Spotty Calcification Typifies the Culprit Plaque in Patients With Acute Myocardial Infarction An Intravascular Ultrasound Study

University of Amsterdam, Amsterdamo, North Holland, Netherlands
Circulation (Impact Factor: 14.43). 11/2004; 110(22):3424-9. DOI: 10.1161/01.CIR.0000148131.41425.E9
Source: PubMed


Calcification is a common finding in human coronary arteries; however, the relationship between calcification patterns, plaque morphology, and patterns of remodeling of culprit lesions in a comparison of patients with acute coronary syndromes (ACS) and those with stable conditions has not been documented.
Preinterventional intravascular ultrasound (IVUS) images of 178 patients were studied, 61 with acute myocardial infarction (AMI), 70 with unstable angina pectoris (UAP), and 47 with stable angina pectoris (SAP). The frequency of calcium deposits within an arc of less than 90 degrees for all calcium deposits was significantly different in culprit lesions of patients with AMI, UAP, and SAP (P<0.0001). Moreover, the average number of calcium deposits within an arc of <90 degrees per patient was significantly higher in AMI than in SAP (P<0.0005; mean+/-SD, AMI 1.4+/-1.3, SAP 0.5+/-0.8). Conversely, calcium deposits were significantly longer in SAP patients (P<0.0001; mean+/-SD, AMI 2.2+/-1.6, UAP 1.9+/-1.8, and SAP 4.3+/-3.2 mm). In AMI patients, the typical pattern was spotty calcification, associated with a fibrofatty plaque and positive remodeling. In ACS patients showing negative remodeling, no calcification was the most frequent observation. Conversely, SAP patients had the highest frequency of extensive calcification.
Our observations show that IVUS allows the identification of vulnerable plaques in coronary arteries, not only by identifying a fibrofatty plaque and positive remodeling, but also by identifying a spotty pattern of calcification.

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    • "Moreover, the extent of calcification in unstable plaques did not change substantially across decades, whereas calcification area in stable plaques increased progressively with increasing age [26]. Intravascular ultrasound (IVUS) studies confirmed that spotty calcification, associated with a fibro-atheromatous plaque and positive remodeling, was the predominant pattern of calcium deposition in patients with AMI, whereas no calcification associated with negative remodeling prevailed in subjects with acute coronary syndrome (ACS) and extensive calcification in those with stable angina pectoris (SAP) [27]. Furthermore, patients with spotty calcification had a more frequent history of AMI "
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    ABSTRACT: Vascular calcification is an unfavorable event in the natural history of atherosclerosis that predicts cardiovascular morbidity and mortality. However, increasing evidence suggests that different calcification patterns are associated with different or even opposite histopathological and clinical features, reflecting the dual relationship between inflammation and calcification. In fact, initial calcium deposition in response to pro-inflammatory stimuli results in the formation of spotty or granular calcification ("microcalcification"), which induces further inflammation. This vicious cycle favors plaque rupture, unless an adaptive response prevails, with blunting of inflammation and survival of vascular smooth muscle cells (VSMCs). VSMCs promote fibrosis and also undergo osteogenic transdifferentiation, with formation of homogeneous or sheet-like calcification ("macrocalcification"), that stabilizes the plaque by serving as a barrier towards inflammation. Unfortunately, little is known about the molecular mechanisms regulating this adaptive response. The advanced glycation/lipoxidation endproducts (AGEs/ALEs) have been shown to promote vascular calcification and atherosclerosis. Recent evidence suggests that two AGE/ALE receptors, RAGE and galectin-3, modulate in divergent ways, not only inflammation, but also vascular osteogenesis, by favoring "microcalcification" and "macrocalcification", respectively. Galectin-3 seems essential for VSMC transdifferentiation into osteoblast-like cells via direct modulation of the WNT-β-catenin signaling, thus driving formation of "macrocalcification", whereas RAGE favors deposition of "microcalcification" by promoting and perpetuating inflammation and by counteracting the osteoblastogenic effect of galectin-3. Further studies are required to understand the molecular mechanisms regulating transition from "microcalcification" to "macrocalcification", thus allowing to design therapeutic strategies which favor this adaptive process, in order to limit the adverse effects of established atherosclerotic calcification. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 12/2014; 238(2):220-230. DOI:10.1016/j.atherosclerosis.2014.12.011 · 3.99 Impact Factor
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    • "Though atherosclerotic calcification is triggered by inflammation, it correlates in a dual manner with inflammation and plaque instability, depending on the pattern of calcium deposition. In fact, previous studies have reported an association of spotty or granular calcification (microcalcification ), and an inverse relation of diffuse, homogeneous calcification (macrocalcification), with morphological (Virmani et al. 2003) and clinical (Ehara et al. 2004; Shaalan et al. 2004; Nandalur et al. 2007; Kataoka et al. 2012) features of plaque instability. As mentioned above "
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    ABSTRACT: Galectin-3 has been increasingly recognized as an important modulator of several biological functions, by interacting with several molecules inside and outside the cell, and an emerging player in numerous disease conditions. Galectin-3 exerts various and sometimes contrasting effects according to its location, type of injury, or site of damage. Strong evidence indicates that galectin-3 participates in the pathogenesis of diabetic complications via its receptor function for advanced glycation (AGE) and lipoxidation (ALE) end-products. AGEs/ALEs are produced to an increased extent in target organs of complications, such as kidney and vessels; here, lack of galectin-3 impairs their removal, leading to accelerated damage. In contrast, in the liver, AGE/ALE tissue content and injury are decreased, because lack of galectin-3 results in reduced uptake and tissue accumulation of these by-products. Some of these effects can be explained by changes in the expression of receptor for AGEs (RAGE), associated with galectin-3 deletion and consequent changes in AGE/ALE tissues levels. Furthermore, galectin-3 might exert AGE/ALE- and RAGE-independent effects, favoring resolution of inflammation and modulating fibrogenesis and ectopic osteogenesis. These effects are mediated by intracellular and extracellular galectin-3, the latter via interaction with N-glycans at the cell surface to form lattice structures. Recently, galectin-3 has been implicated in the development of metabolic disorders because it favors glucose homeostasis and prevents the deleterious activation of adaptive and innate immune response to obesogenic/diabetogenic stimuli. In conclusion, galectin-3 is an emerging all-out player in metabolic disorders and their complications that deserves further investigation as potential target of therapeutic intervention.
    Glycobiology 10/2014; 25(2). DOI:10.1093/glycob/cwu111 · 3.15 Impact Factor
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    • "Indeed, large calcifications easily detected with coronary computed tomography (CT) do not seem to increase plaque vulnerability [4]. However, recent studies indicate an inverse relationship between cardiovascular risk and calcification density [5▪▪], and spotty or speckled areas of calcification, that can be observed in intravascular ultrasound (IVUS) [6] or optical coherence tomography (OCT) [7] are a good indicator of susceptibility of rupture [8]. These observations provide insights into the role calcification may play in the stability of the atherosclerotic plaque and suggest that it is not only the amount of vascular calcification, but the morphology, size and location that affect plaque vulnerability. "
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    ABSTRACT: Purpose of review Atherosclerotic plaque rupture and subsequent acute events, such as myocardial infarction and stroke, contribute to the majority of cardiovascular-related deaths. Calcification has emerged as a significant predictor of cardiovascular morbidity and mortality, challenging previously held notions that calcifications stabilize atherosclerotic plaques. In this review, we address this discrepancy through recent findings that not all calcifications are equivalent in determining plaque stability. Recent findings The risk associated with calcification is inversely associated with calcification density. As opposed to large calcifications that potentially stabilize the plaque, biomechanical modeling indicates that small microcalcifications within the plaque fibrous cap can lead to sufficient stress accumulation to cause plaque rupture. Microcalcifications appear to derive from matrix vesicles enriched in calcium-binding proteins that are released by cells within the plaque. Clinical detection of microcalcifications has been hampered by the lack of imaging resolution required for in-vivo visualization; however, recent studies have demonstrated promising new techniques to predict the presence of microcalcifications. Summary Microcalcifications play a major role in destabilizing atherosclerotic plaques. The identification of critical characteristics that lead to instability along with new imaging modalities to detect their presence in vivo may allow early identification and prevention of acute cardiovascular events.
    Current Opinion in Lipidology 10/2014; 25(5):327-332. DOI:10.1097/MOL.0000000000000105 · 5.66 Impact Factor
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