From Vulnerable Plaque to Vulnerable Patient—Part III: Executive Summary of the Screening for Heart Attack Prevention and Education (SHAPE) Task Force Report

      Screening for early-stage asymptomatic cancers (eg, cancers of breast and colon) to prevent late-stage malignancies has been widely accepted. However, although atherosclerotic cardiovascular disease (eg, heart attack and stroke) accounts for more death and disability than all cancers combined, there are no national screening guidelines for asymptomatic (subclinical) atherosclerosis, and there is no government- or healthcare-sponsored reimbursement for atherosclerosis screening. Part I and Part II of this consensus statement elaborated on new discoveries in the field of atherosclerosis that led to the concept of the “vulnerable patient.” These landmark discoveries, along with new diagnostic and therapeutic options, have set the stage for the next step: translation of this knowledge into a new practice of preventive cardiology. The identification and treatment of the vulnerable patient are the focuses of this consensus statement.
      In this report, the Screening for Heart Attack Prevention and Education (SHAPE) Task Force presents a new practice guideline for cardiovascular screening in the asymptomatic at-risk population. In summary, the SHAPE Guideline calls for noninvasive screening of all asymptomatic men 45–75 years of age and asymptomatic women 55–75 years of age (except those defined as very low risk) to detect and treat those with subclinical atherosclerosis. A variety of screening tests are available, and the cost-effectiveness of their use in a comprehensive strategy must be validated. Some of these screening tests, such as measurement of coronary artery calcification by computed tomography scanning and carotid artery intima–media thickness and plaque by ultrasonography, have been available longer than others and are capable of providing direct evidence for the presence and extent of atherosclerosis. Both of these imaging methods provide prognostic information of proven value regarding the future risk of heart attack and stroke. Careful and responsible implementation of these tests as part of a comprehensive risk assessment and reduction approach is warranted and outlined by this report. Other tests for the detection of atherosclerosis and abnormal arterial structure and function, such as magnetic resonance imaging of the great arteries, studies of small and large artery stiffness, and assessment of systemic endothelial dysfunction, are emerging and must be further validated. The screening results (severity of subclinical arterial disease) combined with risk factor assessment are used for risk stratification to identify the vulnerable patient and initiate appropriate therapy. The higher the risk, the more vulnerable an individual is to a near-term adverse event. Because <10% of the population who test positive for atherosclerosis will experience a near-term event, additional risk stratification based on reliable markers of disease activity is needed and is expected to further focus the search for the vulnerable patient in the future. All individuals with asymptomatic atherosclerosis should be counseled and treated to prevent progression to overt clinical disease. The aggressiveness of the treatment should be proportional to the level of risk. Individuals with no evidence of subclinical disease may be reassured of the low risk of a future near-term event, yet encouraged to adhere to a healthy lifestyle and maintain appropriate risk factor levels. Early heart attack care education is urged for all individuals with a positive test for atherosclerosis. The SHAPE Task Force reinforces existing guidelines for the screening and treatment of risk factors in younger populations.
      Cardiovascular healthcare professionals and policymakers are urged to adopt the SHAPE proposal and its attendant cost-effectiveness as a new strategy to contain the epidemic of atherosclerotic cardiovascular disease and the rising cost of therapies associated with this epidemic.
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        • Mackay J.
        • Mensah G.
        The Atlas of Heart Disease and Stroke.
        (Accessed June 11, 2006)
        • Leeder S.
        • Raymond S.
        • Greenberg H.
        • Liu H.
        • Esson K.
        • et al.
        A Race Against Time: The Challenge of Cardiovascular Disease in Developing Economies.
        (Accessed June 11, 2006)
        • American Heart Association
        Heart Disease and Stroke Statistics – 2006 Update. Dallas, TX: American Heart Association, 2006.
        (Accessed June 11, 2006)
        • Zipes D.P.
        • Wellnes H.J.J.
        Sudden cardiac death.
        Circulation. 1998; 98: 2334-2351
        • Zheng Z.J.
        • Croft J.B.
        • Giles W.H.
        • Ayala C.I.
        • Greenlund K.J.
        • Keenan N.L.
        • Neff L.
        • Wattigney W.A.
        • Mensah G.A.
        State-specific mortality from sudden cardiac death—United States, 1999.
        MMWR Morb Mortal Wkly Rep. 2002; 51: 123-126
        • Yusuf S.
        • Hawken S.
        • Ounpuu S.
        • Dans T.
        • Avezum A.
        • Lanas F.
        • McQueen M.
        • Budaj A.
        • Pais P.
        • Varigos J.
        • Lisheng L.
        • INTERHEART Study Investigators
        Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
        Lancet. 2004; 364: 937-952
        • Stamler J.
        • Stamler R.
        • Neaton J.D.
        • Wentworth D.
        • Daviglus M.L.
        • Garside D.
        • Dyer A.R.
        • Liu K.
        • Greenland P.
        Low risk-factor profile and long-term cardiovascular and noncardiovascular mortality and life expectancy: findings for 5 large cohorts of young adult and middle-aged men and women.
        JAMA. 1999; 282: 2012-2018
        • American Heart Association
        Heart Disease and Stroke Statistics – 2005 Update.
        American Heart Association, Dallas, TX2005
        • United States Cancer Statistics: 2002 Incidence and Mortality [Centers for Disease Control and Prevention Web site]
        Centers for Disease Control and Prevention, US Dept of Health and Human Services.
        (Accessed June 11, 2006)
        • US Preventive Services Task Force
        Screening for Coronary Heart Disease, 2004 [Agency for Healthcare Research and QualityWeb site].
        (Accessed June 11, 2006)
        • Lloyd-Jones D.M.
        • Larson M.G.
        • Leip E.P.
        • Beiser A.
        • D’Agostino R.B.
        • Kannel W.B.
        • Murabito J.M.
        • Vasan R.S.
        • Benjamin E.J.
        • Levy D.
        for the Framingham Heart Study. Lifetime risk for developing congestive heart failure: the Framingham Heart Study.
        Circulation. 2002; 106: 3068-3072
        • Young J.B.
        The global epidemiology of heart failure.
        Med Clin North Am. 2004; 88 (ix): 1135-1143
        • D’Agostino Sr, R.B.
        • Grundy S.
        • Sullivan L.M.
        • Wilson P.
        for the CHD Risk Prediction Group. Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation.
        JAMA. 2001; 286: 180-187
        • Danesh J.
        • Wheeler J.G.
        • Hirschfield G.M.
        • Eda S.
        • Eiriksdottir G.
        • Rumley A.
        • Lowe G.D.
        • Pepys M.B.
        • Gudnason V.
        C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease.
        N Engl J Med. 2004; 350: 1387-1397
        • Cooper J.A.
        • Miller G.J.
        • Humphries S.E.
        A comparison of the PROCAM and Framingham point-scoring systems for estimation of individual risk of coronary heart disease in the Second Northwick Park Heart Study.
        Atherosclerosis. 2005; 181: 93-100
        • Liu J.
        • Hong Y.
        • D’Agostino Sr, R.B.
        • Wu Z.
        • Wang W.
        • Sun J.
        • Wilson P.W.
        • Kannel W.B.
        • Zhao D.
        Predictive value for the Chinese population of the Framingham CHD risk assessment tool compared with the Chinese Multi-Provincial Cohort Study.
        JAMA. 2004; 291: 2591-2599
        • Arad Y.
        • Goodman K.J.
        • Roth M.
        • Newstein D.
        • Guerci A.D.
        Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study.
        J Am Coll Cardiol. 2005; 46: 158-165
        • Grundy S.M.
        The changing face of cardiovascular risk [editorial].
        J Am Coll Cardiol. 2005; 46: 173-175
        • De Backer G.
        • Ambrosioni E.
        • Borch-Johnsen K.
        • Brotons C.
        • Cifkova R.
        • Dallongeville J.
        • Ebrahim S.
        • Faergeman O.
        • Graham I.
        • Mancia G.
        • et al.
        • Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice
        European guidelines on cardiovascular disease prevention in clinical practice.
        (Accessed June 11, 2006)
        • Akosah K.
        • Schaper A.
        • Cogbil C.
        • Schoenfeld P.
        Preventing myocardial infarction in the young adult in the first place: how do the National Cholesterol Education Panel III guidelines perform?.
        J Am Coll Cardiol. 2003; 41: 1475-1479
        • Brindle P.
        • Emberson J.
        • Lampe F.
        • Walker M.
        • Whincup P.
        • Fahey T.
        • Ebrahim S.
        Predictive accuracy of the Framingham coronary risk score in British men: prospective cohort study.
        BMJ. 2003; 327: 1267
        • Empana J.P.
        • Ducimetiere P.
        • Arveiler D.
        • Ferrieres J.
        • Evans A.
        • Ruidavets J.B.
        • Haas B.
        • Yarnell J.
        • Bingham A.
        • Amouyel P.
        • Dallongeville J.
        for the PRIME Study Group. Are the Framingham and PROCAM coronary heart disease risk functions applicable to different European populations? The PRIME Study.
        Eur Heart J. 2003; 24: 1903-1911
        • Neuhauser H.K.
        • Ellert U.
        • Kurth B.M.
        A comparison of Framingham and SCORE-based cardiovascular risk estimates in participants of the German National Health Interview and Examination Survey 1998.
        Eur J Cardiovasc Prev Rehabil. 2005; 12: 442-450
        • Bastuji-Garin S.
        • Deverly A.
        • Moyse D.
        • Castaigne A.
        • Mancia G.
        • de Leeuw P.W.
        • Ruilope L.M.
        • Rosenthal T.
        • Chatellier G.
        for the Intervention as a Goal in Hypertension Treatment Study Group. The Framingham prediction rule is not valid in a European population of treated hypertensive patients.
        J Hypertens. 2002; 20: 1973-1980
        • Bhopal R.
        • Fischbacher C.
        • Vartianen E.
        • Unwin N.
        • White M.
        • Alberti G.
        Predicted and observed cardiovascular disease in South Asians: application of FINRISK, Framingham and SCORE models to Newcastle Heart Project data.
        J Public Health (Oxf). 2005; 27: 93-100
        • Kuller L.H.
        Prevention of coronary heart disease and the National Cholesterol Education Program.
        Circulation. 2006; 113: 598-600
        • Greenland P.
        • Knoll M.D.
        • Stamler J.
        • Neaton J.D.
        • Dyer A.R.
        • Garside D.B.
        • Wilson P.W.
        Major risk factors as antecedents of fatal and nonfatal coronary heart disease events.
        JAMA. 2003; 290: 891-897
        • Wald N.J.
        • Law M.
        • Watt H.C.
        • Wu T.
        • Bailey A.
        • Johnson A.M.
        • Craig W.Y.
        • Ledue T.B.
        • Haddow J.E.
        Apolipoproteins and ischaemic heart disease: implications for screening.
        Lancet. 1994; 343: 75-79
        • Wald N.J.
        • Hackshaw A.K.
        • Frost C.D.
        When can a risk factor be used as a worthwhile screening test?.
        BMJ. 1999; 319: 1562-1565
        • Law M.R.
        • Wald N.J.
        Risk factor thresholds: their existence under scrutiny.
        BMJ. 2002; 324: 1570-1576
        • Law M.R.
        • Wald N.J.
        • Morris J.K.
        The performance of blood pressure and other cardiovascular risk factors as screening tests for ischaemic heart disease and stroke.
        J Med Screen. 2004; 11: 3-7
        • Weissler A.M.
        Traditional risk factors for coronary heart disease [letter].
        JAMA. 2004; 291: 299-300
        • Wald N.J.
        • Law M.R.
        A strategy to reduce cardiovascular disease by more than 80% [published correction appears in BMJ 2003;327:586].
        BMJ. 2003; 326: 1419
        • National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
        Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.
        Circulation. 2002; 106: 3143-3421
        • Grundy S.M.
        • Cleeman J.I.
        • Merz C.N.
        • Brewer Jr, H.B.
        • Clark L.T.
        • Hunninghake D.B.
        • Pasternak R.C.
        • Smith Jr, S.C.
        • Stone N.J.
        Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines.
        Circulation. 2004; 110: 227-239
        • Smith Jr, S.C.
        • Greenland P.
        • Grundy S.M.
        AHA Conference Proceedings.
        Circulation. 2000; 101: 111-116
        • Law M.R.
        • Watt H.C.
        • Wald N.J.
        The underlying risk of death after myocardial infarction in the absence of treatment.
        Arch Intern Med. 2002; 162: 2405-2410
        • Eyre H.
        • Kahn R.
        • Robertson R.M.
        • Clark N.G.
        • Doyle C.
        • Hong Y.
        • Gansler T.
        • Glynn T.
        • Smith R.A.
        • Taubert K.
        • Thun M.J.
        Preventing cancer, cardiovascular disease, and diabetes: a common agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association.
        Circulation. 2004; 109: 3244-3255
        • Naghavi M.
        • Libby P.
        • Falk E.
        • Casscells S.W.
        • Litovsky S.
        • Rumberger J.
        • Badimon J.J.
        • Stefanadis C.
        • Moreno P.
        • Pasterkamp G.
        • et al.
        From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: part I [review].
        Circulation. 2003; 108: 1664-1672
        • Naghavi M.
        • Libby P.
        • Falk E.
        • Casscells S.W.
        • Litovsky S.
        • Rumberger J.
        • Badimon J.J.
        • Stefanadis C.
        • Moreno P.
        • Pasterkamp G.
        • et al.
        From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: part II [review].
        Circulation. 2003; 108: 1772-1778
        • Hoff J.A.
        • Chomka E.V.
        • Krainik A.J.
        • Daviglus M.
        • Rich S.
        • Kondos G.T.
        Age and gender distributions of coronary artery calcium detected by electron beam tomography in 35,246 adults.
        Am J Cardiol. 2001; 87: 1335-1339
        • Arad Y.
        • Spadaro L.
        • Goodman K.
        • Newstein D.
        • Guerci A.D.
        Prediction of coronary events with electron beam computed tomography.
        J Am Coll Cardiol. 2000; 36: 1253-1260
        • Park R.
        • Detrano R.
        • Xiang M.
        • et al.
        Combined use of computed tomography coronary calcium scores and C-reactive protein levels in predicting cardiovascular events in non-diabetic individuals.
        Circulation. 2002; 106: 2073-2077
        • Raggi P.
        • Callister T.Q.
        • Cooil B.
        • et al.
        Identification of patients at increased risk of first unheralded acute myocardial infarction by electron beam computed tomography.
        Circulation. 2000; 101: 850-885
        • Wong N.D.
        • Hsu J.C.
        • Detrano R.C.
        • et al.
        Coronary artery calcium evaluation by electron beam computed tomography and its relation to new cardiovascular events.
        Am J Cardiol. 2000; 86: 495-498
        • Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
        Final Report.
        National Institutes of Health, September, Bethesda, MD2002 (NIH Publication No. 02-5215)
        • Vliegenthart1 R.
        • Oudkerk M.
        • Song B.
        The Rotterdam Coronary Calcification Study: coronary calcification detected by electron-beam computed tomography and myocardial infarction.
        Eur Heart J. 2002; 23: 1596-1603
        • Kondos G.T.
        • Hoff J.A.
        • Sevrukov A.
        • Daviglus M.L.
        • Garside D.B.
        • Devries S.S.
        • Chomka E.V.
        • Liu K.
        Electron-beam tomography coronary artery calcium and cardiac events: a 37-month follow-up of 5635 initially asymptomatic low- to intermediate-risk adults.
        Circulation. 2003; 107: 2571-2576
        • DeBacker G.
        • Ambrosioni E.
        • Borch-Johnson K.
        • Brotons C.
        • Cifkova R.
        • Dallongeville J.
        • Ebrahim S.
        • Faergeman O.
        • Graham I.
        • Mancia G.
        • et al.
        for the European Society of Cardiology Committee for Practice Guidelines. European guidelines on cardiovascular disease prevention in clinical practice (constituted by representatives of eight societies and by invited experts).
        Eur J Cardiovasc Prev Rehabil. 2003; 10: S1-S78
        • Greenland P.
        • Gaziano J.M.
        Clinical practice: selecting asymptomatic patients for coronary computed tomography or electrocardiographic exercise testing [review].
        N Engl J Med. 2003; 349: 465-473
        • Shaw L.J.
        • Raggi P.
        • Schisterman E.
        • Berman D.S.
        • Callister T.Q.
        Prognostic value of cardiac risk factors and coronary artery calcium screening for all-cause mortality.
        Radiology. 2003; 28: 826-833
        • Pletcher M.J.
        • Tice J.A.
        • Pignone M.
        • Browner W.S.
        Using the coronary artery calcium score to predict coronary heart disease events: a systematic review and meta-analysis.
        Arch Intern Med. 2004; 164: 1285-1292
        • Greenland P.
        • LaBree L.
        • Azen S.P.
        • et al.
        Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals.
        JAMA. 2004; 291: 210-215
        • Mosca L.
        • Appel L.J.
        • Benjamin E.J.
        • Berra K.
        • Chandra-Strobos N.
        • Fabunmi R.P.
        • Grady D.
        • Haan C.K.
        • Hayes S.N.
        • Judelson D.R.
        • et al.
        • Expert Panel/Writing Group
        Evidence-based guidelines for cardiovascular disease prevention in women [AHA Guidelines].
        Circulation. 2004; 109: 672-693
        • Vliegenthart R.
        • Oudkerk M.
        • Hofman A.
        • Oei H.H.
        • van Dijck W.
        • van Rooij F.J.
        • Witteman J.C.
        Coronary calcification improves cardiovascular risk prediction in the elderly.
        Circulation. 2005; 112: 572-577
        • Taylor A.J.
        • Bindeman J.
        • Feuerstein I.
        • Cao F.
        • Brazaitis M.
        • O’Malley P.G.
        Coronary calcium independently predicts incident premature coronary heart disease over measured cardiovascular risk factors: mean three-year outcomes in the Prospective Army Coronary Calcium (PACC) Project.
        J Am Coll Cardiol. 2005; 46: 807-814
        • Berman D.S.
        • Wong N.D.
        • Gransar H.
        • Miranda-Peats R.
        • Dahlbeck J.
        • Hayes S.W.
        • Friedman J.D.
        • Kang X.
        • Polk D.
        • Hachamovitch R.
        • Shaw L.
        • Rozanski A.
        Relationship between stress-induced myocardial ischemia and atherosclerosis measured by coronary calcium tomography.
        J Am Coll Cardiol. 2004; 44: 923-930
        • Simons D.B.
        • Schwartz R.S.
        • Edwards W.D.
        • Sheedy P.F.
        • Breen J.F.
        • Rumberger J.A.
        Non-invasive definition of anatomic coronary artery disease by ultrafast CT: a quantitative pathologic study.
        J Am Coll Cardiol. 1992; 20: 1118-1126
        • Rumberger J.A.
        • Simons D.B.
        • Fitzpatrick L.A.
        • Sheedy P.F.
        • Schwartz R.S.
        Coronary artery calcium areas by electron beam computed tomography and coronary atherosclerotic plaque area: a histopathologic correlative study.
        Circulation. 1995; 92: 2157-2162
        • Sangiorgi G.
        • Rumberger J.A.
        • Severson A.
        • Edwards W.D.
        • Gregoire J.
        • Fitzpatrick L.A.
        • Schwartz R.S.
        Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using non-decalcifying methodology.
        J Am Coll Cardiol. 1998; 31: 126-133
        • Chambless L.E.
        • Heiss G.
        • Folsom A.R.
        • Rosamond W.
        • Szklo M.
        • Sharrett A.R.
        • Clegg L.X.
        Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987–1993.
        Am J Epidemiol. 1997; 146: 483-494
        • Chambless L.E.
        • Folsom A.R.
        • Clegg L.X.
        • Sharrett A.R.
        • Shahar E.
        • Nieto F.J.
        • Rosamond W.D.
        • Evans G.
        Carotid wall thickness is predictive of incident clinical stroke: the Atherosclerosis Risk in Communities (ARIC) Study.
        Am J Epidemiol. 2000; 151: 478-487
        • Bonithon-Kopp C.
        • Scarabin P.
        • Taquet A.
        • Touboul P.
        • Malmejac A.
        • Guize L.
        Risk factors for early carotid atherosclerosis in middle-aged French women.
        Arterioscler Thromb. 1991; 11: 966-972
        • Greenland P.
        • Abrams J.
        • Aurigemma G.P.
        • Bond M.G.
        • Clark L.T.
        • Criqui M.H.
        • Crouse III, J.R.
        • Friedman L.
        • Fuster V.
        • Herrington D.M.
        • et al.
        the Writing Group III. AHA Conference Proceedings. Prevention conference V: Beyond secondary prevention: identifying the high-risk patient for primary prevention: noninvasive tests of atherosclerosis burden.
        Circulation. 2000; 101: E16-E22
        • Belcaro G.
        • Nicolaides A.N.
        • Laurora G.
        • Cesarone M.R.
        • De Sanctis M.
        • Incandela L.
        • Barsotti A.
        Ultrasound morphology classification of the arterial wall and cardiovascular events in a 6-year follow-up study.
        Arterioscler Thromb Vasc Biol. 1996; 16: 851-856
        • Touboul P.J.
        • Hennerici M.G.
        • Meairs S.
        • Adams H.
        • Amarenco P.
        • Desvarieux M.
        • Ebrahim S.
        • Fatar M.
        • Hernandez Hernandez R.
        • Kownator S.
        for the Advisory Board of the 3rd Watching the Risk Symposium 2004, 13th European Stroke Conference. Mannheim intima–media thickness consensus.
        Cerebrovasc Dis. 2004; 18: 346-349
        • Stork S.
        • van den Beld A.W.
        • von Schacky C.
        • Angermann C.E.
        • Lamberts S.W.
        • Grobbee D.E.
        • Bots M.L.
        Carotid artery plaque burden, stiffness, and mortality risk in elderly men: a prospective, population-based cohort study.
        Circulation. 2004; 110: 344-348
        • O’Leary D.H.
        • Polak J.F.
        • Kronmal R.A.
        • Manolio T.A.
        • Burke G.L.
        • Wolfson Jr, S.K.
        Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults.
        N Engl J Med. 1999; 340: 14-22
        • Hodis H.N.
        • Mack W.J.
        • LaBree L.
        • Selzer R.H.
        • Liu C.R.
        • Liu C.H.
        • Azen S.P.
        The role of carotid arterial intima–media thickness in predicting clinical coronary events.
        Ann Intern Med. 1998; 128: 262-269
        • Bots M.L.
        • Hoes A.W.
        • Koudstaal P.J.
        • Hofman A.
        • Grobbee D.E.
        Common carotid intima–media thickness and risk of stroke and myocardial infarction: the Rotterdam Study.
        Circulation. 1997; 96: 1432-1437
        • Hollander M.
        • Hak A.E.
        • Koudstaal P.J.
        • Bots M.L.
        • Grobbee D.E.
        • Hofman A.
        • Witteman J.C.
        • Breteler M.M.
        Comparison between measures of atherosclerosis and risk of stroke: the Rotterdam Study.
        Stroke. 2003; 34: 2367-2372
        • van der Meer I.M.
        • Bots M.L.
        • Hofman A.
        • del Sol A.I.
        • van der Kuip D.A.
        • Witteman J.C.
        Predictive value of noninvasive measures of atherosclerosis for incident myocardial infarction: the Rotterdam Study.
        Circulation. 2004; 109: 1089-1094
      1. Brook RD, Bard RL, Patel S, Rubenfire M, Clarke NS, Kazerooni EA, Wakefield TW, Henke PK, Eagle KA. A negative carotid plaque area test is superior to other noninvasive atherosclerosis studies for reducing the likelihood of having underlying significant coronary artery disease. Arterioscler Thromb Vasc Biol 2006;26:656–662.

        • Riley W.A.
        Cardiovascular risk assessment in individual patients from carotid intimal–medial thickness measurements.
        Curr Atheroscler Rep. 2004; 6: 225-231
        • Bots M.L.
        • Evans G.W.
        • Riley W.A.
        • Grobbee D.E.
        Carotid intimal–medial thickness measurements in intervention studies: design options, progression rates, and sample size considerations: a point of view.
        Stroke. 2003; 34: 2985-2994
        • Van Der Meer I.M.
        • De Maat M.P.
        • Hak A.E.
        • Kiliaan A.J.
        • Del Sol A.I.
        • Van Der Kuip D.A.
        • Nijhuis R.L.
        • Hofman A.
        • Witteman J.C.
        C-reactive protein predicts progression of atherosclerosis measured at various sites in the arterial tree: the Rotterdam Study.
        Stroke. 2002; 33: 2750-2755
        • Khera A.
        • de Lemos J.A.
        • Peshock R.M.
        • Lo H.S.
        • Stanek H.G.
        • Murphy S.A.
        • Wians Jr, F.H.
        • Grundy S.M.
        • McGuire D.K.
        Relationship between C-reactive protein and subclinical atherosclerosis: the Dallas Heart Study.
        Circulation. 2006; 113: 38-43
        • Koenig W.
        Predicting risk and treatment benefit in atherosclerosis: the role of C-reactive protein.
        Int J Cardiol. 2005; 98: 199-206
        • Murabito J.M.
        • Evans J.C.
        • Larson M.G.
        • Nieto K.
        • Levy D.
        • Wilson P.W.
        The ankle-brachial index in the elderly and risk of stroke, coronary disease, and death: the Framingham Study.
        Arch Intern Med. 2003; 163: 1939-1942
        • Ostergren J.
        • Sleight P.
        • Dagenais G.
        • Danisa K.
        • Bosch J.
        • Qilong Y.
        • Yusuf S.
        for the HOPE study investigators. Impact of ramipril in patients with evidence of clinical or subclinical peripheral arterial disease.
        Eur Heart J. 2004; 25: 17-24
        • Raggi P.
        • Shaw L.J.
        • Berman D.S.
        • Callister T.Q.
        Prognostic value of coronary artery calcium screening in subjects with and without diabetes.
        J Am Coll Cardiol. 2004; 43: 1663-1669
        • Sobel B.E.
        • Schneider D.J.
        Cardiovascular complications in diabetes mellitus.
        Curr Opin Pharmacol. 2005; 5: 143-148
        • Schneider D.J.
        Abnormalities of coagulation, platelet function, and fibrinolysis associated with syndromes of insulin resistance.
        Coron Artery Dis. 2005; 16: 473-476
        • Tin L.L.
        • Beevers D.G.
        • Lip G.Y.
        Hypertension, left ventricular hypertrophy, and sudden death.
        Curr Cardiol Rep. 2002; 4: 449-457
        • Lipinski M.J.
        • Fuster V.
        • Fisher E.A.
        • Fayad Z.A.
        Technology insight: targeting of biological molecules for evaluation of high-risk atherosclerotic plaques with magnetic resonance imaging.
        Nat Clin Pract Cardiovasc Med. 2004; 1: 48-55
        • Fuster V.
        • Fayad Z.A.
        • Moreno P.R.
        • Poon M.
        • Corti R.
        • Badimon J.J.
        Atherothrombosis and high-risk plaque. Part II.
        J Am Coll Cardiol. 2005; 46: 1209-1218
        • Takaya N.
        • Yuan C.
        • Chu B.
        • Saam T.
        • Polissar N.L.
        • Jarvik G.P.
        • Isaac C.
        • McDonough J.
        • Natiello C.
        • Small R.
        • Ferguson M.S.
        • Hatsukami T.S.
        Presence of intraplaque hemorrhage stimulates progression of carotid atherosclerotic plaques: a high-resolution magnetic resonance imaging study.
        Circulation. 2005; 111: 2768-2775
        • Yuan C.
        • Hatsukami T.S.
        • Cai J.
        MRI plaque tissue characterization and assessment of plaque stability.
        Stud Health Technol Inform. 2005; 113: 55-74
        • Cohn J.N.
        • Quyyumi A.A.
        • Hollenberg N.K.
        • Jamerson K.A.
        Surrogate markers for cardiovascular disease: functional markers [review].
        Circulation. 2004; 109: IV31-IV46
        • Zieman S.J.
        • Melenovsky V.
        • Kass D.A.
        Mechanisms, pathophysiology, and therapy of arterial stiffness.
        Arterioscler Thromb Vasc Biol. 2005; 25: 932-943
        • Bonetti P.O.
        • Lerman L.O.
        • Lerman A.
        Endothelial dysfunction: a marker of atherosclerotic risk [review].
        Arterioscler Thromb Vasc Biol. 2003; 23: 168-175
        • Ganz P.
        • Vita J.A.
        Testing endothelial vasomotor function: nitric oxide, a multipotent molecule [review].
        Circulation. 2003; 108: 2049-2053
        • Widlansky M.E.
        • Gokce N.
        • Keaney Jr, J.F.
        • Vita J.A.
        The clinical implications of endothelial dysfunction [review].
        J Am Coll Cardiol. 2003; 42: 1149-1160
        • Madjid M.
        • Zarrabi A.
        • Litovsky S.
        • Willerson J.T.
        • Casscells W.
        Finding vulnerable atherosclerotic plaques: is it worth the effort?.
        Arterioscler Thromb Vasc Biol. 2004; 24: 1775-1782
        • MacNeill B.D.
        • Bouma B.E.
        • Yabushita H.
        • Jang I.K.
        • Tearney G.J.
        Intravascular optical coherence tomography: cellular imaging.
        J Nucl Cardiol. 2005; 12: 460-465
        • Carlier S.
        • Kakadiaris I.A.
        • Dib N.
        • Vavuranakis M.
        • O’Malley S.M.
        • Gul K.
        • Hartley C.J.
        • Metcalfe R.
        • Mehran R.
        • Stefanadis C.
        • et al.
        Vasa vasorum imaging: a new window to the clinical detection of vulnerable atherosclerotic plaques.
        Curr Atheroscler Rep. 2005; 7: 164-169
        • Fujii K.
        • Carlier S.G.
        • Mintz G.S.
        • Wijns W.
        • Colombo A.
        • Bose D.
        • Erbel R.
        • de Ribamar Costa Jr, J.
        • Kimura M.
        • Sano K.
        • et al.
        Association of plaque characterization by intravascular ultrasound virtual histology and arterial remodeling.
        Am J Cardiol. 2005; 96: 1476-1483
        • Chen J.W.
        • Wasserman B.A.
        Vulnerable plaque imaging.
        Neuroimaging Clin North Am. 2005; 15: 609-621
        • Baldewsing R.A.
        • Schaar J.A.
        • Mastik F.
        • Oomens C.W.
        • van der Steen A.F.
        Assessment of vulnerable plaque composition by matching the deformation of a parametric plaque model to measured plaque deformation.
        IEEE Trans Med Imaging. 2005; 24: 514-528
        • Schoenhagen P.
        • Nissen S.E.
        Assessing coronary plaque burden and plaque vulnerability: atherosclerosis imaging with IVUS and emerging noninvasive modalities.
        Am Heart Hosp J. 2003; 1: 164-169
        • Sattar N.
        • McCarey D.W.
        • Capell H.
        • McInnes I.B.
        Explaining how “high-grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis.
        Circulation. 2003; 108: 2957-2963
        • Gonzalez-Gay M.A.
        • Gonzalez-Juanatey C.
        • Martin J.
        Rheumatoid arthritis: a disease associated with accelerated atherogenesis.
        Semin Arthritis Rheum. 2005; 35: 8-17
        • Joseph A.J.
        • Cohen A.G.
        • Bahr R.D.
        A formal, standardized and evidence-based approach to Chest Pain Center development and process improvement: the Society of Chest Pain Centers and Providers accreditation process.
        J Cardiovasc Manag. 2003; 14: 11-14
        • Luepker R.V.
        • Raczynski J.M.
        • Osganian S.
        • Goldberg R.J.
        • Finnegan Jr, J.R.
        • Hedges J.R.
        • Goff Jr, D.C.
        • Eisenberg M.S.
        • Zapka J.G.
        • Feldman H.A.
        • et al.
        Effect of a community intervention on patient delay and emergency medical service use in acute coronary heart disease: the Rapid Early Action for Coronary Treatment (REACT) Trial.
        JAMA. 2000; 284: 60-67
        • Kalia N.K.
        • Miller L.G.
        • Nasir K.
        • Blumenthal R.S.
        • Agrawal N.
        • Budoff M.J.
        Visualizing coronary calcium is associated with improvements in adherence to statin therapy.
        Atherosclerosis. 2006; 185: 394-399
        • Mark D.B.
        • Shaw L.J.
        • Lauer M.S.
        • O’Malley P.
        • Heidenreich P.
        34th Bethesda Conference: Task force #5—Is atherosclerotic imaging cost effective? From the 34th Bethesda Conference on Atherosclerotic Imaging.
        J Am Coll Cardiol. 2003; 41: 1906-1917
        • Fedder D.O.
        • Koro C.E.
        • L’Italien G.J.
        New National Cholesterol Education Program III guidelines for primary prevention lipid-lowering drug therapy: projected impact on the size, sex, and age distribution of the treatment-eligible population.
        Circulation. 2002; 105: 152-156
        • Nasir K.
        • Michos E.D.
        • Blumenthal R.S.
        • Raggi P.
        Detection of high-risk young adults and women by coronary calcium and National Cholesterol Education Program Panel III guidelines.
        J Am Coll Cardiol. 2005; 46: 1931-1936
        • Centers for Medicare and Medicaid Services (CMS) Proposed Rule for Physician Payments for 2005. [American College of Cardiology Web site.]
        (Accessed April 17)
        • Vivanco F.
        • Martin-Ventura J.L.
        • Duran M.C.
        • Barderas M.G.
        • Blanco-Colio L.
        • Darde V.M.
        • Mas S.
        • Meilhac O.
        • Michel J.B.
        • Tunon J.
        • Egido J.
        Quest for novel cardiovascular biomarkers by proteomic analysis.
        J Proteome Res. 2005; 4: 1181-1191
        • Humphries S.E.
        • Ridker P.M.
        • Talmud P.J.
        Genetic testing for cardiovascular disease susceptibility: a useful clinical management tool or possible misinformation?.
        Arterioscler Thromb Vasc Biol. 2004; 24: 628-636
        • Topol E.J.
        Simon Dack Lecture: The genomic basis of myocardial infarction.
        J Am Coll Cardiol. 2005; 46: 1456-1465
        • Kooi M.E.
        • Cappendijk V.C.
        • Cleutjens K.B.J.M.
        • Kessels A.G.H.
        • Kitslaar P.J.E.H.M.
        • Borgers M.
        • Frederik P.M.
        • Daemen M.J.A.P.
        • van Engelshoven J.M.A.
        Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging.
        Circulation. 2003; 107: 2453-2458
        • Trivedi R.A.
        • U-King-Im J.M.
        • Graves M.J.
        • Cross J.J.
        • Horsley J.
        • Goddard M.J.
        • Skepper J.N.
        • Quartey G.
        • Warburton E.
        • Joubert I.
        In vivo detection of macrophages in human carotid atheroma: temporal dependence of ultrasmall superparamagnetic particles of iron oxide-enhanced MRI.
        Stroke. 2004; 35: 1631-1635
        • Cyrus T.
        • Winter P.M.
        • Caruthers S.D.
        • Wickline S.A.
        • Lanza G.M.
        Magnetic resonance nanoparticles for cardiovascular molecular imaging and therapy.
        Expert Rev Cardiovasc Ther. 2005; 3: 705-715
        • Davies J.R.
        • Rudd J.H.
        • Weissberg P.L.
        Molecular and metabolic imaging of atherosclerosis [review].
        J Nucl Med. 2004; 45: 1898-1907
        • Kietselaer B.L.J.H.
        • Reutelingsperger C.P.M.
        • Heidendal G.A.K.
        • Daemen M.J.A.P.
        • Mess W.H.
        • Hofstra L.
        • Narula J.
        Noninvasive detection of plaque instability with use of radiolabeled annexin A5 in patients with carotid-artery atherosclerosis.
        N Engl J Med. 2004; 350: 1472-1473
        • Davies J.R.
        • Rudd J.H.
        • Fryer T.D.
        • Graves M.J.
        • Clark J.C.
        • Kirkpatrick P.J.
        • Gillard J.H.
        • Warburton E.A.
        • Weissberg P.L.
        Identification of culprit lesions after transient ischemic attack by combined 18F fluorodeoxyglucose positron-emission tomography and high-resolution magnetic resonance imaging.
        Stroke. 2005; 36: 2642-2647
        • Dunphy M.P.
        • Freiman A.
        • Larson S.M.
        • Strauss H.W.
        Association of vascular 18F-FDG uptake with vascular calcification.
        J Nucl Med. 2005; 46: 1278-1284
        • Leber A.W.
        • Knez A.
        • Becker A.
        • Becker C.
        • Reiser M.
        • Steinbeck G.
        • Boekstegers P.
        Visualising noncalcified coronary plaques by CT.
        Int J Cardiovasc Imaging. 2005; 21: 55-61
        • Bonetti P.O.
        • Pumper G.M.
        • Higano S.T.
        • Holmes Jr, D.R.
        • Kuvin J.T.
        • Lerman A.
        Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia.
        J Am Coll Cardiol. 2004; 44: 2137-2141
        • Zalewski A.
        • Macphee C.
        Role of lipoprotein-associated phospholipase A2 in atherosclerosis: biology, epidemiology, and possible therapeutic target.
        Arterioscler Thromb Vasc Biol. 2005; 25: 923-931
        • Schwartz R.S.
        • Bayes-Genis A.
        • Lesser J.R.
        • Sangiorgi M.
        • Henry T.D.
        • Conover C.A.
        Detecting vulnerable plaque using peripheral blood: inflammatory and cellular markers.
        J Interv Cardiol. 2003; 16: 231-242
        • Shah P.K.
        • Chyu K.Y.
        • Fredrikson G.N.
        • Nilsson J.
        Immunomodulation of atherosclerosis with a vaccine.
        Nat Clin Pract Cardiovasc Med. 2005; 2: 639-646
        • Naghavi M.
        The mission of the Association for Eradication of Heart Attack [Association for Eradication of Heart Attack Web site].
        (Accessed June 11, 2006)

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      • Correction
        American Journal of CardiologyVol. 98Issue 10
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          In the “From Vulnerable Plaque to Vulnerable Patient—Part III: Executive Summary of the Screening for Heart Attack Prevention and Education (SHAPE) Task Force Report,” by Naghavi et al (AJC, 2006;98(suppl 1):1–18), there are 2 elements missing from Figure 4: (1) a “→” is missing between Moderately High Risk and High Risk (above Optional); and (2) “>” is missing before “200 mg/dL (5.18 mmol/L).” Also, on page 10H of the supplement, column 2, line 2, the word “molecular” should be removed from “Molecular Pulsewave …”
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