SHAPE Society

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. 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. 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. 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

7. Cohn JN and McVeigh GE et al
The Pathogenesis of CardiovascularThe Pathogenesis of Cardiovascular
DiseaseDisease

8. Arterial Segments CommonlyArterial Segments Commonly
Involved in AtherosclerosisInvolved in Atherosclerosis
Courtesy Ward Riley, MD

9. Carotid Artery WallCarotid Artery Wall
Intima-Media-AdventitiaIntima-Media-Adventitia
Intima
Media
Adventitia
Lumen
0.5cm

10. Normal
Abnormal

11. CCA
ICA
ECA
CCA
bulbbulb
Near wall
Far wall
Intima
Media
Adventitia
Intima
Media
Adventitia
Normal and Abnormal Carotid
Intima-Media Thickness

12. 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

13. Simon A et al. Journal of Hypertension 2002, 20:159±169

14. 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

15. Li, S. et al. JAMA 2003;290:2271-2276.
Carotid IMT Represents Cumulative LDL-C Burden From
Childhood to Adulthood (25-37 yrs)

16. Järvisalo MJ et al Circulation. 2001;104:2943-2947
16 44 28
IMT Is Associated With Risk Factors in Children

17. Eric de Groot et al Circulation. 2004;109[suppl III]:III-33–III-38
IMT Progression in Familial Hypercholesterolemia

18. Distribution of IMT in the General Population (AXA Study)
Gariepy J et al Arterioscler Thromb Vasc Biol 1998; 4: 584–590
(AXA Study)

19. 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

20. Copyright ©1995 American Heart Association
Burke, G. L. et al. Stroke 1995;26:386-391
Carotid IMT and CV Disease Prevalence (ARIC
Study)

21. 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

22. Carotid IMT and Extent of Coronary Artery Disease

23. Adams MR et al Circulation 1995;92:2127-34
Carotid IMT and Prevalent Coronary Artery Disease

25. 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**

26. Relation of Carotid Intima-media Thickness
with CV Events in Asymptomatic Subjects
Simon: J Hypertens, Volume 20(2).February 2002.159-169

27. 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)

28. 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

29. 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)

30. The Rotterdam Study, Circulation 2004;109:1083-94
Predictive Value of Non Invasive Measures
of Atherosclerosis for MI

31. 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

32. 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

33. 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

34. 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

35. 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

36. 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

37. 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

38. 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

39. 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.”

40. 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.”

41. 53 yr old male
T chol: 251
HDL 53
LDL 167
TG 70
Framingham risk:11%
Clinical Utility of Carotid IMT

42. 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

43. A Picture is Worth a Thousand Words..

44. Rajaram V et al. Am J Cardiol 2004;93(suppl):32C–48C
Neovascularization of the Atherosclerotic Plaque

45. Courtesy GE Ultrasound

46. 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

47. 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

48. 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

49. 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

50. 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

51.  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?

54. 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

55. Am J Cardiol 2000;85:949–952
IMT Predicts Prevalent CAD

58. Komorovsky CR et al Heart 2005;91;819-820
Prognostic significance of characteristics of carotid plaques in patients with acute coronary syndromes

59. 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

60. 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

61. 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

64. 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

65. 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

66. 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

67. 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

68. 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

69. 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

70. 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

71. Courtesy GE Ultrasound

72. 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

73. 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

74. 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

75. 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

77. 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

78. 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

79. 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

80. A B
CCA
ICA
ECA
CCA
bulbbulb
Plaque

81. Increase in IMT
Plaques
R
L

82. 2-D PW Doppler
30% Stenosis
30% Stenosis
Classification of Internal Carotid Artery Disease
Vascular Screening Laboratory

83. Simplified AlgorhythmSimplified Algorhythm
Plaque screen
>1.5 mm plaque – stop
No plaque carotid and bulb IMT

85. 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.”

87. Intima
Media
Adventitia
Lumen
IMT Measurement
Near wall
Far wall

88. A B
CCA
ICA
ECA
CCA
bulbbulb
Plaque

89. Increase in IMT
Plaques
R
L

90. 2-D PW Doppler
30% Stenosis
30% Stenosis
Classification of Internal Carotid Artery Disease
Vascular Screening Laboratory

91. 53 yr old male
T chol: 251
HDL 53
LDL 167
TG 70
Framingham risk:11%

92. 61 yr
old female
Tchol:216
HDL:50
LDL:143
TGl:239
162lbs,5’2”
Post menopausal
Depressed
Framingham
Risk score:6%

94. Jaffer et al
Heart Disease Epidemic in Pakistan: Women and Men at Equal Risk

96. Intima
Media
Adventitia
Lumen
What is IMT?

97. Ebrahim et al Stroke. 1999;30:841-850.)

98. Stein JH. Stroke 2004;35:2782-2787

99. (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

100. Reproduced with permission from Mills R, Bhatt DL. The yin and yang of arterial inflammation

101. 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.

102. 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

103. 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

104. 140 Million140 Million
Americans HaveAmericans Have
Average or HighAverage or High
CholesterolCholesterol

106. 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

107. CCA
Carotidbulb
ICA
ECA
SA
*
*
*
*
*
mid
distal
*
*
*
Vertebral
Near wall
Far wall
proximal
*
proximal
mid
distal
Image Acquisition

108. 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.

109. 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.

110. 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.

111. 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)

113. 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*

114. 0.5cm

115. Carotid Artery WallCarotid Artery Wall
Intima-Media-AdventitiaIntima-Media-Adventitia
Intima
Media
Adventitia
Lumen

116. Age (yrs)
Intima-Media Thickness (mm)
M Ludwig 1994

117. R
L

118. 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)

119. 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

122. 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

127. ChallengesChallenges
Physicians, providers, practice, policies,
payers, procedure, political
Methodology, measurement, reporting

128. 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

129. 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

130. ChallengesChallenges
Caliper
Automated
Measurement Method

131. 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?

132. 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

133. What motivates our patientsWhat motivates our patients
more?more?
A scan with some white stuff
Or
Fat inside the artery?

134. 53 yr old male
T chol: 251
HDL 53
LDL 167
TG 70
Framingham risk:11%

135. R
L

136. 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

137. 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])

138. 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