1、匯要內(nèi)容1、 LDLc正常值應(yīng)該多少？2、 LDLc11正常”，進(jìn)一步他汀降脂能否進(jìn)一步獲益?證據(jù)？3、 強(qiáng)化降脂是否獲益更多？4、 強(qiáng)化降脂獲益和足夠安全性能否統(tǒng)一？匯要內(nèi)容中國、美國心血管流行病學(xué)趨勢比較中國人群心血管死亡率強(qiáng)勁上升美國入群血管死亡車顯著下降4003 2 1冊心齦503520059075加453015舊OS 蚪ijk孚瞻1985 1990 1 995 2000 2005 2010年1970 1975 1980 1S85 1990 1995 2000 2005年中國慢瞄報(bào)告(2006)NHLBI Chartbook 2007中國、美國心血管流行病學(xué)趨勢比較中國人群心血管死亡率

2、強(qiáng)勁上不同防治措施對美國冠心病死亡率下降的貢獻(xiàn)PCI for chronic angina (1.3%CABG for chronic anginStatin primary preventionTxofHT 7%T ChoiJ/4.9%Tx of HF Initial Tx for AMI arSmoking 11.7%BP ，.1%24#%Physical A. 5.1 k7Risk factor reductionBMIDM98%44%膽固醇水平 下降貢獻(xiàn) 24. 2%N Engl J Med 2007 June7;356:2388prevent! on| post AM I or PC

3、I including statins)不同防治措施對美國冠心病死亡率下降的貢獻(xiàn)PCI for ch-100019991822 EXTRA DEATHS ATTRIBUTABLE TO RISK FACTOR CHANGES1000500ol es te ro 177%Diabetes BMI Smoking19%4%1%642 FEWER DEATHS BY TREATMENTSAMI treatments Hypertension treatment Secondary prevention Heart failure Aspirin for Angina Angina CABGS PIC

4、A41% 24% 11%10% 10% 2%中國北京地區(qū)冠心病死亡率增加的主要原因是膽固醇水平的增高Circulation 2004 趙冬 110:1236-1244-100019991822 EXTRA DEATHS ATT心皿官炬險(xiǎn)內(nèi)系:水*縱I可殳 化錢衛(wèi)沖等.中國循環(huán)雜志,200*16:47BMIWHRSBPDBPTC男性198420.82.0119187411121 29199222.1 2.4*0.82 0.05119187711*149 33*199822.1 2.9*0.85 0.05*12618*80ir#187 37*#女性198421.1 2.41191873101233

5、1199222.93.0*0.78 0.05118177611*147 36*199822.93.0*0.81 0.06*12521*77 10*#183 30*#中國江蘇:江南某縣樣本人群15年間膽固醇升高了 50%!（LDLc從v70mg/dl很低水平增至100-110mg/dL的“正?！彼蕉龋?，如今CVD成了頭號殺手心皿官炬險(xiǎn)內(nèi)系:水*縱I可殳BMIWHRSBPDBPTC男性現(xiàn)存指南錯誤(過分強(qiáng)調(diào)高血壓危害而 忽視膽固醇升高的更加危害性)中國成人血脂異常防治指南制訂聯(lián)合委員會.中國成人血脂異常防治指南. 中華心血管病雜志2007; 35(5): 390-413.表5血脂異常危險(xiǎn)分層方

6、案危險(xiǎn)分層TC5.18-6.19mmol/l(200-239mg/dl)或LDL-c3.37-4.12mmol/l(130-159mg/dl)TC6.22mmol/l(240mg/dl)或LDL-c 4.14mmol/l(160mg/dl)無高血壓且其他 危險(xiǎn)因素v3低危?高血壓或其他 危險(xiǎn)因素E 3低危中危高血壓且其他 危險(xiǎn)因素約1中危高危冠心病及其等危癥高危高?，F(xiàn)存指南錯誤(過分強(qiáng)調(diào)高血壓危害而 忽視膽固醇升高的更加危害，、食，溪瞬.ELSEVIERAtherosclerosis 168 (2003) 1-14wwwlse /locate/atherosclero sisReviewA r

7、eview on the diagnosis, natural history, and treatment of familial hypercholesterolaemiaDaly a Marksa, Margaret Thorogooda, H. Andrew W. Neilb, Steve E. Humphries 家族性高膽固醇血癥患病率約1/500,全世界約1000萬,中國約260萬病人成人 L DL-c4.9mmol/L,兒童 4.0mmol/L男性到50歲時(shí)圣50%發(fā)生致死性/非致死性冠心病女性到60歲時(shí)芝30%發(fā)生致死性/非致死性冠心病高危，不是低危！，、食，溪瞬.Ather

8、osclerosis 168 (202011 ESC/EAS指南：各危險(xiǎn)人群的描述 把單項(xiàng)LDLc很高或重度（高危）高血壓定為高危人群危險(xiǎn)程度描述極高危CVD:通過侵入或非侵入性檢查（如冠脈造影、核醫(yī)學(xué)成像、超聲心動圖 負(fù)荷試驗(yàn)、超聲發(fā)現(xiàn)頸動脈斑塊）診斷的CVD、陳舊性心梗、ACS、冠脈血 運(yùn)重建（PC域CABG）、其他動脈血運(yùn)重建手術(shù)、缺血性卒中、外周動脈 疾病（PAD）T2DM、T1DM合并靶器官損害（如微量白蛋白尿）中重度 CKD（GFR10%高危單項(xiàng)危險(xiǎn)因素顯著升高（如LDLc顯著升高和重度（高危）高血壓） 5%SCORE 評分 10%中危 1% 6.99 (270)TC 6.22 (

9、240)性 6.22 (240 JTC 4.14 (160)LDL-C 4.14 (160)TC 4.14 (160)CHD等危癥，或 10年危險(xiǎn)性10% 15%值LDL-O2.59 (100)LDLC 4.14 (160)TC 2.07 (80)LDLC50 Age心臟移植的供體（所謂健康人）心臟作血管內(nèi)超聲顯示:冠脈內(nèi) 粥樣斑塊厚度0.5mm從青少年巳開始，至30歲以上60%, 50歲以上80%以上有冠脈內(nèi)粥樣斑塊 JACC 2010；56：63019 y.o man0033 y.o.woman806040美國成人LDLc平均水平遠(yuǎn)高于70mg/dl,在100130mg/dl之間,CDH成

10、為第一殺手靈長類動物,新生兒，守獵群居者，中國貧窮農(nóng)村地區(qū)人群LDLcv70mg/dl,中國貧窮農(nóng)村CHD仍極少見JACC 2010;56:630美國成人LDLc平均水平遠(yuǎn)高于70mg/dl,在10013:所謂正常范圍指以CHD發(fā)病機(jī)制為基礎(chǔ), 既滿足機(jī)體生理需要又不至（或很少）發(fā) 生動脈粥樣硬化（只有通過前瞻性CHD 發(fā)病率調(diào)查或血管內(nèi)超聲檢查來確定）的 LDLc范圍:所謂正常范圍指以CHD發(fā)病機(jī)制為基礎(chǔ), 既滿足機(jī)體生理JACC 2008；51 (15):1512-1524Animal and human trials of dietary and pharmacological inte

11、rventions that reduce LDL cholesterol arc associated with stabilization and regression of atherosclerosis in proportion to the cholesterol lowering achieved, supporting the validity of “the lower the cholesterol the better notion, especially in individuals with established CVD Theoretically, all hum

12、ans should maintam newborn” LDL cholesterol levels of about 50 mg/dl ro prevent atherosclerosis, and thoue widi existing CT) should be treated to siiniLuly low levels. The? lower limit to safe and efieccive cliolesterol loweiiiig has not been established. Individuals with genetic mucadons causing li

13、felong very low LDL cholesterul kvk appear not only to avoid CVI) but also to be free of other almonnalitics that might conceivably he linked to their very low plasma cholesterol levels (6).JACC 2008；51 (15):1512-1524Ani動物和人體的飲食和藥物干預(yù) 試驗(yàn)顯示.這進(jìn)一步支持了LDL-C “低一點(diǎn).好一些”的觀點(diǎn)，特別是在已經(jīng)明 確CVD的患者中。,所有人都應(yīng)該將 LDL-C維持在5

14、0mg/dL的“新生兒” 水平，以預(yù)防動脈粥樣硬化，CVD 患者也應(yīng)該控制在類似低的水平。動物和人體的飲食和藥物干預(yù) 試驗(yàn)顯示.,所有人都應(yīng)該將 LD從循證醫(yī)學(xué)看待他汀強(qiáng)效安全的辯證統(tǒng)一課件答案:否許多AMI或猝死為首發(fā)表現(xiàn)的CHD病人事先無癥狀:一定數(shù)量的無癥狀所謂“健康人早巳 存在亞臨床CAD答案:否許多AMI或猝死為首發(fā)表現(xiàn)的CHDJUPITER -研究設(shè)計(jì)LDLc“正?！?既往無CAD病史 男性N50歲 女性60歲 LDL-C2.0 mg/L安崽布導(dǎo)入瑞舒伐他汀20 mg (n=8901)安慰布(n=8901)隨訪：1234周數(shù)：-6-40136 每個(gè)月結(jié)束導(dǎo)入/ 入選資格 隨機(jī)化血脂

15、CRP耐受性血脂CRP 耐受性中位隨訪時(shí)間1.9年血脂CRP 耐受性 Hb%CAD二冠狀動脈疾??；LDL-C二低密度脂蛋白膽固醵；CRP二C反應(yīng)苗白；HbA1c=ft基化血紅資白RidkprP ai NEngJ Me2008;359: 2195-207JUPITER -研究設(shè)計(jì)既往無CAD病史 男性N50歲 女JUPITER 基線情況*瑞舒伐他汀n=8901安慰劑 n=8901年齡(歲)66 (60-71)66 (60-71) ，男性(%)61.562.1 (種族(%)白人71.471.1黑人12.412.6 (西班牙裔12.612.8 其他3.63.5 !BMI (kg/m2)28.3 (2

16、5.3-32.0)28.4 (25.3-32.0) (收縮壓(mmHg)134 (124-145)134 (124-145)舒弓長壓(mmHg)80 (75-87)80 (75-87)*所有數(shù)值均為中位數(shù)(四分位數(shù)間距)或人數(shù)(%f 一 Ridker P et al.JUPITER 基線情況*瑞舒伐他汀安慰劑 n=8901年JUPITER 總膽固醇(mg/dL)LDL 膽固醇(mg/dL)HDL 膽固醇(mg/dL) 甘油三酯(mg/dL) hsCRP (mg/L) 葡萄糖(mg/dL) HbA1c(%) 腎小球?yàn)V過率 (ml/min/1.73m2)hsCRP的數(shù)值是兩次篩選和隨訪所獲得數(shù)值的

17、均數(shù)JUPITER 總膽固醇(mg/dL)hsCRP的數(shù)值是兩實(shí)驗(yàn)室參數(shù)的基線值*瑞舒伐他汀 n=8901安慰劑n=8901186 (168-200)185 (169-199)108 (94-119)108 (94-119)49 (40-60)49 (40-60)118(85-169)118 (86-169)4.2 (2.8-7.1)4.3 (2.8-7.2)94 (87-102)94 (88-102)5.7 (5.4-5.9)5.7 (5.5-5.9)73.3 (64.6-83.7)73.6 (64.6-84.1)Ridker P eTal. N Eng J Med 2008;359:219

18、5-2207實(shí)驗(yàn)室參數(shù)的基線值*瑞舒伐他汀 n=8901安慰劑186 (JUPITER 病史病史瑞舒伐他汀n=8901安慰劑n=8901目前仍為吸煙者(%)15.716.0 CHD的家族史十(%)11.211.8 (代謝綜合征* (%)41.041.8 )服用阿司匹林()16.616.6 ；按傳統(tǒng)危險(xiǎn)因素計(jì)算:JUPITER人群列為中危，目標(biāo)LDLc2mg/dL是又一個(gè)決定使用他汀的危險(xiǎn)Marker提早發(fā)生CHD的家族史定義為一級親屬中男性在55歲之前、女性在65歲之前就出現(xiàn)CHD； *代謝綜合征根據(jù)AHA/NHLBI共識 標(biāo)準(zhǔn)定義JUPITER 病史病史瑞舒伐他汀安慰劑目前仍為吸煙者(%JU

19、PITER治療12個(gè)月后，對LDL-C, HDL-C, TG和hsCRP的影響; 瑞舒伐他汀和安慰劑之間的變化百分比1-1-2-3-4-5-SLDL-C HDL-C TG hsCRP4%I I Ipo.oor17%p0 00137%p0.00150%p0.001*研究結(jié)束時(shí)（48個(gè)月）的F值二0.34Ridker P 0 Eng J Mpc/2008;359: 2195-2207JUPITER1-1-2-3-4-5-SLDL-C HDL-首次發(fā)生心血管死亡、JUPTER -主要繞點(diǎn)：島黯善翱耘鸛心梗4不穩(wěn)定性心絞痛g風(fēng)險(xiǎn)率0.56（95%可信限0.46069）P 0.00001明顯獲益提前終止

20、瑞舒伐他汀20 mg2 年的 NNT = 955年* 的 NNT = 25O012 3隨訪（年）4存在風(fēng)險(xiǎn)的人數(shù)瑞舒伐他汀8,901安慰劑 8,9018,631 8,4128,621 8,3536,540 3,893 1,958 1,3536,508 3,872 1,963 1,333983 544 157955 534 174ng2OO8;359: 2195-首次發(fā)生心血管死亡、JUPTER -主要繞點(diǎn)：島黯善翱耘鸛心Cardiovascular Event Reduction and Adverse Events Among Subjects Attaining Low-Density L

21、ipoprotein Cholesterol 50 mgdl With RosuvastatinThe JUPITER Trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin)JUPITER 研究中,LDLc 降至 50mg/dL 的 病人CV事件降低和不良反應(yīng) 又是如何？JACC 2011 ;57:1666Cardiovascular Event Reduction治療前基線LDLc水平不管多低，使用可定一致獲益LDLC NPrimary

22、EndpointPrimary Endpoint + Total MortalityPrimary End point + VTE + Total Mortality130mg/dL 17,802120mg/dL 13,972Ml10mg/dL 9,784100mg/dL 6,26990 mg/dL 3,687le-nEnuPlaceboNo LDL-C50 Rosuvastatinc- LDL C50 RosuvastatmFollow-up (years)CV事件發(fā)生率：LDLc降至50mg以下LDLc未降至50mg以下v安慰劑組JACC 2011:57:1666一 - 一 - 一 OPl

23、aceboNo LDL-C50 不良反應(yīng)發(fā)生率RosuvastatinPlacebo (n = 8150)NoLDL-C5Omg/dl (n = 4.000)DL-C 50 mg/dl (n = 4.154)I p Value vs. NoLDLC 3xULN840.5S60.70.06660.70.0070.78CK1OXULN10.00510.010.4510.010.84LOO土 2+ proteinuria3872.22102.50.01259 云2+ hematuria5313.02953.60.0083463.70.003 0.56 IeGFR change.

24、 ml/mln/L73 m2, mean (SD)-9.0(13.5)-9.1(14.1)0.004-7.9(13.1)0.04 05。J降至50mg以下vs未降至50mg以下:二組無差別JACC 2011;57:1666不良反應(yīng)發(fā)生率RosuvastatinPlacebo (n -Placebo-Rosuvastatin (LDL cholesterol al-8 mniol/Lor hsCRP a2 mg/L)-Rosuvastatin (LDLcholesterol 1-8 mmol/Land hsCRP 3,5 mmoDL TC/HDLC 5.0 hs-CRP 2 mg/LMen 50

25、 yearsWomen 60 yearsFamily history and hs-CRP nwdulates risk (RRS)2 mmol/L or apoB 0.80 g/L250% i LDLC Class lla3 level A Class Ila, level A加拿大2009年血脂指南增加JUPITER人群 一級預(yù)防LD動脈粥樣硬化： 和 是動脈粥樣硬化發(fā)生發(fā)展二個(gè)密不可分的最重要因素（不僅僅是LDLc）其他 因素：高血壓、糖尿病、吸煙、肥胖、不運(yùn)動等Ross R.N Engl J Med. 1999;340:115-12動脈粥樣硬化： 和 是動脈粥樣硬化發(fā)生發(fā)展Ros從循證

26、醫(yī)學(xué)看待他汀強(qiáng)效安全的辯證統(tǒng)一課件最新CTT (2010)匯總分析:他汀心血管獲益與降LDL-C的幅度相關(guān) CTT薈萃分析：26項(xiàng)他汀隨機(jī)試驗(yàn)，納入170,000名患者Events (% per annum) RR (Cl) perl mmol/L reduction in LDL-CStatin/more ControVlessVascular causes of deathCUD1887 (0 5%)Other cardiac1446 (0 4%)All cardiac3333 (09%)Ischaetnlc suoke153 (00%)Haenioirliagk suoke102 (0-

27、0%)Unknown stroke228 (01%)Stroke483 (01%)Other vascular404 (01%)Any vascular4220(1-2%)Non-vascular causes of deathCancer1781 (0-5%)Respiratofy224 (01%)Trauma127 (00%)Other non-vascular811(0 2%)Any non-vascular2943(0-8%)Unknown479(0.1%)Any death7642(21%)-99% or 95% Cl2221(0 6%) 1603 (0 4%) 3884(11%)

28、139 (00%)89 (0-0%) 273(01%) 501 (01%) 409 (01%)4794(1-2%)1798(0-5%)237 (01%)127 (00%)832 (0-2%)2994(08%)529(01%)8227 (23%)0 20(074-087) 0 29(0 81 0 98) 0 84 (080-0 88) l-04(0-77-l-41) 112 (077-1-62)0 85(0 66-108) 0-96 (0-84-109) 098 (081-1-18)0-86 (0-82-0-90)0-99 (0-91-109)088 (0-70-111)0 98 (0-70-1

29、38)0-96(0 83-110)0-97 (0-92-103)0-87 (0-73-103)0 90 (087-092)0-5 0-75 1 1-25 1-5Stati n/ more better Control/less betterFigure 5： Effects on cause-specific mortality per 10 mmol/L reduction in LDL cholesterolLDL-C 每降低 1 mmol/L冠心病死亡其他心源性死亡全因死亡如 LDLc 降低 2mmol/L, 上述獲益加倍0最新CTT (2010)匯總分析:他汀心血管獲益與降LDL-CT

30、T(2010)匯總分析：他汀的心血管獲益與基線LDL-C水平無關(guān)Events (% pernnum)RR (Cl)per 1 mmol/L reduction in LDL-CTrendtestStati ff more Co rrt mbl e ss積極V5.常規(guī)他汀VS.對黑所有研究M ore vs kss statin 2 mmolL 7。+4 6*ZtoZ5 mmd/L 1189 (4-2tor2-0 mmnU. 1065。偵初t3to 3 5 mmcl/L 電5 mmoVL Total Statin control 2 mmobL x2 to 2 5 mmcl/L &2-S to.3

31、-O ininokL wNto ? mmd/L5 rnmoV L Total All trials combined 2 inniolL 2 to 2?.g to2-01&66m3 to 3*5 innid/L 35 mmolL Total517 (45為) 303(5-7%) 2827(4-5)206(2-9%) 339(24 SaLfZ-S%) 1490 (2-9%) 4205 (2 9%) 713:6 (N8k)1528(3-6e99% or795 (5 2%) 1317 (4-8 ) 1203 (5-06)633 (58k)-398 (7 -8%) 4416(g.2%217(3-2%)

32、412 (2-9) 10221821 (3-6%) 5338 (3 7%) 8934 (3S2O07-C3-24508(3-O6)IO 973 (3 2%) 13350(4 0)1012 (4 E) 1729 (4-2%) 2235 (4 0%) 2454 (4。%) 5736(3-9%)CviitioVle bcttciStat ii V0-71 ( p=Q 2) 0-64 (0-47-0-86)0-72 (0-66-0-78)0-87 (0-60-1-2 8 O-77 0-77 0.70-0.2g) 0-76 (0-70-0-82) 0-80 (0-76-0-83) 0 78 (O 76-

33、0 80)rl-08 (T3)即使基線LDL-C2mmol/L,也能從他汀治療中獲益CTT(2010)匯總分析：Events (% pernn新指南的推薦基于強(qiáng)化降脂比一般降脂治療獲益更多(CTT 2010) 5項(xiàng)強(qiáng)化vs.常規(guī)他汀隨機(jī)試驗(yàn)(PROVE IT, At。乙TNT, IDEAL, SEARCH)強(qiáng)化vs.常規(guī)他汀治療(1年時(shí)LDL-C差值0.51mmol/L)：-冠脈死亡和非致死性心梗113% (P0.0001)-冠脈血運(yùn)重建19% (P0.0001)-缺血性卒中116% (P=0.005)Everts (% prannum)Unweighted RR (Cl)RR (Cl) pe

34、r 1 mniol/L reduaion in LDL-CStotin/morcContMore rs less statin (five trials： 0-51 nmol兒 LDL difference)Non-fatal Ml1175 (1珈1380(1-5%)CHDcfeath645 (07%)694 (07%)Any major coronary event17(19%)1973(2 2%)CABG637 (0-7%)731(09%)PTCA1S08 (1-8%)Unspecified44? (0-5%|502 (0 6%)Any coronary revascularisation

35、2250(2-6%)2741(3-2%)Ischaeiiic stiole440 (Os“)526 (OS)Haenunhagic stroke69 (01%)57 (01%)Unknown rtroVo63 (0-1%)20 (0.1%)Any stroke572(0 6%)663(07%)Five trials： any major vascular event3837(45%)4416(53%)05(076-0-94) 0-93 (0-81-107) 037 (0 81-0 93) p00001 036(075-0-99) 076 (0-69-0-84) 037(074-103) 031

36、(076-0 85) p 121 (0-76-1-91) 079 (051-1 21) 036(077-0 96) p=0009055 (0 82-0 89) p00001071 (0-58-0-87)0-85 (0-63-115)0 74 (0 65 0 85p00001072(055-095)0-60(0-50-0-71)0-78 (0-58-104)066 (060-073)p000010-69 (0-50-0-95)1-39 (057-339)063 (0 24-166)074(059-092)p=0007072(0-66-078)piPROVEFAtyLx IDEAL-AtvExp

37、Opin Emerg Drugs 2004;9(2):269-279, N Engl J Med 2005;352:1425-1435. JAMA 2005;294:2437; Lancet 2006;368:1155|LDL-C 值 nig/dL (niniol/L)|30臨床試驗(yàn)結(jié)果:LDLc尚沒有探底四Rx -他汀治療alL.Can Low-Density Lipoprotein Be Too Low?The Safety and Efficacy of Achieving Very Low Low-Density Lipoprotein With Intensive Statin Th

38、erapy80-10060-8040-6080-100 n = 25660-80 n = 57640-60 n = 6313x ULN0.18CK 10X ULN000.300.45Rhabdomyolysis00001.0Liver side effectsALT3x ULN323.08Study drug discontinued because of LET2.02,3OrherHemorrhagic stroke0.40.2000.12Retinal AE00.48Suicide/trauma death00

39、001.0Study drug discontinued because of any AE100.99Major cfliLaq measuresDeath0.50.59CHD death00.06Myocardial iiiiarvtivii1.00.009Anv stroke1.60.32Primary composite*20.40.10CV事件危險(xiǎn)度:LDLC越低越少，不良反應(yīng)無差別.Can Low-Density Lipoprotein BIVUST動粥容量百分比變

40、化與LDLc關(guān)系: LDLc降至70mg/dl以下,可望斑塊縮小1.81.2MedianChange 0.6In PercentAtheromaVolume 0(%)-0.650 60 70 80 90 100 110 1201.2On-Treatment LDL-C (mg/dL)JAMA 2006; 295:1556-1565Cleve Clin JIVUST動粥容量百分比變化與LDLc關(guān)系: LDLc降至7EUROPEANSOCIETY OFCARWOLOGT*ESC/EAS Guidelines for the management of dyslipidaemiasThe Task

41、Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society 6EAS1Ill2011年6月28日，歐洲心臟病學(xué)會(ESC)和歐洲 動脈粥樣硬化學(xué)會(EAS )攜手發(fā)布了歐洲血脂異常 管理指南European Heart Journal 2011;32:1769-1818ESC/EAS Guidelines for the ma指南啟動值2004 NCEP atp m指南LDL-C 80mg/dl200

42、9加拿大 指南無須考慮LDLC水平2011 ESC/EAS指南無須考慮LDLC水平指南啟動值2004 NCEP atp m指南LDL-C 100mg/dl (100mg/dl2009加拿大 指南無須考慮LDLC水平2011 ESC/EAS指南LDL-C v70mg/dl考慮藥物治療（若LDL-C 70mg/dl,立即藥物治療）1. European Heart Journal 2011 ;32:1769-18W 2,Can J Cardiol 2009;25(10):567-5793.中華心血管病雜志2007;3&5商&4苻&左 Circulation 2004;n0227-239 指南啟動值

43、2004 NCEP atp m指南LDL-C 12011 ESC/EAS指南對于血脂干預(yù)靶點(diǎn)的推薦推薦意見證據(jù)等級LDL-C是首要治療靶點(diǎn)I/A若其他血脂指標(biāo)情況不明，可考慮將TC作為治療靶點(diǎn)na/A )在治療高TG過程中，可評估TG水平na/B 混合型高脂血癥、糖尿病、代謝綜合征或CKD患者，Non-HDL-C可作為 次要干預(yù)靶點(diǎn)na/B IApo B或非HDLc可作為次要干預(yù)靶點(diǎn)na/B 1HDLC不推薦作為干預(yù)靶點(diǎn)m/c Apo B/Apo AI 和non-HDL-C/HDL-C不作為干預(yù)靶點(diǎn)m/c 1-不推薦作為干預(yù)靶點(diǎn)Europe2011 ESC/EAS指南對于血脂干預(yù)靶點(diǎn)的推薦推薦

44、意見證 68項(xiàng)長期前瞻性研究，N=3025430HDL-C3.5 1o Adjusled for ag? and sex only Further austd foe se-vccal risk factors052.1.0卷p胃工ZBToiX.X In0.340 50 洗 70Usual Mecn LevS mg/dL30The Emerging Risk Factors Collaboration JAMA 2009;302:1993-2 68項(xiàng)長期前瞻性研究，N=3025430HDL-C3.5流行病學(xué)研究證實(shí):IIIHDL-C每升高1mg/dL,心血管病險(xiǎn)降低23%流行病學(xué)研究證實(shí):II

45、IHDL-C每升高險(xiǎn)降低23%但藥物干預(yù)性研究中，HDL-C水平與CVD風(fēng)險(xiǎn)無顯著相關(guān)性Regret ton model and predl cto rChange in risk pr 10 mgfdl Increase In lipid suM faction% (9-5% Cl)Rvalue108項(xiàng)隨機(jī)對照研究（其中他汀 研究62項(xiàng)），包括299,310名有 心血管事件風(fēng)險(xiǎn)的受試者； ：HDvenU(CHD dfcith and non-fa tai Ml) (n*95)fUni variable：Change in LDLA.9(3t& 6.5)2.CXHChange in HOL-S

46、.2 C-24.7 B.1)Q.J2Bivarlabte：Change in LDL5 .1 (玷 to&刃94)L6.0 C-4.2 to 3&笏O.CXH 0.L2HDL-C水平與CVD風(fēng)險(xiǎn)Total death (n*107)t無顯著相關(guān)性Uni variable：Change in LDL2(L.4t0 4.3 TT7 CXChange in LDLChange in HDL4 A(L.6 to 7.2)L1JOC-6-.5IO 28.1)0.21調(diào)整HDL-C水平后， LDLC水平與CVD風(fēng)險(xiǎn)CHD death (n94)tUni variable：Change in LDLChan

47、ge in HDLBlvarlab4e：4.5 (ZA to 6.6) -0.2 C24.0 to 23.1)MQKH0.99仍有顯著相關(guān)性Chang in LDL。息(2.6 to 7.0)O.CXHChange In H DLLI.3 (-10 to 32.9)0.31MultSdablet： .七 -.：!廣.1a L1.1,1 O.C nk | OrtrtQ-QOQChange In HDL L，M-L8.Ho 4L.5) 042 BM J 2UW?0O O但藥物干預(yù)性研究中，Regret ton model andHDL cholesterol and residual risk o

48、f first cardiovascular events after treatment with potent statin therapy: an analysis from theJUPITER trialA B Lancet 2010;376:3332-018 Placeto Rosuvastatm 20 mgSJeaf-uocad 3UVPOU-QI Q2 Q3 Q4 QI Q2 Q3 Q4Quartile of on-tfCdtiiKnt HDL chotestcfol conccntratiofi Quartile of on-treatment apjlipoprctcinA

49、l QorKefitfdtionJUPITER試驗(yàn)分析HDLc和“殘余” CVE結(jié)果顯示：安慰劑組（淺蘭柱）:HDLc越低,CVE越高可定治療組（深蘭柱）:HDLc高低與CV事件無差別說明LDLc降得足夠低（55mg/dL）,HDLc不再是“殘余” CVE的指標(biāo)Lancet 2010:376:333HDL cholesterol and residual r著眼于LDL-C水平， 未區(qū)分CHD患者CHD患者，LDL-C 100mg/dLCHD患者，LDL-C 100mg/dLCHD患者， LDL-C100mg/dL, 可選擇 LDL-C70mg/dLNCEPATPII, JAMA. 1993;

50、269:3015-3023NCEPATPIII, JAMA. 2001;285:2486-2497NCEPATPIII, Circulation. 2004;110: 227-239ATPIV3預(yù)測目標(biāo)值可能是 弊,大劑量他汀安全性在各他汀之間有區(qū)別整體而言,他汀十分安全，利 弊,大劑量他汀安全性在各曰 0 Efficacy and safety of more intensive lowering of LDLi cholesterol: a meta-analysis of data from 170 000 participantsin 26 randomised trialsLance

51、t 2010;376:1670ChlKtmnttEert TridMts (C7T) WdKrafix?EiniiX ptrxsnun;)ffi(Q)prlin rao|f L iwkction In UOL-(tahrncn Ccrth)lnVucufaraiaual duth (WUtiw LnhcAJ.W：kharrc ibekiHwyw4e KnfaiUrirown ibehStrokiDtrvnrJir1KSC05KI 141b !Mt) 33B(M*I 153 ia：50K| 7JBC0WI 聃郵)miiM， 施!MM J-蹌郵.91M-炳(M)。出nwq跖 QI0l-Wl 收|g

52、C圈I -M4QK41)* 1心.町陌網(wǎng)g) 頊(Ml-胸CTT協(xié)作薈萃 結(jié)論：腫瘤發(fā)生并不因強(qiáng)化降脂 而增加，不增加非心血管事件Ary wvjk*V54P3*) 。瑜呻ln-truiDHwftnnvK.laAry rsn-vucdari-atduih714(111aim%)療爐與Sp泠殉099(051-209 。闋例-瑚 DIOyO-tyi O9fr(M3-5 W| 叫做g)強(qiáng)化降脂與一般降脂比: 肌溶發(fā)生增加約 4/10000,此增加只見于 辛伐他汀80mg/d的二個(gè) 研究，而不是阿托伐他汀 或可定UrlxcwnAryduth他mm爆泠旅叫Og臨）- 9*m9s*a0-515Stabrfn

53、MSitiw Coring ha (star即使基線LDLc巳v2mmolL, 進(jìn)一步強(qiáng)化降脂未產(chǎn)生 更多不良反應(yīng)曰 0 Efficacy and safety of mor他汀安全性誤區(qū)：降脂作用越強(qiáng)的他汀越不安全, 降脂作用越弱的他汀越安全他汀安全性誤區(qū)：LDLC降低(%)蕃市6%糖京6%18%3LDTC京 6%8 依遂*一一一。_ko臺gggLDLC降低(%)蕃市6%糖京6%18%3LDTC8 依遂不同劑量級別他汀降LDL-C幅度比較藥物5 mg10 mg20 mg40 mg80 mg立普妥37%(43%49% ： 55%氟伐他汀15%21%27%33%洛伐他汀21%29%37%45%普

54、伐他汀20%24%29%33%瑞舒伐他汀38% (43%48%辛伐他汀27%32%37%42%FDA批準(zhǔn)的瑞舒伐他汀最大使用劑量為40mg,中國最大劑量為20mg 辛伐他汀80mg/d認(rèn)為不安全2003: 326;1-7不同劑量級別他汀降LDL-C幅度比較藥物5 mg10 mg2VOYAGER：再次驗(yàn)證他汀“6原則”劑量(mg)10 20 40 80 10 20 40 80,p0.001瑜舒伐他汀10mg與阿托伐他汀10mg、20mg及辛伐他汀10mg、20mg、40mg相比 tp0.001瑞舒伐他汀20mg與阿托伐他汀20mg、40mg及辛伐他汀20mg、40mg、80mg相比 tp10 x

55、正常上限:LDL-C降低的程度57-對肌肉的影響效益:風(fēng)險(xiǎn)5二2010年3月19日:FDA就增加肌病風(fēng)險(xiǎn)發(fā)出警告Home I Food I Drugs I Medical Devices I Vacdnes, Blood & Biologies | Animal a Veterinary | Cosmetics I Radiation-Emitting Products I Tobacco ProductsFDA NEWS RELEASEFor Immediate Release: March 19, 2010Media Inquiries: Elaine Gansz Bobo, 301-79

56、6-7567; elame.bobo他汀強(qiáng)化降脂治疔不可忽視安全性Review of simvastatin is part of an ongoing FDA effort to evaluate the risk of statin-associated muscle injury and to provide that information to the public as it becomes available,* said Eric Colman, M.D., Deputy Director of FDAs Division of Metabolism and Endocrino

57、logy Products (DMEP). Its important for patients and healthcare professionals to consider all the potential risks and known benefits of any drug before deciding on any one therapy or dose of therapy.”Simvastatin is sold as a single-ingredient generic medication and as the brand-name Zocor. It also i

58、s sold in combination with ezetimibe as Vytorin, and in combination with niacin as Simcor.FDAs review of new Information on the nsk of muscle injury is derived from clinical tnals, observational studies, adverse event reports, and prescnption use data. The agency also is reviewing data from the SEAR

59、CH (Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine) thal, which evaluated major cardiovascular events, such as heart attack, revascularization and cardiovascular death, in patients taking 80 mg compared to 20 mg of simvastatin. SEARCH also included data on muscle injury in patients taking simvastatin.FDA is committed to informing the public about its ongoing safety