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      Association of Matrix Gla protein gene (rs1800801, rs1800802, rs4236) polymorphism with vascular calcification and atherosclerotic disease: a meta-analysis

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          Abstract

          Association between the MGP gene rs1800801, rs1800802, rs4236 polymorphisms and vascular calcification and atherosclerotic disease was inconsistent. To clarify precise association, we performed this meta-analysis. Medline, Embase and China Knowledge Resource Integrated Database were systematically searched through December 2016. A total of 23 case-control studies, consisting of 5280 cases and 5773 controls, were included. The overall results suggested that the -7A polymorphism was associated with an increased risk for vascular calcification and atherosclerotic disease in the recessive model (OR = 1.50, 95% CI 1.01–2.24, P = 0.045). Subgroup analyses of Caucasians showed significant associations in the allelic model, recessive model, and homozygote model: allelic model (OR = 1.19, 95% CI 1.06–1.34, P = 0.004), recessive model (OR = 1.60, 95% CI 1.26–2.03, P < 0.001), homozygote model (OR = 1.83, 95% CI 1.18–2.81, P = 0.006). Subgroup analysis of the Asian population did not demonstrate any significant associations in any of the genetic models. No significant association was found in any genetic model amongst the rs1800802 and rs4236 polymorphisms. The findings of this meta-analysis indicate that the MGP gene rs1800801 polymorphism is significantly associated with vascular calcification and atherosclerotic disease, especially in the Caucasian population.

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          Coronary calcium as a predictor of coronary events in four racial or ethnic groups.

          In white populations, computed tomographic measurements of coronary-artery calcium predict coronary heart disease independently of traditional coronary risk factors. However, it is not known whether coronary-artery calcium predicts coronary heart disease in other racial or ethnic groups. We collected data on risk factors and performed scanning for coronary calcium in a population-based sample of 6722 men and women, of whom 38.6% were white, 27.6% were black, 21.9% were Hispanic, and 11.9% were Chinese. The study subjects had no clinical cardiovascular disease at entry and were followed for a median of 3.8 years. There were 162 coronary events, of which 89 were major events (myocardial infarction or death from coronary heart disease). In comparison with participants with no coronary calcium, the adjusted risk of a coronary event was increased by a factor of 7.73 among participants with coronary calcium scores between 101 and 300 and by a factor of 9.67 among participants with scores above 300 (P<0.001 for both comparisons). Among the four racial and ethnic groups, a doubling of the calcium score increased the risk of a major coronary event by 15 to 35% and the risk of any coronary event by 18 to 39%. The areas under the receiver-operating-characteristic curves for the prediction of both major coronary events and any coronary event were higher when the calcium score was added to the standard risk factors. The coronary calcium score is a strong predictor of incident coronary heart disease and provides predictive information beyond that provided by standard risk factors in four major racial and ethnic groups in the United States. No major differences among racial and ethnic groups in the predictive value of calcium scores were detected. Copyright 2008 Massachusetts Medical Society.
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            Coronary artery calcification: pathogenesis and prognostic implications.

            Coronary artery calcification (CAC) is a risk factor for adverse outcomes in the general population and in patients with coronary artery disease. The pathogenesis of CAC and bone formation share common pathways, and risk factors have been identified that contribute to the initiation and progression of CAC. Efforts to control CAC with medical therapy have not been successful. Event-free survival is also reduced in patients with coronary calcification after both percutaneous coronary intervention (PCI) and bypass graft surgery. Although drug-eluting stents and devices for plaque modification have modestly improved outcomes in calcified vessels, adverse event rates are still high. Innovative pharmacologic and device-based approaches are needed to improve the poor prognosis of patients with CAC.
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              A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps.

              In this article, we advance a hypothesis for the rupture of thin fibrous cap atheroma, namely that minute (10-mum-diameter) cellular-level microcalcifications in the cap, which heretofore have gone undetected because they lie below the visibility of current in vivo imaging techniques, cause local stress concentrations that lead to interfacial debonding. New theoretical solutions are presented for the local stress concentration around these minute spherical inclusions that predict a nearly 2-fold increase in interfacial stress that is relatively insensitive to the location of the hypothesized microinclusions in the cap. To experimentally confirm the existence of the hypothesized cellular-level microcalcifications, we examined autopsy specimens of coronary atheromatous lesions using in vitro imaging techniques whose resolution far exceeds conventional magnetic resonance imaging, intravascular ultrasound, and optical coherence tomography approaches. These high-resolution imaging modalities, which include confocal microscopy with calcium-specific staining and micro-computed tomography imaging, provide images of cellular-level calcifications within the cap proper. As anticipated, the minute inclusions in the cap are very rare compared with the numerous calcified macrophages observed in the necrotic core. Our mathematical model predicts that inclusions located in an area of high circumferential stress (>300 kPa) in the cap can intensify this stress to nearly 600 kPa when the cap thickness is <65 microm. The most likely candidates for the inclusions are either calcified macrophages or smooth muscle cells that have undergone apoptosis.
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                Author and article information

                Contributors
                chenjianghua@zju.edu.cn
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                18 August 2017
                18 August 2017
                2017
                : 7
                : 8713
                Affiliations
                [1 ]ISNI 0000 0004 1759 700X, GRID grid.13402.34, , Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, ; Hangzhou, Zhejiang China
                [2 ]Key Laboratory Of Nephropathy, Hangzhou, Zhejiang China
                [3 ]Kidney Disease Immunology Laboratory, the Third Grade Laboratory, State Administration of Traditional Chinese Medicine, Hangzhou, Zhejiang China
                Article
                9328
                10.1038/s41598-017-09328-5
                5562806
                28821877
                61ec5fc5-0784-4ad5-8262-a344cf641bb7
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 30 January 2017
                : 4 July 2017
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