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  1. 1. Predictive Role of CarotidPredictive Role of Carotid Intima-Media ThicknessIntima-Media Thickness Tasneem Z Naqvi MD, FRCP, FACC, FASE, RVT Associate Professor of Clinical Medicine UCLA Cedars-Sinai Medical Center Los Angeles, CA
  2. 2. How Good Is NCEP III At Predicting MI?How Good Is NCEP III At Predicting MI? JACC 2003:41 1475-9JACC 2003:41 1475-9 (Slide from J. Rumberger)(Slide from J. Rumberger) 222 patients with 1222 patients with 1stst acute MI, no prior CADacute MI, no prior CAD men <55 y/o (75%), women <65 (25%), no DMmen <55 y/o (75%), women <65 (25%), no DMQualify for RxQualify for Rx Not-Qualify for RxNot-Qualify for Rx RiskRisk >20%/>20%/ 10 yrs.10 yrs. RiskRisk 10-20%/10-20%/ 10 yrs.10 yrs. RiskRisk <10%/<10%/ 10 yrs.10 yrs. NCEP GoalNCEP Goal LDL<100LDL<100 NCEP GoalNCEP Goal LDL<160LDL<160 NCEP GoalNCEP Goal LDL<130LDL<130 6%6% 6%6% TotalTotal 12%12% 8%8% 10%10% TotalTotal 18%18% 61%61% 9%9% TotalTotal 70%70% 88% of these “young” patients who suffered a88% of these “young” patients who suffered a first Myocardial Infarction were in thefirst Myocardial Infarction were in the Low to Intermediate “risk” category accordingLow to Intermediate “risk” category according To Framingham Risk AssessmentTo Framingham Risk Assessment andand would have been missed as trulywould have been missed as truly ““High Risk” individuals who shouldHigh Risk” individuals who should have been treated “aggressively”have been treated “aggressively”
  3. 3. CHDCHD RISK IN WOMEN - FRAMINGHAM SCORINGRISK IN WOMEN - FRAMINGHAM SCORING (FRS) - 10 y(FRS) - 10 y Age, y HDL cholesterol < 35 -9 ≥ 60 -3 35-39 -4 50-59 0 40-44 0 45-49 1 45-49 3 35-44 2 50-54 6 < 35 5 55-59 7 Syst BP 60-64 8 < 120 -3 65-69 8 120-129 0 70-74 8 130-139 1 Cholesterol 140-149 2 < 160 -2 > 160 3 169-199 0 Diabetes 200-239 1 No 0 240-279 2 Yes 4 ≥ 280 3 Smoking No 0 Yes 2 Points 0 1 2 3 4 5 6 7 8 9 10 11 12 13 >14 Total CHD (%) 2 3 4 5 7 8 10 13 16 20 25 31 37 45 > 53 Hard CHD (%) 2 2 3 4 5 6 7 9 13 16 20 25 30 35 > 45 Grundy SM, Pasternak R, Greenland P, Smith S, Fuster V, Circ 1999; 100:1481 ATP III - Aggressive Rx: Framingham, Diabetes, Metab. Synd: obese, BP, HDL, TC, Gluc - Physical inactivity JAMA 2001; 285:2475
  4. 4. Age as a Risk Factor: You Are asAge as a Risk Factor: You Are as Old asOld as Your ArteriesYour Arteries Both EBCT and carotid sonography offer the opportunity to modify the age factor according to direct measurements of plaque burden Grundy SM. Am J Cardiol 1999;83:1455-1457
  5. 5. Cohn JN and McVeigh GE et al The Pathogenesis of CardiovascularThe Pathogenesis of Cardiovascular DiseaseDisease
  6. 6. Arterial Segments CommonlyArterial Segments Commonly Involved in AtherosclerosisInvolved in Atherosclerosis Courtesy Ward Riley, MD
  7. 7. Carotid Artery WallCarotid Artery Wall Intima-Media-AdventitiaIntima-Media-Adventitia Intima Media Adventitia Lumen 0.5cm
  8. 8. Normal Abnormal
  9. 9. CCA ICA ECA CCA bulbbulb Near wall Far wall Intima Media Adventitia Intima Media Adventitia Normal and Abnormal Carotid Intima-Media Thickness
  10. 10. Association of IMT and Plaque withAssociation of IMT and Plaque with Risk FactorsRisk Factors Edinburgh Artery Study, UK 1156 60-79 0.79, 0.85 IMT: Fibrinogen, blood viscosity in men Vascular Aging (EVA) Study 1271 59-71 0.65, 0.69 IMT & plaque: age, SBP, cholesterol, DM Bruneck Study, Italy 888 40-79 --------- Plaque: age, SBP, DBP, LDL cholesterol, insulin. Rotterndam Study, Netherlands1000+ 69 0.76, 0.81 IMT: age, SBP, BMI (men), smoking (men) Suita Study, Japan 1445 50-79 0.89, 0.92 IMT & plaque: age, SBP, smoking (men) cholesterol, glucose San Daniele Project, Italy 1348 18-99 --------- IMT & plaque: age, BP, smoking, alcohol, HDL Cardiovascular Health Study 5176 65+ 0.96, 1.04 IMT: age, SBP, smoking, cholesterol, DM Atherosclerosis Risk in Comm. 772, 12841 45-64 0.60, 0.66 IMT & plaque: age, SBP, DBP, BMI smoking, cholesterol, income, education Kourpio Ischaemic Heart 1224 42-60 -------- IMT & plaque: age, DM, SBP, smoking, LDL, Disease (KIHD) h/o IHD, serum copper, education, income, manual occupation MONICA Project, Germany 1338 25-65 -------- Plaque in men: age, cholesterol, DM, h/o IHD Seven Countries Study, 182 70-89 1.5 Plaque: smoking and cholesterol Finland Study N Age IMTccaM Associations Ebrahim et al Stroke. 1999;30:841-850
  11. 11. Simon A et al. Journal of Hypertension 2002, 20:159±169
  12. 12. Paul TK: Am J Med Sci, Volume 330(3). 2005.105-110 Bogalusa Heart Study: Risk Factors and IMT in Young Adults (24-43y) 0 5 10 15 20 25 30 35 40 45 0 1 2 =>3 Bottom 5th Top 5th Number of Risk Factors Prevalence(%) IMT
  13. 13. Li, S. et al. JAMA 2003;290:2271-2276. Carotid IMT Represents Cumulative LDL-C Burden From Childhood to Adulthood (25-37 yrs)
  14. 14. Järvisalo MJ et al Circulation. 2001;104:2943-2947 16 44 28 IMT Is Associated With Risk Factors in Children
  15. 15. Eric de Groot et al Circulation. 2004;109[suppl III]:III-33–III-38 IMT Progression in Familial Hypercholesterolemia
  16. 16. Distribution of IMT in the General Population (AXA Study) Gariepy J et al Arterioscler Thromb Vasc Biol 1998; 4: 584–590 (AXA Study)
  17. 17. 0.64 0.65 0.74 0.8 0.75 0.78 0.93 0.98 0.85 0.85 1.09 1.14 0 0.2 0.4 0.6 0.8 1 1.2 1.4 LCCA RCCA L Bulb R Bulb 0.72 0.71 0.84 0.850.83 0.84 1.03 1.04 0.99 1.01 1.31 1.21 0 0.2 0.4 0.6 0.8 1 1.2 1.4 LCCA RCCA L Bulb R Bulb 0.61 0.61 0.73 0.75 0.71 0.71 0.88 0.91 0.81 0.93 1.09 1.16 0 0.2 0.4 0.6 0.8 1 1.2 1.4 LCCA RCCA L Bulb R Bulb 0.7 0.66 0.82 0.66 0.8 0.77 1.06 0.77 0.93 0.9 1.23 0.9 0 0.2 0.4 0.6 0.8 1 1.2 1.4 LCCA RCCA L Bulb R Bulb Bar graph of 75th percentiles of common carotid artery and carotid artery bifurcation IMT in men and women stratified according to decade of age (45 yrs green, 55 yrs dark blue, 65 years light blue and race. Adapted from Howard G, et al Stroke 1993; 24:1297-1304.). Black Women (n=2219) Black Men (n=1391) White Women (5377) White Men (n=4837) Carotid IMT in the General Population (ARIC)45 yrs 55 yrs 65 yrs
  18. 18. Copyright ©1995 American Heart Association Burke, G. L. et al. Stroke 1995;26:386-391 Carotid IMT and CV Disease Prevalence (ARIC Study)
  19. 19. Prevalence of Cardiovascular Disease for Specific Degrees of Carotid Atherosclerosis Lancet 2000;356:279-84 Differences in Risk Factors, Atherosclerosis and Cardiovascular Disease Between Ethnic Groups in Canada
  20. 20. Carotid IMT and Extent of Coronary Artery Disease
  21. 21. Adams MR et al Circulation 1995;92:2127-34 Carotid IMT and Prevalent Coronary Artery Disease
  22. 22. Carotid IMT/Plaque and Incident CVD in Population-Based Prospective Studies Study n (% male) Age (yrs) Follow- up (yrs) Carotid US Parameters Endpoint Results KIHD 1257 (100) 42-60 2 Normal CCA IMT >1.0 mm Non-stenotic plaque Stenotic plaque MI No increased risk with IMT>1.0 mm Plaque: RR: 4.1 (1.8-9.2) KIHD 2181 (100) 42-60 4 Same as above MI IMT >1.0 mm: RR: 2.1 (1.1-4.1)* Non-stenotic plaque: RR: 3.4 (1.9- 5.9)* Stenotic plaque: RR: 6.3 (3.1-12.6)* Chieti 2000 (56) 30-70 6 Same as above Incidence of MI, angina, CVA, PVD IMT >1.0 mm: 5.5% Plaque: 18.4% Stenotic plaque: 42% ARIC 12841 (43) 45-64 5.2 Mean IMT of 6 sites MI, CHD death IMT<1.0 mm vs. IMT≥1.0 mm Women: HRR: 2.62 (1.55-4.46)** Men: HRR: 1.20 (0.81-1.77)** Rotterdam Study 1470 (38) ≥55 2.7 SD increase in CCA IMT MI Women: OR: 1.26 (0.89-1.79)** Men: OR: 1.25 (0.91-1.72)** IMT>0.908 mm: OR: 1.44 (0.65- 3.16)** CHS 4476 (39) >65 6.2 Quintiles or SD of maximum CCA and/or ICA IMT MI, Stroke Increasing risk per quintile or SD**
  23. 23. Relation of Carotid Intima-media Thickness with CV Events in Asymptomatic Subjects Simon: J Hypertens, Volume 20(2).February 2002.159-169
  24. 24. 0 2 4 6 8 10 12 14 <0.6 0.6-0.7 0.7-0.8 0.8-1.0 >1.0 Women Men Coronary Heart Disease IncidenceCoronary Heart Disease Incidence Rates in ARIC per 1000 Person-Rates in ARIC per 1000 Person- YearsYears Adjusted for Age and Race Carotid Artery Intima-Media Thickness (mm)
  25. 25. 0 1 2 3 4 5 6 7 Women Men CIMT LDL Atherosclerosis Risk in Communities (ARIC) StudyAtherosclerosis Risk in Communities (ARIC) Study (12,800 subjects, 45-64 years of age at baseline)(12,800 subjects, 45-64 years of age at baseline) Hazard Rate Ratio (highest to lowest tertile) for a Clinical EventHazard Rate Ratio (highest to lowest tertile) for a Clinical Event within 5.2 Years of Follow-Up forwithin 5.2 Years of Follow-Up for CIMTCIMT andand LDLLDL Levels inLevels in Women and MenWomen and Men HRR
  26. 26. 1 2.17 4.15 6.71 0 1 2 3 4 5 6 7 8 Normal Thickening Plaque Stenosis Relative Hazard of a Coronary Event Events 5 6 11 2 Men at risk 608 257 386 37 Carotid IMT and Incident Cardiovascular Disease (KIHD Study)
  27. 27. The Rotterdam Study, Circulation 2004;109:1083-94 Predictive Value of Non Invasive Measures of Atherosclerosis for MI
  28. 28. Predictive of IMT in the ElderlyPredictive of IMT in the Elderly CHS StudyCHS Study O'Leary et al. 340 (1): 14, Figure 1 January 7, 1999
  29. 29. Predictive of IMT in the ElderlyPredictive of IMT in the Elderly CHS StudyCHS Study O'Leary et al. 340 (1): 14, Figure 1 January 7, 1999
  30. 30. Copyright ©1996 American Heart Association Belcaro, G. et al. Arterioscler Thromb Vasc Biol 1996;16:851-856 Percent of event-free subjects relative to each ultrasound arterial morphology class in the 6-year follow-up IMT and Incident Cardiovascular Disease
  31. 31. Prognostic Significance of Carotid and Femoral Artery Plaques in Patients with Stable Angina Held C et al. Eur Heart J, Vol. 22, issue 1, January 2001
  32. 32. Held C et al. Eur Heart J, Vol. 22, issue 1, January 2001 Prognostic Significance of Carotid and Femoral Artery Plaques in Patients with Stable Angina
  33. 33. H.N. Hodis, W.J. Mack, L. LaBree, R.H. Selzer, C.R. Liu, C.H. Liu and S.P. Azen , The role of carotid arterial intima-media thickness in predicting clinical coronary events. Ann Intern Med 128 (1998), pp. 262–269 Effect of IMT Progression
  34. 34. Copyright ©2005 American Heart Association Touboul, P.-J. et al. Stroke 2005;36:1741- 1745 Predictive Value of FCRS, IMT, and Carotid Plaques 1.68 2.16 2.73 0 0.5 1 1.5 2 2.5 3 3.5 FRS IMT Plaque
  35. 35. Meta-analysis of Mortality Associated with Abdominal Aortic Aneurysms in the Abdominal Aortic Aneurysm Screening Trials The U.S. Preventive Services Task Force (USPSTF) recommends one-time screening for abdominal aortic aneurysm by abdominal ultrasonography for men between the ages of 65 and 75 who have ever smoked
  36. 36. SignificanceSignificance ofof BaselineBaseline CIMTCIMT  From the text of the AHA Prevention Conference V Writing Group III on Noninvasive Tests of Atherosclerotic Burden: (Circulation 2000;101:e16-e22) “More than 5 published studies found that carotid IMT measurement is a viable predictor of the presence of coronary atherosclerosis and its clinical sequelae. Thus, carotid IMT defined by noninvasive B-mode ultrasound has been shown to be an independent risk factor for CHD events and stroke.”
  37. 37. Clinical Assessment of CIMTClinical Assessment of CIMT  …In asymptomatic persons >45 years old, carefully performed carotid ultrasound examinations with IMT measurement can add incremental information to traditional risk factor assessment. In experienced laboratories, this test can now be considered for further clarification of CHD risk assessment at the request of a physician.”
  38. 38. 53 yr old male T chol: 251 HDL 53 LDL 167 TG 70 Framingham risk:11% Clinical Utility of Carotid IMT
  39. 39. 61 yr old female Tchol:216 HDL:50 LDL:143 TGl:239 162lbs,5’2” Post menopausal Depressed Framingham Risk score:6% Clinical Utility of Carotid IMT
  40. 40. A Picture is Worth a Thousand Words..
  41. 41. Rajaram V et al. Am J Cardiol 2004;93(suppl):32C–48C Neovascularization of the Atherosclerotic Plaque
  42. 42. Courtesy GE Ultrasound
  43. 43. Age as a Risk Factor: You Are asAge as a Risk Factor: You Are as Old asOld as Your ArteriesYour Arteries  There are no acceptable published charts for age-related distributions for either coronary calcium scores or carotid intimalmedial thicknesses. Until these charts become available, adjustment of age scores according to measured plaque burden will not be possible  Measurements made in different laboratories must correlate consistently with those from which age-related distributions of plaque burden were derived Grundy SM. Am J Cardiol 1999;83:1455-1457
  44. 44. LIMITATIONSLIMITATIONS  Methodological criteria taken into account for measuring carotid IMT  Image acquisition Segment: CCA, bulb, ICA, right/left  Wall: far, near  Type of measure Mean of several maximum measures (from 2 to 12)  Mean of randomly selected measures (from 3 to 5)  Mean of measures over 1 cm (> 100)  Measurement Methods
  45. 45. Goal and ChallengesGoal and Challenges  Confidently establish an independent role in cardiovascular risk prediction over and above clinical risk including consideration of newer serologic risk markers such as C-reactive protein  To demonstrate that atherosclerosis imaging techniques favorably impact cardiovascular outcomes in a cost-effective manner  Comparison with newer imaging modalities such as MRI and cine CT for coronary calcification  Incorporate important demographic subgroups including women and ethnic minorities
  46. 46. The 1st National SHAPE Guideline • Coronary Calcium Score • Carotid IMT+ • Coronary Calcium Score • Carotid IMT+ (-) Test(-) Test (+) Test(+) Test •Lifestyle Modification •RF Reduction •EHAC Education •Reassess in 5 year •Lifestyle Modification •RF Reduction •EHAC Education •Reassess in 5 year •Aggressive Lifestyle Modifications •Target LDL <100mg/dl •Intensive EHAC Education •Reassess in 5 years •Aggressive Lifestyle Modifications •Target LDL <100mg/dl •Intensive EHAC Education •Reassess in 5 years •No Treatment •EHAC Education •Reassess in 5 years •No Treatment •EHAC Education •Reassess in 5 years •Aggressive Lifestyle Modifications •Target LDL<130 mg/dl •Intensive EHAC Education •Reassess in 5 years •Aggressive Lifestyle Modifications •Target LDL<130 mg/dl •Intensive EHAC Education •Reassess in 5 years All Asymptomatic Males ≥45y and Females ≥55y with no History of CVDAll Asymptomatic Males ≥45y and Females ≥55y with no History of CVD CCS >400 and CCS ≥ 100th% & >90th% CIMT>1.1 mm, or Positive Plaque CCS >400 and CCS ≥ 100th% & >90th% CIMT>1.1 mm, or Positive Plaque (–)(–) (+)(+) AngiographyAngiography •Target LDL<70 mg/dl •Intensive EHAC Education •Follow Existing Guidelines •Target LDL<70 mg/dl •Intensive EHAC Education •Follow Existing Guidelines + Pending standard practice guidelines.+ Pending standard practice guidelines. +1 RF+1 RF +2 or More RFs+2 or More RFs CCS <75th% & <100th% CIMT <75th% & <1mm and Negative Plaque CCS <75th% & <100th% CIMT <75th% & <1mm and Negative Plaque Very High RiskVery High Risk CCS >75th % or >100th% CIMT>75th% or >1mm or Positive Plaque CCS >75th % or >100th% CIMT>75th% or >1mm or Positive Plaque CRP>4mg/lCRP>4mg/l EHAC: Early Heart Attack CareEHAC: Early Heart Attack Care (Screening for Heart Attack Prevention and Education -SHAPE)(Screening for Heart Attack Prevention and Education -SHAPE) •Target LDL<70 mg/dl •Rest Follows High Risk Group •Target LDL<70 mg/dl •Rest Follows High Risk Group CRP: C Reactive ProteinCRP: C Reactive Protein CIMT: Carotid Intima-Media ThicknessCIMT: Carotid Intima-Media Thickness CCS: Coronary Calcium ScoreCCS: Coronary Calcium Score *Exclude Very-Low-Risk Group*Exclude Very-Low-Risk Group * Known cases of cholesterol <200 mg/dl + blood pressure <120/80 mmHg + no diabetes + no smoking + no family history, and no metabolic syndrome * Known cases of cholesterol <200 mg/dl + blood pressure <120/80 mmHg + no diabetes + no smoking + no family history, and no metabolic syndrome Moderately High Risk Moderately High Risk Ischemia Test Ischemia Test Test for AtherosclerosisTest for Atherosclerosis RF: Risk Factors (high cholesterol, high blood pressure, diabetes, smoking, family history, metabolic syndrome) RF: Risk Factors (high cholesterol, high blood pressure, diabetes, smoking, family history, metabolic syndrome) CVD: angina, heart attack, stroke, peripheral arterial diseaseCVD: angina, heart attack, stroke, peripheral arterial disease High RiskHigh Risk Lower RiskLower Risk Moderate RiskModerate Risk (see SHAPE report for details)(see SHAPE report for details) CCS>0 CIMT detectable CCS>0 CIMT detectable CCS=0 CIMT undetectable CCS=0 CIMT undetectable Positive Plaque: Focal protrusion >1.5 mmPositive Plaque: Focal protrusion >1.5 mm
  47. 47. SummarySummary  Carotid Intima Media Thickness (CIMT) is associated with known and UNKNOWN CV risk risk factors  CIMT and carotid plaques are markers of subclinical atherosclerosis and help in the early identification of presymptomatic individuals  CIMT predicts prevalent CV disease  CIMT predicts incident CV disease  Presence of plaque provides incremental risk  Abdominal ultrasound for AAA in men > 65 yrs is cost effective and decreases mortality from AAA rupture
  48. 48.  Peri and post menopausal women  Family history of premature CHD  African American  Smoker  Total cholesterol level > 240 mg/dl  HDL cholesterol <40 mg/dl  Blood pressure >140/90 mm Hg  Diabetes mellitus  More than 20 pounds overweight  Leading a sedentary lifestyle  Depression? Who Should Be Tested?
  49. 49. 0.81 0.77 0.99 1.17 0.96 1.03 1.47 1.161.12 1.06 1.69 1.83 0 0.5 1 1.5 2 2.5 LCCA RCCA L Bulb R Bulb 0.72 0.73 1.08 1.18 0.91 0.88 1.34 1.38 1.04 1.03 1.89 2.27 0 0.5 1 1.5 2 2.5 LCCA RCCA L Bulb R Bulb 0.89 0.83 1.16 1.36 1 0.96 1.78 1.77 1.3 1.25 1.92 2.5 0 0.5 1 1.5 2 2.5 LCCA RCCA L Bulb R Bulb Black Women (n=2219) Black Men (n=1391) 0.9 0.89 1.31 1.36 1.07 1.05 1.74 1.67 1.43 1.3 2.3 2.16 0 0.5 1 1.5 2 2.5 LCCA RCCA L Bulb R Bulb White Women (5377) White Men (n=4837) Bar graph of 95th percentiles of common carotid artery and carotid artery bifurcation IMT in men and women stratified according to decade of age (45 yrs green, 55 yrs dark blue, 65 years light blue and race. Adapted from Howard G, et al Stroke 1993; 24:1297-1304.). Distribution of IMT in the General Population (ARIC) 45 yrs 55 yrs 55 yrs
  50. 50. Am J Cardiol 2000;85:949–952 IMT Predicts Prevalent CAD
  51. 51. Komorovsky CR et al Heart 2005;91;819-820 Prognostic significance of characteristics of carotid plaques in patients with acute coronary syndromes
  52. 52. CSMC ExperienceCSMC Experience N=35 13F 22 M Age 52±16 yrs 54±11 yrs Weight 147 ±29 lbs 197 ±41 lbs SBP 125±9 mm Hg 128±11 mm Hg DBP 72±10 mm Hg 76±9 mm Hg T chol 186 ±41 198 ±45 mg/dl LDL chol 104 ±44 125 ±40 mg/dl HDL chol 67 ±9 42 ±6 mg/dl
  53. 53. 0.65 0.67 0.74 0.933 0.71 0.7 0.85 0.875 0 0.2 0.4 0.6 0.8 1 1.2 1.4 LCCA RCCA L Bulb R Bulb Bar graph of mean far wall common carotid artery and carotid artery bifurcation IMT in men and women Distribution of IMT in the General Population 0.62 0.68 0.73 0.79 0.68 0.66 0.83 0.84 0 0.2 0.4 0.6 0.8 1 1.2 1.4 LCCA RCCA L Bulb R Bulb Mean IMT Far Wall (CSMC) 50th Centile of Far Wall Mean IMT (ARIC) Female Male
  54. 54. 0.89 0.84 1.2 1.17 0.88 0.91 1.4 1.16 0 0.2 0.4 0.6 0.8 1 1.2 1.4 LCCA RCCA L Bulb R Bulb Max IMT Far Wall Female Male
  55. 55. Table 2. Association [Odds Ratio (95% CI)] of Intima-Media Thickness With Myocardial Infarction and Stroke1 IMT With Myocardial Infarction, mm <0.75 0.75-0.821 0.822-0.907 0.908 <0.75 0.75-0.821 All events n 34 17 18 29 13 19 Model I2 1.0 0.97 (0.52-1.80) 1.09 (0.58-2.74) 1.72 (0.96-3.10) 1.0 2.61 (1.26-5.45 Model II 1.0 0.96 (0.51-1.79) 1.07 (0.58-2.02) 1.65 (0.91-2.99) 1.0 2.28 (1.08-4.84 Model III 1.0 0.86 (0.43-1.70) 1.10 (0.57-2.17) 1.25 (0.64-2.44) 1.0 1.87 (0.86-4.11 First events3 n 23 11 13 21 10 13 Model I 1.0 0.98 (0.46-2.07) 1.29 (0.62-2.65) 2.32 (1.17-4.64) 1.0 2.27 (0.99-5.22 Model III 1.0 0.78 (0.35-1.77) 1.19 (0.55-2.58) 1.44 (0.65-3.16) 1.0 1.83 (0.78-4.33 Bots, M. L. et al. Circulation 1997;96:1432-1437
  56. 56. Carotid Intima-Media Thickness Is Only Weakly Correlated With the Extent and Severity of Coronary Artery Disease Mark R. Adams, MBBS, FRACP; Akihiro Nakagomi, MD; Anthony Keech, MBBS, MEpidemiol, FRACP; Jacqui Robinson, RN; Robyn McCredie, BSc; Brian P. Bailey, MBBS, FRACP; S. Ben Freedman, MBBS, PhD, FRACP; David S. Celermajer, MBBS, PhD, FRACP Circulation 1995;92:2127-34
  57. 57. Copyright ©1997 American Heart Association Bots, M. L. et al. Circulation 1997;96:1432-1437 Schematic presentation of the selection of case and control subjects
  58. 58. Figure 3. Scatterplot of IMT versus A: the number of major coronary arteries with ≥70% stenosis in 350 consecutively studied subjects, B: the modified Gensini score of coronary disease, C: the extent score of coronary disease. A B C Circulation 1995;92:2127-34
  59. 59. Figure 4. Receiver operating characteristic plot for use of carotid IMT to predict the absence of significant coronary disease (mean IMT predicting no vessels with ≥70% stenosis). The "line of chance" is the diagonal line, reflecting a test with no predictive value; the receiver operating characteristic plot is the solid line. There is no value of IMT on this curve, which demonstrates both high (>80%) sensitivity and specificity simultaneously, suggesting that IMT is not a clinically useful test for predicting the absence of significant CAD. Circulation 1995;92:2127-34
  60. 60. Discussion In this study of patients undergoing elective coronary angiography, IMT of the far wall of the CCAs was significantly but only weakly correlated with the extent and severity of CAD, with r<.30and r2 <.10. These data have important implications for theinterpretation of the large number of trials that have used or are using carotid IMT measurement as a noninvasive marker of the atherosclerotic process.15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 The reasons for this relatively poor correlation may be biological, because intima-media thickening is a different pathological process to atheromatous plaque formation1 10 and there are different risk factor influences on the carotid and coronary circulations and technical factors may make contributions, for example, the accuracy of B-mode ultrasonic measurement ofsubmillimeter distances. Circulation 1995;92:2127-34
  61. 61. Discussion ………. ………. Technical Issues: Ultrasonic Resolution The theoretical axial resolution of high-frequency external vascular ultrasound with 7- to 10-MHz transducers is approximately 0.1 mm, but in practice most ultrasound machines use pulses with multiple cycles and have an axial resolution of approximately 0.3 mm.2 16 38 The difference between "control" and "risk factor" groups in many observational studies of carotid IMT has been <0.2 mm.13 15 16 Although the precision to detect differences between group mean values is higher than for individual measurements, most studies measure IMT in individuals to the nearest 0.1 mm or even 0.01 mm, which may be beyond the limits of resolution of the ultrasound used. Circulation 1995;92:2127-34
  62. 62. Courtesy GE Ultrasound
  63. 63. Validation of Carotid Artery Wall Thickness as a Surrogate of Cardiovascular Disease Lancet 2000;356:279-84 Differences in Risk Factors, Atherosclerosis and Cardiovascular Disease Between Ethnic Groups in Canada
  64. 64. Predictors of Cardiovascular Disease by Multivariate Logistic Regression Lancet 2000;356:279-84 Differences in Risk Factors, Atherosclerosis and Cardiovascular Disease Between Ethnic Groups in Canada
  65. 65. Conventional and Novel Risk Factors For Cardiovascular Disease Lancet 2000;356:279-84 Differences in Risk Factors, Atherosclerosis and Cardiovascular Disease Between Ethnic Groups in Canada
  66. 66. Conventional and Novel Risk Factors ForConventional and Novel Risk Factors For Cardiovascular DiseaseCardiovascular Disease Lancet 2000;356:279-84 Differences in Risk Factors, Atherosclerosis and Cardiovascular Disease Between Ethnic Groups in Canada
  67. 67. 0.79 1 1.09 0.9 1.06 1.37 0.73 0.9 1.04 0.86 0.98 1.28 0 0.4 0.8 1.2 1.6 45 55 65 Age (years) IMT(mm) Black Women Black Men White Women White Men Bar graph of 95th percentiles of common carotid artery IMT in men and women stratified according to decade of age and race. Howard G, et al Stroke 1993; 24:1297-1304.). Distribution of IMT in the General Population
  68. 68. H.N. Hodis, W.J. Mack, L. LaBree, R.H. Selzer, C.R. Liu, C.H. Liu and S.P. Azen , The role of carotid arterial intima-media thickness in predicting clinical coronary events. Ann Intern Med 128 (1998), pp. 262–269
  69. 69. Characteristics of Screening Trials for Abdominal Aortic Aneurysm Characteristic MASS22 Western Australia Study23,32 Viborg County Study21 Chichester Study, Men20 Chichester Study, Women20 Location United Kingdom Australia Denmark United Kingdom United Kingdom Age, y 65–74 65–83 65–73 65–80 65–80 Total patients randomly assigned to treatment, n 67,800 38,704 12,658 6433 9342 Mean followup, y 4.1 3.62 5.1 2.5 2.6 Invited for screening, n 33,839 19,352 6339 3205 4682 Attended screening, % 80 63 69 73 65 Uninvited controls, n 33,961 19,352 6319 3228 4660 Outcomes ascertained, % 99 993 100 NR NR Quality Good Fair Fair Fair Fair 1. Values in parentheses are reference numbers. All studies except the Chichester study included only men. MASS= Multicentre Aneurysm Screening Study; NR= not reported.. Median followup. 3. Provided by the study investigators. Fleming C et al. Ann Intern Med 2005;142:203-11
  70. 70. A B CCA ICA ECA CCA bulbbulb Plaque
  71. 71. Increase in IMT Plaques R L
  72. 72. 2-D PW Doppler 30% Stenosis 30% Stenosis Classification of Internal Carotid Artery Disease Vascular Screening Laboratory
  73. 73. Simplified AlgorhythmSimplified Algorhythm Plaque screen >1.5 mm plaque – stop No plaque carotid and bulb IMT
  74. 74. Significance of CIMTSignificance of CIMT ProgressionProgression “Several clinical intervention or prevention trials have illustrated the ability of carotid B-mode ultrasound imaging to monitor changes in IMT over time… In such plaque monitoring studies, quantitative quality control of sonographers … and readers… was found to be critical..., this method would be useful in follow-up of patients treated for plaque progression or regression.”
  75. 75. Intima Media Adventitia Lumen IMT Measurement Near wall Far wall
  76. 76. A B CCA ICA ECA CCA bulbbulb Plaque
  77. 77. Increase in IMT Plaques R L
  78. 78. 2-D PW Doppler 30% Stenosis 30% Stenosis Classification of Internal Carotid Artery Disease Vascular Screening Laboratory
  79. 79. 53 yr old male T chol: 251 HDL 53 LDL 167 TG 70 Framingham risk:11%
  80. 80. 61 yr old female Tchol:216 HDL:50 LDL:143 TGl:239 162lbs,5’2” Post menopausal Depressed Framingham Risk score:6%
  81. 81. Jaffer et al Heart Disease Epidemic in Pakistan: Women and Men at Equal Risk
  82. 82. Intima Media Adventitia Lumen What is IMT?
  83. 83. Ebrahim et al Stroke. 1999;30:841-850.)
  84. 84. Stein JH. Stroke 2004;35:2782-2787
  85. 85. (35.7%) were reclassified as higher risk (14.3%) were reclassified as lower risk Integrating carotid intima-media thickness measurements with global coronary risk assessment. Stein JH et al Clin Cardiol. 2004 Jul;27(7):388-92. Vascular Age Concept
  86. 86. Reproduced with permission from Mills R, Bhatt DL. The yin and yang of arterial inflammation
  87. 87. 150 200 300 No CHD CHD 20/100 40/100 90/100 35% of CHD occurs in people with T chol <200 mg/dl Total Cholesterol mg/dl The incidence of MI in relation to total cholesterol levels in the Framingham Study, 26 year follow-up.
  88. 88. Comparing Framingham Risk Factor ScoreComparing Framingham Risk Factor Score and Coronary Artery Disease (CAD)and Coronary Artery Disease (CAD) 0 2 4 6 8 10 12 14 NO YES CAD FraminghamScore p = 0.447 BAD (Fayad ZA, Mani V, Fuster V et al.) 2005
  89. 89. 76.5 Million76.5 Million AmericansAmericans Have High CRPHave High CRP Correlates of Elevated C-Reactive Protein Among Adults in the United States: Findings From the 1999-2000 National Health and Nutrition Examination Survey
  90. 90. 140 Million140 Million Americans HaveAmericans Have Average or HighAverage or High CholesterolCholesterol
  91. 91. Who Should Be Tested? Intermediate Likelihood of CHD, FRI 10-20 FRI has limitations, does not include family history, obesity, triglycerides, diabetes, sedentary life style, CRP and other emerging risk factors Carotid IMT is an end result of exposure to all known and unknown risk factors
  92. 92. CCA Carotidbulb ICA ECA SA * * * * * mid distal * * * Vertebral Near wall Far wall proximal * proximal mid distal Image Acquisition
  93. 93. FundamentalsFundamentals 1. A propagating ultrasonic pulse is reflected at a boundary between two different tissues. 2. The direction of the incident pulse must be perpendicular to the boundary if the transducer is to detect the reflected pulse. 3. The ultrasonic pulse has a finite duration or pulse length.
  94. 94. FundamentalsFundamentals 4. The total time required for the “leading edge” of the ultrasonic pulse to travel from the transducer face to each boundary and back again is measured by the ultrasound system. 5. We assume that we know the approximate speed of sound (1540 m/s) with which the ultrasonic pulse travels in the intervening tissue or medium.
  95. 95. FundamentalsFundamentals 6. The distance from the transducer face to each boundary can be calculated from distance = (speed x total time) / 2 . 7. The distance between the “leading edges” of two boundaries can be calculated from the difference in the distances calculated for each of the two boundaries.
  96. 96. Paul TK: Am J Med Sci, Volume 330(3).September 2005.105-110 Bogalusa Heart Study: Risk Factors and IMT in Young Adults (24-43y)
  97. 97. Hodis, H. N. et. al. Ann Intern Med 1998;128:262-269 Multivariate Associations of Lipid Levels and Coronary Arterial and Common Carotid Arterial Measures of Atherosclerosis with Risk for Clinical Coronary Events*
  98. 98. 0.5cm
  99. 99. Carotid Artery WallCarotid Artery Wall Intima-Media-AdventitiaIntima-Media-Adventitia Intima Media Adventitia Lumen
  100. 100. Age (yrs) Intima-Media Thickness (mm) M Ludwig 1994
  101. 101. R L
  102. 102. Combined Risk of Heart Attack and Stroke (ARIC) 0 5 10 15 20 25 0.4 0.5 0.6 0.7 0.8 0.9 1 1.1 1.2 1.3 Mean CIMT (mm) Risk(%per10years)
  103. 103. Population-Based Prospective Studies of the Prognostic Utility of Carotid Ultrasonography (USG) Study Population n (% male) Age (yrs) Race Follow -up (yrs) Carotid USG Parameters Endpoint Results KIHD2 Eastern Finland 1257 (100) 42,48,5 4,60 C 2 Normal CCA IMT >1.0 mm Non-stenotic plaque Stenotic plaque MI No increased risk with IMT>1.0 mm Plaque: RR: 4.1 (1.8-9.2) KIHD3 Eastern Finland 2181 (100) 42,48,5 4,60 C 4 Same as above MI IMT >1.0 mm: RR: 2.1 (1.1-4.1)* Non-stenotic plaque: RR: 3.4 (1.9- 5.9)* Stenotic plaque: RR: 6.3 (3.1-12.6)* Chieti4 Italy 2000 (56) 30-70 C 6 Same as above Incidence of MI, angina, CVA, PVD IMT >1.0 mm: 5.5% Plaque: 18.4% Stenotic plaque: 42% ARIC5 United States 12841 (43) 45-64 C, A-A 5.2 Mean IMT of 6 sites MI, CHD death IMT<1.0 mm vs. IMT≥1.0 mm Women: HRR: 2.62 (1.55-4.46)** Men: HRR: 1.20 (0.81-1.77)** Rotterdam Study6 Holland 1470 (38) ≥55 C 2.7 SD increase in CCA IMT MI Women: OR: 1.26 (0.89-1.79)** Men: OR: 1.25 (0.91-1.72)** IMT>0.908 mm: OR: 1.44 (0.65- 3.16)** CHS1 United States 4476 (39) >65 C, A-A 6.2 Quintiles or SD of maximum CCA and/or ICA IMT MI, Stroke Increasing risk per quintile or SD** Abbreviations: KIHD=Kuopio Ischaemic Heart Disease Risk Factor Study, ARIC=Atherosclerosis Risk in Communities, CHS=Cardiovascular Health Study. DM=diabetes mellitus, na=not available, MI=myocardial infarction, C=Caucasian A-A=African-American, RR=relative risk, HRR=hazard rate ratio, OR=odds ratio, SD=standard deviation *Results of Cox regression with CVD risk factors not reported, but results said to still be significant. **Adjusted for CVD risk factors
  104. 104. Table 1. Ultrasound Arterial Morphology Classification : Localized wall thickening and increased density involving all ultrasonic layers. Intima-media thickness >2 mm. Clas s Ultrasound Morphology Score * I Normal: Three ultrasonic layers (intima-media, adventitia, and periadventitia) clearly separated. No disruption of lumen-intima interface for at least 3.0 cm, and/or initial alterations (lumen-intima interface disruption at intervals of <0.5 cm). 2 II Intima-media granulation: Granular echogenicity of deep, normally unechoic intimal-medial layer and/or increased intima-media thickness (>1 mm). 4 III Plaque without hemodynamic disturbance 6 IV Stenotic plaque: As in III, but with hemodynamic stenosis on duplex scanning (sample volume in the center of the lumen), indicating stenosis >50%. 8 The score is relative to one artery. The patient's score is the sum of the scores of all four arteries. Hemodynamic disturbance is defined as moderate spectral broadening (downstroke of systole); systolic window present; diastolic window reduced and/or absent. Ratio a-b/a<0.5, where a is the peak systolic velocity and b, the first peak end-systolic velocity
  105. 105. ChallengesChallenges Physicians, providers, practice, policies, payers, procedure, political Methodology, measurement, reporting
  106. 106. ChallengesChallenges  Near wall, far wall or both Short Axis, long axis 2D or M-mode Lumen yes or no Multiple angles or not CCA, Bulb, ICA One side or both sides Methodological Issues
  107. 107. ChallengesChallenges Implementing in Clinical Practice Sonographer training Time factor in a labor intensive technique Incorporate into cardiology fellowship training Reimbursement Ability to do online measurements
  108. 108. ChallengesChallenges Caliper Automated Measurement Method
  109. 109. ChallengesChallenges Reporting MethodReporting Method  Vascular age  Above or below 1 mm  Average of all measurements, mean and max  How to compare against published norms?  Plot patient on a nomogram?
  110. 110. ChallengesChallenges Risk of a New Technology  Performed by unskilled personnel  Quality  Unnecessary testing and treatment Who should undergo IMT as opposed to coronary calcium? Diabetics, women, blacks, young and the elderly
  111. 111. What motivates our patientsWhat motivates our patients more?more? A scan with some white stuff Or Fat inside the artery?
  112. 112. 53 yr old male T chol: 251 HDL 53 LDL 167 TG 70 Framingham risk:11%
  113. 113. R L
  114. 114. Ischemic stroke Transient ischemic attack Myocardial infarction Angina pectoris (stable, unstable) Sudden death Critical limb ischemia, gangrene, necrosis Atherothrombotic Disease Viles-Gonzalez J, Fuster V, Badimon JJ. EHJViles-Gonzalez J, Fuster V, Badimon JJ. EHJ 20042004; 25:1; 25:1
  115. 115. Survival Curves for Degree ofSurvival Curves for Degree of AtherosclerosisAtherosclerosis The Rotterdam Study, Circulation 2004;109:1083-94 Hazard ratios were equally high for carotid plaques (1.83 [1.27 to 2.62], severe versus no atherosclerosis), carotid IMT (1.95 [1.19 to 3.19]), and aortic atherosclerosis (1.94 [1.30 to 2.90]) and slightly lower for lower-extremity atherosclerosis (1.59 [1.05 to 2.39])
  116. 116. Copyright ©2005 American Heart Association Touboul, P.-J. et al. Stroke 2005;36:1741-1745 OR of Stroke Associated with Tertiles of FCRS, CCA-IMT, and Carotid Plaques

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