PROCAM Heart Study
Mean values for developing atherosclerotic CHD within 6 years
Variable
TC (mg/dl) HDL-C (mg/dl) LDL-C (mg/dl) LDL/HDL ratio TG (mg/dl)
300
Low CHD risk
<3
250
Medium CHD risk
3-5
High CHD risk
>5
CHD Incidence/1000 in 6 years
200
150
100
50
0
<3
<4
<5
>5
>6
>7
LDL/HDL ratio
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag, 1993: 43
Risk Ratio
2.3 2.8 3.7 3.3 3.9 6.4
Predictive Power %
7.5 8.3 12.0 7.1 11.0 16.5
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag, 1993: 43
Part IV
Expert Opinions
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 Women’s Hospital, Boston
PROCAM Heart Study
Predictive value of risk factors for developing atherosclerotic CHD within 6 years
Variable
TG 200 mg/dl TC 250 (mg/dl) LDL-C 195 (mg/dl) LDL-C 155 (mg/dl) HDL-C 35 (mg/dl) LDL/HDL ratio 5
>5
Triglycerides <200 mg/dl Triglycerides >= 200 mg/dl
ASSMANN G and SCHULTE H; Am J Cardiol 1992; 70: 733-737
PROCAM Heart Study
CHD risk according to LDL/HDL ratio at baseline
0.5
0
220
160
100
LDL Cholesterol (mg/dL)
CASTELLI WP. Am J Cardiol 1998; 82:60-65
25 45 65 85
Incidence of cardiac events (per 1000 person-years)
Helsinki Heart Study
34 45 22 39
38 53 18 29
0
LDL<=5 LDL>5
HDL>=1.08 HDL<1.08 LDL/HDL<=5 LDL/HDL>5
MANNINEN V, Leena T, Koskinen P et al. Circulation 1992; 85: 37-45
AFCAPS/TEXCAPS
-20
22% reduction in combined fatal
and non-fatal MI
-25
-30
-35
-31
RUBINS HB et al. New Engl J Med 1999; 341:410
HDL - Cholesterol as Risk Factor for CHD
LRC - CPPT (Placebo) Incidence rate of CHD
65 55 45 35
GORDON DJ et al. Circulation 1989; 79: 8 - 15.
Framingham Heart Study
CAD risk as a function of LDL-C and HDL-C in men (50 to 70 y)
3
2.5
2
1.5
1
CAD Mortality per Quartiles of Increases in HDL-Cholesterol 12
10
8
% Mortality
6
4
2
0
Placebo
Q1
Q2
(low HDL-increase)
KJEKSHUS J & PEDERSEN T (unpublished)
Q3
Q4
现代脂质三联治疗
Part I
Introduction
Efficacy - The Power to Reach Target
Key Factor:
LDL Reduction
+
Differentiators:
TG
HDL
LDL/HDL Ratio
The Lipid Triad
The LDL/HDL Ratio - Our Strength, Our Story!!
40
30
21
20
0 35
35 - 55
55
HDL-C (mg/dL)
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag, 1993: 59
CHD Incidence per 1, 000 in 6 years
PROCAM Heart Study
1.6
1.4
Placebo
1.2
1
Statin
0.8 0.6 0.4 0.2
0 0.8889 0.8898- 1.0252 1.0205
GOTTO A et al. Circulation 2000; 101: 477-484
0.8 0.6 0.4 0.2
0 3.7742 3.7744- .4101 4.4096
PROCAM Heart Study
Incidence of CAD vs LDL/HDL ratio by TG level (n = 4559)
CAD cases per 1,000 subjects in 6 years
300 245
250
200
150
116
100
50
24
31
0
<= 5
LDL / HDL - Ratio
LDL as CHD risk factor showed 177 events
in men aged 40 - 60 years, ( n = 4263)
140
120
120
100
80
60
54
40
20
16
0 135
31 30
135 - 154
155 - 195
LDL-C (mg/dL)
195
ASSMANN G; Lipid Metabolism Disorders and CHD; MMV Medizin Verlag, 1993: 60
LDL
HDL
TG
The Ratio
Additional risk factor, especially in diabetics
Part II
The Lipid Triad and Strategic Rationale
• No scientific evidence • Evidence contradicting this statement • A marketing hypothesis to build their LDL story • Creating the perception of the statin with the
Incidence for cardiac events vs lipid parameter
Gemfibrozil Placebo
LDL-C Tertiles (mmol/L) HDL-C Tertiles (mmol/L) LDL-C/HDL-C Tertiles
16
14
12
10
8
6
4
2 24 46 32 36
The Lipid Triad - Expert Comments
ACCP, March 2000 “Low HDL is a better indicator of CHD than high LDL as seen in epidemiological studies such as the Framingham Study and recently the VA-HIT Study.” Sander Robins, University Medical Center, Boston “Landmark statin trials have shown consistent benefits on CHD reduction after raising HDL by 5 - 10% irrespective of LDL levels” Christie Ballantyne, Baylor College of Medicine, Houston