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Rev Esp Cardiol. 2016;69(9):813–816
Editorial
Aortic Calcium Score and Vascular Atherosclerosis in Asymptomatic
Individuals: Beyond the Coronary Arteries
Cuantificación del calcio aórtico y arteriosclerosis vascular en individuos
asintomáticos: más allá de las arterias coronarias
José F. Rodrı́guez-Palomares* and Artur Evangelista Masip
Servei de Cardiologia, Hospital Vall d’Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
Article history:
Available online 13 July 2016
INTRODUCTION
Atherosclerosis is a generalized, progressive, chronic condition
that can affect the entire vascular tree.1 The clinical manifestations
of atherosclerosis are ischemic heart disease, cerebrovascular
disease, and peripheral arterial disease. Despite the current
prevention strategies and a prompt diagnosis (through diagnostic
imaging techniques), atherosclerosis is a major cause of morbidity
and mortality in Western societies,2,3 responsible for 84.5% of
cardiovascular deaths and 28.2% of deaths due to any cause.4
From a pathophysiological viewpoint, atherosclerosis is a
dynamic process that begins with deposition of lipid particles
on the arterial wall, followed by apoptosis of the vascular smooth
muscle cells and release of matrix vesicles. This process, together
with macrophage infiltration, leads to calcification of the arterial
wall intima. Fragments of the calcified plaque spread through the
surrounding collagen tissue matrix and converge, forming
fibrocalcific plaques.5 Thus, arterial wall calcification is considered
a direct marker of atherosclerotic disease. Over the last 2 decades,
there has been a growing interest in detecting vascular calcifica-
tion by various diagnostic imaging techniques in asymptomatic
individuals with cardiovascular risk factors. The aim is to achieve
improved risk stratification and reduce atherosclerotic disease-
related morbidity and mortality.
Atherosclerosis is a complex phenomenon, involving numerous
factors. An important one is increased blood concentrations of low
density lipoprotein cholesterol, which causes changes in capillary
permeability and gradual alterations in the arterial walls.
Atherosclerosis is more prevalent in older individuals, those with
hypertension, smokers, and patients with diabetes mellitus or
insulin resistance.6 Atherosclerotic plaques in the aorta have been
associated with elevated homocysteine concentrations, prothrom-
botic markers (prothrombin), proinflammatory markers, (eg,
leucocyte count, C-reactive protein concentration), and left
ventricular hypertrophy. Although the white population shows a
SEE RELATED ARTICLE:
http://dx.doi.org/10.1016/j.rec.2016.01.031, Rev Esp Cardiol. 2016;69:827–35.
* Corresponding author: Servei de Cardiologia, Hospital Universitari Vall
d’Hebron, Paseo Vall d’Hebron 119-129, 08035 Barcelona, Spain.
E-mail addresses: jfrodriguezpalomares@gmail.com, jfrodrig@vhebron.net
(J.F. Rodrı́guez-Palomares).
http://dx.doi.org/10.1016/j.rec.2016.05.006
1885-5857/ß 2016 Sociedad Española de Cardiologı́a. Published by Elsevier España, S.L.U. All rights reserved.
lower prevalence of hypertension and diabetes than the black
population, paradoxically, it has a greater atherosclerotic burden.7
There is also some controversy regarding the distribution by sexes:
although coronary disease is less prevalent in women than men,
there is evidence that women have a higher incidence of aortic
atherosclerosis, even at earlier ages and regardless of the presence
of cardiovascular risk factors.8
STRUCTURAL AORTIC WALL CHANGES ASSOCIATED WITH
ATHEROSCLEROSIS
Atherosclerotic plaque formation in the aortic wall causes wall
erosion and degeneration of the normal media layer. Subsequently,
wall atrophy and wall thinning occur, and the vessel dilates in
parallel with increases in the volume of plaque.9 Dilation is
considered a compensatory mechanism to prevent or delay stenosis
of the vessel lumen, but in arteries having a medium-sized or small
diameter and a large atherosclerotic burden, it is sometimes
insufficient and stenosis ensues. In larger vessels, however, dilation
maintains the vessel lumen open for a longer time, avoiding
stenosis but producing a risk of aneurysm formation (Figure 1).
Changes in the aortic media layer are also associated with a
decrease in the elastic properties and distensibility of the vessel. In
this regard, non-oscillatory shear stress on the vessel wall has been
linked with greater fat infiltration and cholesterol-rich plaques,
which perpetuate the dilation process. Aortic calcifications
originate in vessel segments where the wall stress is less intense,
but highly ocillatory. The lesser curvature of the aortic arch and the
posterior wall of the descending aorta are the most commonly
affected areas.
Another factor associated with vascular dilation is the vessel
wall tension. Wall tension is proportional to the radius of the
vessel; thus, with gradual thinning of the arterial wall, the tension
produced suffices to cause a slow increase in the vessel diameter.
This increase then leads to an increase in wall tension, resulting in
a vicious circle of vascular atrophy and dilation. This mechanism
explains why the descending aorta and abdominal aorta are more
prone to develop aneurysms than the coronary or carotid arteries.
The medial layer of the vessel segments most proximal to the
aorta contains vasa vasorum. These structures, which vascularize
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814 J.F. Rodrı´guez-Palomares, A. Evangelista Masip / Rev Esp Cardiol. 2016;69(9):813–816
Figure 1. 3D reconstruction of the aorta showing severe, diffuse
atherosclerosis associated with formation of aortic aneurysms and
increased tortuosity of the vessel. Anterior view (left panel) and posterior
view (right panel) of the aorta.
the vessel wall layers, are not found in the more distal segments.
Hence, when atherosclerotic plaques are present, impeding proper
diffusion and irrigation of the vessel wall from the lumen,
hypoperfusion can occur in this region. This reduction in wall
perfusion also facilitates atrophy and progressive dilatation, and
helps to explain the greater frequency of aneurysms in the
abdominal aorta.10
The aortic flow pattern is another factor that has an influence on
aortic dilatation. A clockwise helicoidal flow pattern has been
described at the level of the aortic arch that protects against plaque
formation in the distal arch and the proximal descending aorta. In
addition, the aorta shows a gradual physiologic narrowing known
as aortic taper, in which the ascending aorta has a larger diameter
than the descending aorta. This results in an acceleration of blood
flow in the descending aorta, which avoids sluggish flow and the
development of atherosclerosis. However, when the descending
aorta progressively dilates as a consequence of diffuse aortic
atherosclerosis, the blood flow slows and this favors progression of
the atherosclerotic plaques.11 Atherosclerosis, together with
Figure 2. 3D reconstruction of an unenhanced computed tomography study showing severe, diffuse aortic calcification (A). Axial tomographic image depicting
aortic calcification determined using the Agatston score (B).
changes in the aortic wall composition and elasticity, lead to
elongation and tortuosity of the aorta.12 These alterations in the
morphology and configuration of the vessel are associated with
wall tension and flow distribution changes, which enhance the
degenerative process.
Thus, there is a relationship between atherosclerosis and
changes in aortic morphology. In a recent study in Revista Española
de Cardiologı´a, Craiem et al. were the first to describe a correlation
between aortic calcification and the diameter of the aortic arch and
descending aorta. These authors also found that the ascending
aorta diameter did not correlate with the total aortic calcium,
suggesting that aortic dilation may have different pathophysio-
logic mechanisms and require different prevention strategies.13
Despite considerable therapeutic advances in secondary
prevention of atherosclerotic disease, achieving a prompt diagno-
sis of the condition in asymptomatic patients (ie, primary
prevention) remains a challenge. That is why huge efforts have
been made in recent years to develop and apply noninvasive
diagnostic imaging techniques to promptly detect atherosclerotic
disease.
DIAGNOSTIC IMAGING TECHNIQUES FOR EARLY DETECTION
OF ATHEROSCLEROSIS
Based on the relationship between vascular calcification and
atherosclerotic disease, several diagnostic imaging techniques
have focused on detection and measurement of vascular calcifica-
tion as a marker of the degree and severity of atherosclerosis.
Radiologic study of vascular calcification by fluoroscopy was
described at the end of the 1950s, and soon after, an association
was established between vascular calcification and episodes
of cardiovascular disease.14 The later development (in the
1980s) of electron beam computed tomography and mutidetector
computed tomography enabled vascular calcification to be
precisely diagnosed and measured (Figure 2A).
Vascular calcium is measured using the Agatson score, which is
the product of the area of each calcification (in pixels, mm2) having
computed tomographic attenuation of at least 130 Hounsfield
units and the density score, obtained by rating the lesion on a
scale.15 The Agatston score has been widely used for studying
coronary atherosclerosis16 because it provides important prog-
nostic information, as will be seen later on.
In an effort to establish prognostic factors and markers of
cerebrovascular and peripheral vascular disease (in addition to
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J.F. Rodrı´guez-Palomares, A. Evangelista Masip / Rev Esp Cardiol. 2016;69(9):813–816
ischemic heart disease), use of the Agatston score has been
extended to other levels of the vascular tree (Figure 2B).
However, the imaging protocol for calculating the score (eg, slice
thickness, kilovoltage) has only been standardized for measur-
ing coronary calcification. Standardized protocols are lacking for
assessment of aortic calcium, and this can lead to considerable
variation.
In determining the coronary calcium score, the software used in
the analysis can generate a certain degree of variability in the
results. Nonetheless, comparisons of intra-scanner measurements
obtained with the same system as well as inter-scanner measure-
ments have shown quite high agreement.17 The variability is
greater, however, when scoring aortic calcium: the score value
increases as slice thickness decreases, and other changes occur
when the remaining imaging parameters used in the reconstruc-
tion are modified. Craiem et al. established a standardized protocol
for quantifying aortic calcification by computed tomography using
2.5-mm slice thickness. The authors determined the calcification
burden in total and by sections, after dividing the aorta into
5 anatomic segments: segment 1, from the sinotubular junction
to the pulmonary bifurcation; 2, from the pulmonary bifurcation to
the brachiocephalic trunk; 3, from the brachiocephalic trunk to the
left subclavian artery; 4, from the left subclavian artery to the
descending aorta at the level of the pulmonary bifurcation; and 5,
the thoracic descending aorta from the pulmonary bifurcation to
the coronary sinus.18
This observational study found that 60% of aortic calcification is
concentrated in the aortic arch and the proximal descending aorta.
The presence of aortic calcium was considered a prognostic risk
factor beyond the conventional factors, able to define a subgroup of
patients who would benefit the most from intensive treatment and
close follow-up.18
VASCULAR CALCIFICATION AND PROGNOSTIC IMPLICATIONS
The importance of scoring vascular calcium resides in the
prognostic implications of the scores obtained in the follow-up of
patients with classic cardiovascular risk factors. Based on the
calcium score, patients with intermediate cardiovascular risk can
be reclassified to the high-risk group. In early studies, coronary
calcium detected by fluoroscopy in patients with coronary disease
was associated with shorter survival during follow-up14 regardless
of the severity of the stenosis seen on coronary angiography. Since
that time, numerous studies have demonstrated the prognostic
value of the calcium score in asymptomatic patients with an
intermediate risk of coronary disease.
In a progressive manner, as in the Framingham risk scale, the
risk for a non-fatal infarction or cardiovascular death is 3.9 times
greater in individuals with an Agatston score of more than
300 than in those with a score of 0. These findings have been
corroborated by other observational studies showing that an
elevated calcium score is linked with higher cardiovascular
mortality, even after adjusting for the classic cardiovascular risk
variables,19,20 as a high score is often associated with the presence
of significant coronary disease. Furthermore, since atherosclerosis
risk increases with age, an Agatston score higher than 615 in
persons older than 65 years would classify them as being at high
risk, whereas a score below 50 would reclassify them into the low-
risk population.
Atherosclerosis is considered a systemic disease, and various
studies have reported an association between coronary calcifica-
tion and vascular disease at other levels. For example, coronary
artery disease is more severe in patients showing greater aortic
calcification.21 This association has led to an increasing interest in
detecting vascular calcifications beyond those occurring in the
815
coronary arteries. The FAPS study reported that patients with
atherosclerotic plaques in the distal ascending aorta and aortic
arch had a higher stroke rate than those with atherosclerosis of the
descending thoracic aorta.22 Later on, a report from the MESA
study, which assessed the correlation between coronary calcifica-
tion and carotid intima-media thickness, found that the coronary
calcification score showed a better correlation with the total of
cardiovascular episodes, whereas intima-media thickness corre-
lated better with cerebrovascular episodes.23
A recent study by Bos et al. in 2408 asymptomatic patients older
than 55 years reported that extension of vascular calcification
beyond the coronary vessels was associated with a higher overall
mortality rate regardless of the classic cardiovascular risk factors.
In addition, calcium in the aortic arch was linked with a higher rate
of cardiovascular mortality.24
There is considerable interest in the prognostic value of
calcification at different levels of the vascular tree, as the additional
data obtained by diagnostic imaging will provide more compre-
hensive information on cardiovascular risk. The ultimate aim is to
achieve earlier and better risk stratification in the asymptomatic
phase, which will help to guide the management of these patients.
However, despite this growing interest, there are several
scientific gaps that deserve further study. First, the optimal imaging
protocol is uncertain and the extent of the vascular tree that should
be examined is unknown. The advantages of prognostic stratifica-
tion must be weighed against the inherent risk of radiation
exposure, which is low but not negligible, considering the
magnitude of the entire vascular tree. Nor is it known how often
these examinations should be carried out to provide a close follow-
up and proper monitoring of the response to treatment. Lastly, the
age range of the population that might benefit the most from these
imaging studies also needs to be defined. In older patients, age itself
and determination of the cardiovascular risk factors would likely
provide sufficient prognostic data, while the diagnostic imaging
findings would not offer additional information.
In conclusion, aortic atherosclerosis leads to changes in the
morphology and configuration of the aorta. In turn, these changes
are an additional factor favoring progression of the atherosclerotic
disease. Therefore, early detection of atherosclerosis in the
subclinical phase would enable initiation of measures to slow
its progression and improve the prognosis of patients with
cardiovascular risk factors. Although further scientific evidence
is needed, the current data indicate that more complete detection
of vascular atherosclerosis beyond the coronary arteries will
provide prognostic information of interest that can be used to
guide the clinical management of these patients.
CONFLICTS DE INTEREST
None declared.
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