The Role of Carotid Intima-Media Thickness (IMT) in Cardiovascular ...


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The Role of Carotid Intima-Media Thickness (IMT) in Cardiovascular ...

  1. 1. Screening for Early Detection and Treatment of Asymptomatic Atherosclerotic PatientsCarotid Intima Media Thickness (CIMT) <br />Daniel H. O’Leary, M.D.<br />
  2. 2. Presenter Disclosure Information<br />Disclosure Information...<br />The following relationships exist related to this presentation:<br />Daniel H. O’Leary, M.D.<br /> - Serves as a consultant to Sanofi-Aventis and AstraZenica<br /> - Owns stock in Medpace, Inc.<br />
  3. 3. Ultrasound measurement of CIMT<br />probe<br />carotid bulb<br />internal carotid artery<br />common carotid artery<br />blood flow<br />carotid dilatation<br />carotid flow<br />divider<br />external carotid artery<br />
  4. 4. CIMT<br />Thin IMT in CCA<br /><ul><li>Thicker IMT in CCA</li></li></ul><li>Near and Far Wall Identification<br />
  5. 5. Some of the major epidemiology studies linking CIMT and incident CVD endpoints<br />Chambless et al. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis in Risk in Communities (ARIC) Study, 1987-1993. Am J Epidemiol 1997;146:483-494<br />Bots et al. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation 1997;96:1432-1437<br />O’Leary et al. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults: the Cardiovascular Health Study. N Engl J Med 1999;340:14-22 <br />Lorenz MW, et al. Carotid Intima-Media Thickening Indicates a Higher Vascular Risk Across a Wide Age Range: Prospective Data from the Carotid Atherosclerosis Study (CAPS) Stroke 2006;37:87<br />(Pignoli P, Tremoli E, Poli A, Paoletti R. Circulation 1986; 74:1399)<br />
  6. 6. Cardiovascular Health Study: Baseline CIMT Predictive of CHD<br />4,476 subject without CHD at baseline<br />Median follow-up 6.2 yrs<br />RR of stroke/MI for highest vs. lowest CIMT quintile was 3.87<br />100<br />95<br />1st Quintile<br />2nd Quintile<br />90<br />3rd Quintile<br />Cumulative Event-free Rate (%)<br />85<br />4th Quintile<br />80<br />75<br />5th Quintile<br />70<br />Years<br />O’Leary et al, N Engl J Med. 1999;340:14-22<br />
  7. 7. Summation of the major studies assessing the value of CIMT in assessing individual risk<br />Meta-analysis involving eight relevant studies representing 37259 subjects<br />Age- and sex-adjusted relative risk of MI was 1.26 per one SD CCA-IMT difference and 1.15 per 0.10mm CCA-IMT difference<br />Age- and sex-adjusted relative risk of stroke was 1.32 per one SD CCA-IMT difference and 1.18 per 0.10mm CCA-IMT difference<br />Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events using carotid intima-media thickness: a systematic review and meta-analysis. Circulation 2007;106:459-467<br />
  8. 8. Hazard ratios for incident CVD event in relation to quartiles of CIMT or CAC in MESA<br /><ul><li>Measure HR
  9. 9. <50th percentile 3rd quartile 4th quartile
  10. 10. age, race, sex-adjusted
  11. 11. CIMT 1.0 1.4 2.2
  12. 12. CAC score 1.0 2.6 5.3</li></ul>Folsom AR, Kronmal RA, Detrano RC, O’Leary DH, et al. Coronary artery calcium compared with carotid intima-media thickness in prediction of cardiovascular disease incidence: the Multi-Ethnic Study of Atherosclerosis (MESA). Arch Intern Med 2008;168:1333-1339<br />
  13. 13. At 4.5 yrs, % remaining alive are:<br />At 4.5 yrs, % remaining alive are:<br />87%<br />84%<br />78%<br />72%<br />85%<br />82%<br />79%<br />75%<br />Newman AB, Naydeck BL, Ives DG, Boudreau RM, Sutton-Tyrrell K, O’Leary DH, Kuller LH. Coronary artery calcium, carotid artery wall thickness, and CVD outcomes in adults 70 to 90 years old. Am J Cardiol 2008; 101:186-192<br />CVD events by coronary artery calcium and internal carotid wall thickness quartiles in CHS<br />
  14. 14. IMT Definition of Plaque<br />a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value<br />or<br />a thickness > 1.5 mm as measured from the media-adventia interface to the intima-lumen interface<br /> Mannheim Carotid Intima-Media Thickness Consensus (2004-2006). CerebrovascDis2007;23:75-80<br />
  15. 15. Ultrasound Reading Center for the following NIH-sponsored studies <br />CHS (Cardiovascular Health Study)<br /> > 5000 X 3 visits (1989, 1993, 1997)<br />IRAS (Insulin Resistance in Atherosclerosis)<br /> 1625 in 1992, 1192 in 1997<br />EDIC (Epidemiology of Diabetes Interventions and Complications<br />1375 in 1994, 1229 in 1998, 1189 in 2006<br />Framingham Heart Study Offspring cohort<br /> 3252 in 1995-98, 3100 in 2005-07<br />MESA (Multi-Ethnic Study of Atherosclerosis)<br /> >6200 in 2000, ½ in 2002, ½ in 2004, ¼ in 2006<br />CARDIA (Cardiovascular Risk Development in young Adults)<br /> 3244 in 2004<br />
  16. 16. Several informed generalizations<br />Plaque characterization is of no value in managing individual patients <br />Sequential ultrasound examinations are of no value in assessing therapeutic response in individuals<br />TPA (Total Plaque Area) measurements are of unclear value to me – need large prospective multicenter studies linked to outcomes<br />
  17. 17. Are there subsets of the population where the value added by bio-imaging could be shown to be cost-effective?<br />Goal is to identify and treat persons at high risk for CVD<br />Treating major CVD risk factors for 1° and 2° prevention works and guidelines support this<br />Framingham risk scores that predict a 10-20% risk of CHD over 10 years are considered at “intermediate risk”, and those with greater risk, at “high risk”<br />Minority of persons who develop CVD are at “high risk”<br />There are 23 million in US population at intermediate risk, having approximately 30,000 CVD events annually<br />There is a paucity of information on effectiveness of screening and treating asymptomatic CHD<br />
  18. 18. Recommendations for screening<br />AHA Prevention V (Greenland et al., Circ. 2000) persons at intermediate risk may be suitable for screening by noninvasive tests, including ABI and carotid US, for those over age 50 years<br />Task force 4, 34th Bethesda Conference (Wilson et al., JACC 2003; 41: 1898-1905) patients at intermediate risk for total CHD event possibly warrant further risk stratification by noninvasive tests to assess atherosclerotic burden<br />ACCF/AHA 2007 clinical expert consensus document on coronary artery scoring by CT on global risk assessment (Greenland et al. J Am CollCardiol 2007) stated it reasonable to obtain CAC in asymptomatic patients with intermediate CHD risk, based on possibility of reclassification to a higher risk status and altered medical management<br />
  19. 19. Consensus statement from the American Society of Echocardiography CIMT Task Force<br />CIMT measurements of far wall CCA only<br />Scan extracranial carotid arteries (CCA, bulb, ICA) for presence of focal plaque<br />Presence of plaque or far wall CCA CIMT greater or equal to the 75th percentile for the patient’s age, sex, and race/ethnicity are indicative of increased CVD risk and may signify the need for more aggressive risk reductions<br />Serial studies of CIMT to address progression or regression are not recommended<br />Stein JH et al. J American Society of Echocardiography 2008;21:93-111<br />
  20. 20. Low<br />Middle<br />High<br />Subclinical Disease Testing and Risk of Disease<br />40<br />Identity Line<br />Positive test stratifies risk upward<br />30<br />Post testing<br />Probability (%)<br />20<br />Negative test does not stratify risk downward<br />10<br />0<br />0<br />10<br />20<br />30<br />40<br />Initial Probability (%)<br />Slide courtesy N Wong (modified by DOL)<br />
  21. 21. The First SHAPE (Screening for Heart Attack Prevention and Education) Guideline<br />Goal to address major shortcoming in existing guidelines in primary prevention of CVD<br />Most heart attacks and strokes occur in people not classified as high risk and thus not aggressively treated<br />Concept that “vulnerable patient” can be identified by bio-imaging rather than screening for risk factors<br />Recommends non-invasive screening of all asymptomatic men 45-75 yrs and asymptomatic women 55-75 yrs (except those defined as very low risk) using either CT or ultrasound as initial test<br />Naghavi et al. Am J Cardiol 2006;98:2H-15H<br />
  22. 22.
  23. 23. How early in life should we be treating individuals to lessen their risk of CVD?<br />“Let the cholesterol fight begin , at age 8” – headline in USA TODAY, July 8, 2008<br />“Strongest guidance ever given on the issue by the American Academy of Pediatrics”<br />“The new advice is based on mounting evidence showing that damage leading to heart disease begins early in life, as well as research showing that cholesterol-fighting drugs are generally safe for children”<br />CIMT correlates better with previously measured risk factors than with those measured concurrently<br />
  24. 24. What do the payers say?<br />Most payers have declared CIMT experimental and not medically indicated<br />Medicare: Category III CPT code 0126T<br />Category III codes apply to new technologies and are not reimbursed by many payers<br />Usual rationale is that there are no convincing studies linking CIMT measurement to improved clinical outcomes<br />
  25. 25. In conclusion, I<br />Would not screen patients >65 years of age<br />Would not screen patients at either high risk or low risk<br />Would not rank Atherosclerosis Test as Step 1<br />Would wait at least 5 years before considering repeat AT<br />Would ask – how many subjects will be reclassified because of AT? How many new patients will be treated, what will be the impact on outcomes, and at what cost?<br />Would focus on early life intervention for a disease that is present decades prior to diagnosis by any imaging test <br />