新的CHD危险因素及评估方法
Magnitude of the Burden—Causes of Death in the United States
Deaths in 1996 (thousands)
CVD
Cancer
Accidents
HIV/AIDS
959.2
544.7
93.8
32.7
American Heart Association. 1999 Heart and Stroke Statistical Update. 1998.
Economic Direct and Indirect Cost of CVD in the United States
Hospital/nursing home
Physicians/other professionals
Drugs
Home health/
other medical durables
Lost productivity/
morbidity
Lost productivity/
mortality
American Heart Association. 1999 Heart and Stroke Statistical Update. 1998.
Total direct and
indirect costs:
$286.5 billion
5-Year Expected Total Cost per Case
Wittels EH et al. Am J Cardiol 1990;65:432–440.
Preventive Medicine Costs
Cost of preventive measures
Treatment
Testing
Complications of preventive measures
Treating cases that arise anyway
Treating diseases discovered
Treating other illnesses in population living longer
Pay “up-front” for benefit later
False positive
Treating those who will not develop disease
Cost-Effectiveness Analysis
Purpose: Consider both the effectiveness and cost of an intervention
Cost = Cost of medical intervention + cost of illness
Effectiveness = quality adjusted life year saved
CE = Cost-effectiveness ratio
Whose Costs Matter?
Patient: The costs the patient bears directly (depends on co-payment)
Insurance: Costs the insurance bears directly
Societal: Includes all costs and avoids double counting
Measuring Costs
Direct Costs: Direct medical costs related to the diagnosis and treatment of the disease + disease-specific costs that may be induced or averted
Indirect Costs: Lost earnings
Other Costs: Prolonged life ??increased cancer, nursing home patients
Premature events, disability payments, reduced productivity
Cost-Effectiveness: Quality Adjusted Life Years
General Guidelines Incremental Cost-Effectiveness (QALY)
Goldman L et al. Circulation 1992;85:1960–1968.
Cholesterol Lowering: Cost-Effectiveness
Goldman L et al. JAMA 1991;265:1145–1151.
Cost Effectiveness of Simvastatin Treatment for 5 Years in 59-Year-Old Patients with CHD and a Pretreatment Total Cholesterol Level of 261 mg/dl
Johannesson M et al. N Engl J Med 1997;336:332–336.
Copyright ?1997 Massachusetts Medical Society.
Cost Per Year of Life Gained in Patients with CHD Who Received Simvastatin Treatment for 5 Years
Johannesson M et al. N Engl J Med 1997;336:332–336.
Copyright ?1997 Massachusetts Medical Society.
WOSCOPS Placebo Group 5-Year Total Event Rates
West of Scotland Coronary Prevention Group. Lancet 1996;348:1339–1342.
New Tests for Risk Assessment
I. Lipoprotein assessment
Lipoprotein(a)* Apoproteins: apo B-100,* A-I, CIII-B LDL particle size Apo E genotype
*Frequently used at Baylor Lipid Metabolism and Atherosclerosis Clinic
Lp(a) in Atherogenesis: Another Culprit?
Identical to LDL particle except for addition of apo(a)
Plasma concentration predictive of atherosclerotic disease in many, although not all, epidemiologic studies
Accumulates in atherosclerotic plaque
Binds apo B–containing lipoproteins and proteoglycans
Taken up by foam cell precursors
May interfere with thrombolysis
Maher VMG et al. JAMA 1995;274:1771-1774.
Stein JH et al. Arch Intern Med 1997;157:1170-1176.
Effects of Lipid-Modulating Drugs on Lp(a)
Niacin and estrogen reduce Lp(a) levels
Apheresis reduces Lp(a) levels
No benefit from statins
No consistent benefit with fibrates, although studies are variable
Apo E Genotype
Apo E mediates the metabolism of chylomicrons, chylomicron remnants, VLDL, IDL, and a subclass of HDL particles.1
The 3 alleles of the apo E gene are associated with variations in LDL-C level, which is higher with ?4 and lower with ?2 compared with ?3.2
LDL-C response to diet is reportedly greater in patients with ?4,3 response to statins greater with ?2 or ?3.
1Mahley RW. Science 1988;240:622-630.
2Davignon J et al. Arteriosclerosis 1988;8:1-21.
3M?ntt?ri M et al. Metabolism 1991;40:217-221.
Intensity of lipid-lowering therapy is dependent upon the absolute risk for CHD events
NCEP Risk Factors in Primary Prevention
Positive Risk Factors
Age
Male ?45 years
Female ?55 years or premature menopause without ERT
Family history of premature CHD
Current cigarette smoking
Hypertension (?140/90 mm Hg or on antihypertensive medication)
Low HDL-C (<35 mg/dl)
Diabetes mellitus
Negative Risk Factor
High HDL-C (?60 mg/dl)
National Cholesterol Education Program. Circulation 1994;89:1329-445.
New Tests for Risk Assessment
Nonlipid risk factors
Homocysteine* Fibrinogen Plasminogen activator inhibitor C-reactive protein Cell adhesion molecules
*Frequently used at Baylor Lipid Metabolism and Atherosclerosis Clinic
Homocysteine as a CVD Risk Factor
High plasma homocysteine may be directly related to atherosclerosis development.
High plasma homocysteine may be related to CVD risk by
Enhancing inflammatory processes
Increasing risk for thrombosis
Decreased folic acid or B12 and B6 may be the primary cause of increased CVD risk.
There may be no causal association between elevated homocysteine and CVD risk.
Kuller LH et al. Circulation 1998;98:196-199.
Plasma Homocysteine and Mortality in CHD Patients
Prospective evaluation of 587 CHD patients, followed up for 4.6 years
Fasting plasma homocysteine measured at baseline
Strong, graded relationship between homocysteine levels and all-cause mortality
Nygard O et al. N Engl J Med 1997;337:230–236.
Nygard O et al. N Engl J Med 1997;337:230–236.
Plasma Homocysteine and Mortality in CHD Patients
Homocysteine in Risk Assessment and Risk Reduction
Mechanisms of atherogenesis from homocysteine are not known, but endothelial injury and/or potentiation of lipoprotein oxidation are possible.
Laboratory testing of homocysteine levels needs to be better standardized
Treatment with high-dose folic acid (1–2 mg/d) and/or pyridoxine (250 mg/d) can lower homocysteine levels; empiric B12 frequently added
Elevated Plasma Fibrinogen A Major and Independent Risk Factor
Epidemiological studies
Cross-sectional analyses
Clinical cohort studies
There is a sizeable body of evidence identifying fibrinogen as a major, independent risk factor
Ernst E, et al. Eur Heart J. 1995;16(supplA):47-53.
Fibrinogen and Atherosclerosis
Presence or Absence of Plaque
Levenson J, et al. Arterioscler Thromb Vasc Biol. 1995;15:1263-1268.
n=652 men
Effects of Lipid-Lowering Agents on Fibrinogen
No consistent benefit seen with statins
Fibrates have shown benefit in most studies
Levels reduced with apheresis
Nicotinic acid has shown a modest reduction in some but not all studies
Circulating Adhesion Molecules in the Atherosclerosis Risk in Communities (ARIC) Study
Biracial population of 15,792 adults, aged 45–64, in 4 U.S. communities
Incident CHD: fatal or nonfatal MI, surgical revascula