title: A mechanistic analysis of the role of microcalcifications in atherosclerotic plaque stability: potential implications for plaque rupture.
abstract: The role of microcalcifications (μCalcs) in the biomechanics of vulnerable plaque rupture is examined. Our laboratory previously proposed (Ref. 44), using a very limited tissue sample, that μCalcs 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-μm resolution and undecalcified histology with special emphasis on calcified particles <50 μm in diameter. Our results reveal the presence of thousands of μCalcs, the vast majority in lipid pools where they are not dangerous. However, 81 μCalcs were also observed in the fibrous caps of nine of the fibroatheroma. All 81 of these μCalcs 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 μCalc and surrounding tissue, μCalc size, and clustering. We found that local tissue stress could be increased fivefold when μCalcs were closely spaced, and the peak circumferential stress in the thinnest nonruptured cap (66 μm) if no μCalcs 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 μCalcs < 15 μm in the caps, not visible at 6.7-μm resolution, and that our failure to find any nonruptured caps between 30 and 66 μm is a strong indication that many of these caps contained μCalcs.
authors: Department of Biomedical Engineering, The City College of New York, The City University of New York, New York, New York 10031, USA.
authors: Natalia
authors: N
authors: Maldonado
authors: Adreanne
authors: A
authors: Kelly-Arnold
authors: Yuliya
authors: Y
authors: Vengrenyuk
authors: Damien
authors: D
authors: Laudier
authors: John T
authors: JT
authors: Fallon
authors: Renu
authors: R
authors: Virmani
authors: Luis
authors: L
authors: Cardoso
authors: Sheldon
authors: S
authors: Weinbaum
mesh_terms: D000368:Aged; D001696:Biomechanical Phenomena; D003198:Computer Simulation; D003324:Coronary Artery Disease / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology; D003331:Coronary Vessels / Q000473:pathology* / Q000503:physiopathology; D055119:Elastic Modulus; D005260:Female; D005355:Fibrosis; D020342:Finite Element Analysis; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D058226:Plaque, Atherosclerotic; D011857:Radiographic Image Interpretation, Computer-Assisted; D012422:Rupture, Spontaneous; D013314:Stress, Mechanical; D061205:Vascular Calcification / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology; D055114:X-Ray Microtomography / Q000379:methods*