Are We Ready for Routine ‘Subclinical’ Atherosclerosis Screening? Not Yet…
2016; Elsevier BV; Volume: 52; Issue: 3 Linguagem: Inglês
10.1016/j.ejvs.2016.06.002
ISSN1532-2165
Autores Tópico(s)Acute Myocardial Infarction Research
ResumoIn the accompanying review by Giannoukas et al., it is suggested that it may be time to commence routine screening for detecting subclinical atheroma in persons over 50 years of age with low Framingham risk, to improve prevention of arterial disease complications.1Giannoukas A. Chadbok M. Spanos K. Nicolaides A. Screening for asymptomatic carotid plaques with ultrasound.Eur J Vasc Endovasc Surg. 2016; 52: 309-312Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Framingham risk scores (FRS) have evolved since the first in 1998, which was designed to estimate the 10-year risk of coronary heart disease (CHD) events (angina, myocardial infarction [MI], coronary insufficiency, coronary heart disease death) in a US community-based cohort without a baseline CHD history in the mid-1970s.2Wilson P.W. D'Agostino R.B. Levy D. Belanger A.M. Silbershatz H. Kannel W.B. Prediction of coronary heart disease using risk factor categories.Circulation. 1998; 97: 1837-1847Crossref PubMed Scopus (7413) Google Scholar In 2008 the model was expanded for prediction of major arterial disease complications across different body parts (“global” risk), namely for CHD, stroke, transient ischaemic attack, intermittent claudication, or heart failure.3D'Agostino Sr., R.B. Vasan R.S. Pencina M.J. Wolf P.A. Cobain M. Massaro J.M. et al.General cardiovascular risk profile for use in primary care: The Framingham Heart Study.Circulation. 2008; 117: 743-753Crossref PubMed Scopus (4635) Google Scholar In 2009 the model was adapted for 30-year risk estimates of “hard” arterial disease complications (coronary death, MI, and stroke).4Pencina M.J. D'Agostino Sr., R.B. Larson M.G. Massaro J.M. Vasan R.S. Predicting the 30-year risk of cardiovascular disease: The Framingham Heart Study.Circulation. 2009; 119: 3078-3084Crossref PubMed Scopus (609) Google Scholar Use of FRS, and other clinical risk factor scoring systems, has been notable in statin treatment guidelines for individuals without clinically overt arterial disease. Such persons would be considered at high-risk of major arterial disease complications if their estimated 10-year risk was > 20%,5International Atherosclerosis Society: Position paper: Global recommendations for the management of dyslipidemia. 2013: 66http://www.athero.org/iaspositionpaper.aspGoogle Scholar at intermediate risk if 10–20%,5International Atherosclerosis Society: Position paper: Global recommendations for the management of dyslipidemia. 2013: 66http://www.athero.org/iaspositionpaper.aspGoogle Scholar or at low risk if < 10% or < 5.0–7.5%.5International Atherosclerosis Society: Position paper: Global recommendations for the management of dyslipidemia. 2013: 66http://www.athero.org/iaspositionpaper.aspGoogle Scholar, 6Stone N.J. Robinson J. Lichtenstein A.H. Merz C.N. Blum C.B. Eckel R.H. et al.2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines.Circulation. 2014; 129: S1-S45Crossref PubMed Scopus (3095) Google Scholar Risk estimates using the Framingham and other models are derived from observations of outcomes according to the detection of selected, proven, “clinical arterial disease risk factors” (determined from a person's history, physical examination, blood tests, or an electrocardiograph).6Stone N.J. Robinson J. Lichtenstein A.H. Merz C.N. Blum C.B. Eckel R.H. et al.2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines.Circulation. 2014; 129: S1-S45Crossref PubMed Scopus (3095) Google Scholar, 7Woodward M. Brindle P. Tunstall-Pedoe H. estimation SgorAdding social deprivation and family history to cardiovascular risk assessment: the ASSIGN score from the Scottish Heart Health Extended Cohort (SHHEC).Heart. 2007; 93: 172-176Crossref PubMed Scopus (497) Google Scholar, 8Hippisley-Cox J. Coupland C. Vinogradova Y. Robson J. Minhas R. Sheikh A. et al.Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2.BMJ. 2008; 336: 1475-1482Crossref PubMed Scopus (1012) Google Scholar For instance, risk factors used in the FRS have been defined according to a man or a woman's age, blood pressure, smoking status, blood cholesterols (or body mass index), and blood sugar level. Current arterial disease prevention therapy is founded upon decades of research demonstrating that where it is possible to modify these, and other clinical risk factors, the risk of future arterial disease complications is substantially reduced in both primary (before symptoms) and secondary (after symptoms) prevention settings.9Smith Jr., S.C. Benjamin E.J. Bonow R.O. Braun L.T. Creager M.A. Franklin B.A. et al.AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American college of Cardiology Foundation.Circulation. 2011; 124: 2458-2473Crossref PubMed Scopus (1171) Google Scholar, 10National Vascular Disease Alliance Guidelines for the management of absolute cardiovascular disease risk.2012: 124https://strokefoundation.com.auGoogle Scholar, 11Abbott A.L. Medical (nonsurgical) intervention alone is now best for prevention of stroke associated with asymptomatic severe carotid stenosis: results of a systematic review and analysis.Stroke. 2009; 40: e573-e583Crossref PubMed Scopus (553) Google Scholar However, a notable limitation of this clinical risk factor approach is that mis-classification of actual risk may occur.1Giannoukas A. Chadbok M. Spanos K. Nicolaides A. Screening for asymptomatic carotid plaques with ultrasound.Eur J Vasc Endovasc Surg. 2016; 52: 309-312Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Atherosclerosis imaging allows direct visualisation of the cumulative effect of all risk factors, measurable and unmeasurable, in an individual.12Blaha M.J. The future of CV risk prediction: multisite imaging to predict multiple outcomes.JACC Cardiovasc Imaging. 2014; 7: 1054-1056Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar However, the role of imaging information in improving outcomes compared with the traditional clinical risk factor approach is particularly unclear in the context of modern primary prevention. The most popular arterial imaging methods for screening and risk stratification studies have been noninvasive and favoured readily accessible sites. Ultrasound detection of carotid plaques is much more predictive of future heart attack or stroke than carotid intima-medial thickness.13Sillesen H. Carotid intima-media thickness and/or carotid plaque: what is relevant?.Eur J Vasc Endovasc Surg. 2014; 48: 115-117Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar Using a three-dimensional bilateral approach to calculate total carotid plaque burden, ultrasound has been found to be comparable to a coronary artery calcium (CAC) score in predicting future major arterial disease complications, while avoiding radiation.14Baber U. Mehran R. Sartori S. Schoos M.M. Sillesen H. Muntendam P. et al.Prevalence, impact, and predictive value of detecting subclinical coronary and carotid atherosclerosis in asymptomatic adults: the BioImage study.J Am Coll Cardiol. 2015; 65: 1065-1074Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar Increasing plaque severity or volume correlates with increasing risk of major arterial disease complications, and detection of plaques at multiple sites is more predictive than detection from one site.14Baber U. Mehran R. Sartori S. Schoos M.M. Sillesen H. Muntendam P. et al.Prevalence, impact, and predictive value of detecting subclinical coronary and carotid atherosclerosis in asymptomatic adults: the BioImage study.J Am Coll Cardiol. 2015; 65: 1065-1074Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, 15Furberg C.D. Adams Jr., H.P. Applegate W.B. Byington R.P. Espeland M.A. Hartwell T. et al.Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) research group.Circulation. 1994; 90: 1679-1687Crossref PubMed Scopus (841) Google Scholar, 16Belcaro G. Nicolaides A.N. Ramaswami G. Cesarone M.R. De Sanctis M. Incandela L. et al.Carotid and femoral ultrasound morphology screening and cardiovascular events in low risk subjects: a 10-year follow-up study (the CAFES-CAVE study(1)).Atherosclerosis. 2001; 156: 379-387Abstract Full Text Full Text PDF PubMed Scopus (243) Google Scholar, 17Detrano R. Guerci A.D. Carr J.J. Bild D.E. Burke G. Folsom A.R. et al.Coronary calcium as a predictor of coronary events in four racial or ethnic groups.N Engl J Med. 2008; 358: 1336-1345Crossref PubMed Scopus (2121) Google Scholar Of concern, imaging often reveals the presence of atheroma in asymptomatic adults, including those with low FRS.14Baber U. Mehran R. Sartori S. Schoos M.M. Sillesen H. Muntendam P. et al.Prevalence, impact, and predictive value of detecting subclinical coronary and carotid atherosclerosis in asymptomatic adults: the BioImage study.J Am Coll Cardiol. 2015; 65: 1065-1074Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, 16Belcaro G. Nicolaides A.N. Ramaswami G. Cesarone M.R. De Sanctis M. Incandela L. et al.Carotid and femoral ultrasound morphology screening and cardiovascular events in low risk subjects: a 10-year follow-up study (the CAFES-CAVE study(1)).Atherosclerosis. 2001; 156: 379-387Abstract Full Text Full Text PDF PubMed Scopus (243) Google Scholar, 18Fernandez-Friera L. Penalvo J.L. Fernandez-Ortiz A. Ibanez B. Lopez-Melgar B. Laclaustra M. et al.Prevalence, vascular distribution, and multiterritorial extent of subclinical atherosclerosis in a middle-aged cohort: the PESA (Progression of Early Subclinical Atherosclerosis) Study.Circulation. 2015; 131: 2104-2113Crossref PubMed Scopus (274) Google Scholar, 19Laclaustra M. Casasnovas J.A. Fernandez-Ortiz A. Fuster V. Leon-Latre M. Jimenez-Borreguero L.J. et al.Femoral and carotid subclinical atherosclerosis association with risk factors and coronary calcium: the AWHS Study.J Am Coll Cardiol. 2016; 67: 1263-1274Crossref PubMed Scopus (129) Google Scholar Further, in prospective cohort studies it has been shown that adding arterial imaging (carotid ultrasound or CAC) to Framingham clinical risk factors results in more accurate prediction of future major arterial disease complications.14Baber U. Mehran R. Sartori S. Schoos M.M. Sillesen H. Muntendam P. et al.Prevalence, impact, and predictive value of detecting subclinical coronary and carotid atherosclerosis in asymptomatic adults: the BioImage study.J Am Coll Cardiol. 2015; 65: 1065-1074Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, 17Detrano R. Guerci A.D. Carr J.J. Bild D.E. Burke G. Folsom A.R. et al.Coronary calcium as a predictor of coronary events in four racial or ethnic groups.N Engl J Med. 2008; 358: 1336-1345Crossref PubMed Scopus (2121) Google Scholar For instance, in the Bioimage study of approximately 5,800 asymptomatic adults, overall, 25% and 23%, respectively, of individuals were reclassified with respect to future risk when CAC or carotid plaque burden were combined with “category-free” FRS.14Baber U. Mehran R. Sartori S. Schoos M.M. Sillesen H. Muntendam P. et al.Prevalence, impact, and predictive value of detecting subclinical coronary and carotid atherosclerosis in asymptomatic adults: the BioImage study.J Am Coll Cardiol. 2015; 65: 1065-1074Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, 20Pencina M.J. D'Agostino Sr., R.B. Steyerberg E.W. Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers.Stat Med. 2011; 30: 11-21Crossref PubMed Scopus (1746) Google Scholar Of particular note, approximately 50% of those with intermediate FRS were reclassified as low or high risk on the basis of either imaging modality.14Baber U. Mehran R. Sartori S. Schoos M.M. Sillesen H. Muntendam P. et al.Prevalence, impact, and predictive value of detecting subclinical coronary and carotid atherosclerosis in asymptomatic adults: the BioImage study.J Am Coll Cardiol. 2015; 65: 1065-1074Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, 21Paynter N.P. Cook N.R. A bias-corrected net reclassification improvement for clinical subgroups.Med Decis Making. 2013; 33: 154-162Crossref PubMed Scopus (27) Google Scholar Question is, what should be done with such information from arterial imaging? Our evidence base regarding what works to reduce the risk of arterial disease complications is based on the definition, identification and treatment of clinically (not imaging) defined risk factors with lifestyle advice and medication. Therefore, how is it possible to improve the outcome of persons with the lowest Framingham risk with what would currently be considered “normal” or optimal blood pressure, cholesterol and sugar levels, and who are nonsmokers, even if the presence of plaque indicates high risk of future complications? Conversely, those with high FRS will have at least several clinical risk factors and some may have no plaque. It would currently be unethical to deny them medication and lifestyle advice because past studies of benefit are based on the presence and treatment of clinical risk factors. Meanwhile, those with intermediate FRS may now qualify for statins, or other medications, given change in medical treatment standards, including more “global” approaches to risk stratification. It is acknowledged that large (n > 900) placebo-controlled, randomised studies of asymptomatic people (at least free of past stroke or MI,22Downs J.R. Clearfield M. Weis S. Whitney E. Shapiro D.R. Beere P.A. et al.Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TEXCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study.JAMA. 1998; 279: 1615-1622Crossref PubMed Scopus (4994) Google Scholar, 23Colhoun H.M. Betteridge D.J. Durrington P.N. Hitman G.A. Neil H.A. Livingstone S.J. et al.Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial.Lancet. 2004; 364: 685-696Abstract Full Text Full Text PDF PubMed Scopus (3259) Google Scholar, 24Nakamura H. Arakawa K. Itakura H. Kitabatake A. Goto Y. Toyota T. et al.Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA study): a prospective randomised controlled trial.Lancet. 2006; 368: 1155-1163Abstract Full Text Full Text PDF PubMed Scopus (738) Google Scholar, 25Everett B.M. Glynn R.J. MacFadyen J.G. Ridker P.M. Rosuvastatin in the prevention of stroke among men and women with elevated levels of C-reactive protein: Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER).Circulation. 2010; 121: 143-150Crossref PubMed Scopus (135) Google Scholar and sometimes with ultrasound evidence of plaque15Furberg C.D. Adams Jr., H.P. Applegate W.B. Byington R.P. Espeland M.A. Hartwell T. et al.Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) research group.Circulation. 1994; 90: 1679-1687Crossref PubMed Scopus (841) Google Scholar) demonstrated that statins lower the risk of future arterial disease complications. However, recommended indications for statins have liberalised. The average male in all these studies would now easily qualify for moderate-to-high-intensity statin treatment given current American College of Cardiology (ACC)/American Heart Association (AHA) guidelines because their estimated 10-year risk of major arterial disease complications (from aggregated scoring of multiple clinical risk factors) is > 7.5%.6Stone N.J. Robinson J. Lichtenstein A.H. Merz C.N. Blum C.B. Eckel R.H. et al.2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines.Circulation. 2014; 129: S1-S45Crossref PubMed Scopus (3095) Google Scholar Although the average woman in most of these studies had an estimated 10-year risk of < 7.5%, statin therapy is now also endorsed depending on a low-density lipoprotein cholesterol level ≥ 160 mg/dL (≥ 4.1 mmol/L), a family history of premature arterial disease, a high sensitivity C-reactive protein level ≥ 2, CAC score ≥ 300 Agatston units or ≥ 75th percentile for age, sex or ethnicity, an ankle–brachial index (ABI) < 0.9 or an “elevated lifetime risk” of stroke, coronary or peripheral vascular disease (undefined).6Stone N.J. Robinson J. Lichtenstein A.H. Merz C.N. Blum C.B. Eckel R.H. et al.2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines.Circulation. 2014; 129: S1-S45Crossref PubMed Scopus (3095) Google Scholar The validity of such guideline recommendations is a topic for separate analysis. Meanwhile, recruitment to major CAC studies of asymptomatic/mostly asymptomatic persons occurred at least 10 and up to 26 years ago and are now outdated given change in medical knowledge since then.17Detrano R. Guerci A.D. Carr J.J. Bild D.E. Burke G. Folsom A.R. et al.Coronary calcium as a predictor of coronary events in four racial or ethnic groups.N Engl J Med. 2008; 358: 1336-1345Crossref PubMed Scopus (2121) Google Scholar, 26Kondos G.T. Hoff J.A. Sevrukov A. Daviglus M.L. Garside D.B. Devries S.S. et al.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: 2571-2576Crossref PubMed Scopus (660) Google Scholar, 27Greenland P. LaBree L. Azen S.P. Doherty T.M. Detrano R.C. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals.JAMA. 2004; 291: 210-215Crossref PubMed Scopus (1484) Google Scholar, 28Arad 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: 158-165Abstract Full Text Full Text PDF PubMed Scopus (854) Google Scholar, 29Taylor 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: 807-814Abstract Full Text Full Text PDF PubMed Scopus (522) Google Scholar, 30Vliegenthart R. Oudkerk M. Hofman A. Oei H.H. van Dijck W. van Rooij F.J. et al.Coronary calcification improves cardiovascular risk prediction in the elderly.Circulation. 2005; 112: 572-577Crossref PubMed Scopus (437) Google Scholar, 31LaMonte M.J. FitzGerald S.J. Church T.S. Barlow C.E. Radford N.B. Levine B.D. et al.Coronary artery calcium score and coronary heart disease events in a large cohort of asymptomatic men and women.Am J Epidemiol. 2005; 162: 421-429Crossref PubMed Scopus (264) Google Scholar Further, these studies generally focused on the coronary circulation, particularly in men. Nevertheless, where sufficient information about baseline prevalence of clinical risk factors was given,17Detrano R. Guerci A.D. Carr J.J. Bild D.E. Burke G. Folsom A.R. et al.Coronary calcium as a predictor of coronary events in four racial or ethnic groups.N Engl J Med. 2008; 358: 1336-1345Crossref PubMed Scopus (2121) Google Scholar, 27Greenland P. LaBree L. Azen S.P. Doherty T.M. Detrano R.C. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals.JAMA. 2004; 291: 210-215Crossref PubMed Scopus (1484) Google Scholar it can be seen that the average male in two of these studies would now easily qualify for moderate-to-high-intensity statin treatment, independently of their CAC score, using 2013 ACC/AHA 10-year risk estimates.6Stone N.J. Robinson J. Lichtenstein A.H. Merz C.N. Blum C.B. Eckel R.H. et al.2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines.Circulation. 2014; 129: S1-S45Crossref PubMed Scopus (3095) Google Scholar While in another study (where the mean baseline age was 43 years), the participants would not easily qualify because the 10-year risk would be < 7.5%.6Stone N.J. Robinson J. Lichtenstein A.H. Merz C.N. Blum C.B. Eckel R.H. et al.2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines.Circulation. 2014; 129: S1-S45Crossref PubMed Scopus (3095) Google Scholar, 28Arad 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: 158-165Abstract Full Text Full Text PDF PubMed Scopus (854) Google Scholar However, it was not shown in this study that prescribing statins, or any other intervention, improved patient outcome.28Arad 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: 158-165Abstract Full Text Full Text PDF PubMed Scopus (854) Google Scholar Further, ideally, CAC testing will be replaced by safer methods.14Baber U. Mehran R. Sartori S. Schoos M.M. Sillesen H. Muntendam P. et al.Prevalence, impact, and predictive value of detecting subclinical coronary and carotid atherosclerosis in asymptomatic adults: the BioImage study.J Am Coll Cardiol. 2015; 65: 1065-1074Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, 19Laclaustra M. Casasnovas J.A. Fernandez-Ortiz A. Fuster V. Leon-Latre M. Jimenez-Borreguero L.J. et al.Femoral and carotid subclinical atherosclerosis association with risk factors and coronary calcium: the AWHS Study.J Am Coll Cardiol. 2016; 67: 1263-1274Crossref PubMed Scopus (129) Google Scholar Investigators need to demonstrate how plaque imaging (and ABI, an indicator of stenosing plaque32Sillesen H. Falk E. Why not screen for subclinical atherosclerosis?.Lancet. 2011; 378: 645-646Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar) improves recipient outcome independently of treating clinical risk factors in the context of all current available scientific evidence (despite variability in risk estimates using different models),33Mortensen M.B. Falk E. Real-life evaluation of European and American high-risk strategies for primary prevention of cardiovascular disease in patients with first myocardial infarction.BMJ Open. 2014; 4: e005991Crossref Scopus (24) Google Scholar that the strategy is cost-effective, and that no better risk stratification methods exist. This has not yet been achieved.34Greenland P. Alpert J.S. Beller G.A. Benjamin E.J. Budoff M.J. Fayad Z.A. et al.2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines.Circulation. 2010; 122: e584-e636Crossref PubMed Scopus (542) Google Scholar, 35Piepoli M.F. Hoes A.W. Agewall S. Albus C. Brotons C. Catapano A.L. et al.2016 European guidelines on cardiovascular disease prevention in clinical practice: the sixth joint task force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice: developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR).Eur Heart J. 2016 May 23; (pii: ehw106 [Epub ahead of print])Google Scholar Hence, calls for routine CAC testing, or other imaging, are premature, particularly for asymptomatic persons.6Stone N.J. Robinson J. Lichtenstein A.H. Merz C.N. Blum C.B. Eckel R.H. et al.2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines.Circulation. 2014; 129: S1-S45Crossref PubMed Scopus (3095) Google Scholar, 34Greenland P. Alpert J.S. Beller G.A. Benjamin E.J. Budoff M.J. Fayad Z.A. et al.2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines.Circulation. 2010; 122: e584-e636Crossref PubMed Scopus (542) Google Scholar In conclusion, although we know that imaging evidence of “subclinical” atherosclerosis is an independent risk factor for future adverse events, we are not yet ready to routinely screen asymptomatic individuals because we do not know if, or how, imaging results can be used to improve outcomes compared with only targeting clinical risk factors. The risk and cost of screening must also be considered. This includes the direct complications of testing (e.g., precipitating cerebral ischaemic events or causing radiation ill-effects),12Blaha M.J. The future of CV risk prediction: multisite imaging to predict multiple outcomes.JACC Cardiovasc Imaging. 2014; 7: 1054-1056Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 36Friedman S.G. Transient ischemic attacks resulting from carotid duplex imaging.Surgery. 1990; 107: 153-155PubMed Google Scholar discovery of incidental “lesions”,12Blaha M.J. The future of CV risk prediction: multisite imaging to predict multiple outcomes.JACC Cardiovasc Imaging. 2014; 7: 1054-1056Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar inaccurate screening results,37LeFevre M.L. U.S. Preventive Services Task ForceScreening for asymptomatic carotid artery stenosis: U.S. Preventive services task force recommendation statement.Ann Int Med. 2014; 161: 356-362Crossref PubMed Scopus (89) Google Scholar and inappropriate management (e.g., surgery or stenting for asymptomatic carotid stenosis—a now “outmoded” strategy).1Giannoukas A. Chadbok M. Spanos K. Nicolaides A. Screening for asymptomatic carotid plaques with ultrasound.Eur J Vasc Endovasc Surg. 2016; 52: 309-312Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 11Abbott A.L. Medical (nonsurgical) intervention alone is now best for prevention of stroke associated with asymptomatic severe carotid stenosis: results of a systematic review and analysis.Stroke. 2009; 40: e573-e583Crossref PubMed Scopus (553) Google Scholar, 37LeFevre M.L. U.S. Preventive Services Task ForceScreening for asymptomatic carotid artery stenosis: U.S. Preventive services task force recommendation statement.Ann Int Med. 2014; 161: 356-362Crossref PubMed Scopus (89) Google Scholar, 38Abbott A.L. Adelman M.A. Alexandrov A.V. Barber P.A. Barnett H.J. Beard J. et al.Why calls for more routine carotid stenting are currently inappropriate: an international, multispecialty, expert review and position statement.Stroke. 2013; 44: 1186-1190Crossref PubMed Scopus (49) Google Scholar It is time to call for the studies we need to see if, and how, detection of “subclinical” atheromatous disease can improve outcomes. These studies must be performed in the context of modern clinical risk factor definitions and proven therapies (which have evolved significantly).11Abbott A.L. Medical (nonsurgical) intervention alone is now best for prevention of stroke associated with asymptomatic severe carotid stenosis: results of a systematic review and analysis.Stroke. 2009; 40: e573-e583Crossref PubMed Scopus (553) Google Scholar These studies must distinguish asymptomatic patients from asymptomatic arteries and consider all proven, modifiable risk factors an individual has plus their risk of any major arterial disease complication. Such studies are ethical because they involve comparisons of new imaging-based approaches with status quo routine practice—one centred on clinical risk factors. For instance, does arterial imaging encourage better identification and modification of clinical risk factors? Should imaging change our definitions of clinical risk factors or treatment standards? How can plaque imaging be used to better personalise medicine and reduce overservicing?32Sillesen H. Falk E. Why not screen for subclinical atherosclerosis?.Lancet. 2011; 378: 645-646Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar, 39Blaha M.J. Cainzos-Achirica M. Greenland P. McEvoy J.W. Blankstein R. Budoff M.J. et al.Role of coronary artery calcium score of zero and other negative risk markers for cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis (MESA).Circulation. 2016; 133: 849-858Crossref PubMed Scopus (266) Google Scholar Can we use plaque imaging to identify currently unknown modifiable risk factors? How do we best treat arteries rather than clinical risk factors?40Spence J.D. Hackam D.G. Treating arteries instead of risk factors: a paradigm change in management of atherosclerosis.Stroke. 2010; 41: 1193-1199Crossref PubMed Scopus (120) Google Scholar Do serial scans improve patient compliance?1Giannoukas A. Chadbok M. Spanos K. Nicolaides A. Screening for asymptomatic carotid plaques with ultrasound.Eur J Vasc Endovasc Surg. 2016; 52: 309-312Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar If so, what is the optimal imaging method and frequency and in which individuals given heterogeneity in atherosclerosis distribution and variable plaque location for best predicting different complications?12Blaha M.J. The future of CV risk prediction: multisite imaging to predict multiple outcomes.JACC Cardiovasc Imaging. 2014; 7: 1054-1056Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 16Belcaro G. Nicolaides A.N. Ramaswami G. Cesarone M.R. De Sanctis M. Incandela L. et al.Carotid and femoral ultrasound morphology screening and cardiovascular events in low risk subjects: a 10-year follow-up study (the CAFES-CAVE study(1)).Atherosclerosis. 2001; 156: 379-387Abstract Full Text Full Text PDF PubMed Scopus (243) Google Scholar, 18Fernandez-Friera L. Penalvo J.L. Fernandez-Ortiz A. Ibanez B. Lopez-Melgar B. Laclaustra M. et al.Prevalence, vascular distribution, and multiterritorial extent of subclinical atherosclerosis in a middle-aged cohort: the PESA (Progression of Early Subclinical Atherosclerosis) Study.Circulation. 2015; 131: 2104-2113Crossref PubMed Scopus (274) Google Scholar How often do totally asymptomatic patients with subclinical atheroma have signs of symptomatic or silent myocardial ischaemia on cardiac exercise testing and how can their outcome be best improved?1Giannoukas A. Chadbok M. Spanos K. Nicolaides A. Screening for asymptomatic carotid plaques with ultrasound.Eur J Vasc Endovasc Surg. 2016; 52: 309-312Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar These are the kinds of pioneering questions to be addressed to create worthwhile applications for routine screening for “subclinical” atherosclerosis. Improved risk stratification does not necessarily mean improved patient outcomes. ALA is a neurologist and receives a part-time salary from the Bupa Health Foundation to continue independent activities to improve outcomes for patients with carotid arterial disease. Screening for Asymptomatic Carotid Plaques with UltrasoundEuropean Journal of Vascular and Endovascular SurgeryVol. 52Issue 3PreviewAtherosclerotic cardiovascular disease (CVD), especially coronary heart disease (CHD), remains the leading cause of premature death worldwide.1 Regrettably, CVD killed 17.5 million people in 2012, which accounts for 3 in every 10 deaths. Of these, 7.4 million people died of ischemic heart disease and 6.7 million from stroke.2 CVD affects both men and women and of all deaths that occur before the age of 75 in Europe, 42% are caused by CVD in women and 38% in men.1 Full-Text PDF Open Archive
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