Article

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

Department of Biomedical Engineering, The City College of New York, The City University of New York, New York, New York
AJP Heart and Circulatory Physiology (Impact Factor: 4.01). 07/2012; 303(5):H619-28. DOI: 10.1152/ajpheart.00036.2012
Source: PubMed

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.

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    • "These include intravascular ultrasound (IVUS) (Rioufol et al 2002, Carlier and Tanaka 2006), optical coherence tomography (OCT) (Jang et al 2002, Tearney et al 2008) and magnetic resonance imaging (IV-MRI) (Larose et al 2005, Briley-Saebo et al 2007). Diagnosis of high-risk atherosclerotic plaques remains problematic as the thickness of the fibrous cap alone is not a sufficient predictor of plaque stability (Virmani et al 2000, Ohayon et al 2008, Fleg et al 2012, Maldonado et al 2012). "
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    • "With evidence that higher plaque stresses are linked to plaque rupture and the selection of critical stress value as the representative value, critical stress values have been used in several studies concerning plaque rupture and assessment. Vengrenyuk et al. (2006, 2008), Bluestein et al. (2008), Maldonado et al. (2012), Cardoso and Weinbaum (2013), and Kelly-Arnold et al. (2013) demonstrated that plaque cap with micro-calcification inclusions are associated with elevated stress levels and may be related to plaque rupture. Gao et al. (2011) studied carotid plaques and found that critical stress values from symptomatic patients were higher that from asymptomatic patients. "
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