Asymptomatic carotid plaque rupture with unexpected thrombosis over a non-canonical vulnerable lesion

Abstract

a b s t r a c tObjective: Several studies have demonstrated that carotid plaque rupture and thrombosis represent the most important factors correlated with the onset of acute cerebrovascular symptoms. Nevertheless, ruptured thrombotic plaques have been described also in asymptomatic patients. What still needs to be clarified is why a plaque rupture leads either to an acute ischemic syndrome or, in a minor group of patients, remains asymptomatic. The purpose of this study was to systematically compare the histologic features of thrombotic plaques both in asymptomatic and symptomatic patients in order to identify specific findings that could explain the peculiar clinical behavior that characterizes each of the clinical settings. Methods: A total of 157 thrombotic plaques from 60 asymptomatic patients and 97 with major stroke who consecutively underwent CEA were serially sectioned and studied by histology. Results: A minute cap disruption very frequently characterizes thrombotic plaques of asymptomatic patients and it was always smaller than large ulcers observed in thrombotic symptomatic plaques (651 ± 687 m vs. 4150 ± 3526, p = 0.001). In asymptomatics this typical feature was associated with fewer inflammatory cells (20.1 ± 8.8 vs. 33.9 ± 26.1 cells × hpf, p = 0.001), smaller lipidic-necrotic core (33.9% ± 2.9% vs. 42.0% ± 2.4%; p = 0.04) and larger calcification (16.2 ± 12.8% vs. 8.1 ± 12.2%, p = 0.02). Symptomatic patients with thrombotic plaques showed higher incidence of metabolic syndrome (p = 0.002) and moderate-high Framingham risk scores (p = 0.001) comparing to asymptomatic individuals. Conclusion: The transformation from a stable to a vulnerable plaque is a gradual process in the natural history of the disease and plaque rupture is an event not necessarily occurring at a late phase but also at earlier one. In this case, the rupture will be most likely smaller and clinically asymptomatic.

Human Coronary Thrombus Formation Is Associated With Degree of Plaque Disruption and Expression of Tissue Factor and Hexokinase II

“…Mauriello et al showed that symptomatic thrombotic carotid plaques have long plaque disruption, severe stenosis, abundant macrophages and a large necrotic core, compared with asymptomatic thrombotic plaques. 23 The present results are compatible with these features except for the macrophage content, which in the present study tended to be larger in symptomatic, than in asymptomatic thrombotic plaques. The difference, however, did not reach statistical significance, because only a few asymptomatic thrombotic plaques in the present study had abundant macrophages.…”

Comparison of Contrast Agents for Atherosclerosis Imaging Using Cultured Macrophages: FDG Versus Ultrasmall Superparamagnetic Iron Oxide

“…However, the contribution of these differently polarized macrophages to vulnerable plaque formation, potentially resulting in plaque rupture, has not yet been fully understood. For example, Mauriello et al recently reported that M2 but not M1 macrophages were present in the fibrous cap near the rupture site in the human carotid artery, suggesting that M2 macrophages might also modulate the process of plaque rupture (32). Although further investigations regarding the roles of M1 and M2 macrophages in atherosclerotic lesions are needed, it is clear that macrophage polarization affects plaque diagnosis and prognosis.…”

FoxO1 regulates asymmetric dimethylarginine via downregulation of dimethylaminohydrolase 1 in human endothelial cells and subjects with atherosclerosis

“…3c), indicating that FoxO1 activity is associated with the regulation of the DDAH1/ADMA system during atherogenesis. In a subset of atherosclerotic plaques with available immunohistochemical analyses (n ¼ 55), classified as stable or unstable according to established criteria [30], we found that both ADMA levels in the sera and FoxO1 nuclear amount in the plaques were significantly higher in patients with features of unstable atherosclerosis (Fig. 3d and e), while DDAH1 mRNA expression was reduced (Fig.…”