cholesterol 1 LCAT cholesterol ( ) HDL nascent HDL(pre- HDL) HDL (Alpha-HDL HDL3 HDL2) HDL2 ( free cholesterol cholesteryl ester core) (1) SR-B1 (2) cholesteryl ester transfer protein (CETP) HDL apo B-containing lipoproteins (VLDL IDL LDL) TG apo B-containing lipoproteins LDL HDL lipid-laden( ) reverse cholesterol transport ( ) HDL HDL HDL 圖 1 膽固醇的再回收機制及 HDL 的角色家庭醫學與基層醫療第四期 95

ester core) (1) SR-B1 (2) cholesteryl ester transfer protein (CETP) HDL apo B-containing lipoproteins (VLDL IDL LDL) TG apo

3 流行病學 HDL-C level HDL HDL-C HDL HDL-C ( 60mg/dL) HDL-C ( < 40mg/dL <50mg/dL) Framingham Heart study LDL-C level HDL-C level 10 HDL-C level LDL-C level 3 LDL- C HDL-C 高密度脂蛋白血症 (Hyperalphalipoproteinemia, HALP) Apo A-I Apo A-II HALP HALP HALP 7.8% 92% 7.9% HALP Apo A-I HDL-C level ( 1992, 1995 Weitzman JB, Hirano K Archives of Pathology & Laboratory Medicine Arteriosclerosis, Thrombosis, and Vascular Biology HDL-C>100mg/dL 1997 Hirano K HDL- C 70mg/dL EKG ST ) HDL-C HALP HDL-C level 90 ( HDL-C mg/dL 72-78mg/dL) (1) HALP CHD (2) CETP deficiency CETP encoding HDL-C level CETP HDL apo B-containing lipoproteins CETP LDL-C level (3) LCAT overexpression HDL 96 家庭醫學與基層醫療第四期

9% HALP Apo A-I HDL-C level ( 1992, 1995 Weitzman JB, Hirano K Archives of Pathology & Laboratory Medicine Arteriosclerosis, Thrombosis, and Vascular Biology HDL-C>100mg/dL 1997

4 表 1 HDL-C level 與心臟疾病的風險關係 Level (mg/dl) Level (mmol/l) Interpretation 男性 <40, 女性 <50 <1.03 低的 HDL-C, 有較高的罹病風險 40~ ~1.55 中等 HDL-C >60 >1.55 高的 HDL-C, 有保護能力資料來源 : Adult Treatment Panel III Executive Summary. National Heart, Lung, and Blood Institute (NHLBI). National Institutes of Health. May CHD (4) Apo A-I up-regulation (Apo A-I ) apo A-I CHD HALP (estrogen), statins, nicotinic acid, phenytoin, fibrates (bezafibrate, clofibrate, fenofibrate, gemifibrozil) HALP HDL-C Juvenile corneal opacification, Multiple symmetric lipomatosis HALP statins, niacins, phenytoin fibrates National Cholesterol Education Program (NCEP) Adult Treatment Panel III 1 HDL-C 的測量 indirect apo B HDL-C HDL-C electrophoresis ( ) measurement Nuclear Magnetic Resonance ( ) measurement HDL HDL-C HDL total HDL- C large HDL HDL-C 異常的臨床處置建議 HDL-C Level American Heart Association National Institutes of Health (NIH) HDL-C omega-3 fatty acid 家庭醫學與基層醫療第四期 97

CHD (4) Apo A-I up-regulation (Apo A-I ) apo A-I CHD HALP (estrogen), statins, nicotinic acid, phenytoin, fibrates (bezafibrate, clofibrate, fenofibrate, gemifibrozil) HALP HDL-C Juvenile corneal

5 niacin fibrates HDL-C LDL-C MRC/ BHF Heart protection study Scandinavian Simvastatin Survival Study(4S) RCT HDL-C 2009 meta-analysis HDL-C Lovaza (omega-3-acid ethyl esters Omacor) Apo-A1 Milano CETP torcetrapib anacetrapib evacetrapib dalcetrapib HDL-C ( torcetrapib dalcetrapib) HDL-C HDL-C Multi-Ethnic Study of Atherosclerosis (MESA ) NMR total large HDL The National Cholesterol Education Program ( Adult Treatment Program III) HDL-C(<40mg/dL) CHD HDL-C 60mg/dL primary target LDL-C non HDL-C (TC- HDL) TG>200mg/dL HDL HDL-C TG<200mg/dL nicotinic acid fibrate therapeutic lifestyle changes ( TLC) HDL-C HALP (longevity) ( CETP deficiency postheparin hepatic triglyceride lipase ) HDL-C 100mg/dL MESA percentile Total HDL particlesμmol/l Large HDL particle μmol/l Interpretation >75% >34.5 >7.3 最低的心血管疾病發生風險 50-75% 中等程度的心血管疾病發生風險 25-50% 高等程度的心血管疾病發生風險 0-25% <26.7 <3.1 最高的心血管疾病發生風險資料來源 :Multi-Ethnic Study of Atherosclerosis: Understanding the NMR LipoProfile test Report ; LipoScience, Inc Sumner Boulevard Raleigh, NC 家庭醫學與基層醫療第四期

Program ( Adult Treatment Program III) HDL-C(<40mg/dL) CHD HDL-C 60mg/dL primary target LDL-C non HDL-C (TC- HDL) TG>200mg/dL HDL HDL-C TG<200mg/dL nicotinic acid fibrate therapeutic lifestyle

6 Harvard School of Public Health researcher Journal of the American Heart Association apolipoprotein C-III (apo C-III proinflammatory protein) HDL protein HDL apo C-III 20% 60% HDL- C HDL apo C-III 結論 HDL- C HALP apoc-iii HDL-C HDL-C (> mg/dL ) ( TG LDL-C ) 參考資料 1. American Heart Association: Good vs. Bad Cholesterol. 12 Oct Retrieved 1 Oct Catherine R: Relation between high-density lipoprotein cholesterol and survival to age 85 years in men (from the VA normative aging study). Am J Cardiol 2011; 107: Marhall WJ, Bangert SK: Clinical biochemistry: Metabolic and clinical aspects. 2nd ed. Edinburgh ; New York : Churchill Livingstone/Elsevier, 2008: Murray RK, Granner DK, Rodwell VW Harper's / Hausenloy DJ, Yellon DM : Targeting residual cardiovascular risk: raising high-density lipoprotein cholesterol levels. Heart 2008; 94: The AIM-HIGH Investigators: Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy. N Engl J Med 2011; 365: Harvard School of Public Health : Some HDL, or good cholesterol, may not protect against heart disease (immediate release) 8. Briel M, Ferreira-Gonzalez I, You JJ, et al: Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis. BMJ 2009; 338:b92. 家庭醫學與基層醫療第四期 99

12. Retrieved 1 Oct. 2013. 2. Catherine R: Relation between high-density lipoprotein cholesterol and survival to age 85 years in men (from the VA normative aging study).

Microsoft PowerPoint - 認識高血脂症931101FINAL.ppt

Microsoft PowerPoint - 認識高血脂症931101FINAL.ppt 認識高血脂症如何降低血油遠離心臟病和腦中風的威脅三軍總醫院內分泌及新陳代謝科謝昌勳 93 年 11 月 1 日臺灣地區主要死因死亡率比較 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 每十萬人口死亡數

膽 固 醇 的 再 回 收 機 制 及 HDL 的 角 色 Apo A-1 ABCA1 (lipid-poor particle) ABCA1 nascent prebeta HDL Phospholipid transfer protein (PLTP) nascent HDL cholester

膽固醇的再回收機制及 HDL 的角色 Apo A-1 ABCA1 (lipid-poor particle) ABCA1 nascent prebeta HDL Phospholipid transfer protein (PLTP) nascent HDL cholester