REVIEW ARTICLE
Clinical Use of Carotid Intima-Media
Thickness: Review of the Literature
R. Todd Hurst, MD, Daniel W. C. Ng, MD, Chris Kendall, BS, RDCS, and
Bijoy Khandheria, MD, FESC, FACC, FASE, Scottsdale, Arizona
Carotid intima-media thickness (CIMT) is a simple
and inexpensive tool to assess the cumulative effect
of atherosclerotic risk factors and is an independent
predictor of future cardiovascular risk. CIMT is com-
monly used as a surrogate end point in research
trials as a marker of atherosclerosis. However, new
software programs have made CIMT a clinically
practical examination for risk evaluation. CIMT cor-
Carotid intima-media thickness (CIMT) is a simple
and inexpensive tool to assess the cumulative effect
of atherosclerotic risk factors and is an independent
predictor of future cardiovascular (CV) risk.1-5 CIMT
is a measure of the thickness of the intima and media
layer of the carotid artery most commonly assessed
by B-mode ultrasound (Figure 1). CIMT is commonly
used as a surrogate end point in research trials as a
marker of atherosclerosis.6 More important from a
clinical perspective, CIMT has been shown to cor-
relate with cardiac risk factors,2,7-9 to improve with
therapy of known benefit in preventing atheroscle-
rotic events,6,10-13 and to be an independent predic-
tor of future myocardial infarction and stroke risk.2-5
As the renowned physician William Osler noted,
“We are as old as our arteries.”14 This statement
rings especially true today, with CV disease being
the leading cause of mortality in the developed
world. Tests for subclinical atherosclerosis, such as
CIMT, will help clinicians to more effectively iden-
tify the vulnerable patient who would benefit from
aggressive prevention intervention.
Prevention of CV Disease
The risk stratification of an individual patient with-
out clinically apparent atherosclerosis (primary pre-
vention) is oftentimes complex. Judging the relative
contribution of various risk factors to the extent of
atherosclerosis, determining the risk of future CV
events, and assessing the risks and benefits of vari-
ous pharmacologic prevention interventions is com-
From the Mayo Clinic.
Reprint requests: R. Todd Hurst, MD, Mayo Clinic, 13400 E Shea
Blvd, Scottsdale, AZ85258 (E-mail: hurst.todd@mayo.edu).
0894-7317/$32.00
Copyright 2007 by the American Society of Echocardiography.
doi:10.1016/j.echo.2007.02.028
relates with cardiac risk factors and is an indepen-
dent predictor of future myocardial infarction and
stroke risk. Tests for subclinical atherosclerosis,
such as CIMT, will help clinicians to more effectively
identify the vulnerable patient who would benefit
from aggressive prevention intervention. (J Am Soc
Echocardiogr 2007;20:907-914.)
monly based on incomplete information. When
there is uncertainty as to the optimal treatment plan,
incremental data can add conviction to the provid-
er’s recommendation and possibly improve patient
compliance. The clinical scenario where the mea-
surement of CIMT is of most apparent benefit is in
the patient who is judged to be at intermediate risk
for future CV events (estimated at 40% of the
population)15 based on risk assessment tools such as
the Framingham Risk Score. In addition, there are
also patient scenarios where an individual is judged
to be at low risk of future CV events by traditional
risk stratification scoring but because of young age,
the presence of a strikingly abnormal single risk
factor, or of an emerging risk factor, the incremental
information provided by a CIMT may more accu-
rately assess this risk. Attractive features of CIMT as
a noninvasive measure of atherosclerosis are that it
is safe with no known adverse biological effects,
relatively inexpensive, and does not require radia-
tion exposure for the patient. The results are highly
reproducible,16 normal values are known, and it is
an independent predictor of CV events in a variety
of populations.2-5 In addition, CIMT adds incremen-
tal information to traditional risk assessment algo-
rithms. In the Paroi Arterielle et Risque Cardio-
vasculaire study of 6416 patients, a significant
correlation between all components of the Framing-
ham Risk Score and CIMT was found, but variations
in one parameter only explained a modest propor-
tion of variance in the other suggesting that CIMT
provides additional information to the Framingham
Risk Score.17 Similar results were shown in a pro-
spective study of 229 patients with diabetes who
were followed up over 5 years. The authors found
that the combination of the Framingham Risk Score
and CIMT significantly improved risk prediction.18
More recently, Gepner et al19 found that more than
907

908 Hurst et al
Figure 1 B-mode ultrasound of right common carotid artery with its midsegment highlighted.
50% of a moderate or moderately high-risk group as
determined by Framingham Risk Score changed risk
category when CIMT results were included in the
analysis.
CIMT and Atherosclerosis Risk Factors
Multiple established and emerging risk factors for
atherosclerosis are associated with CIMT. Tradi-
tional CV risk factors such as age,2,5 hyperten-
sion,7 diabetes,8 hyperlipidemia,2 and smoking9
correlate with increased CIMT. CIMT has also
been shown to correlate with emerging risk fac-
tors such as lipoprotein(a),20 oxidized low-density
lipoprotein,21,22 and homocysteine.2,23,24 Wang et
al25 found an association between common CIMT
and C-reactive protein in women in the Framing-
ham Heart Study, which remained significant even
after adjustment for traditional CV risk factors.
The Rotterdam Study also found C-reactive pro-
tein to be associated with CIMT and predict its
progression.26 Metabolic syndrome, its relation to
CV disease, and possible mechanisms, has re-
cently been a subject of intense research inter-
est.27 Scuteri et al,28 using data from the Baltimore
Longitudinal Study of Aging, found a dispropor-
tionate increase in CIMT in patients with meta-
bolic syndrome, even after adjusting for each
component. In a young population (mean age 32
years), those with metabolic syndrome had a
higher CIMT measurement in the Bogalusa Heart
Study compared with control subjects.29
CIMT and Other Measures of Atherosclerosis
Burden
B-mode measurement of the intima-media thickness
has been shown to reliably correlate with that of
pathological specimens.30 However, a theoretic limita-
tion of CIMT is that the artery being imaged is not a
Journal of the American Society of Echocardiography
July 2007
coronary artery. In other words, is carotid atheroscle-
rosis indicative of coronary or intracerebral atheroscle-
rosis? The general concept that atherosclerosis is a
systemic disease is well supported.31 CIMT has been
found to correlate with coronary artery atherosclerosis
as assessed by both computed tomography coronary
calcification and coronary angiography. The Rotter-
dam Calcification Study quantified coronary calcifica-
tion and performed B-mode ultrasound measurement
of the carotid arteries in 2013 patients. After adjust-
ment for traditional CV risk factors, CIMT was still
associated with computed tomography coronary cal-
cium score.32 The Muscatine Study extended these
findings to a young group of patients (age 33-42 years).
The authors found that although CIMT is statistically
correlated with computed tomography coronary ar-
tery calcium score, CIMT remains significantly associ-
ated with cardiac risk factors even when coronary
artery calcium was included in the multivariate model.
Thus, the association of CIMT and coronary artery
calcium may not be solely a result of shared risk factors
and both examinations may be helpful in assessing risk
in a younger population.33 Kafetzakis et al34 found a
correlation between significant coronary artery disease
(CAD) (defined as stenosis ⬎ 50%) as assessed by
coronary angiography and CIMT. This association in-
creased with the increasing number of coronary ves-
sels affected. Kablak-Ziembicka et al35 evaluated 558
patients who had undergone coronary angiography
with CIMT. They found a strong correlation between
CIMT and significant (⬎50% stenosis) coronary artery
stenosis. An individual with a CIMT of greater than
1.15 mm had a 94% chance of significant CAD in this
study.
CIMT as a Surrogate Marker of CAD
Atherosclerosis is a disease that begins at a young
age and progresses over decades.36 Because of this,
Journal of the American Society of Echocardiography
Volume 20 Number 7
Table 1 Therapeutic interventions that have been shown to influence carotid intima-media thickness
Intervention Risk factors involved
Amlodipine Hypertension
Lisinopril Hypertension
Pravastatin Familial hypercholesterolemia
Diet and exercise
Intensive diabetes therapy vs Diabetes mellitus
conventional therapy
Atorvastatin, pravastatin LDL
Pancreas transplantation Diabetes mellitus
Verapamil Hypertension
Fosinopril Hypertension
Pioglitazones Inflammation, atherosclerosis
Rosiglitazones Nondiabetic CAD
CAD, Coronary artery disease; CIMT, carotid intima-media thickness; LDL, low-density lipoprotein.
studies of clinical adverse CV end points often
require long-term follow-up and extensive re-
sources. Because of its ease of performance, safety,
availability, high reproducibility, and correlation
with CAD and CV events,5 CIMT has been com-
monly used to assess pharmacologic agents of use in
the treatment of CV disease (Table 1). Amlodipine37
and ramipril13 have been shown to decrease CIMT,
whereas verapamil38 and probucol39 have been
shown to slow progression. Long-acting metoprolol
has been shown to significantly decrease CIMT
compared with placebo with a trend toward de-
creased CV events.12 Thiazolidinediones, such as
pioglitazone, have also been shown to decrease
CIMT. In the Pioneer Study, 173 patients with type
2 diabetes mellitus were found to have a significant
reduction at 6 months (⫺54 ⫾ 59 ␮m, P ⬍ .001 vs
baseline), with no statistical change in the
glimepiride group. This result was independent of
long-term glucose control.6 Folic acid did not signif-
icantly affect CIMT or events in patients with
chronic renal failure who were followed up for a
mean of 3.6 years.40
The data for 3-hydroxy-3-methyl glutaryl-CoA re-
ductase inhibitors (statins) have been the most
impressive in regard to their effect on CIMT. The
Asymptomatic Carotid Artery Progression Study
studied 919 asymptomatic men and women with
hypercholesterolemia. In this study, lovastatin de-
creased mean CIMT (P ⬍ .001) and significantly
decreased CV event rate and mortality.41 MacMahon
et al11 extended these findings in 522 patients with
a history of CAD but average or below average
cholesterol levels. After 4 years of follow-up, the
group treated with pravastatin had a 0.014-mm
decrease in CIMT whereas the placebo group had a
0.048-mm increase in CIMT. Two separate studies
have shown a comparably larger decrease in CIMT
with aggressive lipid lowering using high-dose statin
Hurst et al 909
Finding References
61
Decreases CIMT
61
Decreases CIMT
62
Decreases CIMT
41
Decreases CIMT
63
Intensive diabetes therapy results
in less CIMT progression
41
Atorvastatin induced regression of
CIMT
64
Regression of CIMT
37
Regression of CIMT with lower
cardiovascular event rate
37
Stops progression of CIMT
6
Reduction in CIMT, independent
from glucose control
65
Reduction in CIMT progression
therapy. In 325 patients with familial hypercholes-
terolemia, atorvastatin (80 mg) decreased CIMT
(⫺0.031 mm [95% confidence interval ⫺0.007 to
⫺0.055]; P ⫽ .0017), whereas simvastatin (40 mg)
resulted in an increased CIMT (0.036 [0.014-0.058];
P ⫽ .0005) after 2 years.10 In the Arterial Biology for
the Investigation of the Treatment Effect of Reduc-
ing Cholesterol Trial, atorvastatin (80 mg) induced
CIMT regression (⫺0.034 ⫾ 0.021 mm) as com-
pared with pravastatin (40 mg) (0.025 ⫾ 0.017 mm;
P ⫽ .03) at 12 months.42 These studies were pub-
lished before evidence that aggressive cholesterol
lowering with high-dose statin therapy results in a
decrease in adverse CV events in patients with
recent acute coronary syndrome as compared with
less aggressive statin use.43 In contrast to the data
for statins, fibrate therapy does not appear to have
the same effect in decreasing CIMT.44
CIMT as a Clinical Predictor of CV Events
The most clinically relevant and promising aspect of
CIMT measurement is that it is predictive of future
risk for myocardial infarction and stroke. CIMT and
CV event rate risk has been evaluated in large
prospective trials with long-term follow-up in pa-
tients with known CAD, and in individuals 45 years
of age and older without clinically apparent CAD.
Consistently, CIMT is associated with risk of CV
event in these populations. In the Atherosclerosis
Risk in Communities Study, 7289 women and 5552
men age 45 to 70 years with no history of coronary
heart disease were followed up for 4 to 7 years. They
found that hazard rate ratios for myocardial infarc-
tion or coronary heart disease death for high versus
low tertiles were 6.69 for women and 2.88 for men.2
The Cardiovascular Health Study studied 5858 indi-
viduals older than 65 years without clinically appar-
ent coronary heart disease for a median of 6.2 years.
 Journal of the American Society of Echocardiography
910 Hurst et al July 2007

Figure 2 Posterior wall of right common carotid artery of 39-year-old athletic man with significant family
history of premature coronary artery disease and elevated serum lipoprotein(a) level. Vascular age is
estimated to be 50 years with Atherosclerosis Risk in Communities database. This study provides evidence
of advanced atherosclerosis despite low Framingham Risk Score.

Those with the highest quintile of CIMT had a 3.87
relative risk (adjusted for age and sex) of myocardial
infarction or stroke compared with those in the
lowest quintile. CIMT was as strong a predictor of
events as the traditional risk factors and after adjust-
ment for these risk factors, CIMT was the variable
most strongly associated with cardiac events.5 The
Kuopio Ischemic Heart Disease Risk Factor Study
found risk of myocardial infarction increased by 11%
with each 0.1-mm increase of common CIMT.3,4 The
Rotterdam Study was a single-center, nested case-
control study of 7983 patients older than 55 years
with a median follow-up of 2.7 years. When adjusted
for age and sex, the odds ratio for SD increase in
CIMT was 1.41 for stroke and 1.43 for myocardial
infarction.45
To determine a normal or threshold value for
CIMT in an individual, age, sex, and race have to be
taken into consideration. Setting an absolute value as
a threshold for abnormal CIMT without consider-
ation to age would overestimate the risk of CV event
in the older population while underestimating that
in the younger population. The most accurate inter-
pretation of a CIMT value is one compared with
population databases.46 There is commercial soft-
ware currently available that uses available research
databases to compare an individual’s result with that
obtained from a general population (Figure 2). Such
an approach allows for a determination of a vascular
age to an individual patient. When this vascular age
is incorporated into a traditional risk algorithm, this
information can provide an easy-to-understand as-
sessment of risk for patient and provider and may
lead to better matching of prevention recommenda-
tions to risk level and improved compliance.18
Effect of Preventative Interventions on CIMT
Although definitive studies have yet to be published,
there are promising data to suggest that CIMT may
be useful in evaluating the effectiveness of preven-
tion therapy. Lifestyle changes such as smoking
cessation, regular exercise, healthy diet choices, and
weight loss are the initial and most important steps
in any effective prevention regimen and CIMT has
been shown to improve with nonpharmacologic
preventative interventions. The Monitored Athero-
sclerosis Regression Study assessed a multifaceted
approach to prevention and found that reducing
body mass index by 5 kg/m2, quitting a 10-cigarette/
day smoking habit, and reducing dietary cholesterol
intake by 100 mg/day on average would reduce the
annual rate of CIMT progression by 0.13 mm year.47
In the Women’s Healthy Lifestyle Project, CIMT
progression was accelerated during the menopause
transition and a diet/exercise intervention slowed
this progression.48 The Los Angeles Atherosclerosis
Study found that increased activity level49 and in-
creased fiber intake50 is associated with a decreased
progression rate of CIMT. Similarly, good cardiore-
spiratory fitness as associated by cardiopulmonary
fitness (maximal oxygen uptake [mL/kg/min]) is
associated with slower progression of early athero-
sclerosis in middle-aged men.51 Weight loss after
Journal of the American Society of Echocardiography
Volume 20 Number 7
Table 2 Reproducibility of 3 major carotid intima-media thickness studies
Study
62
Rotterdam Study
Atherosclerosis Risk in Communities study63
Paroi Arterielle et Risque Cardiovasculaire Study
CI, Confidence interval.
gastric bypass has also been shown to decrease the
rate of progression of CIMT,52 and improved glyce-
mic control has been shown to slow CIMT progres-
sion in patients who are diabetic.53
Whether serial CIMT measurement predicts fu-
ture risk is still to be determined, but there are
limited initial data. Hodis et al54 performed serial
CIMT measurement and quantitative coronary an-
giography on 146 men age 40 to 59 years with
history of coronary artery bypass graft surgery for
an average follow-up of 8.8 years. For each
0.03-mm increase per year in CIMT there was an
increase in the relative risk of coronary event of
3.1. If a change in serial CIMT measurements in an
individual proves to be predictive, it would be a
powerful clinical tool not only for risk stratifica-
tion, but also for assessing and optimizing preven-
tion recommendations.
CIMT Technical Considerations
CIMT imaging requires methodic attention to ca-
rotid anatomy, ultrasound parameters, and a stan-
dardized measurement protocol that is compared
with a general population database. The primary
objective is to obtain valid and reproducible CIMT
measurements. A detailed carotid plaque screen is
recommended, with particular attention to the ca-
rotid artery bulb and the internal carotid artery. If
potentially obstructive plaque is identified, a dedi-
cated carotid duplex flow scan should be recom-
mended. Incidental findings such as a thyroid cyst or
nodule should also be noted.
To begin the CIMT examination, the patient
should be supine with the sonographer positioned
at the head of the bed. The patient and sonographer
should be comfortable during the examination with
careful attention paid to safe, efficient, and ergo-
nomic scanning positions to minimize the potential
for injury. The time needed for a thorough and
complete examination is dependent on the protocol
and sonographer experience, but typically is 15 to
60 minutes. During the scan the patient should have
minimal support under the neck to aid in neck
extension and rotation that will aid in positioning of
the carotid artery for optimal imaging. Linear-array
transducer frequency is best between 8 to 12 MHz
Hurst et al 911
Reproducibility
SD between paired measurements of sonographers, readers, and
visits were ⫺0.004, 0.066, and ⫺0.013 mm
Between-reader reliability coefficients ranging from 0.78 to 0.93
and coefficients of variation ranging from 13.1% to 18.3%
Intraclass correlation coefficient was 0.98 (95% CI 0.966-0.985),
and SD of the error measurement: 0.0185 mm (total 283
centers)
using fundamental frequency only. There should be
no harmonic or compound imaging as this will
“bloom” the returning signals and can create a
falsely thickened CIMT. The far wall CIMT should be
seen as a double line representing the lumen-intima
and media-adventitia interface. The best image reso-
lution is obtained when the ultrasound beam is
perpendicular to the structure being imaged, which
may require the scanner to manipulate transducer,
ie, heel-to-toe and/or rotation motions, to optimize
the intima-media image. Setting the focal position on
the far common carotid artery wall and using overall
gain, time gain compensation and postprocessing
functions (eg, dynamic range, edge, space/time) can
further enhance the quality of the images.
Reliability and Reproducibility
The difference in thickness between a normal scan
and an abnormal scan can be small and a common
concern for those who have not previously per-
formed CIMT measurement is whether the measure-
ment is accurate and reproducible. Data from pub-
lished research centers that have an expertise at
performing CIMT have consistently shown that the
measurement is highly reproducible, although this
varies somewhat depending on sites measured, num-
ber of measurements, and whether mean or maxi-
mum values were used (Table 2).
Newer semiautomated border detection programs
are available that are less time-consuming and more
reproducible for less experienced users (Figure 3). A
recent study compared a novice reader with a
reference laboratory using a semiautomated border
detection program. The novice reader results were
bioequivalent to the reference laboratory with small
absolute differences (experienced 0.011 ⫾ 0.004
mm, novice 0.022 ⫾ 0.004 mm) in CIMT and high
reproducibility (coefficients of variation: experi-
enced 3.1%, novice 7.8%).55
Carotid Plaque
As would be expected, the presence of carotid
plaque predicts an increased risk of future CV
events.56-58 In fact, the presence of plaque may be
a stronger predictor of future event risk than
increased CIMT.59,60 In the CAFES-CAVE study,

912 Hurst et al
Figure 3 Example of semiautomated border detection programs that allow more efficient carotid
intima-media thickness measurement for less experienced operators. Box, Area of interest with intima and
media highlighted for automated measurement. Operators may choose to manually adjust measurement
parameters in magnified view.
10,000 individuals at low risk had their femoral
and carotid arteries imaged with ultrasound and
were followed up for 10 years. The CV event rates
were 10 of 7989 in those with normal arteries, 81
of 930 (8.6%) in those with intima-media thicken-
ing, 239 of 681 (39.6%) in those with nonstenos-
ing plaque, and 381 of 470 (81%) in those with
stenosing plaques.66 Because plaque is a strong
predictor of risk and the primary goal of a test for
subclinical atherosclerosis is to identify those at
higher than expected risk, it has been suggested
that an efficient method to evaluate risk would be
complete if carotid plaque is found. If there is no
plaque, then determination of the CIMT would be
performed.67
Future Needs and Direction
Although measurement of CIMT has been correlated
with CV risk factors, has become a surrogate marker
for the effect of interventions targeting atherosclerosis,
and has shown to be predictive of future myocardial
infarction and stroke, it has remained primarily a
research tool until more recently. The introduction of
software that allows for less experienced laboratories
to efficiently and reproducibly measure CIMT and
compare those results with general population data-
bases has allowed CIMT to become a clinically practi-
cal test. Expert guidelines that establish training and
competency criteria and that recommend a protocol
for obtaining an accurate measure in an efficient and
clinically feasible manner is forthcoming from the
American Society of Echocardiography. Another factor
Journal of the American Society of Echocardiography
July 2007
that has limited more widespread use of CIMT is
reimbursement. Lack of reimbursement by traditional
health care payers is a common issue with preventa-
tive measures in general and this also applies to CIMT.
However, a Medicare Current Procedural Terminology
code has been created for CIMT, and as the focus of
medical care shifts from care of established diseases to
a focus on prevention of disease, health care payers
may be more likely to reimburse preventative care.
Although the research database for CIMT is one of
its strengths, further research is still needed to
possibly expand the use of CIMT in clinical practice.
Selected areas of investigation may include assessing
if the use of CIMT can lead to lower event rates by
identifying individuals at higher risk for preventative
measures. The role of CIMT in the assessment of the
effectiveness of an individual’s prevention regimen
will also need to be defined.
CIMT is a safe, reproducible test that is effective in
the risk stratification of selected individuals for
future CV events. Normal values are known in
diverse population studies to allow accurate inter-
pretation of the test results. Software programs with
semiautomated border detection capability and that
compare the result with the large population data-
bases to render a percentile score and a vascular age
combined with an imaging protocol that focuses on
the common carotid artery and the presence or
absence of atherosclerotic plaque will make CIMT a
test that is useful and practical in a clinical setting.
Challenges are apparent, but the future of CIMT in
CV disease risk stratification is bright.
Journal of the American Society of Echocardiography
Volume 20 Number 7
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