Eur J Vasc Endovasc Surg (2016) 52, 309e312
FOR DEBATE
Screening for Asymptomatic Carotid Plaques with Ultrasound
GLOBAL BURDEN OF CARDIOVASCULAR DISEASE
Atherosclerotic cardiovascular disease (CVD), especially
coronary heart disease (CHD), remains the leading cause of
premature death worldwide.1 Regrettably, CVD killed 17.5
million people in 2012, which accounts for 3 in every 10
deaths. Of these, 7.4 million people died of ischemic heart
disease and 6.7 million from stroke.2 CVD affects both men
and women and of all deaths that occur before the age of 75 in
Europe, 42% are caused by CVD in women and 38% in men.1
The total number of deaths from specific causes does not
provide a good metric for informing public health priorities,
hence years of life lost (YLL) has been introduced as a
measure of premature mortality that takes into account
both the frequency of deaths and the age at which death
occurs. YLL are calculated from the number of deaths at
each age multiplied by a global standard life expectancy for
the age at which death occurs.3 Ischemic heart disease and
stroke were among the top three causes of YLL in 2012.3 In
2012, global life expectancy from birth was 68.1 years for
men and 72.7 years for women, which had increased by 6
years since 1990.3 The incidence of CVD increases sharply
with age, and, given the current longevity seen in the
developed countries, the number of patients is expected to
increase. Despite gaps in our understanding, there is ample
evidence to justify intensive public health and individual
preventive efforts.1
THE PROBLEM WITH TRADITIONAL RISK FACTORS
Risk factors for atherosclerotic CVD are well known
(smoking, dyslipidemia, high blood pressure, diabetes)4 and
are used within the traditional risk factor-based approach,
such as the Framingham risk scores,5 to identify high-risk
groups. However, although these equations do identify
high-risk groups, in the subsequent 10 years, at best, only
40% of the heart attacks and strokes that will occur will be
contained in these high-risk groups.6 The remaining events
will occur in the low-risk group, which is very large involving
three-quarters of the population.6 Thus, contrary to
expectation, the risk factors causing atherosclerotic CVD are
not very useful in identifying the majority of individuals who
will develop CVD in the next 10 years.7e9
A recent study of risk prediction in 1.8 million population
without CVD confirmed that the application of existing CVD
risk scores (Framingham, ASSIGN, and QRISK2) may result in
DOI of original article: http://dx.doi.org/10.1016/j.ejvs.2016.06.002
1078-5884/Ó 2016 European Society for Vascular Surgery. Published by
Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ejvs.2016.04.013
considerable misclassification of high-risk status as these
risk scores do not predict the presence of high CVD risk well
and consistently.6 Therefore, cardiovascular risk calculated
from conventional risk factors (age, gender, raised choles-
terol, diabetes, elevated blood pressure, family history,
smoking) using the Framingham or PROCAM equations
leaves a lot to be desired, mainly because such equations
are age-driven. For example, a 40-year-old female who is a
heavy smoker, hypercholesterolemic, and hypertensive, has
a low 10-year Framingham risk in contrast with a 70-year-
old male who has no other risk factors and yet has a much
higher 10-year risk because of his age.
Risk may also be higher than indicated by risk estimation
charts in asymptomatic individuals with preclinical evidence
of atherosclerosis, for example plaque on carotid ultraso-
nography and in those with moderate to severe chronic
kidney disease (glomerular filtration rate [GFR] <60 mL/
min/1.73 m2).1 Individuals with documented asymptomatic
carotid plaque on ultrasound, peripheral arterial disease
(PAD), diabetes mellitus, and severe chronic kidney disease
are at very high risk.1
It is currently recommended that asymptomatic men
over the age of 40 and women over 50 years or post-
menopausal women should undergo risk factor screening
including lipid profile.10 Prevention efforts have been highly
promoted in recent years and evidence shows that 50% of
the reductions seen in coronary heart disease (CHD) mor-
tality relate to changes in risk factors, and 40% to improved
treatments.1 Data from high-income countries also indicate
that falls in mortality from cardiovascular diseases are the
main driver of rising life expectancy at age 60 for both men
and women.3 Although women appear to be at lower CVD
risk than men, this is misleading as risk is deferred by 10
years rather than avoided.1 It is well understood that the
higher the risk, the greater the benefit from preventive
efforts.1 The absolute reduction in atherosclerotic CVD
events is proportional to baseline absolute atherosclerotic
CVD risk.11 The question is how best to identify high-risk
groups that will contain the majority of cardiovascular
events that will occur subsequently, and how to identify
individuals at moderate or high risk in the absence of
conventional risk factors.
THE VALUE OF DETECTING SUBCLINICAL
ATHEROSCLEROSIS
Early detection of arterial disease in apparently healthy
individuals has focused on the peripheral arterial territory
and especially on the carotid arteries as they are easily
accessible and because atherosclerosis in one arterial
310
territory is often associated with involvement of other
territories.12 Ultrasound imaging of the carotid bifurcations
is a non-invasive means of assessing subclinical athero-
sclerosis. Carotid plaques are related to both coronary
obstructive disease13 and the risk of cerebrovascular
events.1
It has recently been demonstrated that screening with
ultrasound is particularly useful in the absence of risk fac-
tors.14 Thus, the detection of subclinical carotid or coronary
atherosclerosis improves risk predictions and reclassifica-
tion compared with conventional risk factors, with compa-
rable results for either modality.14 In one study, 47% of
asymptomatic individuals at low 10-year Framingham risk
(<10%) screened with ultrasound had carotid plaques.15
Such individuals should be reclassified as intermediate
(10e20%) or high risk (>20%) according to plaque number
and area present. In the CAFES-CAVE study, 10,000
asymptomatic, non-diabetic, normotensive individuals with
total cholesterol <5.2 mmol/L had both carotid and com-
mon femoral bifurcations scanned with ultrasound and
followed-up for 10 years.16 In the absence of plaques (90%
of the population), the average annual event rate was 0.1%.
In the presence of at least one plaque, the annual event
rate was 5% (mainly myocardial infarction). The annual
event rate was 3% if the plaque produced <50% stenosis
and 8% in the presence of >50% stenosis. Subsequent
studies have substantiated these findings and have
demonstrated that the presence of carotid plaques, how-
ever small, place an individual in a high-risk group.13,16e18
In addition, the bigger the plaque as measured by thick-
ness and preferably area, the higher is the risk.13,18 High
cardiovascular mortality in patients with asymptomatic ca-
rotid stenosis >50% was consistently reported in recent
publications (2006e2014) in which only some patients were
on statins.19e23 In these publications, the average annual
mortality was 5e6%. When causes of death were reported,
67% of deaths were from cardiac ischemic events.24e27
The above findings indicate that the presence of a carotid
plaque, however small, places an asymptomatic individual
in a high-risk group (10-year cardiac event rate >20% or
annual rate of >2%).
In future three-dimensional ultrasound may provide
better characterization of carotid atheroma with the assis-
tance of computer-based software, and thus may prove a
more accurate tool in the detection of early atherosclerosis.
SCREENING GUIDELINES: RESOLVING THE CONFUSION
The 2014 update of the 2007 U.S. Preventive Services Task
Force (USPSTF) recommendation statement on screening
for carotid artery stenosis recommends against screening
for asymptomatic carotid artery stenosis in the general
adult population.28 This recommendation is centered on
asymptomatic carotid artery disease producing 60e99%
stenosis, which has been traditionally considered as a cri-
terion for carotid surgery. Although the recommendation
against screening to identify those with >60% stenosis with
the view to offer surgery to non-selected patients is
For Debate
relevant, the statement significantly fails to address
asymptomatic carotid stenosis as subclinical atherosclerotic
disease which is a marker for all cardiovascular events and
could enable better targeting of intensive medical therapy.
The latest ACC/AHA guidelines published in November
2013 recommend that non-diabetic individuals without
clinical (i.e. asymptomatic) atherosclerotic cardiovascular
disease (ASCVD) and an LDL-C of 70e189 mg/dL (1.8e
4.9 mmol/L) should be treated aggressively with statins in
addition to other risk factor modifications when the 10-year
risk of ASCVD is >7.5% (average annual risk >0.75%).11 This
is because randomized controlled trials (RCTs) have
demonstrated that in such individuals the reduction in
ASCVD risk by statin therapy occurs regardless of risk factor
characteristics in both primary and secondary prevention
and outweighs potential harm from side effects. Thus, the
high incidence of myocardial infarction and mortality in
patients with asymptomatic carotid atherosclerotic plaques
as outlined above, and by the latest ACC/AHA guidelines
(2013), has resulted in a new concept of the value of
screening with ultrasound.
NEW CONCEPT OF SCREENING FOR ASYMPTOMATIC
CAROTID ATHEROSCLEROSIS WITH ULTRASOUND
Screening for asymptomatic carotid stenosis (ACS) in the
past was based on the belief that it was possible to prevent
strokes by operating or stenting the majority of moderate to
severe stenotic lesions. This practice, which is a legacy of
the ACAS29 and ACST30 trials, is now outmoded. This is
because recent reviews of cohort studies on the outcomes
of patients with ACS given medical intervention alone
(including the medical arms of randomized carotid endar-
terectomy trials) indicate that the average annual risk of
ipsilateral stroke has fallen to approximately 1% or less.31e
33
With the current annual stroke risk of
1%, carotid
endarterectomy or stenting is likely to produce more
strokes than it can prevent,34,35 unless it becomes possible
to identify a minority of patients at high risk for ipsilateral
stroke36,37 despite optimal medical therapy.
Screening for the presence of asymptomatic atheroscle-
rotic carotid plaques is a relatively new concept.38,39 The
presence of plaques, however small or large, is a marker of
high risk for myocardial infarction and death indicating the
need for optimal medical therapy (cessation of smoking,
lifestyle changes, adequate control of diabetes, BP control
to predefined targets, antiplatelet therapy, and high-
intensity statin therapy) according to current guidelines
for high-risk individuals. This need is supported by a wealth
of compelling evidence. Admittedly this evidence is not
from RCT, but it is unlikely that a RCT with a control group
receiving suboptimal medical therapy will ever be consid-
ered in such high-risk individuals for ethical reasons. In
addition, it indicates that such patients who are often
considered to be healthy or at low risk need a full cardiac
assessment with appropriate management. This is a unique
opportunity that may never again occur in their lifetime.
The cost-effectiveness of such screening programs should
For Debate
be evaluated in future studies, taking into consideration not
only impact (or lack of impact) on the prevention of future
neurologic events but on the total prevention of cardio-
vascular disease and mortality.
Arguably, individuals over the age of 50 at low Framing-
ham risk should have an arterial scan using ultrasound. If
negative, it does not need to be repeated until 3e5 years
later.38 If plaques are present, prophylactic medical therapy
is indicated with annual repeat scans to monitor plaque
progression or regression. Measuring plaque progression or
regression by an annual scan has an added value because it
is a strong motivation to individuals to adhere to prophy-
laxis with enthusiasm. It should be noted that in the
absence of plaques, risk factor modification is still indicated
in individuals at high Framingham risk. The notion that in
the presence of normal arteries risk factor modification is
unnecessary risk in such individuals is not supported by any
data.
In conclusion, ultrasonic screening for asymptomatic ca-
rotid disease maybe of paramount importance mainly as a
tool to identify high-risk individuals for cardiovascular dis-
ease and treat them aggressively rather than to identify
high-grade asymptomatic carotid stenosis requiring inter-
vention. The pros and the cons of such strategy should be
evaluated in a balanced critical analysis of the existing
literature.
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A.D. Giannoukas*
Department of Vascular Surgery, University Hospital of
Larissa, Faculty of Medicine, School of Health Sciences,
University of Thessaly, Larissa, Greece
M. Chabok
Department of Surgery and Cancer, Imperial College London,
UK
K. Spanos
Department of Vascular Surgery, University Hospital of
Larissa, Faculty of Medicine, School of Health Sciences,
University of Thessaly, Larissa, Greece
A. Nicolaides
Imperial College, London, UK
Nicosia Medical School, University of Nicosia, Cyprus
*Corresponding author. 13 Agorogianni str, 41335 Larissa,
Greece.
Email-addresses: agiannoukas@hotmail.com,
giannouk@med.uth.gr (A.D. Giannoukas)