HDL和LDL风险评估与治疗
The Pyramid of Recent Trials Relative Size of the Various Segments of the Population
4S
CARE
WOSCOPS
AFCAPS/TexCAPS
LIPID
Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) (1998)
Evaluated the effects of lovastatin on first acute major coronary event in 6605 men and women without any coronary or vascular disease and with
TC 180-254 mg/dl
HDL-C ?45 mg/dl in men and ?47 mg/dl in women
LDL-C 130-190 mg/dl, or
LDL-C 125-129 mg/dl with TC/HDL-C ratio >6
Randomized to lovastatin 20 mg vs. placebo with titration to 40 mg with goal of LDL-C ?110 mg/dl
Mean follow-up 5 years
Downs JR et al. JAMA 1998;279:1615-1622.
AFCAPS/TexCAPS Results
?37%
?40%
1st acute major coronary event
p<0.001
Fatal or nonfatal MI
p=0.002
Risk Reduction with Rx
150
115
25% reduction
Downs JR et al. JAMA 1998;279:1615-1622.
AFCAPS/TexCAPS Tertiary Endpoint Analysis: Mortality
*Too few for survival analyses
NCEP Adult Treatment Panel II Guidelines
National Cholesterol Education Program Circulation 1994;89:1329–1445.
Pravastatin
Pravastatin
Pravastatin
Placebo
Placebo
Placebo
CARE: Is There a Lower Threshold?
Sacks FM et al. N Engl J Med. 1996;335:1001-1009.
Copyright ? 1996 Massachusetts Medical Society. All rights reserved.
LDL-C <125 mg/dl
LDL-C 125–150 mg/dl
LDL-C >150 mg/dl
Change in risk +3%
p=0.85
Change in risk –35%
p=0.008
Change in risk –26%
p<0.001
Incidence (%)
Years
Years
Years
On-Treatment LDL Levels and Correlation with Major Coronary Events in 4S
Circulation 1997;96:I-717
Pitt B et al. N Engl J Med 1999;341:70-76.
CAD 31 lesion 350% stenosis LDL-C 3115 mg/dL (33.0 mmol/L) LVEF 340% Bruce protocol treadmill test or 20-W/min bicycle exercise test 34 min
Atorvastatin 80 mg/d + usual medical therapy n=164*
Angioplasty + usual care, including lipid lowering n=177?
18 months
Occurrence of ischemic events (death from cardiac causes, resuscitation after cardiac arrest, nonfatal MI, CVA, CABG, angioplasty, worsening angina verified by objective evidence resulting in hospitalization)
Time to first ischemic event
Safety
*1 patient did not receive atorvastatin.
?11 patients did not have baseline revascularization.
AVERT: Study Design
Pitt B et al. N Engl J Med 1999;341:70-76.
Results - Intent to Treat
Pitt B et al. N Engl J Med 1999;341:70-76.
Copyright ? 1999 Massachusetts Medical Society. All rights reserved.
Time to First Ischemic Event:Intent-to-Treat Analysis
*Significantly different from angioplasty/UC (p<0.05).
? To convert TG to mmol/L, multiply by 0.011.
Note: 73% of angioplasty/UC-treated patients were on lipid-lowering medication.
18%
ˉ
31%
ˉ
*
46%
ˉ
*
10%
ˉ
10%
-
11%
ˉ
*
8%
-
11%
-
250
(6.5)
200
(5.2)
150
(3.9)
100
(2.6)
50
(1.3)
0
?
LDL-C
TC
TG
HDL-C
mg/dL
(mmol/L)
Atorvastatin baseline
Atorvastatin end of study
Angioplasty/UC baseline
Angioplasty/UC end of study
Pitt B et al. N Engl J Med 1999;341:70-76.
Copyright ? 1999 Massachusetts Medical Society. All rights reserved.
Summary of Lipid Parameters
Ballantyne CM. Am J Cardiol. 1998;82:3Q-12Q.
Reprinted with permission from Excerpta Medica Inc.
Clinical Event Rates by LDL-C Achieved in Statin Trials
How Low Should You Go?
SEARCH: Study of the Effectiveness of Additional Reductions of Cholesterol and Homocysteine
Simvastatin 20 mg vs. 80 mg
TNT: Treating to New Targets
Atorvastatin 10 mg vs. 80 mg
Clinical Judgment
The NCEP ATP II guidelines recommend the use of clinical judgment in deciding whether to initiate drug therapy in
Patients with CHD and LDL-C 100–129 mg/dl
Patients without CHD who have ?2 risk factors and LDL-C 130–159 mg/dl
Middle-aged and older patients without CHD who have <2 risk factors and LDL-C 160–189 mg/dl
National Cholesterol Education Program Circulation 1994;89:1329–1445.
NHANES III Adult Population Estimates by ATP II Risk Category
Jacobson TA et al. Arch Intern Med. 2000;160(9):1361-9.
LDL-C (mg/dl)
Number of US Adults (millions)
without CHD and with ?2 RF
with CHD
LDL-C Distribution in U.S. Adults Data from NHANES III, 1988–1994
Jacobson TA et al. Arch Intern Med. 2000;160(9):1361-9.
US Adults Requiring Drug Therapy Assuming 10% LDL-C Reduction with Diet
<2 RF
?2 RF
CHD
Total
Number of US Adults (millions)
1.6
4.1
5.5
17.5
3.3
6.8
10.4
28.4
Jacobson TA et al. Arch Intern Med. 2000;160(9):1361-9.
Effect of Statin Therapy on CHD: Clinical Events Trials
Jacobson TA et al. Arch Intern Med 1998;158:1977–1989.
*Nonfatal MI or CHD death in WOSCOPS, CARE, LIPID; nonfatal or fatal MI, unstable angina, or sudden cardiac death as first event in AFCAPS; nonfatal MI, coronary death, or resuscitated cardiac arrest in 4S.
?vs. placebo
LDL and HDL Impact on CHD Risk A Compounded Rather Than Additive Impact
0
100
200
300
400
<35
35-55
>55
<135
135-154
155-195
>195
HDL-cholesterol (mg/dL)
LDL-cholesterol (mg/dL)
Incidence per
1000 (in 6 years)
Assmann G, et al. Atherosclerosis 1996;124(suppl):S11-S20.
Reprinted with permission from Elsevier Science.
HDL is a major factor in predicting CAD
Assmann G, et al. Atherosclerosis 1996;124(suppl):S11-S20.
Reprinted with permission from Elsevier Science.
HDL-C Distribution in US Adults
Data from NHANES III, 1988–1994.
HDL-C in Clinical Practice
Risk assessment
Routinely measured in all adult patients
HDL-C <35 mg/dL is a major positive risk factor
HDL-C ?60 mg/dL is a negative risk factor; subtract 1 risk factor from total
Risk reduction
Nonpharmacologic therapy (exercise, weight loss, smoking cessation)
Pharmacologic therapy
Clinical trial data show decreased CAD progression and decreased CAD events with increased HDL-C
Ballantyne CM et al. Circulation 1999;99:736-743.
Reduction in CAD Progression with Fluvastatin in Low vs. High HDL-C Patients
Ballantyne CM et al. Circulation 1999;99:736-743.
Fluvastatin
Placebo
HDL-C <35 mg/dl
p=0.002
Fluvastatin
HDL-C ?35 mg/dl
p=0.232
Probability of event-free survival
Years
Placebo
Reduced CAD Events with Fluvastatin in Low HDL-C Patients
Angiographic Trials in Low–HDL-C Patients
Ballantyne CM et al. Circulation 1999;99:736-743.
Atherosclerosis Progression and Baseline HDL-C: Results from Post-CABG
Hunninghake D et al. Circulation 1997;96:I-413.
Adapted from Ballantyne CM et al. Circulation 1999;99:736-743.
Event Reduction with Statin Therapy in Patients with Low vs. High HDL-C
Kaplinsky E et al. Presented at ESC, 1998
Bezafibrate Infarction Prevention (BIP) Study Results
VA-HIT Design
Hypothesis: Gemfibrozil treatment of "isolated" low HDL-C in CHD patients will decrease CHD events
Subjects:
2531 male veterans aged ?74 years (mean 64)
2° prevention (MI, revascularization, angina, angio)
Mean baseline HDL-C 32 mg/dl, LDL-C 111 mg/dl, TG 161 mg/dl
Treatment: gemfibrozil
Endpoints: nonfatal MI, CHD death
Follow-up: 5.1 years
Rubins HB et al. Am J Cardiol 1993;71:45-52.
VA-HIT Results
Rubins HB et al. N Engl J Med 1999;341:410-418.
Nonpharmacologic Treatment of Low HDL-C
Physical activity
Smoking cessation
Weight loss
Effects of Drugs on HDL-C Levels
Nicotinic acid ? 15–35%
Fibrates ? 10–15%
Estrogens ? 10–15%