识别和治疗高危患者的新方法ppt课件

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 5574 137 fatal and nonfatal CHD events during follow-up,1.1,1.11.01,1.00.91,0.90.71,0.7,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 4589) operated on for AAA, separated into 4 groups based on preoperative CHD history and ECG Follow-up: 611 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 (197175) and NHANES II (198284). 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,P0.001,P0.001,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 (2.373.49),Malmberg K et al. Circulation 2000;102:1014-1019. 2000 Lippincott Williams & Wilkins.,24,RR=1.99 (1.522.60),RR=1.71 (1.442.04),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 (contd),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 benefit will be achieved from aggressive LDL-lowering therapy Post-hoc analysis of all statin trials showed a trend for benefit of LDL lowering in persons with diabetes,ATP III: Management of Diabetic Dyslipidemia,Primary target of therapy: LDL-C Diabetes: CHD risk equivalent Therefore, goal for persons with diabetes: 100 mg/dL Therapeutic options: LDL-C 100129 mg/dL: increase intensity of TLC; add drug to modify atherogenic dyslipidemia (fibrate or nicotinic acid); intensify statin therapy LDL-C 130 mg/dL: simultaneously initiate TLC and LDL-Clowering drugs After LDL-C goal is met, if TG 200 mg/dL: nonHDL-C (130 mg/dl) becomes secondary target,Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.,The Metabolic Syndrome,Metabolic syndrome is a secondary target of therapy in ATP III. Primary interventions are behavioral, with pharmacological agents suggested to treat components such as hypertension and dyslipidemia. Components of the metabolic syndrome have been shown to be strongly predictive of cardiovascular disease.1 Although insulin concentrations strongly predict the development of multiple metabolic disorders2 and cardiovascular disease,3 insulin resistance is present in only one or two components in the Framingham Study.4,5,1Isomaa B et al. Diabetes Care 2001;24:683-689. 2Haffner SM et al. Diabetes 1992;41:715-722. 3Pyorala M et al. Circulation 1998;98:398-404. 4Meigs JB. Am J Epidemiol 2000;152:908-911. 5Meigs JB et al. Diabetes 1997;46:1594-1600.,ATP III: The Metabolic Syndrome,Diagnosis is established when 3 of these risk factors are present.,Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.,Comparison of ATP III Risk Factor Counting and the Metabolic Syndrome,*TG 200 mg/dL part of criteria to determine whether non-HDL-C should be targeted. Diabetes is a CHD risk equivalent. Diabetes plus IFG.,Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.,Comparison of ATP III Risk Factor Counting and the Metabolic Syndrome (contd),Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.,Relationship of Fasting Insulin Levels to Relative Risk for Multiple Metabolic Disorders: San Antonio Heart Study,Haffner SM et al. Diabetes 1992;41:715-722.,Risk of Major CHD Event Associated with Insulin Quintiles in Nondiabetic Subjects: Helsinki Policemen Study,Years,5,10,20,0,15,25,Pyorala M et al. Circulation 1998;98:398-404. 1998 Lippincott Williams & Wilkins.,Log rank: Overall P = .001 Q5 vs. Q1 P .001,Q1,Q2,Q3,Q4,Q5,Clinical Management of Metabolic Syndrome,Management of underlying causes Weight control enhances LDL lowering and reduces all risk factors Physical activity reduces VLDL and LDL and increases HDL Treat lipid and nonlipid risk factors Hypertension Aspirin in CHD patients Elevated triglycerides Low HDL,Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.,Multiple Risk Factors: Additive Risk,The total severity of multiple low-level risk factors often exceeds that of a single severely elevated risk factor.,8%,Grundy SM et al. J Am Coll Cardiol 1999;34:1348-1359.,BP 165/95 mm Hg,BP 165/95 mm Hg Age 56 years,BP 165/95 mm Hg Age 56 years LDL-C 155 mg/dL,BP 165/95 mm Hg Age 56 years LDL-C 155 mg/dL Smoker,13%,19%,27%,Mean Absolute Risk (%),CHD Risk Equivalent Summary,Patients with established CHD have a risk for recurrent MI and CHD death that exceeds 20% per 10 years. Clinically evident noncoronary atherosclerosis, as well as type 2 diabetes mellitus, impose an approximately equal risk for developing CHD in patients without clinical CHD. CHD risk equivalents: Multiple risk factors (20% 10-year CHD risk) Type 2 diabetes mellitus 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.,Classification of Serum Triglycerides,Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 1993;269:3015-3023. | Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.,Rationale for Change in the Categorization of Triglyceride Levels in ATP III,ATP III gives additional emphasis to moderate elevations of triglycerides (150200 mg/dL) for the following reasons: New meta-analysis suggests that raised triglyceride levels may be an independent risk factor for CHD.12 Elevated triglycerides are associated with components of the metabolic syndrome such as glucose intolerance, low HDL, inflammation, and prothrombotic state.3 Subjects with modestly elevated triglyceride levels have atherogenic remnant lipoproteins.3 Increased triglycerides are not a specific target for intervention in ATP III but enter into the determination of whether to target non-HDL-C.,1 Austin MA. Can J Cardiol 1998;14:14B-17B. 2 Assmann G et al. Eur Heart J 1998;19:M8-M14. 3 Grundy SM. Am J Cardiol 1998;81:18B-25B.,Classification of Serum HDL-C Levels,Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 1993;269:3015-3023. | Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.,Rationale for Change in the Low HDL-C Category in the ATP III Guidelines,The inverse association between HDL-C concentrations and CHD risk is continuous; no threshold relationship has been identified. Clearly, low HDL-C levels predict CHD at levels above 35 mg/dL.1 Women typically have higher HDL-C levels than men, and a cutpoint of 40 mg/dL will identify more men than women with low HDL-C, i.e., approximately one-third of men and one-fifth of women in the general population.,1 Wilson PW et al. Circulation 1998;97:1837-1847.,Atherogenic Particles,Apolipoprotein B,Non-HDL-C,MEASUREMENTS:,TG-rich lipoproteins,VLDL,VLDLR,IDL