3/21/2012

Carotid IMT Carotid IMT for Risk Prediction

for Risk Prediction
Charles H. Tegeler, MD
McKinney-Avant Professor of Neurology
Director, Telestroke Services
Director, Ward A. Riley Ultrasound Center
Outline
• What is IMT
• What is the evidence?
• How are the data collected and read?
• Ongoing quality assessment
• WFSM IMT for CVD Risk Prediction Program

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Schematic diagram with lesions at the BIF and ICA

Carotid IMT Definition

• IMT is an acronym often used to refer to

the phrase “intima-media thickness” .
• IMT refers to the combined thickness of
th intimal
the i ti l andd medial
di l llayers off th
the
arterial wall.
• Carotid IMT is measured from two-
dimensional noninvasive B-mode
ultrasound images.

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Carotid IMT Definition (Cont’) Clinical Value of Carotid IMT

Anatomic Basis for IMT
• Prediction of risk for cardiovascular events
• Histological slices show the intima
using traditional risk factors, such as
intimal and medial layers of Framingham Risk Score (ATP-III risk
two atherosclerotic arteries
with B-mode Carotid IMT media
assessment tool), is somewhat limited.
Definition ((different p
plaque
q di
media
characteristics). adventitia
• The maximum IMT of each • Many cardiovascular events cannot be
wall is indicated by the predicted from traditional risk factors
vertical yellow line.
intima (lipids, blood pressure, smoking, etc.).
• This thickness includes
that of both the media (M) intima
and the plaque (P). The media
plaques affect both the media
intima and the media. adventitia

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Clinical Value of Carotid IMT (Cont’)

Absolute IMT and Risk of CHD
• Carotid IMT is an independent predictor of Atherosclerosis Risk in Communities (ARIC)
cardiovascular events in general 14

Male

r 1,000 person
populations after adjustment for traditional 12
Female
12.9
11.7
„ N=12,841
risk factors 10 10.7
„ Age: 45~64
years

CHD Incidence ( per

8

6
„ ‘Healthy’, No
• Observational studies have found that for 6.5
CVD symptom
an absolute carotid IMT difference of 0.1 4 4.4
3.8
„ Follow-up: 4~7
3
3.4 years
mm, the future risk of MI increases by 10% 2
1.8 „ Adjusted for
to 15%, and the stroke risk increases by 0
0.6
age, center and
13% to 18%
<0.6 0.6-0.7 0.7-0.8 0.8-1.0 >1.0
race
mean IMT (mm)

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Adapted from Lorenz MW, et al. Circulation 2007;115 Wake Forest Baptist Health
Adapted from Chambless LE et al. Am J Epidemiol 1997;146

Absolute IMT and Risk of Stroke Absolute IMT and Risk of Stroke or MI
Atherosclerosis Risk in Communities (ARIC) Cardiovascular Health Study (CHS)
per 1,000 person/year)

45
1,000 person/year)

6 40.9 • N=4,476
Male • N=14,214 40
5 • Age: >65 years
Female
5.1 5.1 • Age: 45~64 years 35
• ‘Healthy’ , No CVD symptom
4
4 • ‘Healthy’ without 30 • Follow-Up: 7 years
Incidence Rate of Stroke or MI ( p
Stroke Incidence (per 1

3 3.6 CVD symptom • After controlling for age/sex，the

25
22.2 odds ratio of MI or stroke was 4.5 for
2 • Followed-up: 6~9 the highest IMT quintile as compared
2.4 20 18.4
years to the lowest quintile
1 1.4 1.3 1.2 1.3 • Adjusted for age,
15 13.6
• The possibility of stroke or MI
0.6 incidence was 4% for the lowest IMT
0 center and race 10 7.8 quintile, 26% for the highest quintile
<0.6 0.6-0.7 0.7-0.8 0.8-1.0 >1.0 5 • Compared to other risk factors, IMT
was the strongest predictor of stroke
mean IMT (mm) 0 or MI
<0.9 0.91-1.10 1.11-1.39 1.40-1.80 >1.80

Adapted from Chambless LE et al. Am J Epidemiol 1997;146 Mean IMT (mm) Adapted from O’Leary DH, et al. N Engl J Med 1999;340

Absolute IMT and Risk for Stroke Absolute IMT and Risk of Stroke
The Rotterdam Study Japanese Elderly Men
5
Model 1 Model 2
4.8 • N=1,683
20
• Age > 55 years • N=1,289
Stroke Incidence (per 1000 person

4 18 18.7
16
• Model 1- adjusted for
14
• Age: 60~74 years
3 age/sex
Odds Ratiio

32
3.2 12
2.8 • Model 2- adjusted for • ‘‘Healthy’ without
10
2 2.3 2.3 age/sex, stroke history, BMI, 8
CVD history
smoke, SBP, TPC, HDL-C, 9.2
1.8 6
DM 5.8
• Follow-up: 4.5
1 4
1 1 • With every 0.15 mm 2 3.1
years
increase in Baseline IMT, the 0
0
10 year absolute risk for
<0.75 0.75-0.82 0.82-0.91 >0.91 1st 2nd 3rd 4th
stroke increased by 4.1%
CCA IMT (mm) CCA and ICA Max IMT Quartile
Adapted from Bots et al. Circulation 1997; 96
Adapted from Kitamura A, et al. Stroke 2004;35

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Comparison with Other Risk Comparison with Other Risk Assessment Tools
The Rotterdam Study
Assessment Tools
Atherosclerosis Risk in Communities (ARIC) 3
IMT Aortic calcification Ankle-brachial index • N=6,913
Hazard Rate Ratio (highest to lowest tertile) for Clinical Event 2.42
2.5
8 2.23 • Follow-up: 6.1 years (mean)
6.69 • Follow-up: 5.2

Relative Risk of Str

7 IMT LDL-C
Hardard Rate Ra

6 years (mean) 2 1 89
1.89 • Relative Risk (highest to
5 1.63 lowest tertile) of Stroke
1.55
4 1.5
2.88 1.28
3 2.54 • Model-1: Adjusted for age
1.95
2 and sex
1
1
0 • Model-2: adjusted for age,
Women Men 0.5 sex, diabetes mellitus,
smoking, systolic and
0
diastolic BP, total-C and
Model-1 Model-2
HDL-C, history of CVD
Adapted from Chambless LE, et al. Am J Epidemiol 1996;146 Adapted from Hollander et al. Stroke 2003;34

Comparison with Other Risk Assessment Tools

The Multi-Ethnic Study of Atherosclerosis (MESA) IMT and Stroke Risk in MESA
Hazard Ratio of the 4th Quartile for an
incidence in relation to <50th%ile Reference
12
z Score max IMT
CAC Score • N=6,698
10
10.3 • Age: 45~84 years
0.01
p<0

8 • ‘Healthy’, free of CVD

Hazard Rat

6 • Followed-up: 5.3 years

• Adjusted for age, sex
p<0.001

p<0.01

4
and race
p=N.S.

2 2.4
2.1
1.2
0
CHD Stroke
Adapted from Folsom AR et al. Arch Intern Med 2008;168
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Polak JF, et al, Stroke, 2011

Change in Maximum Carotid Intima-Media Thickness (CIMT) for the Primary End Point

AstraZeneca Research
• METEOR International Study used CIMT to assess and measure
change in the carotid artery of asymptomatic subjects with early
atherosclerotic disease and at low CHD risk.
• First study to show positive benefit on atherosclerosis for people
with early signs of diseased arteries.
• FDA approved expanded marketing of Crestor based on CIMT
data in the METEOR Study (drug halted progression of disease)
• Data showed a 0.0014 mm/yr decrease in the mean maximum
carotid intima-media thickness—a marker of atherosclerotic
burden, of Crestor patients, compared to a progression of 0.0131
mm/yr for those on placebo.
• The Ward A Riley Ultrasound Center was the Core Reading
Laboratory and Ultrasound Training and Quality Control/Quality
Assurance Center for the United States as well as an IMT
Scanning site for this important pharmaceutical trial. Crouse, J. R. et al. JAMA 2007;297:1344-1353.

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Copyright restrictions may apply.

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Summary of Research American Heart Association

„ Absolute carotid IMT is an independent predictor Prevention Conference V
of MI, TIA and stroke incidence
„ The progression of carotid IMT is associated with Carotid IMT
increased risk of MI, TIA and stroke event „ Is an independent predictor of TIA, stroke,
and coronary events such as MI
„ Carotid IMT is a stronger
g p predictor of clinical
events than cholesterol and some measures of
atherosclerotic burden
Recommendation
„ Carotid IMT progression can be significantly „ Can be considered for CHD risk assessment
reduced or possibly halted in certain populations in asymptomatic persons > 45 years old in
„ Such reduced carotid IMT progression could experienced labs
profoundly affect the incidence of CHD or stroke
over the long-term.

Screening for Heart Attack Prevention

and Education (SHAPE) Task Force CIMT Appropriate Use Criteria

1st Guideline:
• Age: Males: 45-75 years
Females: 55 -75 years

• Apparently healthy: No known history of CHD

NOT at very low risk

• Carotid IMT evaluation for CHD risk assessment

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Adapted from Naghavi M et al. Am J Cardiol 2006;98 Wake Forest Baptist Health

Appropriate Use Criteria Appropriate Use Criteria

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Prevalence of Carotid Disease and ABI in ARIC

Importance of Plaque

• Presence of plaque predicts increased risk,

irrespective of IMT values
• Exact definition and cut points have varied
• Most protocols include assessment and
reporting of plaque in addition to the IMT data
• Acoustic shadowing confers increased risk
• Effects seen across age, race, and gender

Zheng ZJ, et al, Atherosclerosis,1997

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Plaque and CVD risk in NOMAS

by Max Carotid Plaque Thickness (MCPT) Impact of Plaque by Age, Race, Ethnicity
N = 1,263

Model: (1) MCPT only; (2) model (1) adjusted for age, gender, race, education; (3) model (2) adjusted for
BP, DM, heart disease, ETOH, smoking, HDL, LDL, BMI, use of ASA, lipid lowering meds

Rundek et al, Neurology, 2008

Rundek et al, Neurology, 2008

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Impact of Plaque on FRS Values Plaque and Acoustic Shadowing

Rundek et al, Neurology, 2008

Prabhakaran et al, Atherosclerosis, 2007

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Impact of Plaque w/wo Shadowing in NOMAS Plaque Shadowing in NOMAS

(N= 1,118)

Prabhakaran et al, Atherosclerosis, 2007

Prabhakaran et al, Atherosclerosis, 2007

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CVD Risk Assessment Using IMT Carotid IMT Protocols

Ultrasound Direction
Lack of Universal Standardized Protocol: Skin
• What to measure
ICA Bifurcation CCA
• Where to measure
• How to measure

Blood Flow Direction

ECA

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Interrogation Angle
Carotid IMT Protocols

„ Interrogation Angle: Circumferential

Fixed-Angle

„ Arterial Site: CCA Far Wall

Multiple Sites*

(*Multiple sites: Far and Near walls of the CCA, Bulb, ICA)

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Stein JH, et al, ASE Consensus Statement, 2008

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Carotid IMT Protocols (Cont’) Carotid IMT Protocols (Cont’)

Carotid IMT by Wall, Segment and Angle
Interrogation Angle – Average of 856 Subjects
1.25
Fixed- Near Wall
Angle Circumferential 1.15

mm
Far Wall

CIMT (m
Technical effort ↓ ↑ 1.05

Measurement Error ↑ ↓ 0.95

Reliability ↓ ↑ 0.85

Missing the max 0.75

IMT ↑ ↓ A O-A L O-P P A O-A L O-P P

Wall & Angle of Interogation

CCA BIF ICA

Carotid IMT Protocols (Cont’) Carotid IMT Protocols (Cont’)

Arterial Site
For valid, reliable IMT measurement and CVD
CCA FW F & N W of CCA+BIF+ICA risk assessment, the protocol must
Tech effort Less More
„ Angulations: be circumferential, or
Reliability Best Lower
h
have multiple
lti l defined
d fi d
Auto software Yes No angles
Association with „ Anatomical site(s): include the maximum IMT
risk factors Weaker Stronger measurements from
IMT progression Slow Faster multiple carotid sites
Lesion present Latest BIF→ICA →CCA
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Carotid IMT Measurement Precision

Carotid IMT Measurement Precision Carotid IMT in 45 year old women
Percentile Mean CIMT (mm) Difference (mm)
• Carotid IMT measurement requires very
high (submillimeter) precision to permit 5th 0.38 -
reliable percentile classification of 10th 0.41 0.03
individuals for accurate risk assessment in 25thh 0.47 0.06
a clinical setting.
50th 0.53 0.06
75th 0.61 0.08
90th 0.68 0.07
95th 0.73 0.05
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Adapted from Howard G, et al. Stroke 1993;24

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Operator Related Variability (Cont’) Common Errors in Carotid IMT Evaluation

Frame Selection
Criteria for frame Selection
• Arterial wall is perpendicular to sound beam
• Both lumen/intima and media/adventitia interfaces are
defined
• The two interfaces are moving in the same direction
and at the same pace with arterial pulsation and
transducer movement
• Gain/TGC settings are low enough to eliminate artifact,
especially when measuring the near wall IMT
• Incorrect segment identification - Key anatomical
reference: Tip of the flow divider
• Ultrasound beam not perpendicular to the arterial wall
- missing IMT interfaces; over estimate of IMT
• Measurement of artifact - be careful with automated
and/or semi-automated software
• IMT measurement oblique – be careful with
automated and/or semi-automated programs

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IMT Measurement by IMT Measurement by

Automated Edge Detection IMT Software Automated Edge Detection IMT Software (Cont’)

•Sharp interfaces

•Artifact not present

•Correct edge detection

•Perpendicular to wall

1. Sharp interfaces. •Valid IMT measurement

2. Correct edge detection.
3. Valid IMT measurement.
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IMT Measurement by Carotid IMT Quality Assurance

Automated Edge Detection IMT Software (Cont’)
Quality Control Procedures

Error Source Quality Control Procedures

Machine „Standardization

„Frequency, pixel size, resolution

Interface lumen/Intima
NOT visualized
Protocol „Standardization

„Circumferential, multiple sites

1. False edge detection.
2. Measurement line oblique to wall. Operator „Standardized training
3. Invalid IMT measurement! „Certification

„Routine quality control Procedures

Operator editing is required for a valid IMT measurement!
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Carotid IMT Screening in CVD Prevention Carotid IMT Screening in CVD Prevention
in Private non-University Clinical Practice in Private non-University Clinical Practice

• Patients: N=209; Age=55.7+8.9 yrs

Change of Carotid IMT after 1-year
• Global risk assessment: Treatment of Multiple Risk Factors
• Lipids, Smoking, DM, BP, Diet, Obesity, etc. 5

# of Site with IMT >= 1.2

0.8
P<0.001 P<0 001
P<0.001
• Carotid
C tid IMT evaluation
l ti @ bbaseline
li and
d year-1
1 4

CCA IMT (mm

4.2 0.78
• standardized protocols 3.7
3 0.76 0.771
• standardized trained and certified CIMT sonographers
2 0.74
• Treatment of multiple risk factors
0.736
1 0.72
• Lifestyle modification
• medication prescription and adjustment to control/reduce known CV 0 0.7
risk factors Baseline Year-1 Baseline Year-1

Wake Forest Baptist Health Adapted from Bale, et al. Atherosclerosis 2006;7:161 Adapted from Bale, et al. Atherosclerosis 2006;7:161

Ultrasound Screening in Asymptomatic Patients: CIMT Risk Screening at WFUMS

Carotid IMT Screening Target Population
• May allow treatment or intervention years prior to a clinical Patients with the following clinical circumstances
event; focus on younger patients without known heart or are considered for CIMT Evaluation:
vascular disease
• Potential role as motivational tool
1 IIndividuals
1. di id l without
ith t established
t bli h d
• Requires careful attention to protocols, training, reading, cardiovascular disease (coronary heart
QA/QC disease, cerebrovascular disease, peripheral
• CIMT Risk Prediction Exams are becoming available arterial disease, abdominal aortic aneurysm)
• In USA, Texas is to cover cost of IMT or CAC and with two CVD risk factors other than
age (especially any combination of high
• ICAVL/CAMS now accredits IMT testing blood pressure, obesity, smoking, or
dyslipidemia)
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CIMT Risk Screening at WFUMS

Target Population

• Family history of premature CVD in a first-

degree relative (men < 55 years old, women
< 65 years old)
• Severe abnormalities in a single risk
factor (e.g. genetic dyslipidemia) who
otherwise would not be candidates for
pharmacotherapy may be considered for
screening

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Initial Overview

CHD RISK SCORE

2.4
2.2
2
Relative Risk

18
1.8
1.6
1.4
1.2
1
0.8
0 10 20 30 40 50 60
Number of Patients = 63

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Patient Statistics Overall

Patients Scanned Patients Average Age
725

Initial Overview
53.43
474 52.57
51.72
251

MEDIAN Men Women Overall Men Women Overall

CHD RISK SCORE

1.5
1.45 Patients Average Thickness Patients Average Relative Risk Value
1.68
1.4
e Risk

1.22
1.63 1.16
1.35
Median Relative

1 57
1.57 1 10
1.10
1.3
1.25 1.26
1.2 Men Women Overall Men Women Overall

1.15
1.1
1.08 Patients Average Plaque Thickness
1.05
1
2.74
Overall (N=763) see19%
2.54

Males Females 2.33 prevalence of plaque of

January 1 2009 ‐ March 31 2009 2 mm or greater
Men Women Overall
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Ongoing QA for CIMT at WARUC
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Alternatives:
IMT and CAC
• IMT may be useful to use with FRS to identify
risk when CAC score is zero (Lester SJ, et al,
Mayo Clin Proc 2009)
• IMT may be useful to identify risk in those
missed by traditional RF screening (Adolphe A, et
al, Mayo Clin Proc 2009)
• ASE published guidelines for clinical use of IMT
(Stein JH, et al, JASE 2008)
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Thank you for your attention
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3/21/2012
Alternatives:
IMT and Coronary Artery Calcium
• Unique strengths and weaknesses
• Assess different issues along the continuum of
atherosclerosis
• Different body and length of experience
• Radiation dose with CAC
• Problems with low or zero calcium score
• Good CAC association for CVD outcome
(MESA), but IMT better predictor for stroke
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Measurement of Carotid Artery IMT
Wrap-up
• Can predict risk of CHD, Stroke and other CVD
• Helps PCPs improve CVD risk assessment and make
decisions on appropriate risk reduction management
• Motivates patients compliance
• Can evaluate risk reduction treatment efficacyy
• Must use standardized protocols and QC procedures to
ensure measurement validity and reliability for accurate risk
assessment and monitoring change over time
• Level 3 CPT code at present (0126T); some insurance
reimbursing in a few States. Now ICAVL/CAMS accreditation
• Potential for collaboration to perform readings and provide risk
prediction reports for other labs
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