Published online before print February 9, 2006, doi: 10.1161/01.STR.0000208558.95300.9a
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(Stroke. 2006;37:759.)
© 2006 American Heart Association, Inc.
Editorials |
Looking Beyond the Lumen to Predict Cerebrovascular Events
"The Road Less Travelled By"
From the University of Bonn, Department of Radiology, Bonn, Germany.
Correspondence to Winfried A. Willinek, University of Bonn, Department of Radiology, Sigmund-Freud-Str. 25, Bonn D-53105, Germany. E-mail winfried.willinek{at}ukb.uni-bonn.de
Key Words: atherosclerosis • carotid artery disease • magnetic resonance
See related article, pages 818–823.
I am not Robert Frost and this is not a literary review journal. I am a radiologist and it is my job to identify carotid artery disease. But of course, it is not unusual to dream as a physician that it would be possible, at some point, to identify the patient at risk and to predict future events in asymptomatic patients rather than just to detect carotid artery disease in symptomatic patients.
Carotid artery stenosis is a frequent finding in the general population with a prevalence of 75% in men and 62% in women over 64 years as determined by ultrasonography in the Cardiovascular Health Study.1 Since the introduction of catheter angiography in the early 20th century,2 luminal narrowing has become the standard parameter to report on the extent and severity of carotid artery stenosis. This is primarily related to several randomized clinical trials including the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST) which relied on assessment of luminal narrowing. These trials demonstrated a significant reduction in stroke risk, after carotid endarterectomy compared with medical treatment alone, in patients with luminal stenosis of >69%.3,4 However, the benefit of surgical treatment remains less clear in patients with lower grade carotid artery stenosis. Parameters other than luminal narrowing are needed to predict the risk of cerebrovascular events more reliably and to assess the potential benefit of carotid endarterectomy, particularly in the group of patients with moderate stenosis of 30% to 69%.5 Furthermore, as we know well from the coronary circulation, arterial remodelling is present even during early plaque formation. Angiography is not able to detect this early stage of atherosclerosis because luminal narrowing begins only when >40% of the area of the vessel wall is occupied by the plaque.6 Plaque rupture may occur in the presence of low grade stenosis in the coronaries and the degree of stenosis is a poor predictor of myocardial events.7 We also know from the coronaries that in >75% of acute myocardial infarctions, thromboembolism arises from plaque rupture8,9 and is more common in plaques with lesser luminal narrowing. Although less data are available for the carotid arteries, plaque rupture even in low-grade disease seems to play a similar role in the development of cerebrovascular events.10
Epidemiologically, it is important to recognize that, although carotid artery disease is common in the general population, the prevalence of stenosis with luminal narrowing >50% is rare (eg, <8% in the Cardiovascular Health Study). We know that the 5-year risk of stroke in asymptomatic patients with <60% carotid artery stenosis is 
8% (and 1.6% annually).11 Therefore, although the individual risk for cerebrovascular events with low- and moderate-grade luminal narrowing is relatively low, the implication for the overall risk of cerebrovascular events may be significant because of the high prevalence of this finding.
In previous decades, imaging of the lumen was the "diagnostic road" in the work-up of carotid artery disease. Techniques of "lumenography" included invasive digital subtraction angiography, noninvasive computed tomography angiography and magnetic resonance angiography. Although these techniques have been continuously improved, they have not reached the diagnostic goal of identifying "vulnerable" high-risk plaque that is likely to rupture (ie, to identify the patient at risk) and thereby to predict cerebrovascular events especially in less advanced disease.
Ultrasound has proven to be able to characterize plaque components and to assess stroke risk12; however, it is limited by low soft tissue contrast and low reliability in distinguishing hemorrhage from the lipid core.13 Multisequence MRI (MRI) has been shown to be reliable in identifying the plaque size and composition and, in contrast to ultrasound, allows differentiation between hemorrhage and lipid.14 Although several groups recently looked beyond the lumen for plaque characterization, little data are available on the relation between MRI features of carotid plaques and cerebrovascular events.
Now is the right time for the article by Takaya and colleagues: specific improvements in MR technology have resulted in the ability to quantify plaque components with high spatial resolution.15 In addition, with recent improvements in receiver coil design and developments in imaging sequences, MR imaging of atherosclerotic plaques is likely to be more widely used in clinical practice.16 Takaya et al prospectively studied the association between plaque composition and cerebrovascular events in 154 asymptomatic patients with ultrasonographically proven 50% to 79% carotid artery stenosis over a time period of at least 12 months.17 They found that the presence of a thin or ruptured fibrous cap, intraplaque hemorrhage, larger mean intraplaque hemorrhage area, larger maximum percentage of lipid-rich/necrotic core and larger maximum wall thickness accounted for an increased risk of subsequent ipsilateral cerebrovascular events. Thereby, they prospectively confirmed the well-established findings from retrospective trials that thin or ruptured fibrous caps and intraplaque hemorrhage are linked with cerebrovascular events.18 It is noteworthy, however, that the presence of lipid-rich/necrotic core without intraplaque hemorrhage was not significantly associated with subsequent ischemic events.
What can we conclude from these results? Should we now change the diagnostic work-up and include multisequence plaque MRI for risk stratification in every patient with carotid artery disease? Certainly not, it would be too early; we need more data to corroborate these findings. One limitation of the results of Takaya et al is the small number of cerebrovascular events in their population (n=14). Furthermore, the more general limitations of in vivo multisequence MRI of carotid artery plaques should not be overlooked, such as the relatively long total acquisition time as compared with other modalities (which is especially critical in the setting of acute stroke), the small volume coverage (usually imaging only the carotid bifurcation) and variable image quality (29 of the 183 patients selected by Takaya et al were excluded from the analysis because of nondiagnostic image quality).5,17 These limitations may become less relevant with the advent of an MR system operating at higher field strength (ie, 3.0T and above).
In summary, Takaya et al are one of the first to investigate the association between plaque components (most importantly a disrupted fibrous cap and intraplaque hemorrhage) and subsequent cerebrovascular events prospectively in asymptomatic patients as assessed by means of in vivo MRI. Larger prospective population-based multicenter trials are still needed and are underway to evaluate the role of carotid plaque MRI for risk stratification, especially in asymptomatic patients. Nevertheless, it is the right direction, although more investigators need to follow the road that was taken by Takaya and colleagues. Let us take the "road less traveled by" and it may make "all the difference"!
Footnotes
The opinions in this editorial do not necessarily reflect those of the editors or of the American Heart Association.
References
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Related Article:
Stroke 2006 37: 818-823.
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