A mechanistic analysis of the role of microcalcifications in atherosclerotic plaque stability: potential implications for plaque rupture

Maldonado N, Kelly-Arnold A, Vengrenyuk Y, Laudier D, Fallon JT, Virmani R, Cardoso L, Weinbaum S. A mechanistic analysis of the role of microcalcifications in atherosclerotic plaque stability: potential implications for plaque rupture. Am J Physiol Heart Circ Physiol 303: H619-H628, 2012. First published July 9, 2012; doi:10.1152/ajpheart.00036.2012.-The role of microcalcifications (mu Calcs) in the biomechanics of vulnerable plaque rupture is examined. Our laboratory previously proposed (Ref. 44), using a very limited tissue sample, that mu Calcs embedded in the fibrous cap proper could significantly increase cap instability. This study has been greatly expanded. Ninety-two human coronary arteries containing 62 fibroatheroma were examined using high-resolution microcomputed tomography at 6.7-mu m resolution and undecalcified histology with special emphasis on calcified particles <50 mu m in diameter. Our results reveal the presence of thousands of mu Calcs, the vast majority in lipid pools where they are not dangerous. However, 81 mu Calcs were also observed in the fibrous caps of nine of the fibroatheroma. All 81 of these mu Calcs were analyzed using three-dimensional finite-element analysis, and the results were used to develop important new clinical criteria for cap stability. These criteria include variation of the Young's modulus of the mu Calc and surrounding tissue, mu Calc size, and clustering. We found that local tissue stress could be increased fivefold when mu Calcs were closely spaced, and the peak circumferential stress in the thinnest nonruptured cap (66 mu m) if no mu Calcs were present was only 107 kPa, far less than the proposed minimum rupture threshold of 300 kPa. These results and histology suggest that there are numerous mu Calcs < 15 mu m in the caps, not visible at 6.7-mu m resolution, and that our failure to find any nonruptured caps between 30 and 66 mu m is a strong indication that many of these caps contained mu Calcs.