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1、现代脂质三联治疗,Introduction,Part I,Efficacy - The Power to Reach Target,Key Factor: + Differentiators:LDL Reduction TGHDLLDL/HDL RatioThe Lipid Triad,The LDL/HDL Ratio - Our Strength, Our Story!,A new perception of efficacy,LDL,HDL,Additional risk factor, especially in diabetics,The Lipid Triad - Overview
2、,TG,The Lipid Triad,The Ratio,The Lipid Triad and Strategic Rationale,Part II,No scientific evidence Evidence contradicting this statementA marketing hypothesis to build their LDL storyCreating the perception of the statin with the strongest efficacy,The lower. .the better?,Its logical,Its measurabl
3、e,Its practicable,The Lipid Triad - The GPs Perspective,HDL,LDL,Supporting Data from Landmark Studies,Part III,121086420,% Mortality,Placebo Q1 Q2 Q3 Q4(low HDL-increase) (high HDL-increase),4S - Study,CAD Mortality per Quartiles of Increases in HDL-Cholesterol,KJEKSHUS J & PEDERSEN T (unpublished),
4、HDL Intervention Trial (VA-HIT),RUBINS HB et al. New Engl J Med 1999; 341:410,0,6,-31,-4,-35,-30,-25,-20,-15,-10,-5,0,5,10,Cholesterol LDL-C HDL-C Triglycerides,Percent change compared to placebo at 1 year,Secondary Prevention in 2531 men with low HDL-C & LDL-C showed a 22% reduction in combined fat
5、al and non-fatal MI,HDL - Cholesterol as Risk Factor for CHD,LRC - CPPT (Placebo),MRFIT (usual care),Incidence rate of CHD,Incidence rate of CHD,12 10 8 6 4 2 0,100 130 160 190,GORDON DJ et al. Circulation 1989; 79: 8 - 15.,HDL - C mg / dl 65 55 45 35,LDL - Cholesterol mg / dl,LDL - Cholesterol mg /
6、 dl,12 10 8 6 4 2 0,100 130 160 190,0,0.5,1,1.5,2,2.5,3,Framingham Heart Study,CAD risk as a function of LDL-C and HDL-Cin men (50 to 70 y),CASTELLI WP. Am J Cardiol 1998; 82:60-65,220 160 100,85,65,45,25,HDL-Cholesterol (mg/dl),LDL Cholesterol (mg/dL),0,2,4,6,8,10,12,14,16,LDL5,HDL=1.08,HDL1.08,LDL
7、/HDL5,Incidence of cardiac events,(per 1000 person-years),Gemfibrozil,Placebo,LDL-C Tertiles (mmol/L),HDL-C Tertiles (mmol/L),LDL-C/HDL-C Tertiles,Incidence for cardiac events vs lipid parameter,Helsinki Heart Study,MANNINEN V, Leena T, Koskinen P et al. Circulation 1992; 85: 37-45,AFCAPS/TEXCAPS,Ap
8、o B/A1 Tertiles,LDL-C/HDL-C Tertiles,1.6,1.4,1.2,1,0.8,0.6,0.4,0.2,0,1.6,1.4,1.2,1,0.8,0.6,0.4,0.2,0,Event Rate per 100 Patient-Years of Risk,Event Rate per 100 Patient-Years of Risk, 0.8889,0.8898- 1.0205,1.0252, 3.7742,3.7744-4.4096,4.4101,GOTTO A et al. Circulation 2000; 101: 477-484,LDL/HDL Rati
9、o as Therapeutic Success,Placebo,Statin,24,116,31,245,0,50,100,150,200,250,300, 5,LDL / HDL - Ratio,Triglycerides = 200 mg/dl,CAD cases per 1,000 subjects in 6 years,ASSMANN G and SCHULTE H; Am J Cardiol 1992; 70: 733-737,Incidence of CAD vs LDL/HDL ratio by TG level (n = 4559),PROCAM Heart Study,0,
10、50,100,150,200,250,300,3,4,5,6,7,LDL/HDL ratio,CHD Incidence/1000 in 6 years,CHD risk according to LDL/HDL ratio at baseline,ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag, 1993: 43,5,High CHD risk,Medium CHD risk,Low CHD risk,3-5,3,PROCAM Heart Study,Mean values for developing at
11、herosclerotic CHD within 6 years,Variable CHD Development No CHD Development (n = 186) (n = 4221)TC (mg/dl) 251.8 222.9 HDL-C (mg/dl) 39.5 45.2 LDL-C (mg/dl) 176.2 147.1 LDL/HDL ratio 4.72 3.4 TG (mg/dl) 163.0 134.5,ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag, 1993: 41,PROCAM H
12、eart Study,Predictive value of risk factors for developing atherosclerotic CHD within 6 years,Variable Risk Ratio Predictive Power % TG 200 mg/dl 2.3 7.5 TC 250 (mg/dl) 2.8 8.3 LDL-C 195 (mg/dl) 3.7 12.0 LDL-C 155 (mg/dl) 3.3 7.1 HDL-C 35 (mg/dl) 3.9 11.0 LDL/HDL ratio 5 6.4 16.5,ASSMANN G; Lipid Me
13、tabolism Disorders and CHD; MMV Medizin Verlag, 1993: 43,PROCAM Heart Study,HDL as CHD risk factor showed 186 events, in men aged 40 - 60 years (n = 4407),CHD Incidence per 1, 000 in 6 years,0,20,40,60,80,100,120,140,160, 35 35 - 55 55,HDL-C (mg/dL),110,30,21,ASSMANN G; Lipid Metabolism Disorders an
14、d CHD; MMV Medizin Verlag, 1993: 59,PROCAM Heart Study,LDL as CHD risk factor showed 177 events in men aged 40 - 60 years, ( n = 4263),CHD Incidence per 1, 000 in 6 years,0,20,40,60,80,100,120,140, 135 135 - 154 155 - 195 195,LDL-C (mg/dL),54,30,16,31,120,ASSMANN G; Lipid Metabolism Disorders and CH
15、D; MMV Medizin Verlag, 1993: 60,PROCAM Heart Study,Expert Opinions,Part IV,The Lipid Triad - Expert Comments,AHA, November 1999“Evaluating the risk on the bases of LDL alone, is naive”Valentin Fuster, Mount Sinai Medical Center, New York“The LDL/HDL ratio is a much stronger predictor for the CHD risk than LDL alone”Paul Ridker, Brigham Institute for Womens Hospital, Boston,
