ATPIII：识别和治疗高危患者的新方法
ATP III: New Approaches in Identifying and Treating High-Risk Patients Steven Haffner, MD
Hospitalization for MI Has Not Declined
Hospitalization for MI (per 1,000)*
* Age-adjusted
Rosamond WD et al. N Engl J Med 1998;339:861-867.
?1998 Massachusetts Medical Society. All rights reserved.
Men
Women
Criteria for Accepting Cardiovascular Risk Factor Management as Similar in CHD Equivalents as in CHD Patients
The risk of vascular disease is similar in CHD equivalents and in patients with CHD.
Lipid interventions to reduce CHD can be equally effective in CHD equivalent and CHD patients.
In diabetic patients, glycemia alone will not completely eliminate the excess CHD risk.
New CHD Risk Equivalents
>20% 10-year risk of CHD (Framingham projections)
Diabetes
Other forms of clinical atherosclerotic disease:
– Peripheral arterial disease
– Abdominal aortic aneurysm
– Carotid artery disease
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.
Noncoronary Atherosclerosis: Overview
Atherosclerotic disease in one region of the arterial tree is associated with and predicts disease in other arterial regions
– Pathobiology and predisposing risk factors are similar for atherosclerosis in coronary, peripheral, and carotid arteries
Thus, clinical atherosclerotic disease in noncoronary arteries is a powerful predictor of CHD
Peripheral Arterial Disease (PAD)
Studies of patients with atherosclerotic PAD support the concept that PAD, regardless of diagnosis by ABI, lower limb blood flow studies, or clinical symptoms, is a CHD risk equivalent
Edinburgh Artery Study
Ankle/brachial blood pressure index (ABI) in randomly selected population, 5-year follow-up
1592 men and women, 614 with CHD, aged 55–74
137 fatal and nonfatal CHD events during follow-up
>1.1
1.1–1.01
1.0–0.91
0.9–0.71
<0.7
ABI
CHD Event Outcomes per Year (%)
Leng GC et al. BMJ 1996;313:1440-1444.
1.4%
3.8%
Abdominal Aortic Aneurysm (AAA)
Study population: 300 men and 43 women (aged 45–89) operated on for AAA, separated into 4 groups based on preoperative CHD history and ECG
Follow-up: 6–11 years
Results: annual CHD mortality
– 1.9% in persons with no symptoms, no prior history of CHD, and normal ECG (31%)
– 2.0% in persons with no symptoms, but previous MI by ECG (33%)
– 3.9% in persons with angina/prior MI (30%)
Because the rate of CHD events is at least twice that of CHD mortality, patients with no previous history of CHD events would fall into the CHD risk equivalent category
Hertzer NR. Ann Surg 1980;192:667-673.
Carotid Artery Disease: Symptomatic
North American Symptomatic Carotid Endarterectomy Trial (NASCET)
– Symptomatic patients undergoing carotid endarterectomy had an average 10-year CHD mortality of 19%
European Carotid Surgery Trial (ECST)
– Symptomatic patients had very high death rates from nonstroke vascular disease regardless of the percent of carotid artery stenosis at the onset
– 72% of deaths were due to nonstroke vascular disease and thus 10-year CHD death is estimated at 30%
Ferguson GG et al. Stroke 1999;30:1751-1758. | Barnett HJ et al. N Engl J Med 1998;339:1415-1425. | ECST Collaborative Group. Lancet 1998;351:1379-1387.
Mayo Asymptomatic Carotid Atherosclerosis Study
– Subjects
— 158 patients, 40% with history of CAD, 15% diabetic
– Disease severity
— Asymptomatic stenosis ? 50%
— Trial stopped because of high MI and TIA event rate in surgical arm secondary to cessation of medical therapy (aspirin)
– CHD events
— After 2.5-year follow-up: 12 CHD events
— Estimated 10-year CHD event rate = 30%
Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995;273:1421-1428.
Carotid Artery Disease: Asymptomatic
Heart Protection Study: Vascular Events by Baseline Disease
Collins R. Presented at AHA, Anaheim, California, 13 November 2001.
Risk ratio and 95% CI
Statin better
Statin worse
? 24 ± 2.6% (2P <0.00001)
0.4
0.6
0.8
1.0
1.2
1.4
* In national sample of adults in NHANES I (1971–75) and NHANES II (1982–84).
Gu K et al. JAMA 1999;281:1291-1297.
Changes in CHD Mortality Rates in Patients with and without Diabetes *
% Change in Mortality
–16.6
10.7
–43.8
–20.4
Nondiabetics
Diabetics
P=0.46
P=0.76
P=0.001
P=0.12
Men
Women
Men
Women
CVD Death Rate/10,000 Person
Years (Age-Adjusted)
Stamler J et al. Diabetes Care 1993;16:434-444.
MRFIT: Diabetes Amplifies Risk from Other Risk Factors
No. of Additional RFs*
No Diabetes
Diabetes
0
1
2
3
6
31
12
59
22
91
47
125
*TC > 200 mg/dL SBP > 120 mm Hg Current smoker
% Mortality
Men
Miettinen H et al. Diabetes Care 1998;21:69-75.
1-Year Mortality in Diabetic and Nondiabetic Subjects after a First MI
Women
Diabetes
No Diabetes
Diabetes
No Diabetes
28.6
11.0
5.5
22.1
7.5
3.0
10.9
20.0
7.6
11.9
7.9
2.2
Haffner SM et al. N Engl J Med 1998;339:229-234.
Incidence of MI during a 7-Year Follow-up in a Finnish Population
Fatal or Nonfatal MI (%)
Prior MI
18.8
3.5
45.0
20.2
P<0.001
P<0.001
Prior MI
No prior MI
No prior MI
Nondiabetic subjects
Diabetic subjects
(n=1373)
(n=1059)
OASIS Study: Total Mortality
Event Rate
Months
6
9
15
3
18
21
12
RR=2.88 (2.37–3.49)
Malmberg K et al. Circulation 2000;102:1014-1019.
?2000 Lippincott Williams & Wilkins.
24
RR=1.99 (1.52–2.60)
RR=1.71 (1.44–2.04)
RR=1.00
Diabetes/CVD (n = 1148)
No Diabetes/CVD (n = 3503)
Diabetes/No CVD (n = 569)
No Diabetes/No CVD (n = 2796)
CHD Prevention Trials with Statins in Diabetic Subjects: Subgroup Analyses
*LDL-C values for overall group
Downs JR et al. JAMA 1998;279:1615-1622. | HPS Investigators. Presented at AHA, 2001. | Goldberg RB et al. Circulation 1998;98:2513-2519. | Pyorala K et al. Diabetes Care 1997;20:614-620. | Haffner SM et al. Arch Intern Med 1999;159:2661-2667. | LIPID Study Group. N Engl J Med 1998;339:1349-1357.
CHD Prevention Trials with Statins in Diabetic Subjects: Subgroup Analyses (cont’d)
Downs JR et al. JAMA 1998;279:1615-1622. | HPS Investigators. Presented at AHA, 2001. | Goldberg RB et al. Circulation 1998;98:2513-2519. | Pyorala K et al. Diabetes Care 1997;20:614-620. | LIPID Study Group. N Engl J Med 1998;339:1349-1357. | Haffner SM et al. Arch Intern Med 1999;159:2661-2667.
CHD Prevention Trials with Fibrates in Diabetic Subjects: Subgroup Analyses
*Median value
Koskinen P et al. Diabetes Care 1992;15:820-825. | Rubins HB et al. N Engl J Med 1999;341:410-418. | DAIS Investigators. Lancet 2001;357:905-910.
Adler AI et al. BMJ 2000;321:412-419. | Stratton IM et al. BMJ 2000;321:405-412.
Reprinted with permission from the BMJ Publishing Group.
Adjusted incidence per 1000 person-years (%)
Updated mean HbA1c concentration (%)
Updated mean systolic BP (mm Hg)
Adjusted incidence per 1000 person-years (%)
5
6
7
8
9
10
11
110
120
130
140
150
160
170
MI
Microvascular end points
Microvascular end points
MI
MI and Microvascular End Points: Incidence by Mean Systolic BP and HbA1c Concentration in UKPDS
Summary: Diabetes as a CHD Risk Equivalent
Implies that enhanced