LATEST DEVELOPMENTS IN NON-INVASIVE
IMAGING OF ATHEROSCLEROSIS USING
CAROTID ULTRASOUND (CIMT AND
PLAQUE) IN THE NEW ERA OF PCI
Preventive Cardiovascular Imaging
Tasneem Z Naqvi, MD, FRCP (UK), RVT, MMM
Director Non-invasive Cardiology and Echocardiography
Professor of Medicine and Clinical Scholar
Keck School of Medicine
University of Southern California, Los Angeles
DISCLOSURE
I personally perform carotid IMT
and plaque assessment for CV risk
assessment in my patients
(often free of charge!)
PCI (IMT) IS IN THE GUIDELINES!
“a Reasonable Test”
Benefit >> Risk
For CAD risk assessment in
asymptomatic adults at intermediate
risk (Level of Evidence B)
IIa
2010 ACCF/AHA Guidelines
CAROTID ARTERY WALL LAYERS
External
carotid artery
Transducer
Near wall
Noninvasive, no radiation
Tip of the
flow divider
(10 mm)
(10 mm)
Internal
Carotid
carotid artery bifurcation
Far wall
(10 mm)
Common
carotid artery
CCA
bulb
• IMT is a normal structure, made up of about 80% media and 20% intima
• Atherosclerosis is largely an intimal process
bulb
CCA
CAROTID ARTERY INTIMA MEDIA THICKNESS
ASSESSMENT, MEASUREMENT & REPORTING
• Varying comprehensivenss– single vs. multiple
segments, single vs. multiple angles, far wall only, far
and near wall, plaque inclusive vs. plaque exclusive
• Phase of cardiac cycle, single vs. multiple frames
• IMT measure - average mean, mean max, max, caliper
vs. automated
CAROTID ARTERY INTIMA MEDIA THICKNESS
ASSESSMENT, MEASUREMENT & REPORTING
• 75th percentile, standard deviation, upper and lower
quartile or tertile, >0.9 mm
• ASE and ACC/AHA recommend 75 th percentile
• Differences in Pixel resolution among US systems and
transducers
PLAQUE DEFINITION AND ASSESSMENT IN
CLINICAL STUDIES
Focal thickening of the carotid wall that is at least 0.5 mm or
50% of surrounding IMT value
Focal region with CIMT 1.5 mm that is distinct from adjacent
boundary and protrudes into the lumen
Quantitative Assessment
Categorical: Yes and No
Quantitative Plaque Burden
Number of plaques, Plaque thickness, Area, Plaque volume, Vessel volume
Qualitative Assessment
• Plaque heterogeneity, irregularity, plaque vascularity, plaque
calcification
PLAQUE
MORPHOLOGY
PREDICTIVE VALUE OF IMT VS. PLAQUE IN
POPULATION BASED STUDIES - FUTURE MI
Meta-analysis,11studies, 54,336 patients
Sensitivity
SROC Curve
1-specificity
Inaba Y et al Atherosclerosis Volume 220,2012 128 - 133
Prediction of Clinical Cardiovascular Events
with Carotid Intima-media Thickness
N=37,197
FU 5.5 yrs
RR
MI & stroke
1.26 & 1.32 per
1 SD CCA IMT
difference
1.15 & 1.18
per 0.10-mm
CCA IMT
difference
*Adjusted for age, sex, body mass index, systolic and diastolic blood pressure, LDL cholesterol, smoking and diabetes.
†Adjusted for age, sex, systolic and diastolic blood pressure, smoking, and diabetes.
‡Adjusted for age, sex, BMI, systolic and diastolic blood pressure, total and HDL cholesterol, smoking, and diabetes.
§Adjusted for age, sex, systolic and diastolic blood pressure, total and HDL cholesterol, smoking, diabetes, and cardiovascular disease.
Lorenz M W et al. Circulation 2007;115:459-467
Common Carotid Intima-Media Thickness Measurements in
Cardiovascular Risk Prediction: A Meta-analysis
N=45,828, FU 11 yrs
FRS C statistic 0.757
FRS and CIMT 0.759
NRI with common CIMT was 0.8%
In Intermediate risk, NRI improvement 3.6%
Ruizter H et al. JAMA. 2012;308(8):796-803
ARIC STUDY - EVALUATION OF
PREDICTIVE ROLE OF IMT AND PLAQUE
n=13145 (5682 men, 7463 women)
n=13145 (5682 men, 7463 women
At each category of CIMT the presence of plaque is associated with higher
incidence of CHD
Nambi V, et al. JACC 2010;55:1600-1607
ARIC Study Net Reclassification Index Using
Various Models
Model
Overall
Men
Women
NRI
(%)
Clinical
NRI (%)
NRI
(%)
Clinical
NRI (%)
NRI
(%)
Clinical
NRI (%)
TRF vs. TRF+CIMT
7.1
16.1
8.9
15.7
6.1
15.9
TRF vs. TRF + plaque
7.7
17.7
4.2
10.5
10.2
25.6
TRF vs. TRF+CIMT+
plaque
9.9
21.7
8.9
16.3
9.7
25.4
Nambi V, et al. JACC 2010;55:1600-1607
Predictive Role of Carotid Plaque and IMT in Older Adults
Non adjusted probability of first
coronary event
Non adjusted probability of first
coronary event
5895 CHD-free adults aged 65–85years, FU 5.4 yrs
No Plaque
Plaques at 1 site
Plaques at 2 sites or more
p= <.001
HR plaques: 1 site = 1.5
plaques at ≥2 sites = 2.2
ROC curve - 0.728 to 0.745
NRI =13.7%
<0.61mm
0.61-0.67mm
0.67-0.73mm
0.73-0.81mm
>0.81mm
HR IMT: 0.8
Follow- up (Months)
Follow- up (Months)
p= 0.30
Celermajerc D et al Atherosclerosis Volume 219, 2011 917 - 924
Cumulative probability
of myocardial infarction
Cumulative probability of
myocardial infarction
Proportion of MI According to Total Plaque Area
Men
No Plaque
1. tertile
2. tertile
3. tertile
Women
N=6226, FU 6 yrs, age 25-84
HR 1.56
Follow-up time, years
No Plaque
1. tertile
2. tertile
3. tertile
Adj. RR highest plaque tertile vs. no plaque
HR 3.95
Follow-up time, years
Johnsen S H et al. Stroke 2007;38:2873-2880
Proportion of MI According to IMT
Cumulative probability of
myocardial infarction
Men
Cumulative probability of
myocardial infarction
0
1. quartile
2. quartile
3. quartile
4. quartile
1
2
HR 1.73
3
4
5
6
Follow-up time, years
Women
0
1
1. quartile
2. quartile
3. quartile
4. quartile
2
Adj. RR highest vs. lowest IMT quartile
No predictive value if bulb IMT excluded
HR 2.86
3
4
5
6
Follow-up time, years
Johnsen S H et al. Stroke 2007;38:2873-2880
Proportion of Ischemic Stroke According to Total Plaque Area
Hazard Ratio highest quartile vs. no plaque
1.73, p, 0.04
1.62, p, 0.03
Mathiesen E B et al. Stroke 2011;42:972-978
Proportion of Ischemic Stroke According to IMT
No diff in stroke risk across quartiles of IMT
HR 1 SD IMT 8%
HR 1 SD IMT 24%
Mathiesen E B et al. Stroke 2011;42:972-978
Internal Carotid Artery IMT and Plaque and not CCA IMT
Predicts Probability of New Onset CVD
2965 Framingham Offspring Study FU 7.2 yrs
HR 1SD IMT
Mn CCA IMT
1.13
Max ICA IMT
1.21
NRI max , mean CCA IMT 0%, Max ICA IMT 7.6%, plaque presence 7.3% Polak et al N Engl J Med 2011; 365:213-221
EFFECT OF PLAQUE THICKNESS ON
VASCULAR EVENTS
N=2189
FU 6.9 yrs
HR: 2.8
44% of low FRS
Had 18% risk if plaque present
Rundek T et al. Neurology 2008 ;70(14):1200-7
Carotid intima-media Thickness Progression
to Predict Cardiovascular Events in the
General Population
16 studies, 36 984 participants, FU 7 yrs
Lorenz M et al The Lancet Volume 379, Issue 9831 2012 2053 - 2062
CAROTID PLAQUE MORPHOLOGY IMPROVES
STROKE RISK PREDICTION
N=1,348 FU 12 yr
TPRS
• Stenosis degree
• Plaque surface
irregularity
• Echolucency
• Texture
Prati P et al Cerebrovasc Dis 2011;31(3):300-
Carotid Plaque Burden as a Measure of Subclinical Atherosclerosis :
Comparison With Other Tests for Subclinical Arterial Disease
Chi Square: 450
Chi Square: 24
...
Sillesen H et al. JACC Imag 2012;;5, 681 - 689
High Prevalence of Carotid
Atherosclerosis in Subjects with Low FRS
100
Chi square=15.12, Pr=0.001
No Plaque
100
Plaque
80
80
60
60
40
40
20
20
0
0
CAC 0
CAC 1-99
CAC =or>100
Chi square=9.1, Pr=0.01
IMT <75%
CAC 0
IMT>75%
CAC 1-99
CAC =or>100
Naqvi TZ et al. J Am Soc Echocardiogr. 2010;23:809-15
The Multi-Ethnic Study of Atherosclerosis (MESA)
• Prospective epidemiologic study
• Study population: White (38%), African American
(28%), Hispanic (22%), Chinese(12%)
• N=6698 (47.2% M), age 45-84
• Median follow up: 3.9 years
• HR for highest vs. lowest quartile:
-HR: 3.3 for maximal internal carotid IMT
-HR: 2.3 for maximal common carotid IMT
Folsom, A. R. et al. Arch Intern Med 2008;168:1333-1339
Baseline Plaque Area
& Plaque Progression
Predicts CV Events
5 yr risk 5.6% vs. 19.5%
N=1686
N=1085
5 yr risk 9.4% vs. 15.7%
Spence JD. Et al Stroke 2002 Dec;33(12):2916-22
3D Plaque Volume and Vessel Volume
Ainsworth C D et al. Stroke 2005;36:1904-1909
Shai I et al. Circulation 2010;121:1200-1208
SUMMARY
• Lack of uniform definition of IMT and of plaque
• CCA IMT alone without plaque assessment does not appear to
be clinically useful over and above FRS compared to IMT
inclusive of bulb and ICA
• Plaque predicts CV events better than IMT
• Plaque burden assessment and assessment of plaque
charateristics are better measures of atherosclerosis and CV
risk than presence or absence of plaque
• Plaque progression and regression may be a powerful tool to
evaluate effect of therapy
PLAQUE VS. IMT
• The dynamic range of measurements varies by
∼100-fold for TPV compared to ∼2-fold for the
IMT
• The resolution of carotid ultrasound is ∼0.2 mm,
whereas the annual change of IMT is ∼0.15
mm, so change cannot be measured within
individuals in clinically meaningful time frames
• Carotid TPA changes on average by ∼10 mm2
allowing measurement of progression or
regression within months
PLAQUE IS A GREAT EQUALIZER
• 12, 576 individuals
• 15.2 yr mean follow up
• CHD end points, no stroke
• Mean IMT of CCA IMT vs All segment IMT mean
C statistic
• ACRS 0.741
• All IMT and plaque 0.754
• CCA mean and plaque 0.753
Nambi V et al. Eur eart H2012;33:183-90
Presence of Calcified Carotid Plaque
Predicts Vascular Events: The Northern
Manhattan Study
Prabhakaran S et al Atherosclerosis 2007;195”e197 - e201
Common Carotid Intima-Media Thickness
Measurements in Cardiovascular Risk
Prediction: A Meta-analysis
Ruizter H et al. JAMA. 2012;308(8):796-803
HRP - BIOIMAGE STUDY - 63% > 2 RISK FACTORS
No CVD
or Significant Others
Control
Phone
6104
4 Baseline Imag.
Control
No Imaging
1085
3 Advanced Imag.
Am Heart J. 2010 Jul;160(1):49-57.e1.
PREDICTIVE VALUE OF IMT VS. PLAQUE
DIAGNOSTIC COHORT STUDIES - CAD
Metanalysis, 27 diagnostic cohort studies,
4,878 patients
Sensitivity
SROC Curve
1-specificity
Diagnostic accuracy of carotid
ultrasound for the detection of CAD
Inaba Y et al Atherosclerosis Volume 220, Issue 1 2012 128 - 133
Definitions of the Carotid Segments
Lorenz M W et al. Circulation 2007;115:459-467