Editors' ChoiceCardiology

Twinkle, Twinkle, Little Plaque

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Science Translational Medicine  10 Jul 2013:
Vol. 5, Issue 193, pp. 193ec115
DOI: 10.1126/scitranslmed.3006922

Akin to a thin-skinned personality, thin-capped regions of atherosclerotic plaque are believed to be vulnerable to insult. Abrupt rupture of these coronary artery plaques, with its accompanying thrombosis and consequent myocardial cell death, is the mechanism of most heart attacks [myocardial infarction (MI)]. However, only the minority of atherosclerotic plaques are truly vulnerable, and thus, the ability to specifically pinpoint which plaques are likely to rupture is of vital clinical importance. Large deposits of coronary calcification, as seen by using conventional computed tomography (CT), typically correlate with stable atherosclerotic plaque. However, using higher-resolution CT, Kelly-Arnold et al. show that vulnerable atherosclerotic plaques contain previously unseen microcalcifications that may act as local, destabilizing stress concentrators.

Vulnerable plaques contain and often rupture at a region called a thin-capped fibroatheroma, in which a necrotic core exists in a pool of lipids and inflammatory cells, braced by only a relatively thin (<65 μm) layer of connective tissue. In this work, the authors used a micro-CT scanner capable of 2.1-μm resolution to reanalyze 92 formaldehyde-fixed autopsy specimens of coronary arteries that had been studied previously with a scanner capable of 6.7-μm resolution. Whereas the previous technology suggested microcalcification to be a relatively rare feature of fibroatheromas, at higher resolution, nearly one third of fibroatheromas displayed a significant number of microcalcifications (a mean of 1564 microcalcifications per fibroatheroma). The vast majority of these were between 5 and 15 μm in diameter and thus not visible with previous technology. Using three-dimensional finite element models, the authors then discussed the implications of the shear forces introduced by the microcalcification. The effect of two microcalcifications on local stress concentrations within the atheroma critically depends on the ratio of the distance between the two microcalcifications (the gap) to the diameter of the microcalcification; when this ratio fell below 0.4, the local stress concentration increases asymptotically. Only 3 of the 193 analyzed pairs of microcalcifications in these unruptured fibroatheromas met this criterion. Additional studies of patients with ruptured coronary plaques are thus needed to determine whether geometric relationships between microcalcifications correlate with plaque rupture, perhaps as part of the causal pathway.

Remarkable improvements in clinical outcomes after MI have been achieved over the past three decades. Indeed, a patient has a 95% chance of survival if he or she makes it to the hospital. However, MI remains a leading cause of death worldwide. Because atherosclerotic plaque rupture typically occurs insidiously and without warning, better methods to predict cardiac events are needed. Thus, further advancements in our ability to assess plaque characteristics in vivo will likely improve our understanding of the basic pathophysiology of plaque instability and lead to better predictive tools for the prevention of coronary artery disease.

A. Kelly-Arnold et al., Revised microcalcification hypothesis for fibrous cap rupture in human coronary arteries. Proc. Natl. Acad. Sci. U.S.A., published online 3 June 2013 (10.1073/pnas.1308814110). [Abstract]

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