| Most acute coronary related deaths are caused by the rupture of a fibrous cap atheroma, a complex biomechanical phenomenon, not yet fully understood. While it is generally accepted that plaque rupture occurs in the fibrous cap at the location where the local tissue stress exceeds a certain critical peak circumferential stress, the mechanism of rupture remains unknown and the current clinical criteria are unable to predict rupture before the cardiac event occurs.;The most widely accepted factor for increasing plaque vulnerability is the thickness of the fibrous cap overlying the necrotic core. However, the cap thickness criterion seems insufficient to fully predict the risk of atheroma rupture. Vengrenyuk et al. (PNAS, 2006) proposed an alternative hypothesis, namely that cellular size microcalcifications (µCalcs) embedded in the fibrous cap proper could greatly increase cap instability, by introducing a 2-fold increase in local tissue stress.;Here, the µCalcs hypothesis is re-evaluated using high resolution micro-computed tomography (µCT) and undecalcified histology with special emphasis on calcified particles <50 µm diameter. The results reveal the presence of thousands of µCalcs, observed embedded in 35% of the fibrous caps. These µCalcs were analyzed using 3D finite element analysis (FEA) to predict local tissue stress, and the results were used to develop important new clinical criteria for cap stability. Aside from cap thickness, µCalc size and interparticle spacing are hypothesized to be the principal determinants of cap rupture risk. A theoretical model based on classic studies in polymeric materials by Gent (1980) is developed herein, which indicates that cavitation as opposed to interfacial debonding is the more likely mechanism for cap rupture, produced by µCalcs 5 to 70µm diameter. Calcified particles <5µm, including calcified matrix vesicles, would not trigger cap rupture, yet, they could be the initiation of larger, dangerous µCalcs. This hypothesis for cap rupture is strongly supported by µCT studies in which voids were observed in the vicinity of µCalcs within fibrous caps in human coronaries. |
