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Nakahashi, Takuya ; Tada, Hayato ; Sakata, Kenji ; Nomura, Akihiro ; Ohira, Miho ; Mori, Mika ; Takamura, Masayuki ; Hayashi, Kenshi ; Yamagishi, Masakazu ; Kawashiri, Masa-aki ; 多田, 隼人 ; 坂田, 憲治 ; 野村, 章洋 ; 大平, 美穂 ; 森, 三佳 ; 高村, 雅之 ; 林, 研至 ; 山岸, 正和 ; 川尻, 剛照
出版情報: Journal of Atherosclerosis and Thrombosis.  25  pp.709-719,  2018.  日本動脈硬化学会 = Japan Atherosclerosis Society
URL: http://hdl.handle.net/2297/00053009
概要: 金沢大学附属病院循環器内科<br />Aim: To assess whether combining measurements obtained from carotid ultrasonography in addition to th e age, creatinine, and ejection fraction (ACEF) score would improve the predictive ability of outcome in patients with acute coronary syndrome (ACS).\nMethods: We examined 264 patients with ACS (194 men; mean age: 68±11 years) who underwent percutaneous coronary intervention. The carotid plaque score (cPS) and intima–media thickness (cIMT) were determined by carotid ultrasonography. The modified ACEF score was calculated using the following formula: (age/left ventricular ejection fraction) +1 point for every 10 mL/min reduction in creatinine clearance below 60 mL/min per 1.73 m2. The endpoint of this study was major adverse cardiovascular and cerebrovascular events (MACEs), defined as all-cause death, myocardial infarction, stoke, and target vessel revascularization.\nResults: During the median 4-year follow-up, there were 121 incidents of MACEs. Multivariate Cox proportional hazard regression analysis revealed that cPS ≥9.8 (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.01–2.31) and ACEF score ≥1.20 (HR, 1.62; 95% CI, 1.11–2.39) were significantly associated with MACEs, whereas cIMT was not. When the new combined risk score was calculated by multiplying the cPS by the modified ACEF score, the freedom from MACEs at 5 years was 71% and 31% for the lower and higher scores, respectively (p<0.001). The area under the receiver-operating characteristic curve for MACEs for the ACEF score, cPS, and combined risk score were 0.65, 0.66, and 0.71, respectively (p<0.05).\nConclusion: The cPS offers an incremental predictive value when combined to the simple ACEF score in ACS.<br />This article distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License. 続きを見る
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Tada, Hayato ; Kawashiri, Masa-aki ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Yasuda, Kenji ; Mabuchi, Hiroshi ; Yamagishi, Masakazu ; Hayashi, Kenshi ; 多田, 隼人 ; 川尻, 剛照 ; 野原, 淳 ; 稲津, 明広 ; 小林, 淳二 ; 馬淵, 宏 ; 山岸, 正和 ; 林, 研至
出版情報: Journal of Atherosclerosis and Thrombosis.  24  pp.338-345,  2017.  日本動脈硬化学会 = Japan Atherosclerosis Society
URL: http://hdl.handle.net/2297/00053012
概要: 金沢大学附属病院循環器内科<br />Aim: The Japan Atherosclerosis Society (JAS) guidelines for the prevention of atherosclerotic disease s 2012 (JAS2012) proposed lipid management targets; however, less data is available regarding the attainment rates of each target in community-based settings. Therefore, we assessed the attainment rates of lipid management targets among subjects who underwent Japanese specific health checkups.\nMethods: A total of 85,716 subjects (male=29,282, 34.2%) aged 40–74 years who underwent specific health checkups from 2012 to 2014 in Kanazawa city, Japan, were included in this study. We evaluated the attainment rates of the lipid management targets according to the JAS2012 guideline and investigated the clinical characteristics of the subjects without achieving the targets.\nResults: The target for LDL cholesterol (LDL-C) was the least attained in all risk categories, 89, 72, 50, and 34% for category I, II, III, and secondary prevention, respectively, in 2014. In addition, these rates inversely correlated with the grade of risk categories (p-value for trends <0.001). Attainment rate of the LDL-C target in the suspected chronic kidney disease (CKD) group was significantly lower than in the groups with diabetes, stroke, or absolute risk in category III (49.2, 60.3, 63.5, 54.4%, respectively, p-value <0.001 for each). Moreover, the attainment rate of the LDL-C target was significantly lower in subjects that did not receive lipid-lowering therapy than in those who received it in the secondary prevention (27.7 and 40.6%, respectively, p-value <0.001).\nConclusions: Lipid management is inadequate in community-based settings, particularly, in subjects with CKD and secondary prevention.<br />This article distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License. 続きを見る
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Sakamoto, Aiji ; Sugamoto, Yuka ; Tokunaga, Y. ; Yoshimuta, Tsuyoshi ; Hayashi, Kenshi ; Konno, Tetsuo ; Kawashiri, Masa-aki ; Takeda, Yoshiyu ; Yamagishi, Masakazu ; 林, 研至 ; 今野, 哲雄 ; 川尻, 剛照 ; 武田, 仁勇 ; 山岸, 正和
出版情報: Journal of International Medical Research.  39  pp.522-527,  2011.  SAGE Publications
URL: http://hdl.handle.net/2297/00050263
概要: 金沢大学医薬保健研究域医学系<br />Ephrin B1 and its cognate receptor, Eph receptor B2, key regulators of embryogenesis, are expressed in human atherosclerotic plaque and inhibit adult human monocyte chemotaxis. Few data exist, however, regarding the gene expression profiles of the ephrin (EFN) and Eph receptor (EPH) family of genes in atherosclerosis-related human cells. Gene expression profiles were determined of all 21 members of this gene family in atherosclerosis-related cells by reverse transcription-polymerase chain reaction analysis. The following 17 members were detected in adult human peripheral blood monocytes: EFNA1 and EFNA3 - EFNA5 (coding for ephrins A1 and A3 - A5); EPHA1, EPHA2, EPHA4 - EPHA6 and EPHA8 (coding for Eph receptors A1, A2, A4 - A6 and A8); EFNB1 and EFNB2 (coding for ephrins B1 and B2); and EPHB1 - EPHB4 and EPHB6 (coding for Eph receptors B1 - B4 and B6). THP-1 monocytic cells, Jurkat T cells and adult arterial endothelial cells also expressed multiple EFN and EPH genes. These results indicate that a wide variety of ephrins and Eph receptors might affect monocyte chemotaxis, contributing to the development of atherosclerosis. Their pathological significance requires further study. © 2011 Field House Publishing LLP. 続きを見る
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Tada, Hayato ; Kawashiri, Masa-aki ; Konno, Tetsuo ; Yamagishi, Masakazu ; Hayashi, Kenshi ; 多田, 隼人 ; 川尻, 剛照 ; 今野, 哲雄 ; 山岸, 正和 ; 林, 研至
出版情報: Journal of Atherosclerosis and Thrombosis.  23  pp.241-256,  2016.  Japan Atherosclerosis Society = 日本動脈硬化学会
URL: http://hdl.handle.net/2297/00050285
概要: 金沢大学医薬保健研究域医学系<br />Blood lipid levels are highly heritable and modifiable risk factors for coronary artery disease (CAD ), and are the leading cause of death worldwide. These facts have motivated human genetic association studies that have the substantial potential to define the risk factors that are causal and to identify pathways and therapeutic targets for lipids and CAD. The success of the HapMap project that provided an extensive catalog of human genetic variations and the development of microarray based genotyping chips (typically containing variations with allele frequencies >5%) facilitated common variant association study (CVAS; formerly termed genomewide association study, GWAS) identifying disease-associated variants in a genome-wide manner. To date, 157 loci associated with blood lipids and 46 loci with CAD have been successfully identified, accounting for approximately 12%– 14% of heritability for lipids and 10% of heritability for CAD. However, there is yet a major challenge termed “missing heritability problem,” namely the observation that loci detected by CVAS explain only a small fraction of the inferred genetic variations. To explain such missing portions, focuses in genetic association studies have shifted from common to rare variants. However, it is challenging to apply rare variant association study (RVAS) in an unbiased manner because such variants typically lack the sufficient number to be identified statistically. In this review, we provide a current understanding of the genetic architecture mostly derived from CVAS, and several updates on the progress and limitations of RVAS for lipids and CAD. © 2016, Japan Atherosclerosis Society. All rights reserved.<br />出版者照会後に全文公開 続きを見る
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Uchiyama, K. ; Ino, H. ; Hayashi, Kenshi ; Fujioka, K. ; Takabatake, S. ; Yokawa, J. ; Namura, M. ; Mizuno S. ; Tatami, R. ; Kanaya, H. ; Nitta, Y. ; Michishita, I. ; Hirase, H. ; Ueda, K. ; Aoyama, T. ; Okeie, K. ; Haraki, T. ; Mori, K. ; Araki, T. ; Minamoto, M. ; Oiwake, H. ; Konno, Tetsuo ; Sakata, Kenji ; Kawashiri, Masa-aki ; Yamagishi, Masakazu ; 林, 研至 ; 山岸, 正和
出版情報: Journal of International Medical Research.  39  pp.549-557,  2011.  SAGE Publications
URL: http://hdl.handle.net/2297/00050292
概要: 金沢大学医薬保健研究域医学系<br />Percutaneous coronary intervention (PCI) using a drug-eluting stent (DES) leads to less re-stenosis than PCI using a bare metal stent (BMS), however there is still controversy whether use of a DES for severe coronary disease leads to an acceptable outcome in patients with diabetes mellitus (DM). In this study 8159 lesions were treated in 6739 patients (mean age 68.9 years) with coronary artery disease. Use of a DES significantly decreased the re-stenosis rate compared with BMS in both DM (9.6% versus 21.3%) and non-DM (9.5% versus 17.1%) patients. The re-stenosis rate was significantly higher in DM than in non-DM patients in the BMS group but not in the DES group. There was no statistically significant difference in event-free survival after stenting of patients with left main coronary artery (LMCA) disease between the BMS and DES groups. It was concluded that, compared with BMS, DES reduced re-stenosis in patients with DM, however, we advise careful treatment after using DES for severe coronary disease, including LMCA lesions, in patients with DM. © 2011 Field House Publishing LLP. 続きを見る
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Oka, Rie ; Yamada, Takayoshi ; Nakanishi, Chiaki ; Konno, Tetsuo ; Kawashiri, Masa-aki ; Hayashi, Kenshi ; Nohara, Atsushi ; Inazu, Akihiro ; Yamagishi, Masakazu ; 大家, 理恵 ; 八木, 邦公 ; 今野, 哲雄 ; 川尻, 剛照 ; 林, 研至 ; 野原, 淳 ; 稲津, 明広 ; 山岸, 正和
出版情報: Journal of Atherosclerosis and Thrombosis.  21  pp.582-592,  2014.  Japan Atherosclerosis Society = 日本動脈硬化学会
URL: http://hdl.handle.net/2297/00050638
概要: 金沢大学医薬保健研究域医学系<br />Aim: The commonly observed relationship between increased visceral adiposity and metabolic abnormali ties may be partly mediated by a concomitant increase in liver fat content. We evaluated the independent association between the level of alanine aminotransferase (ALT) as a surrogate marker of the liver fat content and the incidence of metabolic abnormalities after adjusting for the amount of visceral adipose tissue (AT). Methods: The subjects included 1,118 Japanese individuals (44% women) who underwent computed tomography to assess the amount of visceral AT on medical checkups. Cross-sectional associations between the serum ALT, visceral AT and metabolic risk factors were examined. Results: The ALT level and visceral AT were found to show a significant correlation (r =0.41 in men and r =0.36 in women, p<0.001). In a multivariable linear regression analysis, the ALT level and visceral AT were found to be independently associated with blood pressure in men and triglycerides and 2-hour post-challenge glucose in both genders (p<0.01), whereas only visceral AT was found to be associated with HDL-cholesterol (p<0.01). When the participants were classified into four subgroups based on the 75th percentiles of ALT and visceral AT, the low-ALT/high-visceral AT group, but not the high-ALT/low-visceral AT group, had a significantly higher odds ratio for low HDL-cholesterol among both genders (p<0.05) and for hypertriglyceridemia in men only (p<0.05). Meanwhile, the high-ALT/low-visceral AT group, but not the low-ALT/high-visceral AT group, had a significantly higher odds ratio for IGT among women (p<0.05). Conclusions: Although the ALT level and visceral AT were found to be independently associated with most metabolic risk factors, visceral AT had a dominant association with dyslipidemia in both genders, while the ALT level appeared to have a closer association with IGT in women.<br />出版者照会後に全文公開 続きを見る
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Fujino, Noboru ; Yoshimuta, Tsuyoshi ; Ichida, Fukiko ; Kinugawa, Koichiro ; Usuda, Kazuo ; Kitayama, Michihiko ; Ino, Hidekazu ; Kuroda, Shigetoshi ; Tada, Hiroshi ; Mizuno, Sumio ; Hayashi, Kenshi ; Takemura, Hirofumi ; Yamagishi, Masakazu ; 藤野, 陽 ; 吉牟田, 剛 ; 林, 研至 ; 竹村, 博文 ; 山岸, 正和
出版情報: Circulation Journal.  81  pp.1261-1267,  2017.  Japanese Circulation Society = 日本循環器学会
URL: http://hdl.handle.net/2297/00050640
概要: 金沢大学医薬保健研究域医学系<br />The 81st Annual Scientific Meeting of the Japanese Circulation Society was held in Kanazawa, Japan, on March 17-19, 2017 under a miraculously clear sky. The frontlines of healthcare and medicine are dramatically changing. Thus, “Cardiovascular Medicine for Next Generation” was chosen as the main theme of this meeting. The program was constructed around major identified issues, including renewal of our understanding of basic cardiovascular medicine, translational research, and preventive molecular medicine, all of which are anticipated to transcend the medical field over the next generation. Despite the provincial location, 15,672 participants, including more than 400 from overseas countries, attended the 3-day meeting, and there were in-depth discussions in the various sessions. In particular, to our great pleasure, Her Imperial Highness Princess Takamado kindly attended the opening ceremony and extended congratulations to us. The meeting successfully completed and we sincerely appreciate the great cooperation and support from all affiliates. © 2017 Circulation Journal. All rights reserved.<br />出版者照会後に全文公開 続きを見る
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Nomura, Akihiro ; Konno, Tetsuo ; Fujita, Takashi ; Tanaka, Yoshihiro ; Nagata, Yoji ; Tsuda, Toyonobu ; Hodatsu, Akihiko ; Sakata, Kenji ; Nakamura, Hiroyuki ; Kawashiri, Masa-aki ; Fujino, Noboru ; Yamagishi, Masakazu ; Hayashi, Kenshi ; 今野, 哲雄 ; 坂田, 憲治 ; 川尻, 剛照 ; 藤野, 陽 ; 山岸, 正和 ; 林, 研至
出版情報: Circulation Journal.  79  pp.136-143,  2014-12-19.  Japanese Circulation Society = 日本循環器学会
URL: http://hdl.handle.net/2297/00050641
概要: 金沢大学医薬保健研究域医学系<br />Background: Although fragmented QRS complex (frag-QRS) reflecting intra-ventricular conduction delay has been shown to be a prognostic marker for cardiac events, few data exist regarding the impact of frag-QRS on cardiac events in hypertrophic cardiomyopathy (HCM).Methods and Results: Ninety-four HCM patients (56 male; mean age, 58}17 years) were retrospectively investigated. Frag-QRS was defined as the presence of various RsR’ patterns in at least 2 contiguous ECG leads. Major arrhythmic events (MAE) were defined as sudden cardiac death, and combined sustained ventricular tachycardia/ventricular fibrillation. New-onset atrial fibrillation (AF) was diagnosed based on ECG during provisional or routine medical examination. Heart failure (HF) with hospitalization was defined as hospital admission due to subjective or objective symptoms. Frag-QRS was detected in 31 patients (33%). TNNI3 was the most frequent disease-causing gene. Median follow-up was 4.6 years. The 4-year cumulative survival rates of cardiac death, MAE, new-onset AF and HF with hospitalization were 97.6%, 94.6%, 87.5% and 89.3%, respectively. On multivariate analysis, frag-QRS was significantly associated with HF with hospitalization (adjusted hazard ratios [95% confidence intervals]: 5.4 [1.2–36], P=0.03). Moreover, HF-free survival was significantly lower in the frag-QRS (+) group compared to the frag-QRS (–) group (79.0% vs. 95.1%, P=0.03).Conclusions: Frag-QRS is associated with HF with hospitalization in HCM patients who had a unique distribution of gene mutations. © 2014, The Japanese Circulation Society<br />出版者照会後に全文公開 続きを見る
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Nakanishi, Chiaki ; Nagaya, Noritoshi ; Ohnishi, Shunsuke ; Yamahara, Kenichi ; Takabatake, Shu ; Konno, Tetsuo ; Hayashi, Kenshi ; Kawashiri, Masa-aki ; Tsubokawa, Toshinari ; Yamagishi, Masakazu ; 中西, 千明 ; 今野, 哲雄 ; 林, 研至 ; 川尻, 剛照 ; 山岸, 正和
出版情報: Circulation Journal.  75  pp.2260-2268,  2011-09.  Japanese Circulation Society = 日本循環器学会
URL: http://hdl.handle.net/2297/00050643
概要: 金沢大学医薬保健研究域医学系<br />Background: Mesenchymal stem cells (MSC) are multipotent and reside in bone marrow (BM), adipose tis sue and many other tissues. However, the molecular foundations underlying the differences in proliferation, differentiation potential and paracrine effects between adipose tissue-derived MSC (ASC) and BM-derived MSC (BM-MSC) are not well-known. Therefore, we investigated differences in the gene and secretory protein expressions of the 2 types of MSC. Methods and Results: ASC and BM-MSC were obtained from subcutaneous adipose tissue and BM of adult Lewis rats. ASC proliferated as rapidly as BM-MSC, and had expanded 200-fold in approximately 2 weeks. On microarray analysis of 31,099 genes, 571 (1.8%) were more highly (>3-fold) expressed in ASC, and a number of these genes were associated with mitosis and immune response. On the other hand, 571 genes (1.8%) were more highly expressed in BM-MSC, and some of these genes were associated with organ development and morphogenesis. In secretory protein analysis, ASC secreted significantly larger amounts of growth factor and inflammatory cytokines, such as vascular endothelial growth factor, hepatocyte growth factor and interleukin 6, whereas BM-MSC secreted significantly larger amounts of stromal-derived factor-1α. Conclusions: There are significant differences between ASC and BM-MSC in the cytokine secretome, which may provide clues to the molecule mechanisms associated with tissue regeneration and alternative cell sources.<br />出版者照会後に全文公開 続きを見る
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Funada, Akira ; Konno, Tetsuo ; Fujino, Noboru ; Muramoto, Akihiko ; Hayashi, Kenshi ; Tsubokawa, Toshinari ; Sakata, Kenji ; Kawashiri, Masa-aki ; Takeda, Yoshiyu ; Ino, Hidekazu ; Yamagishi, Masakazu ; 舟田, 晃 ; 今野, 哲雄 ; 藤野, 陽 ; 林, 研至 ; 坂田, 憲治 ; 川尻, 剛照 ; 武田, 仁勇 ; 井野, 秀一 ; 山岸, 正和
出版情報: Circulation Journal.  74  pp.2674-2680,  2010.  Japanese Circulation Society = 日本循環器学会
URL: http://hdl.handle.net/2297/00050644
概要: 金沢大学医薬保健研究域医学系<br />Background: Although the renin - angiotensin system (RAS) can affect the development of left ventric ular (LV) hypertrophy, few data exist regarding the relationships between RAS polymorphisms and alteration of LV function. The effect of RAS polymorphisms on LV function in genotyped hypertrophic cardiomyopathy (HCM) was examined in the present study. Methods and Results: The study group comprised 126 carriers with sarcomere gene mutations from 49 HCM families (64 males, mean age 51±21 years). LV morphology and function were evaluated by echocardiography. In angiotensin-converting enzyme (ACE) insertion/deletion (I/D), the D allele (n=81) exhibited significantly larger LV end-systolic dimension (LVDs) (32±11 mm) and lower ejection fraction (56±15%) than those with the II genotype (28±7 mm and 62±12%, respectively, P<0.05; n=45). Although angiotensin II type 1 receptor (AT1-R) A/C1166 polymorphism did not affect echocardiographic parameters, the presence of the ACE D allele with the AT1-R C1166 allele (n=9) was associated with larger LVDs (37±17 mm) and lower ejection fraction (48±20%) compared with other genotypes (30±9 mm and 58±14%, respectively, P<0.05; n=117). Under these conditions, severe LV hypertrophy was frequently associated with LV wall thinning. Conclusions: The presence of both the ACE D and AT1-R C1166 allele is associated with LV dilation with systolic dysfunction in genotyped HCM. In addition to the severity of LV hypertrophy, screening for these RAS polymorphisms could contribute to further risk stratification of patients with HCM, although other genetic polymorphisms should be further examined.<br />出版者照会後に全文公開 続きを見る
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Konno, Tetsuo ; Hayashi, Kenshi ; Fujino, Noboru ; Nagata, Yoji ; Hodatsu, Akihiko ; Masuta, Eiichi ; Sakata, Kenji ; Nakamura, Hiroyuki ; Kawashiri, Masa-aki ; Yamagishi, Masakazu ; 今野, 哲雄 ; 林, 研至 ; 藤野, 陽 ; 永田, 庸二 ; 寳達, 明彦 ; 坂田, 憲治 ; 中村, 裕之 ; 川尻, 剛照 ; 山岸, 正和
出版情報: PLoS ONE.  9  pp.e101465-,  2014-07-07.  Public Library of Science
URL: http://hdl.handle.net/2297/00050649
概要: 金沢大学医薬保健研究域医学系<br />Background: Myocardial scarring can be assessed by cardiac magnetic resonance imaging with late gado linium enhancement and by endomyocardial biopsy. However, accuracy of late gadolinium enhancement for predicting microscopic myocardial scarring in biopsied specimens remains unknown in hypertrophic cardiomyopathy. We investigated whether late gadolinium enhancement in the whole heart reflects microscopic myocardial scarring in the small biopsied specimens in hypertrophic cardiomyopathy. Methods and Results: Twenty-one consecutive patients with hypertrophic cardiomyopathy who were examined both by cardiac magnetic resonance imaging and by endomyocardial biopsy were retrospectively studied. The right interventricular septum was the target site for endomyocardial biopsy in all patients. Late gadolinium enhancement in the ventricular septum had an excellent sensitivity (100%) with a low specificity (40%) for predicting microscopic myocardial scarring in biopsied specimens. The sensitivity of late gadolinium enhancement in the whole heart remained 100% with a specificity of 27% for predicting microscopic myocardial scarring in biopsied specimens. Quantitative assessments of fibrosis revealed that the extent of late gadolinium enhancement in the whole heart was the only independent variable related to the microscopic collagen fraction in biopsied specimens (β = 0.59, 95% confident interval: 0.15-1.0, p = 0.012). Conclusions: Although there was a compromise in the specificity, the sensitivity of late gadolinium enhancement was excellent for prediction of microscopic myocardial scarring in hypertrophic cardiomyopathy. Moreover, the severity of late gadolinium enhancement was independently associated with the quantitative collagen fraction in biopsied specimens in hypertrophic cardiomyopathy. These findings indicate that late gadolinium enhancement can reflect both the presence and the extent of microscopic myocardial scarring in the small biopsied specimens in hypertrophic cardiomyopathy. © 2014 Konno et al. 続きを見る
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Tagawa, Shotoku ; Nakanishi, Chiaki ; Mori, Masayuki ; Yoshimuta, Tsuyoshi ; Yoshida, Shohei ; Shimojima, Masaya ; Yokawa, Junichiro ; Kawashiri, Masa-aki ; Yamagishi, Masakazu ; Hayashi, Kenshi ; 田川, 庄督 ; 中西, 千明 ; 吉牟田, 剛 ; 吉田, 昌平 ; 川尻, 剛照 ; 山岸, 正和 ; 林, 研至
出版情報: International Journal of Vascular Medicine.  2015  pp.674213-,  2015.  Hindawi Publishing Corporation
URL: http://hdl.handle.net/2297/00050665
概要: 金沢大学医薬保健研究域医学系<br />The clinical implications of early and late endothelial progenitor cells (EPCs) in coronary artery d isease (CAD) remain unclear. We investigated endothelial dysfunction in CAD by simultaneously examining early and late EPC colony formation and gene expression of specific surface markers in EPCs. EPCs were extracted from a total of 83 subjects with (n=47) and without (n=36) CAD. Early and late EPC colonies were formed from mononuclear cells extracted from peripheral blood. We found that fewer early EPC colonies were produced in the CAD group (7.2 ± 3.l/well) than those in the control group (12.4 ± 1.4/well, p<0.05), and more late EPC colonies were produced in the CAD group (0.8 ± 0.2/well) than those in the control group (0.25 ± 0.02/well, p<0.05). In the CAD group, the relative expression of CD31 and KDR of early and late EPCs was lower than in the control group. These results demonstrate that CAD patients could have increased late EPC density and that early and late EPCs in CAD patients exhibited immature endothelial characteristics. We suggest that changes in EPC colony count and gene expression of endothelial markers may have relation with development of CAD. © 2015 Shotoku Tagawa et al. 続きを見る
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Al Mahmuda, Naila ; Yokoyama, Shigeru ; Huang, Jian-Jun ; Liu, Li ; Munesue, Toshio ; Nakatani, Hideo ; Hayashi, Kenshi ; Yagi, Kunimasa ; Yamagishi, Masakazu ; Higashida, Haruhiro
出版情報: International Journal of Molecular Sciences.  17  pp.00772-,  2016-05-01.  Multidisciplinary Digital Publishing Institute (MDPI)
URL: http://hdl.handle.net/2297/45573
概要: Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with complex genetic etiology. Recent studies have indicated that children with ASD may have altered folate or methionine metabolism, suggesting that the folate-methionine cycle may play a key role in the etiology of ASD. SLC19A1, also referred to as reduced folate carrier 1 (RFC1), is a member of the solute carrier group of transporters and is one of the key enzymes in the folate metabolism pathway. Findings from multiple genomic screens suggest the presence of an autism susceptibility locus on chromosome 21q22.3, which includes SLC19A1. Therefore, we performed a case-control study in a Japanese population. In this study, DNA samples obtained from 147 ASD patients at the Kanazawa University Hospital in Japan and 150 unrelated healthy Japanese volunteers were examined by the sequence-specific primer-polymerase chain reaction method pooled with fluorescence correlation spectroscopy. p < 0.05 was considered to represent a statistically significant outcome. Of 13 single nucleotide polymorphisms (SNPs) examined, a significant p-value was obtained for AA genotype of one SNP (rs1023159, OR = 0.39, 95% CI = 0.16-0.91, p = 0.0394; Fisher’s exact test). Despite some conflicting results, our findings supported a role for the polymorphism rs1023159 of the SLC19A1 gene, alone or in combination, as a risk factor for ASD. However, the findings were not consistent after multiple testing corrections. In conclusion, although our results supported a role of the SLC19A1 gene in the etiology of ASD, it was not a significant risk factor for the ASD samples analyzed in this study. © 2016 by the authors; licensee MDPI, Basel, Switzerland. 続きを見る
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Munesue, Toshio ; Yokoyama, Shigeru ; Nakamura, Kazuhiko ; Anitha, Ayyappan ; Yamada, Kazuo ; Hayashi, Kenshi ; Asaka, Tomoya ; Liu, Hong-Xiang ; Jin, Duo ; Koizumi, Keita ; Islam, Mohammad Saharul ; Huang, Jian-Jun ; Ma, Wen-Jie ; Kim, Uh-Hyun ; Kim, Sun-Jun ; Park, Keunwan ; Kim, Dongsup ; Kikuchi, Mitsuru ; Ono, Yasuki ; Nakatani, Hideo ; Suda, Shiro ; Miyachi, Taishi ; Hirai, Hirokazu ; Salmina, Alla ; Pichugina, Yu A. ; Soumarokov, Andrei A. ; Takei, Nori ; Mori, Norio ; Tsujii, Masatsugu ; Sugiyama, Toshiro ; Yagi, Kunimasa ; Yamagishi, Masakazu ; Sasaki, Tsukasa ; Yamasue, Hidenori ; Kato, Nobumasa ; Hashimoto, Ryota ; Taniike, Masako ; Hayashi, Yutaka ; Hamada, Jun-ichiro ; Suzuki, Shioto ; Ooi, Akishi ; Noda, Mami ; Kamiyama, Yuko ; Kido, Mizuho A. ; Lopatina, Olga ; Hashii, Minako ; Amina, Sarwat ; Malavasi, Fabio ; Huang, Eric J. ; Zhang, Jiasheng ; Shimizu, Nobuaki ; Yoshikawa, Takeo ; Matsushima, Akihiro ; Minabe, Yoshio ; Higashida, Haruhiro
出版情報: Neuroscience Research.  67  pp.181-191,  2010-06-01.  Elsevier / the Japan Neuroscience Society = 日本神経科学学会
URL: http://hdl.handle.net/2297/24571
概要: 金沢大学医薬保健研究域医学系<br />The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the rol e of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (p< 0.040) and rs3796863 (p< 0.005) showed significant associations with a subset of ASD (IQ > 70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD. © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. 続きを見る
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Gamou, Tadatsugu ; Sakata, Kenji ; Tada, Hayato ; Konno, Tetsuo ; Hayashi, Kenshi ; Ino, Hidekazu ; Yamagishi, Masakazu ; Kawashiri, Masa-aki ; on behalf of the MILLION Study Group ; 坂田, 憲治 ; 多田, 隼人 ; 今野, 哲雄 ; 林, 研至 ; 井野, 秀一 ; 山岸, 正和 ; 川尻, 剛照
出版情報: Circulation journal.  81  pp.1490-1495,  2017-09-25.  Japanese Circulation Society = 日本循環器学会
URL: http://hdl.handle.net/2297/48523
概要: Background:The MILLION study, a prospective randomized multicenter study, revealed that lipid and blood pressure (BP)-lo wering therapy resulted in regression of coronary plaque as determined by intravascular ultrasound (IVUS). In the present study we performed additional analysis to investigate the associated factors with regression of coronary plaque. Methods and Results:We investigated serial 3D IVUS images from 68 patients in the MILLION study. Standard IVUS parameters were assessed at both baseline and follow-up (18–24 months). Volumetric data were standardized by length as normalized volume. In patients with plaque regression (n=52), plaque volumenormalizedsignificantly decreased from 64.8 to 55.8 mm3(P<0.0001) and vessel volumenormalizedsignificantly decreased from 135.0 to 127.5 mm3(P=0.0008). There was no difference in lumen volumenormalizedfrom 70.1 to 71.8 mm3(P=0.27). There were no correlations between % changes in vessel volume and cholesterol or BP. On the other hand, negative correlations between % change in vessel volume and vessel volumenormalizedat baseline (r=−0.352, P=0.009) or plaque volumenormalizedat baseline (r=−0.336, P=0.01) were observed. Conclusions:The current data demonstrated that in patients with plaque regression treated by aggressive lipid and BP-lowering therapy, the plaque regression was derived from reverse vessel remodeling determined by vessel volume and plaque burden at baseline irrespective of decreases in lipids and BP.<br />出版者照会後に全文公開 続きを見る
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Funada, Akira ; Masuta, Eiichi ; Fujino, Noboru ; Hayashi, Kenshi ; Ino, Hidekazu ; Kita, Yoshihito ; Ikeda, Hiroko ; Fujii, Takahiko ; Nakanuma, Yasuni ; Yamagishi, Masakazu
出版情報: International Heart Journal.  51  pp.214-217,  2010-01-01.  International Heart Journal Association
URL: http://hdl.handle.net/2297/31473
概要: Hypertrophic cardiomyopathy (HCM) is associated with gene mutations that encode sarcomeric proteins. However, the relationship between genotype and histopathologic fndings is unclear. We report on two autopsy cases with advanced HCM associated with deletion of lysine 183 mutation in the cardiac troponin I gene. One case, a 74-year-old female exhibited dilated cardiomyopathy-like features. Transmural scarring was diffuse and circumferential, involving the whole left ventricle, especially the ventricular septum which was replaced with extensive fbrosis and showed marked wall thinning. The other case, a 92-year-old male revealed typical HCM fndings. Patchy scars which corresponded to replacement fbrosis were found extending from the septum to the anterior wall. These two autopsy cases indicate the clinical heterogeneity of HCM even within the same disease-causing mutation and suggest that the degree and extent of fbrosis determine differences in the clinical manifestations of HCM. This is the frst autopsy report that demonstrates identical sarcomeric gene mutations causing different clinical manifestations and histologic fndings. The fndings suggest that additional genetic or environmental factors infuence the phenotypic expressions and clinical courses of HCM caused by genetic mutation of sarcomeric proteins. 続きを見る
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Konno, Tetsuo ; Hayashi, Kenshi ; Fujino, Noboru ; Yamagishi, Masakazu
出版情報: Internal Medicine.  55  pp.545-546,  2016-03-01.  Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/48441
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Yoshimuta, Tsuyoshi ; Yokoyama, Hiroyuki ; Okajima, Toshiya ; Tanaka, Hiroshi ; Toyoda, Kazunori ; Nagatsuka, Kazuyuki ; Higashi, Masahiro ; Hayashi, Kenshi ; Kawashiri, Masa-aki ; Yasuda, Satoshi ; Yamagishi, Masakazu ; 林, 研至 ; 川尻, 剛照 ; 山岸, 正和
出版情報: Circulation journal.  79  pp.1841-1845,  2015-07-24.  Japanese Circulation Society = 日本循環器学会
URL: http://hdl.handle.net/2297/48526
概要: Background:Plasma d-dimer is known to be a useful clinical marker of thrombogenic status, and d-dimer is used as a diagn ostic marker for acute aortic dissection (AAD). Little is known, however, regarding the clinical value of d-dimer for diagnosis of asymptomatic AAD in patients with ischemic stroke. We investigated whether d-dimer could be used for early diagnosis of AAD with isolated neurological symptoms in ischemic stroke patients.Methods and Results:We evaluated a total of 1,236 consecutive patients with symptomatic ischemic stroke without chest or back pain who underwent either head computed tomography or magnetic resonance imaging. d-dimer was measured within 24 h after onset. There were 9 patients with Stanford type A AAD and they had significantly higher d-dimer than the patients without AAD (mean, 46.47±54.48 μg/ml; range, 6.9–167.1 μg/ml vs. 2.33±3.58 μg/ml, 0.3–57.9 μg/ml, P<0.001). When a cut-off of 6.9 μg/ml was adopted for d-dimer on the basis of receiver operating characteristics analysis, the sensitivity and specificity for AAD were 100% and 94.8%, respectively, while the positive and negative predictive values were 14.7% and 100%, respectively.Conclusions:d-dimer might be a useful marker for the early diagnosis of AAD with isolated neurological symptoms in ischemic stroke patients. Whole-body contrast-enhanced computed tomography should be performed in ischemic stroke patients who have high d-dimer. (Circ J 2015; 79: 1841–1845)<br />出版者照会後に全文公開 続きを見る
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Tada, Hayato ; Kawashiri, Masa-aki ; Yamagishi, Masakazu ; Hayashi, Kenshi ; 多田, 隼人 ; 川尻, 剛照 ; 山岸, 正和 ; 林, 研至
出版情報: Journal of Atherosclerosis and Thrombosis.  22  pp.881-885,  2015-01-01.  Japan Atherosclerosis Society = 日本動脈硬化学会
URL: http://hdl.handle.net/2297/48549
概要: 出版者照会後に全文公開
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Funada, Akira ; Goto, Yoshikazu ; Tada, Hayato ; Teramoto, Ryota ; Shimojima, Masaya ; Hayashi, Kenshi ; Yamagishi, Masakazu ; 舟田 , 晃 ; 後藤, 由和 ; 多田, 隼人 ; 寺本, 了太 ; 下島, 正也 ; 林, 研至 ; 山岸, 正和
出版情報: Circulation journal.  81  pp.652-659,  2017-04-25.  Japanese Circulation Society = 日本循環器学会
URL: http://hdl.handle.net/2297/48500
概要: Background:The appropriate duration of prehospital cardiopulmonary resuscitation (CPR)administered by emergency medical service (EMS) providers for patients with out-of-hospital cardiac arrest (OHCA) necessary to achieve 1-month survival with favorable neurological outcome (Cerebral Performance Category 1 or 2, CPC 1–2) is unclear and could differ by age. Methods and Results:We analyzed the records of 35,709 adult OHCA patients with return of spontaneous circulation (ROSC) before hospital arrival in a prospectively recorded Japanese registry between 2011 and 2014. The CPR duration was defined as the time from CPR initiation by EMS providers to prehospital ROSC. The rate of 1-month CPC 1–2 was 21.4% (7,650/35,709). The CPR duration was independently and inversely associated with 1-month CPC 1–2 (adjusted odds ratio, 0.93 per 1-min increment; 95% confidence interval, 0.93–0.94). The CPR duration increased with age (P<0.001). However, the CPR duration beyond which the proportion of OHCA patients with 1-month CPC 1–2 decreased to <1% declined with age: 28 min for patients aged 18–64 years, 25 min for 65–74 years, 23 min for 75–84 years, 20 min for 85–94 years, and 18 min for ≥95 years. Conclusions:In patients who achieved prehospital ROSC after OHCA, the duration of CPR administered by EMS providers necessary to achieve 1-month CPC 1–2 varied by age.<br />出版者照会後に全文公開 続きを見る
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Sakamoto, Aiji ; Kawashiri, Masaaki ; Ishibashi-Ueda, Hatsue ; Sugamoto, Yuka ; Yoshimuta, Tsuyoshi ; Higashikata, Takeo ; Ogino, Hitoshi ; Tada, Hayato ; Konno, Tetsuo ; Hayashi, Kenshi ; Yamagishi, Masakazu
出版情報: International Journal of Vascular Medicine.  2012  pp.127149-,  2012-09-15.  Hindawi Publishing Corporation
URL: http://hdl.handle.net/2297/48407
概要: We examined the expression of ephrin-B1 and its cognate receptor EphB2, key regulators of angiogenesis and embryogenesis , in human abdominal aortic aneurysm (AAA) and analyzed their functional roles in cell migration. From 10 patients (9 males and 1 female; age, 68.5 ± 2.4) who underwent vascular surgery for AAA, we obtained AAA and adjacent control tissues. Using real-time RT-PCR, we analyzed expression of ephrin-B1 and EphB2. We also histologically localized these molecules in AAA tissues. Finally, effects of ephrin-B1 and EphB2 on inflammatory cell chemotaxis were examined by cell migration assay. Expression levels of ephrin-B1 (0.410 ± 0.046 versus 1.198 ± 0.252, P = 0.027) and EphB2 (0.764 ± 0.212 versus 1.272 ± 0.137, P = 0.594) were higher in AAA than normal control. Both ephrin-B1 and EphB2 were expressed in macrophages, T lymphocytes, and endothelial cells within AAA. In chemotaxis assay, ephrin-B1 and EphB2 inhibited mononuclear-cell chemotaxis induced by stromal derived factor-1 down to 54.7 ± 12.7 (P = 0.01) and 50.7 ± 13.1 (P = 0.01), respectively. These data suggest that ephrin-B1 and EphB2 might be functional in human adult inflammatory cells and involved in the pathogenesis of AAA, although specific roles of these molecules should further be sought. © 2012 Aiji Sakamoto et al. 続きを見る
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Shimojima, Masaya ; Kawashiri, Masa-aki ; Nitta, Yutaka ; Yoshida, Taiji ; Katsuda, Shouji ; Kaku, Bunji ; Taguchi, Tomio ; Hasegawa, Akira ; Konno, Tetsuo ; Hayashi, Kenshi ; Yamagishi, Masakazu
出版情報: American Journal of Cardiovascular Research.  2  pp.84-88,  2012-05-15.  e-Century Publishing
URL: http://hdl.handle.net/2297/48420
概要: Although intensive lipid lowering by statins can enhance plaque stability, few data exist regarding how early statins ch ange plaque composition and morphology in clinical setting. Therefore, to examine early changes in plaque composition and morphology by intensive lipid lowering with statins, we evaluate coronary plaques from acute coronary syndrome (ACS) before and 3 weeks after lipid lowering by coronary CT angiography. We enrolled 110 patients with suspected ACS and underwent coronary CT. We defined plaque as unstable when CT number of plaque< 50HU and remodeling index (lesion diameter/reference diameter) >1.10. Rosuvastatin (5 mg/day) or atorvastatin (20 mg/day) were introduced to reduce low density lipoprotein cholesterol (LDL-C). Then, CT was again performed by the same condition 3 weeks after lipid lowering therapy. Total 10 patients (8 men, mean age 72.0 years), in whom informed consent regarding serial CT examination was obtained, were analyzed. Among them, 4 patients who denied to have intensive lipid lowering were served as controls. In remaining 6 patients, LDL-C reduced from 129.5±26.9 mg/dl to 68.5±11.1 mg/dl after statin treatment. Under these conditions, CT number of the targeted plaque significantly increased from 16.0±15.9 to 50.8±35.0 HU (p<0.05) and remodeling index decreased from 1.22±0.11 to 1.11±0.06 (p<0.05), although these values substantially unchanged in controls. These results demonstrate that MDCT-determined plaque composition as well as volume could be changed within 3 weeks after intensive lipid lowering. This may explain acute effects of statins in treatment of acute coronary syndrome. 続きを見る
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Onoe, Tamehito ; Konoshita, Tadashi ; Tsuneyama, Koichi ; Hamano, Ryoko ; Mizushima, Ichiro ; Kakuchi, Yasushi ; Yamada, Kazunori ; Hayashi, Kenshi ; Kuroda, Masahiro ; Kagitani, Satoshi ; Nomura, Hideki ; Yamagishi, Masakazu ; Kawano, Mitsuhiro
出版情報: American Journal of Case Reports.  14  pp.20-25,  2013-01-28.  International Scientific Information
URL: http://hdl.handle.net/2297/48240
概要: Background: Situs inversus is a rare complication of cystic kidney diseases. Only three genes, INVS (NPHP2), NPHP3 and PKD2 have been proved to be responsible for some cases, while the responsible genes in many others are still unknown. Case Reports: Here we report two male patients with situs inversus combined with cystic kidney disease without any family history of polycystic kidney disease. Their renal function was normal in childhood but culminated in end stage renal disease in middle age. No pathogenic mutations were found in mutation analysis of INVS, IFT88, PKD2, UMOD or NPHP3 in them. Conclusions: Past reported cases of situs inversus and cystic kidney diseases were divided into three groups, i.e., gestational lethal renal dysplasia group, infantile or juvenile nephronophthisis group and polycystic kidney disease group. The present patients are different from each of these groups. Moreover, the renal lesions of the present two cases are quite different from each other, with one showing mildly atrophic kidneys with small numbers of cysts and the other an enlarged polycystic kidney disease, suggesting very heterogeneous entities. 続きを見る
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Ma, Wen-Jie ; Hashii, Minako ; Munesue, Toshio ; Hayashi, Kenshi ; Yagi, Kunimasa ; Yamagishi, Masakazu
出版情報: Molecular Autism.  4  pp.22-,  2013-07-01.  BioMed Central
URL: http://hdl.handle.net/2297/48354
概要: Background: The human oxytocin receptor (hOXTR) is implicated in the etiology of autism spectrum disorders (ASDs) and is a potential target for therapeutic intervention. Several studies have reported single-nucleotide polymorphisms (SNPs) of the OXTR gene associated with ASDs. These SNPs, however, reside outside the protein-coding region. Not much is known about genetic variations that cause amino acid substitutions that alter receptor functions. Methods. Variations in the OXTR gene were analyzed in 132 ASD patients at Kanazawa University Hospital in Japan and 248 unrelated healthy Japanese volunteers by re-sequencing and real-time polymerase chain reaction-based genotyping. Functional changes in variant OXTRs were assessed by radioligand binding assay and measurements of intracellular free calcium concentrations ([Ca§ssup§2+§esup§]§ssub§i§esub§) and inositol 1,4,5-trisphosphate (IP§ssub§3§esub§) levels. Results: Six subjects (4.5%) in the ASD group and two in the control group (0.8%) were identified as heterozygotes carrying the R376G variation (rs35062132; c.1126C>G); one individual from the ASD group (0.8%) and three members of the control group (1.2%) were found to be carrying R376C (c.1126C>T). The C/G genotype significantly correlated with an increased risk of ASDs (odds ratio (OR) = 5.83; 95% confidence interval (CI) = 1.16 to 29.33; P = 0.024, Fisher's exact test). Consistently, the G allele showed a correlation with an increased likelihood of ASDs (OR = 5.73; 95% CI = 1.15 to 28.61; P = 0.024, Fisher's exact test). The frequencies of the C/T genotype and the T allele in the ASD and control groups did not differ significantly. We also examined changes in agonist-induced cellular responses mediated by the variant receptors hOXTR-376G and hOXTR-376C. OXT-induced receptor internalization and recycling were faster in hOXTR-376G-expressing HEK-293 cells than in cells expressing hOXTR-376R or hOXTR-376C. In addition, the elevation in [Ca§ssup§2+§esup§]§ssub§i§esub§ and IP§ssub§3§esub§ formation decreased in the cells expressing hOXTR-376G and hOXTR-376C tagged with enhanced green fluorescent protein (EGFP), in comparison with the cells expressing the common-type hOXTR-376R tagged with EGFP. Conclusions: These results suggest that the rare genetic variation rs35062132 might contribute to the pathogenesis of ASDs, and could provide a molecular basis of individual differences in OXTR-mediated modulation of social behavior. © 2013 Ma et al.; licensee BioMed Central Ltd. 続きを見る
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Shimojima, Masaya ; Yuasa, Shinsuke ; Motoda, Chikaaki ; Yozu, Gakuto ; Nagai, Toshihiro ; Ito, Shogo ; Lachmann, Mark ; Kashimura, Shin ; Takei, Makoto ; Kusumoto, Dai ; Kunitomi, Akira ; Hayashiji, Nozomi ; Seki, Tomohisa ; Tohyama, Shugo ; Hashimoto, Hisayuki ; Kodaira, Masaki ; Egashira, Toru ; Hayashi, Kenshi ; Nakanishi, Chiaki ; Sakata, Kenji ; Yamagishi, Masakazu ; Fukuda, Keiichi
出版情報: Scientific Reports.  7  pp.44312-,  2017-03-14.  Nature Publishing Group
URL: http://hdl.handle.net/2297/48359
概要: Alteration of the nuclear Ca2+ transient is an early event in cardiac remodeling. Regulation of the nuclear Ca2+ transie nt is partly independent of the cytosolic Ca2+ transient in cardiomyocytes. One nuclear membrane protein, emerin, is encoded by EMD, and an EMD mutation causes Emery-Dreifuss muscular dystrophy (EDMD). It remains unclear whether emerin is involved in nuclear Ca2+ homeostasis. The aim of this study is to elucidate the role of emerin in rat cardiomyocytes by means of hypertrophic stimuli and in EDMD induced pluripotent stem (iPS) cell-derived cardiomyocytes in terms of nuclear structure and the Ca2+ transient. The cardiac hypertrophic stimuli increased the nuclear area, decreased nuclear invagination, and increased the half-decay time of the nuclear Ca2+ transient in cardiomyocytes. Emd knockdown cardiomyocytes showed similar properties after hypertrophic stimuli. The EDMD-iPS cell-derived cardiomyocytes showed increased nuclear area, decreased nuclear invagination, and increased half-decay time of the nuclear Ca2+ transient. An autopsied heart from a patient with EDMD also showed increased nuclear area and decreased nuclear invagination. These data suggest that Emerin plays a crucial role in nuclear structure and in the nuclear Ca2+ transient. Thus, emerin and the nuclear Ca2+ transient are possible therapeutic targets in heart failure and EDMD. © The Author(s) 2017. 続きを見る
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Oe, Kotaro ; Araki, Tsutomu ; Hayashi, Kenshi ; Yamagishi, Masakazu
出版情報: Internal Medicine.  56  pp.381-382,  2017-02-01.  Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/48443
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Tada, Hayato ; Kawashiri, Masa-aki ; Yoshida, Taiji ; Teramoto, Ryota ; Nohara, Atsushi ; Konno, Tetsuo ; Inazu, Akihiro ; Mabuchi, Hiroshi ; Yamagishi, Masakazu ; Hayashi, Kenshi ; 多田, 隼人 ; 川尻, 剛照 ; 寺本, 了太 ; 野原, 淳 ; 稲津, 明広 ; 馬渕, 宏 ; 山岸, 正和 ; 林, 研至
出版情報: Circulation journal.  80  pp.512-518,  2016-01-25.  Japanese Circulation Society = 日本循環器学会
URL: http://hdl.handle.net/2297/48509
概要: Background:It has been shown that serum lipoprotein(a) [Lp(a)] is elevated in familial hypercholesterolemia (FH) with mu tation(s) of the LDL receptor (LDLR) gene. However, few data exist regarding Lp(a) levels in FH with gain-of-function mutations of the PCSK9 gene.Methods and Results:We evaluated 42 mutation-determined heterozygous FH patients with aPCSK9gain-of-function mutation (FH-PCSK9, mean age 52, mean LDL-C 235 mg/dl), 198 mutation-determined heterozygous FH patients with aLDLRmutation (FH-LDLR, mean age 44, mean LDL-C 217 mg/dl), and 4,015 controls (CONTROL, mean age 56, mean LDL-C 109 mg/dl). We assessed their Lp(a), total cholesterol, triglycerides, HDL-C, LDL-C, use of statins, presence of hypertension, diabetes, chronic kidney disease, smoking, body mass index (BMI) and coronary artery disease (CAD). Multiple regression analysis showed that HDL-C, use of statins, presence of hypertension, smoking, BMI, and Lp(a) were independently associated with the presence of CAD. Under these conditions, the serum levels of Lp(a) in patients with FH were significantly higher than those of the CONTROL group regardless of their causative genes, among the groups propensity score-matched (median Lp(a) 12.6 mg/dl [IQR:9.4–33.9], 21.1 mg/dl [IQR:11.7–34.9], and 5.0 mg/dl [IQR:2.7–8.1] in the FH-LDLR, FH-PCSK9, and CONTROL groups, respectively, P=0.002 for FH-LDLR vs. CONTROL, P=0.002 for FH-PCSK9 vs. CONTROL).Conclusions:These data demonstrate that serum Lp(a) is elevated in patients with FH caused by PCSK9 gain-of-function mutations to the same level as that in FH caused by LDLR mutations. (Circ J 2016; 80: 512–518)<br />出版者照会後に全文公開 続きを見る
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Tada, Hayato ; Kawashiri, Masa-aki ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Yasuda, Kenji ; Mabuchi, Hiroshi ; Yamagishi, Masakazu ; Hayashi, Kenshi ; 多田, 隼人 ; 川尻, 剛照 ; 野原, 淳 ; 稲津, 明広 ; 小林, 淳二 ; 馬渕, 宏 ; 山岸, 正和 ; 林, 研至
出版情報: Journal of Atherosclerosis and Thrombosis.  24  pp.338-345,  2017-03-01.  Japan Atherosclerosis Society = 日本動脈硬化学会
URL: http://hdl.handle.net/2297/48527
概要: Aim: The Japan Atherosclerosis Society (JAS) guidelines for the prevention of atherosclerotic diseases 2012 (JAS2012) pr oposed lipid management targets; however, less data is available regarding the attainment rates of each target in community-based settings. Therefore, we assessed the attainment rates of lipid management targets among subjects who underwent Japanese specific health checkups. Methods: A total of 85,716 subjects (male=29,282, 34.2%) aged 40–74 years who underwent specific health checkups from 2012 to 2014 in Kanazawa city, Japan, were included in this study. We evaluated the attainment rates of the lipid management targets according to the JAS2012 guideline and investigated the clinical characteristics of the subjects without achieving the targets. Results: The target for LDL cholesterol (LDL-C) was the least attained in all risk categories, 89, 72, 50, and 34% for category I, II, III, and secondary prevention, respectively, in 2014. In addition, these rates inversely correlated with the grade of risk categories (p-value for trends <0.001). Attainment rate of the LDL-C target in the suspected chronic kidney disease (CKD) group was significantly lower than in the groups with diabetes, stroke, or absolute risk in category III (49.2, 60.3, 63.5, 54.4%, respectively, p-value <0.001 for each). Moreover, the attainment rate of the LDL-C target was significantly lower in subjects that did not receive lipid-lowering therapy than in those who received it in the secondary prevention (27.7 and 40.6%, respectively, p-value <0.001). Conclusions: Lipid management is inadequate in community-based settings, particularly, in subjects with CKD and secondary prevention.<br />出版者照会後に全文公開 続きを見る
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Oka, Rie ; Yagi, Kunimasa ; Sakurai, Masaru ; Nakamura, Koshi ; Nagasawa, Shin-ya ; Miyamoto, Susumu ; Nohara, Atsushi ; Kawashiri, Masa-aki ; Hayashi, Kenshi ; Takeda, Yoshiyu ; Yamagishi, Masakazu ; 八木, 邦公 ; 櫻井, 勝 ; 中村, 幸志 ; 野原, 淳 ; 川尻, 剛照 ; 林, 研至 ; 武田, 仁勇 ; 山岸, 正和
出版情報: Journal of Atherosclerosis and Thrombosis.  19  pp.814-822,  2012-09-24.  Japan Atherosclerosis Society = 日本動脈硬化学会
URL: http://hdl.handle.net/2297/48542
概要: Aim: The enlargement of visceral adipose tissue (VAT) is considered to mediate the close relationship between obesity an d insulin resistance. We aimed to determine whether a stronger association of VAT compared to subcutaneous adipose tissue (SAT) with insulin resistance could be confirmed and generalized in non-diabetic Japanese men and women. Methods: Participants were 912 non-diabetic Japanese (636 men and 276 women, mean age 52.4±7.0 years, and mean BMI 24.9±3.1 kg/m2). VAT and SAT were measured through the use of computed tomography scanning. Homeostatic model for the assessment of insulin resistance (HOMA-IR) and Matsuda insulin sensitivity index (ISI) were calculated based on results from the oral glucose tolerance test. Results: For both genders, subjects in higher tertiles of SAT as well as VAT showed significantly higher levels of HOMA-IR and lower levels of Matsuda ISI (p<0.001). In multiple regression analyses with VAT and SAT included in the model, only VAT, but not SAT, was independently associated with Matsuda ISI in women (p<0.001), whereas both SAT and VAT were independently associated with HOMA-IR and with Matsuda ISI in men (p<0.001). When VAT and waist circumference were jointly included in the model, only VAT, but not waist circumference, was independently associated with Matsuda ISI in women (p<0.001) but not in men. Conclusion: VAT had a stronger association with insulin resistance than SAT or waist circumference in women but not in men. BMI showed a comparable association with insulin resistance to VAT in this population.<br />出版者照会後に全文公開 続きを見る
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Tada, Hayato ; Kawashiri, Masa-aki ; Okada, Hirofumi ; Endo, Saori ; Toyoshima, Yuka ; Konno, Tetsuo ; Nohara, Atsushi ; Inazu, Akihiro ; Takao, Akira ; Mabuchi, Hiroshi ; Yamagishi, Masakazu ; Hayashi, Kenshi ; 多田, 隼人 ; 川尻, 剛照 ; 今野, 哲雄 ; 野原, 淳 ; 稲津, 明広 ; 馬渕, 宏 ; 山岸, 正和 ; 林, 研至
出版情報: Journal of Atherosclerosis and Thrombosis.  23  pp.884-890,  2016-07-01.  Japan Atherosclerosis Society = 日本動脈硬化学会
URL: http://hdl.handle.net/2297/48532
概要: Whole exome sequencing (WES) technologies have accelerated genetic studies of Mendelian disorders, yielding approximatel y 30% diagnostic success. We encountered a 13-year-old Japanese female initially diagnosed with familial hypercholesterolemia on the basis of clinical manifestations of severe hypercholesterolemia (initial LDL cholesterol=609 mg/dl at the age of one) and systemic intertriginous xanthomas with histories of recurrent self-limiting episodes of fever and arthritis. Both her phenotypes seemed to co-segregate in a recessive manner. We performed WES on this patient, who was considered a proband. Among 206,430 variants found in this individual, we found 18,220 nonsense, missense, or splice site variants, of which 3,087 were rare (minor allele frequency ≤ 0.01 or not reported) in 1000 Genome (Asian population). Filtering by assuming a recessive pattern of inheritance with the use of an in silico annotation prediction tool, we successfully narrowed down the candidates to the compound heterozygous mutations in the ABCG5 gene (c.1256G>A or p.Arg419His/c.1763-1G>A [splice acceptor site]) and to the double-compound heterozygous mutations in the MEFV gene (c.329T>C/C or p.Leu110Pro/c.442G>C/C or p.Glu148Val). The patient was genetically diagnosed with sitosterolemia and familial Mediterranean fever using WES for the first time. Such a comprehensive approach is useful for identifying causative mutations for multiple unrelated inheritable diseases.<br />出版者照会後に全文公開 続きを見る
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Teramoto, Ryota ; Sakata, Kenji ; Miwa, Kenji ; Matsubara, Takao ; Yasuda, Toshihiko ; Inoue, Masaru ; Okada, Hirofumi ; Kanaya, Honin ; Kawashiri, Masa-aki ; Yamagishi, Masakazu ; Hayashi, Kenshi ; 寺本, 了太 ; 坂田, 憲治 ; 川尻, 剛照 ; 山岸, 正和 ; 林, 研至
出版情報: Journal of Atherosclerosis and Thrombosis.  23  pp.1313-1323,  2016-12-01.  Japan Atherosclerosis Society = 日本動脈硬化学会
URL: http://hdl.handle.net/2297/48550
概要: Aim: Although distal embolization during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) deteriorates cardiac function, whether distal protection (DP) can improve prognosis is still controversial. We investigated whether a filter-type DP device, Filtrap®, could improve long-term outcomes after PCI for AMI. Method: We studied 164 patients (130 men, mean age: 65.7 years) who underwent PCI. Patients were divided into two groups based on the use of Filtrap®. The occurrence of congestive heart failure (CHF) and major adverse cardiac events (MACE) defined as cardiac death, recurrent AMI, and target vessel revascularization were compared. Result: Between DP (n=53, 41 men, mean age: 65.5 years) and non-DP (n=111, 89 men, mean age: 65.8 years) groups, although there was significantly greater plaque area in the DP group than in the non-DP group, there were no significant differences in coronary reperfusion flow after PCI. Interestingly, patients with CHF in the non-DP group exhibited a higher CK level than those in the DP group. During a 2-year follow-up period, cumulative CHF was significantly lower in the DP group than in the non-DP group (log-rank p=0.018), and there was no significant difference in the MACE rate (log-rank p=0.238). The use of DP device could not predict MACE, but could predict CHF by multivariate analysis (odds ratio=0.099, 95% CI: 0.02–0.42, p=0.005). Conclusion: These results demonstrate that favorable clinical outcomes could be achieved by the filter-type DP device in AMI, particularly in patients with CHF.<br />出版者照会後に全文公開 続きを見る
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Yamamoto, Ryusuke ; Tada, Hayato ; Tsubokawa, Toshinari ; Konno, Tetsuo ; Hayashi, Kenshi ; Saito, Takekatsu ; Kawashiri, Masa-aki ; Ohta, Kunio ; Yachie, Akihiro ; Yamagishi, Masakazu
出版情報: Journal of the American College of Cardiology.  60  pp.2419-,  2012-12-11.  Elsevier B.V.
URL: http://hdl.handle.net/2297/33431
33.

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Tada, Hayato ; Tsubokawa, Toshinari ; Konno, Tetsuo ; Hayashi, Kenshi ; Uchiyama, Katsuharu ; Kawashiri, Masa-aki ; Tomita, Shigeyuki ; Ino, Hidekazu ; Watanabe, Go ; Yamagishi, Masakazu
出版情報: Journal of the American College of Cardiology.  58  pp.654-,  2011-08-01.  Elsevier
URL: http://hdl.handle.net/2297/29210
34.

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Tada, Hayato ; Tsubokawa, Toshinari ; Konno, Tetsuo ; Hayashi, Kenshi ; Uchiyama, Katsuharu ; Kawashiri, Masa-aki ; Tomita, Shigeyuki ; Ino, Hidekazu ; Watanabe, Go ; Yamagishi, Masakazu
出版情報: Journal of the American College of Cardiology.  58  pp.654-,  2011-08-02.  American College of Cardiology
URL: http://hdl.handle.net/2297/29291
35.

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論文
Tada, Hayato ; Kawashiri, Masa-aki ; Ohtani, Rumiko ; Noguchi, Tohru ; Nakanishi, Chiaki ; Konno, Tetsuo ; Hayashi, Kenshi ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Mabuchi, Hiroshi ; Yamagishi, Masakazu
出版情報: Atherosclerosis.  219  pp.663-666,  2011-12-01.  Elsevier
URL: http://hdl.handle.net/2297/29748
概要: Background: Autosomal recessive hypercholesterolemia (ARH) is an extremely rare inherited hypercholesterolemia, the caus e of which is mutations in low-density lipoprotein (LDL) receptor adaptor protein 1 (LDLRAP1) gene. Methods: A total of 146 heterozygous familial hypercholesterolemic (FH) patients with a mutation in LDLR gene were screened for genes encoding proprotein convertase subtilisin/kexin type 9 (PCSK9) and LDLRAP1. Results: Among the 146 subjects, we identified a 79-year-old Japanese female with double mutations in LDLR gene (c.2431A > T) and LDLRAP1 gene (c.606dup). Two other relatives with double mutations in those genes in her family were also identified. Although the proband exhibited massive Achilles tendon xanthoma and coronary and aortic valvular disease, serum LDL-C level of subjects with double mutations was similar with that of subjects with single LDLR mutation (284.0 ± 43.5 versus 265.1 ± 57.4. mg/dl). Conclusion: Additional mutation in LDLRAP1 may account for severer phenotype in terms of xanthoma and atherosclerotic cardiovascular disease in FH patients. © 2011 Elsevier Ireland Ltd. 続きを見る
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論文
Tada, Hayato ; Konno, Tetsuo ; Aizu, Motohiko ; Yokawa, Junichiro ; Tsubokawa, Toshinari ; Fujii, Hiroshi ; Hayashi, Kenshi ; Uchiyama, Katsuharu ; Matsumura, Masami ; Kawano, Mitsuhiro ; Kawashiri, Masa-aki ; Yamagishi, Masakazu
出版情報: Journal of Cardiology Cases.  5  pp.e44-e47,  2012-02-01.  Japanese College of Cardiology / Elsevier
URL: http://hdl.handle.net/2297/30140
概要: We report a case with pulmonary veno-occlusive disease (PVOD) associated with systemic sclerosis which exhibits strong r esistance to pulmonary vasodilator. A 55-year-old female with severe pulmonary hypertension was admitted to our hospital to be introduced to epoprostenol infusion therapy. She was diagnosed as having pulmonary arterial hypertension (PAH) associated with systemic sclerosis at the age of 51. Several aggressive treatments with pulmonary vasodilators, including oral prostaglandin, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors, failed to improve her symptoms. We introduced continuous intravenous epoprostenol therapy from 2 μg/kg/min for her. However, pulmonary edema appeared and worsened in a dose-dependent manner. We made a diagnosis of PVOD clinically at that time. Thereafter, pulmonary edema gradually disappeared consistent with the reduction of the dose of epoprostenol infusion. She died of renal failure and infection 4 months after the introduction of epoprostenol infusion therapy. A histological examination revealed severe stenosis and occlusions of pulmonary veins as well as pulmonary arteries over a wide area. We suggest that prevalence of veno-occlusive type of disease could be one of the major mechanisms of less responsive or even refractory to pulmonary vasodilator therapies in patients with PAH associated with connective tissue disease. © 2011 Japanese College of Cardiology. 続きを見る
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Tada, Hayato ; Kawashiri, Masa-aki ; Ohtani, Rumiko ; Noguchi, Tohru ; Nakanishi, Chiaki ; Konno, Tetsuo ; Hayashi, Kenshi ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Mabuchi, Hiroshi ; Yamagishi, Masakazu
出版情報: Atherosclerosis.  219  pp.663-666,  2011-12-01.  Elsevier
URL: http://hdl.handle.net/2297/30139
概要: Background: Autosomal recessive hypercholesterolemia (ARH) is an extremely rare inherited hypercholesterolemia, the caus e of which is mutations in low-density lipoprotein (LDL) receptor adaptor protein 1 (LDLRAP1) gene. Methods: A total of 146 heterozygous familial hypercholesterolemic (FH) patients with a mutation in LDLR gene were screened for genes encoding proprotein convertase subtilisin/kexin type 9 (PCSK9) and LDLRAP1. Results: Among the 146 subjects, we identified a 79-year-old Japanese female with double mutations in LDLR gene (c.2431A > T) and LDLRAP1 gene (c.606dup). Two other relatives with double mutations in those genes in her family were also identified. Although the proband exhibited massive Achilles tendon xanthoma and coronary and aortic valvular disease, serum LDL-C level of subjects with double mutations was similar with that of subjects with single LDLR mutation (284.0 ± 43.5 versus 265.1 ± 57.4. mg/dl). Conclusion: Additional mutation in LDLRAP1 may account for severer phenotype in terms of xanthoma and atherosclerotic cardiovascular disease in FH patients. © 2011 Elsevier Ireland Ltd. 続きを見る
38.

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論文
Tada, Hayato ; Konno, Tetsuo ; Aizu, Motohiko ; Yokawa, Junichiro ; Tsubokawa, Toshinari ; Fujii, Hiroshi ; Hayashi, Kenshi ; Uchiyama, Katsuharu ; Matsumura, Masami ; Kawano, Mitsuhiro ; Kawashiri, Masa-aki ; Yamagishi, Masakazu
出版情報: Journal of Cardiology Cases.  5  pp.e44-e47,  2012-02-01.  Elsevier / Japanese College of Cardiology
URL: http://hdl.handle.net/2297/30319
概要: We report a case with pulmonary veno-occlusive disease (PVOD) associated with systemic sclerosis which exhibits strong r esistance to pulmonary vasodilator.A 55-year-old female with severe pulmonary hypertension was admitted to our hospital to be introduced to epoprostenol infusion therapy. She was diagnosed as having pulmonary arterial hypertension (PAH) associated with systemic sclerosis at the age of 51. Several aggressive treatments with pulmonary vasodilators, including oral prostaglandin, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors, failed to improve her symptoms. We introduced continuous intravenous epoprostenol therapy from 2. μg/kg/min for her. However, pulmonary edema appeared and worsened in a dose-dependent manner. We made a diagnosis of PVOD clinically at that time. Thereafter, pulmonary edema gradually disappeared consistent with the reduction of the dose of epoprostenol infusion. She died of renal failure and infection 4. months after the introduction of epoprostenol infusion therapy. A histological examination revealed severe stenosis and occlusions of pulmonary veins as well as pulmonary arteries over a wide area. We suggest that prevalence of veno-occlusive type of disease could be one of the major mechanisms of less responsive or even refractory to pulmonary vasodilator therapies in patients with PAH associated with connective tissue disease. © 2011 Japanese College of Cardiology. 続きを見る
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Sakamoto, Aiji ; Kawashiri, Masaaki ; Ishibashi-Ueda, Hatsue ; Sugamoto, Yuka ; Yoshimuta, Tsuyoshi ; Higashikata, Takeo ; Ogino, Hitoshi ; Tada, Hayato ; Konno, Tetsuo ; Hayashi, Kenshi ; Yamagishi, Masakazu
出版情報: International Journal of Vascular Medicine.  pp.127149-,  2012-01-01.  Hindawi Publishing Corporation
URL: http://hdl.handle.net/2297/32857
概要: We examined the expression of ephrin-B1 and its cognate receptor EphB2, key regulators of angiogenesis and embryogenesis , in human abdominal aortic aneurysm (AAA) and analyzed their functional roles in cell migration. From 10 patients (9 males and 1 female; age, 68.5 ± 2.4) who underwent vascular surgery for AAA, we obtained AAA and adjacent control tissues. Using real-time RT-PCR, we analyzed expression of ephrin-B1 and EphB2. We also histologically localized these molecules in AAA tissues. Finally, effects of ephrin-B1 and EphB2 on inflammatory cell chemotaxis were examined by cell migration assay. Expression levels of ephrin-B1 (0.410 ± 0.046 versus 1.198 ± 0.252, P = 0.027) and EphB2 (0.764 ± 0.212 versus 1.272 ± 0.137, P = 0.594) were higher in AAA than normal control. Both ephrin-B1 and EphB2 were expressed in macrophages, T lymphocytes, and endothelial cells within AAA. In chemotaxis assay, ephrin-B1 and EphB2 inhibited mononuclear-cell chemotaxis induced by stromal derived factor-1 down to 54.7 ± 12.7 (P = 0.01) and 50.7 ± 13.1 (P = 0.01), respectively. These data suggest that ephrin-B1 and EphB2 might be functional in human adult inflammatory cells and involved in the pathogenesis of AAA, although specific roles of these molecules should further be sought. © 2012 Aiji Sakamoto et al. 続きを見る
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Funada, Akira ; Goto, Yoshikazu ; Maeda, Tetsuo ; Teramoto, Ryota ; Hayashi, Kenshi ; Yamagishi, Masakazu
出版情報: Circulation Journal.  80  pp.1153-1162,  2016-01-01.  日本循環器学会 = The Japanese Circulation Society
URL: http://hdl.handle.net/2297/44912
概要: Background:There is sparse data regarding the survival and neurological outcome of elderly patients with out-of-hospital cardiac arrest (OHCA).Methods and Results:OHCA patients (334,730) aged ≥75 years were analyzed using a nationwide, prospective, population-based Japanese OHCA database from 2008 to 2012. The overall 1-month survival with favorable neurological outcome (Cerebral Performance Category Scale, category 1 or 2; CPC 1-2) rate was 0.88%. During the study period, the annual 1-month CPC 1-2 rate in whole OHCA significantly improved (0.73% to 0.96%, P for trend <0.001). In particular, outcomes of OHCA patients aged 75 to 84 years and those aged 85 to 94 years significantly improved (0.98% to 1.28%, P for trend=0.01; 0.46% to 0.70%, P for trend <0.001, respectively). However, in OHCA patients aged ≥95 years, the outcomes did not improve. Multivariate logistic regression analysis indicated that younger age, shockable first documented rhythm, witnessed arrest, earlier emergency medical service (EMS) response time, and cardiac etiology were significantly associated with the 1-month CPC 1-2. Under these conditions, elderly OHCA patients who had cardiac etiology, shockable rhythm and had a witnessed arrest had acceptable 1-month CPC1-2 rate; 7.98% in cases where OHCA was witnessed by family, 15.2% by non-family, and 25.6% by EMS.Conclusions:The annual 1-month CPC 1-2 rate after OHCA among elderly patients significantly improved, and the resuscitation of elderly patients in a selected population is not futile. 続きを見る
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論文
Tada, Hayato ; Kawashiri, Masa-aki ; Okada, Hirofumi ; Teramoto, Ryota ; Konno, Tetsuo ; Yoshimuta, Tsuyoshi ; Sakata, Kenji ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Mabuchi, Hiroshi ; Yamagishi, Masakazu ; Hayashi, Kenshi
出版情報: American Journal of Cardiology.  115  pp.724-729,  2015-03-15.  Elsevier
URL: http://hdl.handle.net/2297/41369
概要: The aims of this study were (1) to determine whether the accumulation of coronary plaque burden assessed with coronary c omputed tomography angiography (CCTA) can predict future events and (2) to estimate the onset and progression of coronary atherosclerosis in patients with familial hypercholesterolemia (FH). Consecutive 101 Japanese patients with heterozygous FH (men= 52, mean age 56 ± 16years, mean low-density lipoprotein cholesterol 264 ± 58mg/dl) who underwent 64-detector row CCTA without known coronary artery disease were retrospectively evaluated by assigning a score (0 to 5) to each of 17 coronary artery segments according to the Society of Cardiovascular Computed Tomography guidelines. Those scores were summed and subsequently natural log transformed. The periods to major adverse cardiac events (MACE) were estimated using multivariable Cox proportional hazards models. During the follow-up period (median 941days), 21 MACE had occurred. Receiver operating characteristic curve analyses identified a plaque burden score of 3.35 (raw score 28.5) as the optimal cutoff for predicting a worse prognosis. Multivariate Coxregression analysis identified the presence of a plaque score ≥3.35 as a significant independent predictor of MACE (hazard ratio= 3.65; 95% confidence interval 1.32 to 25.84, p<0.05). The regression equations were Y= 0.68. X- 15.6 (r= 0.54, p <0.05) in male and Y= 0.74. X- 24.8 (r= 0.69, p <0.05) in female patients with heterozygous FH. In conclusion, coronary plaque burden identified in a noninvasive, quantitative manner was significantly associated with future coronary events in Japanese patients with heterozygous FH and that coronary atherosclerosis may start to develop, on average, at age 23 and 34years in male and female patients with heterozygous FH, respectively. 続きを見る