rusconi.qxp 18/7/08 12:21 pm Page 13
Cardiovascular Risk Assessment and Primary Prevention in the Era of Plaque Imaging
that increased carotid IMT and the presence of plaques reflect the traditional risk factors). In my experience, direct patient involvement in the
presence of cardiovascular risk factors, are early markers of visualisation and discussion of his or her ultrasound findings increases
atherosclerosis, are associated with CAD, can predict clinical coronary patient co-operation in the risk-assessment process, the decision-making
events and can help in monitoring the effects of treatment as well as process and follow-up adherence to a treatment plan. A similar impact of
establishing its aggressiveness.
16–20
As suggested in a recent review anatomically based screening on patient management in a primary
paper,
20
evidence exists from both observational and intervention studies prevention setting has been documented in a recent six-year study using
indicating the appropriateness of using carotid IMT as a surrogate marker CCS.
39
It has been suggested that biomarkers of pre-clinical disease
for CAD and that its application in studies is based on the assumption progression, such as those obtainable using plaque imaging, could help to
that carotid plaques and changes in carotid IMT are related to the enhance the process of new drug development and characterisation several
presence of coronary atherosclerosis and the incidence of CAD years before the results from clinical end-point trials become available.
20
events, respectively.
Carotid Plaque Echolucency by Back-scatter Analysis
Predicting Coronary Artery Disease Events Demonstration of the extensibility of the carotid plaque findings to other
It has been shown that in patients with multiple focal thickening, the sum arterial territories, and to coronary arteries in particular, has been obtained
of the area of all focal lesions observed in the carotid tree is a superior in a very interesting study by Honda et al.
40
Seventy-one patients with acute
correlate of risk factors and a better prognosticator than IMT alone.
21,22
In CAD syndrome and 215 with stable CAD were submitted to coronary
general, a greater IMT value is associated with a greater event risk, and an angiography and carotid ultrasonography with integrated back-scatter (IBS)
increased IMT value has been found to correlate with cardiovascular risk analysis to objectively assess plaque echolucency, an indicator of plaque lipid
factors and CAD and to predict cardiovascular events,
23–29
as well as to content. Three major findings emerged from this study: patients with acute
identify patients who remained event-free in the follow-up period based on CAD had more echolucent carotid plaques; echolucent carotid plaques
their low IMT value.
28
accurately predicted the presence of complex coronary plaques by coronary
angiography (predictive power 83%); and stable CAD patients with
In the Kuopio Study,
27
the risk of myocardial infarction increased by 11% for echolucent carotid plaques showed a very high risk of future coronary
each 0.1mm increase in IMT of the common carotid artery. However, due to events in the 30-month follow-up period independently of other risk factors.
the influence of non-lipid factors such as age or hypertension, which induce In another study comparing middle-aged and elderly subjects with
medial hypertrophy, an increase in IMT value may be observed myocardial infarction patients, it has been shown that despite similar IMT
independently of the atherosclerotic process. Accordingly, early studies values in the three groups, IBS was significantly higher in elderly subjects and
demonstrated that CAD events are best predicted by plaque rather than lower in high-risk middle-aged subjects and myocardial infarction patients,
IMT imaging.
6–9
This correlation is higher, and the prognostic value of IMT with 11% of low-risk middle-age subjects, 29% of high-risk middle-age
measurements for predicting future CAD events is increased, when data subjects and 63% of myocardial infarction patients exhibiting lipid-rich
from all three segments (common carotid artery, carotid bifurcation and regions of carotid arteries.
41
These data strongly suggest that, in conjunction
internal carotid segments) are combined.
9
Moreover, studies showed that with conventional IMT measurements, IBS analysis allows us to identify
crude measures directly assessing plaques are equally good or better at high-risk subjects requiring aggressive risk-factor reduction.
predicting the risk of future CAD events.
30,31
Of note, risk estimates for
femoral artery atherosclerosis
30
were slightly weaker than those for In order to increase the diffusion and usefulness of carotid scanning
measures of carotid or aortic atherosclerosis. Evidence from intervention to facilitate clinical screening for subclinical atherosclerosis in assisting with
studies reinforces the observational data linking carotid IMT with CAD cardiovascular risk prediction, an abbreviated protocol has been proposed.
42
events. A significant positive association between the progression of carotid This protocol has combined plaque screening and isolated IMT
IMT over the two to four years of therapy and combined incidence of non- measurement of the common carotid artery’s far wall and exhibited a 100%
fatal myocardial infarction and coronary death has in fact been observed in sensitivity for an increased IMT. If either plaque or increased IMT of the
a long-term follow-up of patients in the Cholesterol-lowering common carotid artery is identified, a more aggressive risk factor
Atherosclerosis Study (CLAS) trial who received colestipol–niacin or placebo modification should be considered. A similar statement has been reported in
following coronary artery bypass graft (CABG) surgery.
32
A recent meta- a recent report from the American Society of Echocardiography (ASE) and
analysis of seven statin trials
33
showed a significant relationship between the the Society of Vascular Medicine.
19
progression of carotid IMT and the incidence of CAD events. In this meta-
analysis it has been suggested that carotid IMT met clinical and statistical Atherosclerosis Imaging in Metabolic Syndrome
criteria for use as a surrogate end-point for cardiovascular events in clinical According to recent European guidelines,
1
the metabolic syndrome identifies
trials of statins. individuals with an increased risk of developing cardiovascular disease in
accordance with the clustering of cardiovascular risk factors in individuals
Atherosclerosis Regression Studies with obesity or insulin resistance, but does not indicate risk of cardiovascular
Randomised trials using carotid ultrasonography have demonstrated that disease over and above the effect of the risk factors involved. An increasing
intensive lipid-lowering therapy can induce atherosclerosis regression
34–36
or frequency of the components of metabolic syndrome since paediatric age
reduce its progression even in low-risk individuals.
37
This was true not only has recently been observed,
43
and in a cohort study of 280,678 Danish
in a primary prevention setting but also in patients with known CAD despite schoolchildren followed up for decades it has been shown that the risk of
normal/below average cholesterol levels,
38
ultimately indicating that non- CAD events later in life was positively associated with BMI at seven to 13
invasive modalities of atherosclerosis imaging by ultrasound are mature years of age for boys and 10 to 13 years of age for girls,
44
confirming that
enough to be incorporated by cardiologists into their office-based CAD risk atherosclerosis is a paediatric problem and needs intervention even during
assessment (mostly in patients deemed intermediate-risk for future events by childhood to reduce the risk of future CAD.
EUROPEAN CARDIOLOGY 13
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