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Atherosclerotic Plaque Morphology and the Conundrum of the Vulnerable Plaque

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Cholesterol Crystals in Atherosclerosis and Other Related Diseases

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Abstract

The reason why stable atherosclerotic plaques rupture or erode leading to atherothrombosis remains a conundrum. While occasionally myocardial infarction follows an “acute external triggering event,” most appear to occur at random.

The concept of a “vulnerable plaque primed to rupture” was based on post-mortem studies that found atherothrombosis was frequently associated with ruptured plaques that had a thin fibrous cap, a large lipid core, and inflammatory infiltration in its shoulder regions. However, these morphologic descriptors do not explain the processes that occurred within the plaque prior to rupture, and do not explain why in up to one third of cases atherothrombosis is associated with plaque erosion in the absence of inflammation.

Although non-invasive imaging has been able to identify that plaques with a large lipid rich core associated with inflammation are at somewhat higher risk of future injury, most such plaques remain stable.

Together these observations indicate that the vulnerability of plaques is dynamic and raises the possibly that instability relates to ongoing changes in the physiochemistry of the lipid core that at times favors the formation of cholesterol crystals that can “change the destiny of a plaque” by causing traumatic injury and changing the trajectory of the inflammatory milieu in the plaque bed so that it begins to favor persistent inflammatory injury rather than healing.

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Nidorf, S.M., Madder, R., Elshafie, A., Abela, G.S. (2023). Atherosclerotic Plaque Morphology and the Conundrum of the Vulnerable Plaque. In: Abela, G.S., Nidorf, S.M. (eds) Cholesterol Crystals in Atherosclerosis and Other Related Diseases. Contemporary Cardiology. Humana, Cham. https://doi.org/10.1007/978-3-031-41192-2_9

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