Stroke, TIA, and determining "plaquetivity"
This is the largest study of excised carotid plaques to date. All patients were symptomatic. Although not all plaques could be analyzed for each category (which excluded 94 plaques from cap analysis), this remains the largest histological study of its kind.
This is the largest study of excised carotid plaques (N = 526) to date. All patients were symptomatic (159 with stroke and 367 with transient ischemic attack [TIAs]). Although not all plaques could be analyzed for each category (which excluded 94 plaques from cap analysis), this remains the largest histological study of its kind. The histological studies employed were quite detailed and give interesting insights into the similarities and differences between coronary and carotid “vulnerable plaque.” The findings support current published data in this field: symptomatic plaques have a large lipid core with foam cells and intraplaque hemorrhage (“echolucent plaque”) while unstable plaque (cap rupture) is associated with an inflammatory process. These features of plaque morphology have been well described in the literature.
The authors suggest that stroke is associated with more rapid resolution of inflammation than TIA and posit that there are different etiologies for the 2 processes; ie, TIA is a more active inflammatory process than stroke. Their analysis of inflammation over time in the stroke and TIA patients seems to bear this out, although there is significant overlap in the confidence limits between the 2 groups for all plaque characteristics other than macrophage infiltration. While these data drive an interesting hypothesis, the small numbers of specimens in the delayed (>180 day groups) are sufficient to prove the hypothesis. Looking at a comparison of inflammatory markers as displayed in
of the paper, it seems that the relative differences between plaques associated with stroke and TIA vary across time periods. For example, there seems to be more inflammation in the stroke group at 31 to 90 days and 90 to 180 days while there is less in the > 180 day group. Given these findings firm conclusions cannot be drawn.
This excellent study is hampered by several limitations, which the authors acknowledge. Foremost is the fact that the timing of intervention was not dictated by a protocol, but by clinical practice. It is standard practice to defer carotid endarterectomy after stroke for 6 weeks or more in many centers. Conversely, patients who present with TIAs are operated on much more quickly. In both situations surgery is often times based on the severity of stenosis, characteristics of the plaque (ie, ulceration), and the neurological status of the patient. Therefore while it is possible that stroke and TIA are different pathophysiologically, it is equally plausible that they are different stages in the same spectrum. Patients who present with stroke may have had silent TIAs or even strokes in the past. Observations made decades ago and confirmed on multiple occasions indicate that patients with stroke, TIA, and even high-grade “asymptomatic” stenoses may have CT evidence of infarction. These observations reinforce the fact that clinical presentation may not reflect plaque activity. Unfortunately these authors do not provide us with information on brain imaging studies, number, location, and size of brain infarctions. This would be of great help in further analysis.
Like many interesting studies this one raises more questions than it answers. Why do some plaques cause stroke while others only produce TIA? While the authors suggest it is the degree of inflammation, there are many other possibilities. Could it be the size of breach of the cap, the content of the plaque, the hemodynamics of the stenosis, or some combination of the above? It is easiest to believe that the size of the embolus is what differentiates TIA from stroke, in which case some combination of degree of plaque disc rupture and volume of echolucent plaque might be important. These authors suggest that the degree of inflammation is a unifying concept to explain such differences, but offer no data to directly answer or prove their point. Finally, the major distinction between coronary and carotid plaque remains unexplained. In the carotid bifurcation plaques, the more severe the stenosis, the higher the likelihood that plaque will be “unstable” and that symptoms will result. The direct correlation between degree of stenosis and symptoms has been confirmed not only histologically but by several large prospective randomized trials. In contrast, most acute coronary syndromes are caused by plaque rupture in unstable plaques associated with moderate rather than severe stenosis. Why there is a different relationship between plaque stability and diameter stenosis in the carotid and coronary circulations remains a mystery. Perhaps the hemodynamics in each circulation (differences in systolic and diastolic flow and/or conformational changes of the plaque) will shed some light on this in the future.
