Cập nhật khuyến cáo về điều trị rối loại lipid máu

1CAÄP NHAÄT KHUYEÁN CAÙO VEÀ ÑIEÀU TRÒ ROÁI Ä Ä Á Ù À À Á LOAÏN LIPID MAÙU Ï Ù GS TS Ñaëng Vaïn Phöôùc Tröôøng ÑH Y Döôïc TP. Hoà Chí Minh 2XÔ VÖÕA ÑOÄNG MAÏCH: BEÄNH TOAØN THAÂNÕ Ä Ï Ä Ø Â 3QUAÙ TRÌNH XÔ VÖÕA ÑOÄNG MAÏCHÙ Õ Ä Ï 4Maõngõ xô vöõaõ oånå ñònh 5Maõngõ xô vöõaõ khoângâ oånå ñònh 6Plaque vulnerability Key role of macrophages 7HIEÄN TÖÔÏNG VIEÂM:Ä Ï Â Yeáuá toáá quan troïngï trong ñoää oånå ñònh cuûaû maõngõ xô vöõaõ 8Khoângâ trieäuä chöùngù + trieäuä chöùngù Quaùù trình dieãnã tieáná cuûaû xô vöõaõ ñoängä maïchï : TG (naêmê ) Coùù trieäuä chöùngù Sang thöông tieáná trieånå Beänhä maïchï vaønhø Beänhä maïchï maùuù naõoõ Beänhä maïchï maùuù ngoaïiï bieânâ 9CHIEÁN LÖÔÏC PHOØNG NGÖØA BEÄNH TIM DO ÑOÄNG Á Ï Ø Ø Ä Ä MAÏCH VAØNHÏ Ø 1. Chieán löôïc chung cho coäng ñoàng: caûi thieän loái soáng vaø caùc yeáu toá moâi tröôøng coù khaû naêng laøm taêng nguy cô cuûa beänh tim do ñoäng maïch vaønh trong toaøn theå coäng ñoàng. 2. Chieán löôïc cho caùc ñoái töôïng nguy cô cao: xaùc ñònh caùc caù theå coù nguy cô cao vaø baét ñaàu ñaùnh giaù ñeå kieåm soaùt caùc yeáu toá nguy cô 3. Phoøng ngöøa thöù phaùt: phoøng ngöøa söï tieán trieån cuûa beänh tim do ñoäng maïch vaønh coù trieäu chöùng vaø phoøng ngöøa caùc bieán chöùng cuûa beänh naøy 10 XEÁP LOAÏI CAÙC YEÁU TOÁ NGUY CÔ CHO 3 BIEÅÅU Á Ï Ù Á Á ÅÅ HIEÄN LAÂM SAØNG CUÛA TÌNH TRAÏNG XÔ VÖÕAÄ Â Ø Û Ï Õ Beänh Xeáp loaïi caùc yeáu toá nguy cô Beänh tim do ñoäng maïch vaønh 1. Taêng vaø roái loaïn lipoprotein maùu 2. Huùt thuoác laù 3. Taêng huyeát aùp 4. Tieåu ñöôøng 5. Beùo phì Beänh maïch maùu naõo 1. Taêng huyeát aùp 2. Beänh thieáu maùu cuïc boä 3. Tieåu ñöôøng 4. Beùo phì Beänh ngheõn ñoäng maïch ngoaïi bieân 1. Huùt thuoác laù 2. Taêng vaø roái loaïn lipoprotein maùu 3. Tieåu ñöôøng 11 TAÀM QUAN TROÏNG TÖÔNG ÑOÁI CUÛA TÖØNG YEÁU À Ï Á Û Ø Á TOÁ NGUY CÔ TIM MAÏCH VAØ CUÛA NHOÙM CAÙC Á Ï Ø Û Ù Ù YEÁU TOÁ NGUY CÔ TIM MAÏCHÁ Á Ï „MRFIT: Multiple Risk Factor Intervention Trial study (300.000 ngöôøi/naêm) „ PROCAM: Prospective Cardiovascular Munster Study (20.000 ngöôøi tham döï, tuoåi töø 16 - 65, keùo daøi 6 - 7 naêm) 12 NGUY CÔ CUÛA BEÄNH ÑMV ÔÛ NGÖÔØI TAÊNG HUYEÁÁT AÙP Û Ä Û Ø Ê ÁÁ Ù TAÊNG THEO SOÁ LÖÔÏNG CAÙC YEÁU TOÁ NGUY CÔÊ Á Ï Ù Á Á 0 10 20 30 40 50 T a à n s u a á t m a é c b e ä n h t r o n g 1 0 n a ê m Women Man HBP (150-160) + + + + + + HDL (33-35) - + + + + + Chol (240-262) - - + + + + Cigarettes - - - + + + Diabetes - - - - + + LVH - - - - - + Subjects Aged 42-43 years 13 TAÊNG LIPOPROTEIN MAÙU VAØ ROÁI Ê Ù Ø Á LOAÏN LIPOPROTEIN MAÙU LAØ NHÖÕNG Ï Ù Ø Õ YEÁU TOÁ NGUY CÔ CHÍNH CUÛA XÔ Á Á Û VÖÕA ÑOÄNG MAÏCHÕ Ä Ï 14 KEÁT QUA Û& KEÁT LUAÄN CUÛA NGHIEÂN CÖÙU Á Û Á Ä Û Â Ù PROCAM 16 31 54 120 0 20 40 60 80 100 120 195 I n c i d e n c e ( p e r 1 , 0 0 0 i n 6 y e a r s ) LDL cholesterol (mg/dl) NGUY CÔ BEÄNH ÑMV TÍNH THEO LDL 177 events: 4263 men aged 40 - 65 years 15 KEÁT QUA Û& KEÁT LUAÄN CUÛA NGHIEÂN CÖÙU Á Û Á Ä Û Â Ù PROCAM 20 46 77 64 0 20 40 60 80 400 I n c i d e n c e ( p e r 1 , 0 0 0 i n 6 y e a r s ) Triglycerides (mg/dl) NGUY CÔ BEÄNH ÑMV TÍNH THEO TRIGLYCERIDE 186 events: 4407 men aged 40 - 65 years 16 KEÁT QUA Û& KEÁT LUAÄN CUÛA NGHIEÂN CÖÙU Á Û Á Ä Û Â Ù PROCAM 214 110 44 31 103 5947 13 111 443116 0 100 200 300 >300 250-300 200-249 <200 2 0 0 - 4 0 0 1 5 0 - 1 9 9 < 1 5 0 Cholesterol (mg/dl) Triglycerides (mg/dl) I n c i d e n c e ( p e r 1 , 0 0 0 i n 6 y e a r s ) 186 events: 4407 men aged 40 - 65 years NGUY CÔ BEÄNH ÑMV TÍNH THEO TRIGLYCERIDE VAØ CHOLESTEROL 17 KEÁT QUA Û& KEÁT LUAÄN CUÛA NGHIEÂN CÖÙU Á Û Á Ä Û Â Ù PROCAM 209 101 50 25 112 4748 14 77 412113 0 100 200 300 >195 155-195 135-154 <135 2 0 0 - 4 0 0 1 5 0 - 1 9 9 < 1 5 0 LDL cholesterol (mg/dl) Triglycerides (mg/dl) I n c i d e n c e ( p e r 1 , 0 0 0 i n 6 y e a r s ) 177 events: 4263 men aged 40 - 65 years NGUY CÔ BEÄNH ÑMV TÍNH THEO LDL VAØ TRIGLYCERIDE 18 KEÁT QUA Û& KEÁT LUAÄN CUÛA NGHIEÂN CÖÙU Á Û Á Ä Û Â Ù PROCAM 294 211 110 33 117 432516 133 33146 0 100 200 300 >300 250-300 200-249 <200 < 3 5 3 5 - 5 5 > 5 5 Total cholesterol (mg/dl) HDL cholesterol (mg/dl) I n c i d e n c e ( p e r 1 , 0 0 0 i n 6 y e a r s ) 186 events: 4407 men aged 40 - 65 years NGUY CÔ BEÄNH ÑMV TÍNH THEO HDL VAØ CHOLESTEROL TOAØN PHAÀN 19 KEÁT QUA Û& KEÁT LUAÄN CUÛA NGHIEÂN CÖÙU Á Û Á Ä Û Â Ù PROCAM 292 183 83 38 78 352313 127 11243 0 100 200 300 >195 155-195 135-154 <135 < 3 5 3 5 - 5 5 > 5 5 LDL cholesterol (mg/dl) HDL cholesterol (mg/dl) I n c i d e n c e ( p e r 1 , 0 0 0 i n 6 y e a r s ) 177 events: 4236 men aged 40 - 65 years NGUY CÔ BEÄNH ÑMV TÍNH THEO HDL VAØ LDL CHOLESTEROL 20 KEÁT QUA Û& KEÁT LUAÄN CUÛA NGHIEÂN CÖÙU Á Û Á Ä Û Â Ù PROCAM 128 40 109 112 2747 83 27 10 0 100 200 <35 35-55 >55 > 2 0 0 1 5 0 - 1 9 9 < 1 5 0 HDL cholesterol (mg/dl) Triglycerides (mg/dl) I n c i d e n c e ( p e r 1 , 0 0 0 i n 6 y e a r s ) 186 events: 4407 men aged 40 - 65 years NGUY CÔ BEÄNH ÑMV TÍNH THEO TRIGLYCERIDE VAØ HDL 21 KEÁT QUA Û& KEÁT LUAÄN CUÛA NGHIEÂN CÖÙU Á Û Á Ä Û Â Ù PROCAM 14 28 44 140 200 255 0 50 100 150 200 250 300 6.99 I n c i d e n c e ( p e r 1 , 0 0 0 i n 6 y e a r s ) LDL cholesterol / HDL cholesterol ratio NGUY CÔ BEÄNH ÑMV TÍNH THEO TÆ SOÁ LDL / HDL 177 events, 4263 men aged 40 - 65 years 22 KEÁT QUA Û& KEÁT LUAÄN CUÛA NGHIEÂN CÖÙU Á Û Á Ä Û Â Ù PROCAM 103 66 48 37 2714 172219 0 50 100 150 >163 32-163 >132 > 2 7 7 2 3 6 - 2 7 7 < 2 3 6 LDL cholesterol (mg/dl) Fibrinogen (g/l) I n c i d e n c e ( p e r 1 , 0 0 0 i n 6 y e a r s ) 80 events, 1983 men aged 40 - 65 years NGUY CÔ BEÄNH ÑMV TÍNH THEO NOÀNG ÑOÄ FIBRINOGEN VAØ LDL 23 PHAÂN TÍCH HOÀI QUI ÑA BIEÁN ÑEÅ ÖÔÙC LÖÔÏNG TAÀN SUAÁT  À Á Å Ù Ï À Á BÒ NMCT VAØ BÒ BEÄNH ÑMV TUØY THEO CAÙC BIEÁN SOÁ Ø Ä Ø Ù Á Á NGUY CÔ KHAÙC NHAUÙ Nguy cô maïch maùu töông ñoái Bieán soá NMCT (n=107) Beänh ÑMV (n=74) Chæ soá khoái cô theå (BMI)) > 30 kg/m2 1.5 1.5 Huyeát a ùp > 160/95 mmHg 1.9* 2.0* Ñöôøng huyeát > 150 mg/dl 3.1** 1.9* Huùt thuoác la ù 2.1** 1.6 Coù tie àn söû gia ñình 4.2*** 1.9 Cholesterol > 240 mg/dl 4.6*** 2.1 LDL > 190 mg/dl 7.4*** 3.4*** Triglycerides > 200 mg/dl 2.8** 1.4 VLDL > 30 mg/dl 2.2** 1.2 HDL < 35 mg/dl 3.1*** 1.5 *p<0.05 **p<0.01 ***p<0.001 ( Theo Cremer P, nagel D, Seidel D: Gottingen Risk, Incidence and Prevalence Study (GRIPS) 1990) 24 ÑÖÔØNG CHUYEÅN HOÙA CÔ BAÛN CUÛA LDL HUYEÁT Ø Å Ù Û Û Á THANH 25 VAI TROØ CUÛA LDL TRONG XÔ VÖÕA ÑOÄNG MAÏCHØ Û Õ Ä Ï „ Thaønh phaàn cholesterol trong caùc maûng xô vöõa haàu heát laø cholesterol töø LDL. Tuy nhieân, söï tích tuï lipid vaø söï taïo thaønh maûng xô vöõa chæ seõ xaûy ra khi noàng ñoä LDL vöôït quaù möùc ngöôõng 100 mg/dl (2,6 mmol/l). Noàng ñoä ngöôõng naøy chính laø cô sôû cuûa khaùi nieäm LDL-100. Söï taïo thaønh XVÑM baét ñaàu khi noàng ñoä LDL taêng cao hôn giôùi haïn 100 mg/dl. 26 VAI TROØ CUÛA LDL OXY HOÙA TRONG XÔ VÖÕA Ø Û Ù Õ ÑOÄNG MAÏCHÄ Ï Endothelium LDL LDL Lipid oxidation MM-LDL Smooth muscle cell Foam cell Fatty streak M-CSF IL-1 Smooth muscle cell proliferationROS Modified LDL uptake Ox-LDL Oxidation Differentiation X-LAM + Adhesion Monocyte MCP-1 M-CSF Macrophage + MCP-1 + Entry 27 CAÙC YEÁU TOÁ THAM DÖÏ TRONG XVÑMÙ Á Á Ï Giaûi phoùng caùc chaát trung gian •Phôi baøy caùc glycoprotein maøng teá baøo Noäi maïc Söï bieán ñoåi sinh hoïc cuûa caùc lipoprotein Di truyeàn Tuoåi Noäi tieát toá Cheá ñoä aên Caùch soáng Tích tuï ngoaøi teá baøo caùc thaønh phaàn: cholesterol, calcium LDL, LDL oxid hoùa, caùc töï khaùng theå, caùc saûn phaåm baát thöôøng cuûa söï chuyeån hoùa chaát neàn chuyeân bieät cuûa maûng xô vöõa Maûng xô vöõa Tieåu caàu BC ñôn nhaân Ñaïi thöïc baøo Teá baøo cô trôn Teá baøo lympho T Gia ñình thuaän lôïi Roái loaïn lipid maùu ↑Lp (a), ↓ HDL Huùt thuoác laù Taêng huyeát aùp Tieåu ñöôøng Beùo phì Khoâng hoaït ñoäng theå löïc Tuoåi / phaùi tính LDL IDL 100 Caùc yeáu toá tham döï trong XVÑM (theo Seidel 1993) 28 BAÈNG CHÖÙNG VEÀ VAI TROØ SINH XÔ VÖÕA CUÛA È Ù À Ø Õ Û LDL OXID HOÙAÙ „ Coù söï hieän dieän cuûa caùc maûnh LDL ñaõ oxid hoùa trong caùc maûng moâ xô, caùc maûnh naøy khaùng vôùi söï thöïc baøo cuûa ñaïi thöïc baøo „ Coù baèng chöùng mieãn dòch hoùa teá baøo cuûa LDL oxid hoùa trong caùc sang thöông xô vöõa „ LDL ly trích töø caùc sang thöông coù caùc tính chaát veà sinh hoùa, veà mieãn dòch, veà sinh hoïc cuûa LDL oxid hoùa „ Trong huyeát thanh coù söï hieän dieän caùc töï khaùng theå, söï hieän dieän cuûa IgG phaûn öùng vôùi LDL oxid hoùa trong caùc sang thöông 29 CAÙC TAÙC DUÏNG GAÂY XÔ VÖÕA CUÛA LDL OXID Ù Ù Ï Â Õ Û HOÙAÙ „ LDL oxid hoùa ñöôïc caùc ñaïi thöïc baøo thu nhaän nhanh choùng vaø daãn ñeán tình traïng tích tuï cholesterol trong ñaïi thöïc baøo „ LDL oxid hoùa laø hoùa öùng ñoäng cho BC ñôn nhaân, öùc cheá söï di ñoäng cuûa ñaïi thöïc baøo „ LDL oxid hoùa laø chaát ñoäc teá baøo „ LDL oxid hoùa toái thieåu coù theå laøm thay ñoåi söï theå hieän gen taïo ra caùc teá baøo noäi maïc ñoäng maïch ñeå phôi baøy protein hoùa öùng ñoäng BC ñôn nhaân I (MCPI) Anuual Review of Medicine, Vol 42, 1992 30Anuual Review of Medicine, Vol 42, 1992 CAÙC TAÙC DUÏNG GAÂY XÔ VÖÕA CUÛA LDL OXID Ù Ù Ï Â Õ Û HOÙAÙ „ LDL oxid hoùa laøm taêng söï phôi baøy caùc phaàn töû keát dính ôû beà maët teá baøo noäi maïc „ LDL oxid hoùa öùc cheá söï thö giaõn phuï thuoäc noäi maïc „ LDL oxid hoùa laøm taêng söï gaén keát vôùi collagen típ I „ LDL oxid hoùa coù theå aûnh höôûng xaáu ñeán con ñöôøng ñoâng maùu „ LDL oxid hoùa laø chaát gaây mieãn dòch 31 ÑIEÀU HOØA SÖÏ PHAÂN BOÁ CAÙC LOAÏI LDLÀ Ø Ï Â Á Ù Ï Chylomycrons VLDL I II III I II III Kieåu A cuûa maãu ñieän di LDL Kieåu B cuûa maãu ñieän di LDL LDL-I/II CE IG CE CE TG HL CETP FA LDL-III TG ↑ HL ↑ TG ↓ LpL ↑ Receptors Gut Liver LpL LDL coù 3 daïng: LDL-I, LDL-II, LDL-III * ÔÛ ngöôøi coù TG thaáp: coù nhieàu LDL-I vaø LDL-II (LDL kích thöôùc lôùn) * ÔÛ ngöôøi coù TG cao: coù nhieàu LDL-III (LDL nhoûm ñaëc) Giaû thuyeát veà söï chyeån ñoåi töø LDL lôùn thaønh LDL nhoû hôn, ñaëc hôn ñöôïc trình baøy ôû sô ñoà treân 32 1970s 1988 Söïï phaùtù trieånå cuûaû khuyeáná caùoù ñieàuà trò roáiá loaïnï lipid maùuù NCEP-ATP: 1993 2001 ATP I ATP II ATP III „ Framingham „ MRFIT „ LRC-CPPT „ Coronary Drug Project „ Helsinki Heart Study „ CLAS „Angiographic Trials „(FATS, POSCH, SCOR, STARS, Ornish, MARS) „Meta-Analyses „(Holme, Rossouw) „ 4S, WOSCOPS, CARE, LIPID, AFCAPS/TexCAPS, VA-HIT, others 2004 ATP III Update „ Allhat, ProveIT, ASCOT LLA, HPS 33 LDL-C: Muïcï tieâuâ ñieàuà trò quan troïngï nhaátá LDL-C laø muïc tieâu ñieàu trò quan troïng nhaát trong ñieàu trò roái loaïn lipid maùu, ñoù laø keát quaû töø: - Caùc nghieân cöùu cô baûn - Caùc thöû nghieäm treân ñoäng vaät - Caùc nghieân cöùu dòch teã - Caùc daïng taêng cholesterol coù tính di truyeàn - Caùc thöû nghieäm laâm saøng coù kieåm chöùng Circulation. 2004;110:227-239 Nghieân cöùu ASCOT-LLA Nghieân cöùu PROVE-IT Atorvastatin Giaûm LDL-C Giaûm bieán coá 34 ATP III: Nhoùmù nguy cô, LDL-C muïcï tieâuâ Nhoùm nguy cô LDL-C muïc tieâu (mg/dL) BMV hoaëc töông ñöông (nguy cô 10 naêm >20%) <100 (2,6mmol/L) (Muïc tieâu khaùc: < 70*~1,82mmol/L) ≥2 YTNC (nguy cô 10 naêm ≤20%) <130 (~3,4mmol/L) 0–1 YTNC* <160 (4,2mmol/L) * Beänh nhaân coù nguy cô raát cao caàn ñaët muïc tieâu LDL < 70mg/dL* (~1,82mmol/L) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486- 2497. Circulation. 2004;110:227-239 35Seven-year incidence in a Finnish-based cohort. *P < 0.001 NGHIEÂN CÖÙU EAST ٠-WEST: BEÄNH NHAÂN ÑTÑ COÙ NGUY CÔ TÖÔNG ÑÖÔNG VÔÙI Ä Â Ù Ù BEÄNH NHAÂN NMCT KHOÂNG ÑTÑÄ Â Â 3.5% 20.2%18.8% 45.0% 0% 10% 20% 30% 40% 50% BN khoâng ÑTÑ (n = 1,373) BN ÑTÑ type 2 (n = 1,059) N g u y c ô N M C T t ö û v o n g h o a ë c k h o â n g t ö û v o n g Khoâng NMCT tröôùc ñoù Ñaõ bò NMCT * * Adapted from Haffner SM. New Engl J Med 1998; 339:229–234. 36 0.00 0.05 0.10 0.15 0.20 T æ l e ä t a i b i e á n NGHIEÂN CÖÙU OASIS:  ٠BEÄNH NHAÂN ÑTÑ COÙ NGUY CÔ TÖÔNG ÑÖÔNG Ä Â Ù VÔÙI BEÄNH NHAÂN BEÄNH TIM MAÏCH KHOÂNG ÑTÑÙ Ä Â Ä Ï Â Adapted from Malmberg K et al. Circulation. 2000;102:1014-1019. 3 6 9 12 15 18 21 24 ÑTÑ + Beänh TM ÑTÑ (-)/beänh TM(+) RR=1.71 (1.41, 2.06) ÑTÑ (-)/ beänh TM(-) RR=1.00 ÑTÑ/beänh TM(+) RR=2.85 (2.30, 3.53) ÑTÑ/beänh TM(-) RR=1.71 (1.25, 2.33) Months Khoâng ÑTÑ + Beänh TM ÑTÑ + khoâng beänh TM Khoâng ÑTÑ + khoâng beänh TM N=8013 OASIS=Organization to Assess Strategies for Ischemic Syndromes. 37 ATP III NHAÁN MAÏNH : ÑAÙI THAÙO ÑÖÔØNG ÑÖÔÏC XEM NHÖ LAØ MOÄT NGUY CÔ TÖÔNG ÑÖÔNG BEÄNH TIM MAÏCH VAØNH (CHD RISK EQUIVALENT) 38 Nguy cô töông ñöông BMV „ Caùc daïng laâm saøng cuûa XVÑM (beänh ñoäng maïch ngoaïi bieân, phình taùch ñoäng maïch chuû buïng, beänh ñoäng maïch caûnh coù trieäu chöùng) „ Tieåu ñöôøng „ Ña YTNC vôùi nguy cô 10 naêm >20% 39 ATP III: Framingham Point Scores Estimate of 10-year Risk for Men HDL = high-density lipoprotein. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. SBP mm Hg If Untreated <120 120-129 130-139 140-159 ≥160 0 0 1 1 2 HDL mg/dL Points ≥60 50-59 40-49 <40 -1 0 1 2 TC <160 160-199 200-239 240-279 ≥280 0 4 7 9 11 0 3 5 6 8 0 2 3 4 5 0 1 1 2 3 0 0 0 1 1 Age 20-39 Nonsmoker Smoker 0 8 Age 50-59 0 3 Age 60-69 0 1 Age 70-79 0 1 Point Total 10-Year Risk, % <0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 ≥17 <1 1 1 1 1 1 2 2 3 4 5 6 8 10 12 16 20 25 ≥30 1 3 5 4 6 2 Age Points 20-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 -9 -4 0 3 6 8 10 11 12 13 If Treated 0 1 2 2 3 Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 Age 40-49 0 5 40 ATP III: Framingham Point Scores Estimate of 10-year Risk for Women SBP mm Hg If Untreated <120 120-129 130-139 140-159 ≥160 0 1 2 3 4 HDL mg/dL Points ≥60 50-59 40-49 <40 -1 0 1 2 TC <160 160-199 200-239 240-279 ≥280 0 4 8 11 13 0 3 6 8 10 0 2 4 5 7 0 1 2 3 4 0 1 1 2 2 Age 20-39 Nonsmoker Smoker 0 9 Age 40-49 0 7 Age 50-59 0 4 Age 60-69 0 2 Age 70-79 0 1 Point Total 10-Year Risk, % <9 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 ≥25 <1 1 1 1 1 2 2 3 4 5 6 8 11 14 17 22 27 ≥30 1 3 5 4 6 2 Age Points 20-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 -7 -3 0 3 6 8 10 12 14 16 If Treated 0 3 4 5 6 Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. 41 Framingham: 10-year Risk of CHD in Men *Low absolute risk level = 10-year risk for total CHD end points for a person the same age, BP <120/<80 mm Hg, TC 160-199 mg/dL, HDL cholesterol ≥45 mg/dL, nonsmoker, no diabetes. Percentages show 10-year absolute risk for total CHD end points. †Framingham points. ‡10-year absolute risk for total CHD end points estimated from Framingham data corresponding to Framingham points. ¶10-year absolute risk for hard CHD end points approximated from Framingham data corresponding to Framingham points. Grundy S, et al. Circulation. 1999;100:1481-1492. Age 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 (Low-risk level)* (2%) (3%) (3%) (4%) (5%) (7%) (8%) (10%) (13%) Absolute Risk Absolute Risk‡ Points† Total CHD‡ Hard CHD¶ 0 1.0 2% 2% 1 1.5 1.0 1.0 2 2.0 1.3 1.3 1.0 3 2.5 1.7 1.7 1.3 1.0 4 3.5 2.3 2.3 1.8 1.4 5 4.0 2.6 2.6 2.0 1.6 1.1 6 5.0 3.3 3.3 2.5 2.0 1.4 1.3 7 6.5 4.3 4.3 3.3 2.6 1.9 1.6 1.3 8 8.0 5.3 5.3 4.0 3.2 2.3 2.0 1.6 1.2 9 10.0 6.7 5.0 4.0 2.9 2.5 2.0 1.5 10 12.5 8.3 6.3 5.0 3.6 3.1 2.5 1.9 11 15.5 10.3 7.8 6.1 4.4 3.9 3.1 2.3 12 18.5 12.3 9.3 7.4 5.2 4.6 3.7 2.8 13 22.5 15.0 11.3 9.0 6.4 5.6 4.5 3.5 > 14 26.5 >17.7 >13.3 >10.6 >7.6 >6.6 >5.3 >4.1 Green Blue Yellow Red Below average risk Average risk Moderately above average risk High risk 3% 2% 4% 3% 5% 4% 7% 5% 8% 6% 10% 7% 13% 9% 16% 13% 20% 16% 25% 20% 31% 25% 37% 30% 45% 35% >53% >45% 6.7 8.3 10.3 12.3 15.0 >17.7 1.0 1.0 1.0 1.0 Color Key for Relative Risk 42 Khuyeáná caùoù NCEP 2004 – Treânâ cô sôûû cuûaû caùcù coângâ trình nghieânâ cöùuù 43 Caùcù thöûû nghieämä laâmâ saøngø sau ATP NCEP III „ HPS (simvastatin 40) „ PROSPER (pravastatin 40) „ ALLHAT-LLT (pravastatin 40) „ ASCOT-LLA (atorvastatin 10) „ PROVE IT (pravastatin 40 vs. atorvastatin 80) 44 NGUY CÔ NMCT TÍNH THEO NOÀNG ÑOÄ LDL VAØ À Ä Ø PHOÁI HÔÏP VÔÙI MOÄT SOÁ YEÁU TOÁ NGUY CÔ KHAÙC Á Ï Ù Ä Á Á Á Ù „ RF: khoâng coù theâm YTNC khaùc „ H: giaûm HDL „ X: taêng huyeát aùp hoaëc huùt thuoác laù hoaëc taêng ñöôøng huyeát „ F: tieàn caên gia ñình thuaän lôïi cho NMCT „ (theo Cremer P, Nagel D, Der Internist 1992: 33:32-7) 45 MOÁI LIEÂN QUAN COÙ THEÅ GIÖÕA LDLÁ Â Ù Å Õ -C VAØ NGUY CÔ Ø BEÄNH MAÏCH VAØNH (2001): Ä Ï Ø Caùcù giaûû thuyeátá Nguy cô BMV 100 LDL-C (mg/dL) Ngöôõng: Khoâng caàn thieát phaûi haï quaù thaáp õöôõ : âoâ àcaà t i áteá ûiaû ïaï ùuaù t áaá Ñöôøng thaúng: Caøng thaáp caøng toátøöôø t úaú : øaø t áaá øcaø t átoá Ñöôøng cong: Caøng thaáp, caøng toát, vôùi lôïi ích giaûm daàn øöôø :co øaø t áaá , øcaø t átoá , ùivôù l ïiôï íc i ûaû àaà 0 1 46 0 1 Baèngè chöùngù veàà Ñöôøngø cong trong moáiá lieânâ quan giöõaõ LDL-C nguy cô BMV (2001) Ñöôøng cong nguy cô BMV 100 LDL-C (mg/dL) ? Caùc thöû nghieäm laâm saøng Dòch teå hoïc 47 Heart Protection Study (Nghieânâ cöùuù keùoù daøiø 5 naêmê ) 0 1 Nguy cô BMV 100 LDL-C (mg/dL) Simvastatin 40 mg 60 Giaûm 26% nguy cô BMV Giaûm 22% nguy cô BMV Simvastatin 40 mg Heart Protection Study Collaborative Group. Lancet 2002;360:7–22. 48 PROVE IT–TIMI 22 (Nghieânâ cöùuù trong 2 naêmê ) 0 1 Nguy cô BMV 100 Möùc LDL-C60 Pravastatin 40 mg Giaûm 16% nguy cô BMV Atorvastatin 80 mg Cannon CP et al. N Engl J Med 2004;350:1495-1504. 49 Keátá luaänä töøø caùcù nghieânâ cöùuù : Vôùiù muïcï tieâuâ LDL “Caøngø thaápá – caøngø toátá ” Nguy cô BMV (Log Scale) 3.7 2.9 2.2 1.7 1.3 1.0 LDL-C (mg/dL) 40 70 100 130 160 190 0 1 Grundy SM et al. Circulation 2004;110:227–239. 50 Cô sôûû cho choïnï löïaï muïcï tieâuâ ñieàuà trò môùiù : LDL-C muïcï tieâuâ raátá thaápá <70 mg/dL „ Keát quaû nghieân cöùu HPS „ Keát quaû nghieân cöùu PROVE IT „ Chôø keát quaû töø nhöõng nghieân cöùu coù LDL-C muïc tieâu raát thaáp „ TNT „ IDEAL „SEARCH 51 Ñoáiá töôïngï cho möùcù LDL-C muïcï tieâuâ raátá thaápá <70 mg/dL „ Beänh nhaân coù nguy cô raát cao „ Beänh XVÑM vaønh „+ Ña yeáu toá nguy cô (ñaëc bieät laø tieåu ñöôøng) „+ Yeáu toá nguy cô naëng vaø khoâng ñöôïc kieåm soaùt toát (chaúng haïn huùt thuoác laù) „+ Hoäi chöùng chuyeån hoùa (TG cao, HDL-C thaáp) „+ Hoäi chöùng maïch vaønh caáp (PROVE IT) 52 MUÏC TIEÂU LDLÏ Â -C THEO KHUYEÁN CAÙO ATPÁ Ù -III BEÄNH NHAÂN NGUY CÔ RAÁT CAO: Beänh maïch vaønh keøm: 1. Ña yeáu toá nguy cô (ñaëc bieät laø ñaùi thaùo ñöôøng) 2. Coù caùc yeáu toá nguy cô nguy nghieâm troïng hoaëc yeáu toá nguy cô khoâng ñöôïc kieåm soaùt toát (ñaëc bieät laø huùt thuoác laù lieân tuïc) 3. Ña yeáu toá nguy cô cuûa hoäi chöùng chuyeån hoùa (ñaëc bieät laø triglyceride > 200mg/dL keøm non-HDL-C > 130 mg/dL (~3,4) vaø HDL-C thaáp < 40mg/dL (~1,0mmol/L) 4. Beänh nhaân coù hoäi chöùng maïch vaønh caáp LDL-C < 70 mg/dl (~1,8mmol/L) Ä Â Á ä ï ø ø á á ë ä ø ù ù ø ù ù á á â ï ë á á â ï å ù á ë ä ø ù á ù â ï á á û ä ù å ù ë ä ø ø ø á ä â ù ä ù ï ø á Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486- 2497. Circulation. 2004;110:227-239 53 MUÏC TIEÂU LDLÏ Â -C THEO KHUYEÁN CAÙO ATPÁ Ù -III BEÄNH NHAÂN NGUY CÔ CAO: (Beänh maïch vaønh, ñaùi thaùo ñöôøng, beänh ñoäng maïch ngoaïi bieân…) LDL-C < 100 mg/dl (~2,6mmol/L) Ä Â ä ï ø ù ù ø ä ä ï ï â Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486- 2497. Circulation. 2004;110:227-239 54 Khaùcù bieätä giöõaõ NCEP ATP III naêmê 2001 vaøø 2004 (1) Patient risk category NCEP ATP III New NCEP ATP report Goal: <2.6 mmol/L (100 mg/dL) Goal: <2.6 mmol/L (100 mg/dL)(Optional: <1.8 mmol/L [70 mg/dL]) Consider therapy: ≥3.4 mmol/L (130 mg/dL)(Optional: 2.6 mmol/L [100 mg/dL] to 3.3 mmol/L [129 mg/dL]) Initiate TLC: ≥2.6 mmol/L [100 mg/dL] Consider drug therapy: ≥2.6 mmol/L [100 mg/dL] (<2.6 mmol/L [100 mg/dL]: consider drug options) High risk: CHD or CHD risk equivalents 55 Khaùcù bieätä giöõaõ NCEP ATP III naêmê 2001 vaøø 2004 (2) Patient risk category NCEP ATP III New NCEP ATP report Goal: <3.4 mmol/L (130 mg/dL) Goal: <3.4 mmol/L [130 mg/dL] (Optional: <2.6 mmol/L [100 mg/dL]) Consider therapy: ≥3.4 mmol/L (130 mg/dL) Initiate TLC: ≥3.4 mmol/L [130 mg/dL]§ Consider drug therapy: ≥3.4 mmol/L (130 mg/dL) (2.6 mmol/L [100 mg/dL] to 3.3 mmol/L [129 mg/dL]: consider drug options) Moderately high risk:≥2 risk factors#(10-year risk 10%-20%) 56 Khaùcù bieätä giöõaõ NCEP ATP III naêmê 2001 vaøø 2004 (3) Patient risk category NCEP ATP III New NCEP ATP report Goal: <3.4 mmol/L (130 mg/dL) Goal: <3.4 mmol/L (130 mg/dL) Consider therapy: ≥4.1 mmol/L (160 mg/dL) Initiate TLC: ≥3.4 mmol/L (130 mg/dL)Consider drug therapy: ≥4.1 mmol/L (160 mg/dL) Moderate risk:≥2 risk factors (10-year risk <10%) 57 Khaùcù bieätä giöõaõ NCEP ATP III naêmê 2001 vaøø 2004 (4) Patient risk category NCEP ATP III New NCEP ATP report Goal: <4.1 mmol/L (160 mg/dL) Goal: <4.1 mmol/L (160 mg/dL) Consider therapy: ≥4.9 mmol/L (190 mg/dL)(Optional: 4.1 mmol/L [160 mg/dL] to <4.9 mmol/L [189 mg/dL]) Initiate TLC: ≥4.1 mmol/L (160 mg/dL)Consider drug therapy: ≥4.9 mmol/L (190 mg/dL)(4.1 mmol/L [160 mg/dL] to <4.9 mmol/L [189 mg/dL]: LDL-C–lowering drug optional) Lower risk:0 or 1 risk factor 58 PHAÂN LOAÏI MÖÙC TRIGLYCERIDE MAÙU:Â Ï Ù Ù ≥500 mg/dL (~5,62)Raát cao 200–499 mg/dL (~2,24-5,61)Cao 150–199 mg/dL (~1,69-2,24)Giôùi haïn cao <150 mg/dL (~1,69mmol/L)Bình thöôøng Möùc TGNhoùm Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 1993;269:3015-3023. | Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497. 59 Phaânâ loaïiï möùcù HDL-C maùuù : ≥60 mg/dL (1,6mmol/L)HDL-C cao <40 mg/dL (1,0mmol/L)HDL-C thaáp Möùc HDL-CNhoùm Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 1993;269:3015-3023. | Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497. 60 Non-HDL-C Goals in Patients with TG ≥200 mg/dL Risk category Non-HDL-C goal (mg/dL) CHD or CHD risk equivalents (10-yr risk >20%) <130 (~3,4mmol/L) 2+ risk factors (10-yr risk ≤20%) <160 (~4,2) 0–1 risk factor <190 (~4,9) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497. 61 Ñieàuà trò taêngê cholesterol maùuù Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497. LDL-C cao- Ñieàu trò thay ñoåi loái soángi àà trò t åiå l áiá áá Duøng thuoácøø t áá Thuoác öu tieân: Statináác ti ââ : t ti Nhoùmù thay theáá: Resin hoaëcë niacin 62 Ñieàuà trò taêngê cholesterol maùuù phoáiá hôïpï Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497. LDL-C vaø TGs cao- øø Ñieàu trò thay ñoåi loái soángi àà trò t åiå l áiá áá Duøng thuoácøø t áá Ñaïtï möùcù LDL-C muïcï tieâuâ1Böôùcù Ñaïtï möùcù non-HDL-C muïcï tieâuâ Coáá gaéngé giaûmû theâmâ LDL-C hoaëcë theâmâ fibrate, niacin hoaëcë daàuà caùù 2Böôùcù 63 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. ATP III: Ñieàu trò taêng TG à ê Caàn ñieàu trò Triglyceride ñeå traùnh vieâm tuïy caáp Sau khi TG < 500 (~5,62mmol/L) mg/dL, muïc tieâu ñieàu trò chính laø LDL-C à à å ù â ï á ï â à ø ≥ 500 (~5,62)Raát caoá Muïc tieâu ñieàu trò chính laø LDL-Cï â à ø150–499 (~1,69-5,61mmol/L) Giôùi haïn cao vaø cao ù ï ø Ñieàu tròàMöùc TG (mg/dL) ùPhaân loaïiâ ï 64 HDL < 40 mg/dL (~1,0mmol/L) Caûiû thieänä loáiá soángá LDL cao + TG bt Statin Theâmâ Niacin HDL < 40 mg/dL TG cao LDL < 130 mg/dL Fibrate LDL > NCEP target LDL < NCEP ATP target HDL < 40 mg/dL Statin hay ezetimibe HDL < 40 mg/dL Theâmâ Niacin Theâmâ Niacin Circulation. 2004;109:1809-1812 LDL >130 mg/dL Statin Non HDL > NCEP ATP target HDL < 40 mg/dL Theâmâ Fibrate HDL < 40 mg/dL Theâmâ Niacin Chæ HDL thaápá Tieànà söûû gia ñình coùù BMV. Hay nguy cô Framingham 10 naêmê > 20% Statin HDL < 40 mg/dL Theâmâ Niacin 65 ÑIEÀU TRÒ HOÄI CHÖÙNG X CHUYEÅN HOÙA KHUYEÁN CAÙO ÑIEÀU TRÒ NCEP – ATP III (2001) MUÏC TIEÂU CHÍNH LAØ: + Ñieàu trò haï LDL (LDL – Lowering therapy) + Muïc tieâu phuï laø haï cholesterol khoâng phaûi HDL (Non – HDL cholesterol) 66 ÑIEÀU TRÒ HOÄI CHÖÙNG X CHUYEÅN HOÙA MUÏC TIEÂU PHUÏ: NON – LDL CHOLESTEROL ™ Non – HDL cholesterol = VLDL + LDL cholesterol = (Total cholesterol – HDL cholesterol) ™ Non – HDL cholesterol laø muïc tieâu phuï quan troïng khi Triglycerid maùu ≥ 200 mg/dl (ví duï 200 – 499 mg/dl) 67 ÑIEÀU TRÒ HOÄI CHÖÙNG X CHUYEÅN HOÙA MUÏC TIEÂU ÑIEÀU TRÒ HAÏ NON - HDL - CHOLESTEROL Nhoùm nguy cô Muïc tieâu LDL – C (mg/dl) Muïc tieâu Non- HDL – C (mg / dl) Beänh maïch vaønh vaø nguy cô töông ñöông beänh maïch vaønh < 100 < 130 Nhieàu yeáu toá nguy cô (2+) < 130 < 160 Khoâng hoaëc chæ moät yeáu toá nguy cô < 160 < 190 Muïc tieâu haï Non-HDL cholesterol baèng muïc tieâu haï LDL – cholesterol coäng vôùi 30 68 CHD Patient Treatment Gap: Community Pearson TA et al. Arch Intern Med 2000;160:459-467. 0 20 40 60 80 100 18 Provider awareness does not equal successful implementation 95 Physician Awareness of NCEP ATP Guidelines Patient Treated to Goal P e r c e n t P e r c e n t 69 Adherence to NCEP ATP Treatment Goals in Patients with CHD: Quality Assurance Program Sueta CA et al. Am J Cardiol 1999;83:1303-1307. LDL < 100 (~2,6mmol/L), on Rx LDL < 100, no Rx LDL > 100, on Rx LDL > 100, no Rx No LDL, on Rx No LDL, no Rx 7% 5% 18% 16% 12% 42% n = 58,890; 140 US practices, chart audit 7/94–10/96 70 Drug Class LDL-C HDL-C Triglycerides Statins* ↓ 18% to 60%*** ↑ 5% to 15% ↓ 7% to 37%*** Bile Acid ↓ 15% to 30% ↑ 3% to 5% No change or Sequestrants increase Nicotinic Acid ↓ 5% to 25% ↑ 15% to 35% ↓ 20% to 50% Fibric Acids ↓ 5% to 20%** ↑ 10% to 20% ↓ 20% to 50% Thuoácá ñieàuà trò roáiá loaïnï lipid maùuù *Lovastatin (20 to 80 mg), pravastatin (20 to 40 mg), simvastatin (20 to 80 mg), fluvastatin (20 to 80 mg), atorvastatin (10 to 80 mg), and rosuvastatin (10 to 40 mg). **May be increased in patients with high triglycerides. ***Up to 60% reduction in LDL-C, and 37% reduction in triglycerides, as indicated in the atorvastatin PI. Adapted from NCEP Expert Panel. JAMA. 2001;285:2486-2497. 71 Downs JR et al. JAMA 1998;279:1615-1622. | Shepherd J et al. N Engl J Med 1999;333:1301-1307. | Scandinavian Simvastatin Study Group. Lancet 1994;344:1383-1389. | Sacks FM et al. N Engl J Med 1996;335:1001-1009. | LIPID Study Group. N Engl J Med 1998;339:1349-1357. | Schwartz GG et al. JAMA 2001;285:1711-1718. | Pitt B et al. N Engl J Med 1999;341:70-76. Ann Pharmacother 2001; 35: 1599-607 So saùnhù baèngè chöùngù cuûaû caùcù nhoùmù thuoácá Nhoùm thuoác Baèng chöùng giaûm xuaát ñoäbieán coá Baèng chöùng giaûm xuaát ñoä töû vong chung Fibrate WHO (-) WOSCOPS, LIPID AFCAPS/TexCAPS 4S, HPS (-) AVERT, MIRACL, GREACE, ASCOT, CARDs, PROVE IT Clofibrate LRC-CPPT (-) (-) Pravastatin LIPID Rosuvastatin (-) Atorvastatin (Lipitor) GREACE, PROVE IT (-) 4S, HPS Fenofibrate Lovastatin Simvastatin Statin Nhoùm khaùc (-)Cholestyramine 72 Statins: Cô cheáá taùcù duïngï LDL receptor–mediated hepatic uptake of LDL and VLDL remnants Serum VLDL remnants Serum LDL-C Cholesterol synthesis LDL receptor (B–E receptor) synthesis Intracellular Cholesterol Apo B Apo E Apo B Systemic CirculationHepatocyte Reduce hepatic cholesterol synthesis, lowering intracellular cholesterol, which stimulates upregulation of LDL receptor and increases the uptake of non-HDL particles from the systemic circulation. LDL Serum IDL VLDLRR VLDL 73 So saùnhù hieäuä quaûû cuûaû caùcù statin treânâ LDL-C Source: Law et al. BMJ. 2003;326:1-7. 0 -5 -10 -15 -20 -25 -30 -35 -40 -45 -50 -55 -60 Atorvastat in (n=2217) Simvastati n (n=4906) Pravastati n (n=5474) Rosuvasta tin (n=394) R e d u c t i o n i n L D L ( % ) 10 mg 20 mg 40 mg 80 mg 74 Taùc ñoäng cuûa statin:ù ä û Reduction of lipids + ƒ Reduction in lipid core and plaque stabilization ƒ Anti-inflammatory effects ƒ Improved endothelial function ƒ Antioxidant effects 75 *Nonfatal MI or CHD death; **ischemic events D._.