著者
Jun-ichi Kawabe Fumitaka Ushikubi Naoyuki Hasebe
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.74, no.5, pp.836-843, 2010 (Released:2010-04-23)
参考文献数
86
被引用文献数
81 86

Prostacyclin (PGI2) is one of the important vascular prostanoids, the effects of which counteract those of thromboxane (TXA2), and these 2 prostanoids provide an important balance in cardiovascular homeostasis. The clinical experience of COX-2 selective inhibitors having unexpected adverse effects in patients with cardiovascular risk has opened up a debate about the role of COX-2-derived prostanoids in vascular pathophysiology. PGI2 is a major anti-atherogenic prostanoid produced by COX-2 in vascular cells, including endothelial and vascular smooth muscle cells. The balance between COX-2-derived PGI2, COX-1-derived TXA2, and other COX-2-mediated atherogenic prostanoids is a crucial factor in determining pathophysiological outcomes. Recent studies using stable PGI2 analogs and genetically deficient mice have revealed novel effects of PGI2 on its target cells, such as endothelial and endothelial progenitor cells. The role PGI2 in the physiology and pathophysiology of vascular diseases is reviewed and the recent findings linking PGI2, COX-2 and atherothrombosis are summarized. (Circ J 2010; 74: 836 - 843)
著者
Masafumi Nakayama Nobuhiro Tanaka Kunihiro Sakoda Yohei Hokama Kou Hoshino Yo Kimura Masashi Ogawa Jun Yamashita Yuichi Kobori Takashi Uchiyama Yoshifusa Aizawa Akira Yamashina
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.79, no.3, pp.530-536, 2015-02-25 (Released:2015-02-25)
参考文献数
38
被引用文献数
20 19

Background:Papaverine is useful for evaluating the functional status of a coronary artery, but it may provoke malignant ventricular arrhythmia (VA). The aim of this study was to investigate the incidence, and clinical and ECG characteristics of patients with papaverine-induced VAs.Methods and Results:The 182 consecutive patients underwent fractional flow reserve (FFR) measurement of 277 lesions. FFR was determined after intracoronary papaverine administration by standard procedures. The clinical and ECG characteristics were compared between patients with and without ventricular tachycardia (VT: ≥3 successive premature ventricular beats (PVBs), or ventricular fibrillation (VF)). After papaverine administration, the QTc interval, QTUc interval, and T-peak to U-end interval were prolonged significantly. Single PVBs on the T-wave or U-wave type developed in 29 patients (15.9%). Polymorphic VT (torsade de pointes) occurred in 5 patients (2.8%), and of those, VF developed in 3 patients (1.7%). No clinical and baseline ECG parameters were predictors for VT or VF except for sex and administration of papaverine into the left coronary artery. Excessive prolongation of QT (or QTU), T-peak to U-end intervals and giant T-U waves were found immediately prior to the ventricular tachyarrhythmias (VTAs), which were unpredictable from the baseline data.Conclusions:Intracoronary administration of papaverine induced fatal VTAs, although the incidence is rare. Excessive prolongation of the QT (and QTU) interval appeared prior to VTAs; however, they were unpredictable. (Circ J 2015; 79: 530–536)
著者
Chih-Chun Lee Dong-Yi Chen Yi-Hsin Chan Victor Chien-Chia Wu Yu-Ting Cheng Kuo-Chun Hung Chia-Pin Lin Ying-Chang Tung Fu-Chih Hsiao Jih-Kai Yeh Pao-Hsien Chu Shao-Wei Chen
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-23-0146, (Released:2023-08-29)
参考文献数
28

Background: In Taiwan, infective native aortic aneurysms (INAAs) are relatively common, so the aim of present study was to demonstrate the comparative outcomes of endovascular repair for thoracic and abdominal INAAs.Methods and Results: Patients with naïve thoracic or abdominal INAAs managed with endovascular repair between 2001 and 2018 were included in this multicenter retrospective cohort. The confounding factors were adjusted with propensity score (PS). Of the 39 thoracic and 43 abdominal INAA cases, 41 (50%) presented with aneurysmal rupture, most of which were at the infrarenal abdominal (n=35, 42.7%) or descending thoracic aorta (n=25, 30.5%). Salmonella spp. was the most frequently isolated pathogen. The overall in-hospital mortality rate was 18.3%. The risks of in-hospital death and death due to rupture were significantly lower with thoracic INAAs (12.8% vs. 23.3%; PS-adjusted odds ratio (OR) 0.24, 95% confidence interval (CI) 0.06–0.96; 0.1% vs. 9.3%; PS-adjusted OR 0.11, 95% CI 0.01–0.90). During a mean follow-up of 2.5 years, the risk of all-cause death was significantly higher with thoracic INAAs (35.3% vs. 15.2%; PS-adjusted HR 6.90, 95% CI 1.69–28.19). Chronic kidney disease (CKD) was associated with death.Conclusions: Compared with thoracic INAAs, endovascular repair of abdominal INAAs was associated with a significantly higher in-hospital mortality rate. However, long-term outcomes were worse for thoracic INAAs, with CKD and infections being the most important predictor and cause of death, respectively.
著者
Teruhiko Imamura Koichiro Kinugawa Naoko Kato Hironori Muraoka Takeo Fujino Toshiro Inaba Hisataka Maki Osamu Kinoshita Masaru Hatano Shunei Kyo Minoru Ono
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.78, no.3, pp.625-633, 2014 (Released:2014-02-25)
参考文献数
34
被引用文献数
56 57

Background: The continuous flow (CF) left ventricular assist device (LVAD) has replaced the pulsatile flow (PF) LVAD because of its advantages of better patient survival and higher quality of life. However, “late-onset right ventricular failure (RVF)” after CF LVAD implantation has emerged as an increasing concern, but little is known about the mechanism. Methods and Results: We retrospectively analyzed the 3-month hemodynamic and echocardiographic data from 38 consecutive patients who had received CF LVADs, and from 22 patients who had received PF LVADs. Late-onset RVF was defined as persistent right ventricular stroke work index (RVSWI) <4.0g/m2 at any rotation speed and after saline infusion test at 5 weeks after implantation of CF LVAD. Patients with late-onset RVF had significantly impaired exercise tolerance indicated by shorter 6-min walking distance and lower peak VO2, and worsened tricuspid regurgitation, together with enlargement of the RV under CF LVAD treatment (all P<0.05). Univariable analyses demonstrated that preoperative smaller LV diastolic diameter (LVDd) was the risk factor for late-onset RVF with a cutoff value of 64mm calculated by ROC analysis (area under curve, 0.925). In contrast, there was no correlation between preoperative LVDd and postoperative RVSWI in the PF LVAD group, though their preoperative background was worse than that of the CF group. Conclusions: In the setting of preoperative small LVDd, CF LVAD may cause late-onset RVF by leftward shift of the interventricular septum.  (Circ J 2014; 78: 625–633)
著者
Lijuan Liu Yanbin Liu Weijun Tong Hong Ye Xianyu Zhang Wuchun Cao Yonghong Zhang
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.71, no.11, pp.1761-1764, 2007 (Released:2007-10-25)
参考文献数
27
被引用文献数
22 26

Background Associations between pathogens and hypertension (HT) has been reported, but few studies have focused on the relationship between aggregate pathogens and HT. The present study explored whether the risk of HT is associated with each pathogen (defined as Chlamydia pneumoniae (C. pneumoniaee), Mycoplasma pneumoniae (M. pneumoniae), Helicobacter pylori (H. pylori) and Coxsackie virus) or with aggregate pathogens in Chinese Mongolians. Methods and Results One thousand and thirty Chinese Mongolians aged 30 years or more were recruited, including 488 hypertensive and 942 normotensive subjects. Enzyme-linked immunosorbent assay was used to detect IgG antibodies for C. pneumoniaee, M. pneumoniae, H. pylori and Coxsackie virus. The seroprevalence of Coxsackie virus was significantly associated with HT (odds ratio (OR) 3.7 after adjustment for risk factors), but no significant association was found for C. pneumoniae, M. pneumoniae and H. pylori (OR 1.32, 0.75 and 1.19, respectively). The results also showed that the risk of HT was associated with the aggregate pathogens: it increased with the increasing number of pathogens, and the ORs were 1.629, 2.653, 2.129, and 5.146 for 1, 2, 3 and 4 pathogens, respectively, after controlling for risk factors. Conclusion The risk of HT is associated with Coxsackie virus and aggregate pathogen load. The mechanism(s) underlying the associations remain to be elucidated further. (Circ J 2007; 71: 1761 - 1764)
著者
Takahisa Kondo Shigeki Osugi Keiko Shimokata Haruo Honjo Yasuhiro Morita Kengo Maeda Kentaro Yamashita Takashi Muramatsu Satoshi Shintani Kunihiro Matsushita Toyoaki Murohara
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.75, no.12, pp.2885-2892, 2011 (Released:2011-11-25)
参考文献数
35
被引用文献数
48 51

Background: Smoking is still a major health problem among males in Japan. The effects of smoking and quitting on mortality and cardiovascular disease (CVD) need updating. Methods and Results: This was a prospective cohort study with a median follow-up of 7.5 years of a total of 25,464 healthy male Japanese workers aged 20-61 years who were not on any medication. The adjusted hazard ratios (HR; 95% confidence interval) for all-cause death were 1.51 (0.73, 2.94), 1.68 (1.07, 2.70), 1.30 (0.70, 2.34), and those for total CVD events 1.91 (0.72, 4.67), 2.94 (1.65, 5.63), and 3.25 (1.69, 6.54) for light smokers (1-10cigarettes/day), moderate smokers (11-20/day), and heavy smokers (≥21/day) compared to never-smokers, respectively. Total CVD events increased dose-dependently as the number of cigarettes/day increased. Acute myocardial infarction was increased at any level of smoking. Stroke was increased at a moderate level of smoking. Quitting for ≥4 years, compared with continuing smokers, reduced the HR for all-cause death to 0.64 (0.38, 1.01), and total CVD events to 0.34 (0.17, 0.62). Conclusions: In healthy young- and middle-aged Japanese males, a significant increase in HR for total CVD events was confirmed for a smoking level of 11-20 cigarettes/day. Quitting reduced the HR for total CVD events, with quitting for ≥4 years being statistically significant. A similar trend was observed for all-cause mortality. (Circ J 2011; 75: 2885-2892)
著者
Philippe Gabriel Steg Grégory Ducrocq
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.80, no.5, pp.1067-1072, 2016-04-25 (Released:2016-04-25)
参考文献数
33
被引用文献数
26 33

With ongoing progress in the prevention and treatment of coronary artery disease (CAD), a continued decrease in prevalence and lethality is expected in high-income countries. Prevention will include lipid-lowering, antithrombotic and anti-inflammatory therapies. With respect to the former, potent, safe and prolonged drugs (such as generic forms of PCSK9 inhibitors relying on monoclonal antibodies or miRNA) should result in a decreased incidence of acute coronary syndromes. Another key aspect will be the ability to identify genetic predictors of CAD and therefore implement targeted personalized prevention early in life. Curative treatment will involve a short course of potent and reversible antithrombotics, but long-term therapy will rely on the ability to stabilize or even regress plaque (eg, using PCSK9 inhibition or modified high-density lipoprotein infusions or anti-inflammatory therapies). Antithrombotic therapy will rely on highly reversible agents (or agents with specific titratable antagonists), and on personalized therapies in which the doses, combinations and duration of therapy will be determined differentially for each patient on the basis of clinical characteristics, genetic profiling and biomarkers. Finally, the need for revascularization in stable CAD will be rare, given the expected progress in prevention. The main challenge, 20 years from now, is likely to be the provision of such effective care at acceptable costs in low- and middle-income countries. (Circ J 2016; 80: 1067–1072)
著者
Kentaro Hori Atsuko Nakayama Daichi Kobayashi Yuichi Adachi Kotaro Hirakawa Tomoki Shimokawa Mitsuaki Isobe
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-23-0102, (Released:2023-05-02)
参考文献数
36

Background: We investigated the components of frailty associated with hospitalization-associated disability (HAD) after cardiac surgery.Methods and Results: This retrospective, observational study evaluated 1,446 older patients after elective cardiac surgery at the Sakakibara Heart Institute. We examined the association between HAD and 7 domains of frailty assessed by the Kihon Checklist. HAD was defined as a decline in the ability to perform activities of daily living (ADL) between admission and discharge, as assessed by the Barthel Index. Logistic regression and decision tree analysis were used to identify associations between the number and type of frailty components and HAD. Of the 1,446 patients, 190 were excluded, and 90 (7%) developed HAD. An increase in the number of frailty components was a risk factor for HAD (odds ratio: 1.88, 95% confidence interval: 1.62–2.17). Decision tree analysis identified physical functional decline, depression, and cognitive dysfunction as factors associated with HAD. The incidence of HAD was highest in cases of physical functional decline (21%) and lowest for cases in which the 3 aforementioned factors were absent (2.8%).Conclusions: An increased number of frailty factors increased the risk of HAD and the findings also reaffirmed the importance of a comprehensive assessment to evaluate the risk of HAD, including evaluation of physical function, cognitive function, and depression.
著者
Daehoon Kim Pil-Sung Yang Tae-Hoon Kim Jae-Sun Uhm Junbeom Park Hui-Nam Pak Moon-Hyoung Lee Boyoung Joung
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.82, no.8, pp.1999-2006, 2018-07-25 (Released:2018-07-25)
参考文献数
36
被引用文献数
8 9

Background:Both atrial fibrillation (AF) and osteoporosis are common in older adults. The purpose of this study was to investigate whether comorbid AF in patients with osteoporosis is associated with fracture incidence, or death after fracture.Methods and Results:From the National Health Insurance Service database of Korea, we selected 31,778 patients with osteoporosis. During a median follow-up of 48 months, the incidence of bone fractures was higher in AF patients than in non-AF patients (3.20 vs. 2.18 per 100 person-years), respectively. In the multivariate Cox regression analysis, AF was associated with fracture independently of other risk factors with an adjusted hazard ratio (HR) of 1.21 (95% confidence interval [CI], 1.02–1.41; P=0.031). The mortality rate after fracture was significantly higher in AF patients than it was in non-AF patients (adjusted HR, 1.92; 95% CI, 1.35–3.27; P=0.016). After propensity score-matching, AF was consistently associated with a higher risk of osteoporotic fracture and subsequent death after fracture. In AF patients, older age, female sex, being underweight (body mass index <18.5 kg/m2), decreased physical activity (exercise <3 times/week), history of stroke or transient ischemic attack, thiazide use, sedative use, and higher CHADS2(≥2 points) or CHA2DS2-VASc (≥2 points) scores were associated with the incidence of fractures.Conclusions:Comorbid AF in patients with osteoporosis was associated with an increased risk of bone fracture and death after fracture.
著者
Donald D. Heistad Yoshinobu Wakisaka Jordan Miller Yi Chu Ricardo Pena-Silva
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.73, no.2, pp.201-207, 2009 (Released:2009-01-23)
参考文献数
44
被引用文献数
101 107

Oxygen radicals, and other reactive oxygen species, may play an important role in the pathophysiology of atherosclerosis, stroke, and other cardiovascular diseases. Mechanisms that account for oxidative stress in different cardiovascular diseases are diverse; for example, increases in activity of NAD(P)H oxidase, "uncoupling" of nitric oxide synthase, and maladaptive changes in expression of antioxidants can all contribute to increases in oxidative stress. Very different patterns of pro-and antioxidant mechanisms that contribute to increases in oxygen radicals in atherosclerotic plaques, hemorrhagic strokes, and aortic valve stenosis have been observed. A disappointment, in relation to the hypothesis that oxygen radicals contribute to cardiovascular risk, is that many studies indicate that antioxidant vitamins fail to reduce the risk of cardiovascular disease. Better understanding of mechanisms that lead to increases in oxidative stress in different cardiovascular diseases may lead to more effective antioxidant prevention or treatment of diseases. (Circ J 2009; 73: 201 - 207)
著者
Alvaro Yogi Glaucia E. Callera Tayze T. Antunes Rita C. Tostes Rhian M. Touyz
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.75, no.2, pp.237-245, 2011 (Released:2011-01-25)
参考文献数
126
被引用文献数
47 57

Decreased Mg2+ concentration has been implicated in altered vascular reactivity, endothelial dysfunction and structural remodeling, processes important in vascular changes and target organ damage associated with hypertension. Unlike our knowledge of other major cations, mechanisms regulating cellular Mg2+ handling are poorly understood. Until recently little was known about protein transporters controlling transmembrane Mg2+ influx. However, new research has uncovered a number of genes and proteins identified as transmembrane Mg2+ transporters, particularly transient receptor potential melastatin (TRPM) cation channels, TRPM6 and TRPM7. Whereas TRPM6 is found primarily in epithelial cells, TRPM7 is ubiquitously expressed. Vascular TRPM7 has been implicated as a signaling kinase involved in vascular smooth muscle cell growth, apoptosis, adhesion, contraction, cytoskeletal organization and migration, and is modulated by vasoactive agents, pressure, stretch and osmotic changes. Emerging evidence suggests that vascular TRPM7 function might be altered in hypertension. The present review discusses the importance of Mg2+ in vascular biology in hypertension and focuses on transport systems, mainly TRPM7, that might play a role in the control of vascular Mg2+ homeostasis. Elucidation of the relationship between the complex systems responsible for regulation of Mg2+ homeostasis, the role of TRPM7 in vascular signaling, and the cardiovascular impact will be important for understanding the clinical implications of hypomagnesemia in cardiovascular disease. (Circ J 2011; 75: 237-245)
著者
Soichiro Fuke Kiyoaki Maekawa Kenji Kawamoto Hironori Saito Tetsuya Sato Toru Hioka Tohru Ohe
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.71, no.2, pp.220-225, 2007 (Released:2007-01-25)
参考文献数
28
被引用文献数
89 93

Background Sirolimus inhibits endothelial cell proliferation in vitro, but although the sirolimus-eluting stent (SES) is widely used because of the very low rates of in-stent restenosis, the influence of SES on coronary endothelial vasomotor function in humans is not well known. Methods and Results The present study included 21 patients treated with SES, and 12 patients treated with conventional bare metal stent (BMS). Endothelium-dependent vasomotor function was evaluated 6 months after stent implantation, using intracoronary acetylcholine infusion. Changes in diameter at the 5-mm proximal and distal edges of the stent, and at the control segment were assessed by quantitative coronary angiography. To evaluate native endothelial function, an intracoronary acetylcholine test was performed before stenting. In the 21 SES patients acetylcholine infusion at 10-8 mol/L and 10-7 mol/L produced significant vasoconstriction in the proximal stent segment (-11.3±10.3%, and -14.1±11.3%, respectively) and the distal stent segment (-13.7±9.3%, and -17.5±12.5%, respectively). In contrast, in the 12 BMS patients, acetylcholine infusion at the same concentrations did not produce a vasoconstrictive response in the proximal stent segment (5.0±8.2% and 4.9±9.1%, respectively) or the distal stent segment (4.2±7.6% and 5.1±7.7%, respectively). Intracoronary nitroglycerin induced a similar grade of vasodilation in the peri-stent area in both groups. Local endothelial function before SES implantation showed no vasoconstrictive response. Conclusions In contrast to vasodilation in BMS patients, SES implantation in the peri-stent area resulted in a vasoconstrictive response to acetylcholine. SES implantation may impair endothelial function in humans. (Circ J 2007; 71: 220 - 225)
著者
Hun-Jun Park Hee-Yeol Kim Jong-Min Lee Yoon Seok Choi Chul-Soo Park Dong-Bin Kim Sung Ho Her Yoon Seok Koh Mahn Won Park Beom-June Kwon Pum Joon Kim Kiyuk Chang Wook Sung Chung Ki-Bae Seung
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.76, no.4, pp.868-875, 2012 (Released:2012-03-23)
参考文献数
32
被引用文献数
37 43

Background: Limited data are available regarding the direct comparison of angiographic and clinical outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) for chronic total occlusion (CTO). Methods and Results: A prospective, randomized, multicenter trial was conducted to evaluate the non-inferiority of a zotarolimus-eluting stent (ZES; Endeavor Sprint®, n=80) to a sirolimus-eluting stent (SES; Cypher®, n=80) in patients with CTO lesion with a reference vessel diameter ≥2.5mm. The primary endpoint was in-segment binary restenosis rate at 9-month angiographic follow-up. Key secondary endpoints included target vessel failure (TVF; including cardiac death, myocardial infarction, and target vessel revascularization) and Academic Research Consortium-defined definite/probable stent thrombosis (ST) within 12 months. The ZES was non-inferior to the SES with respect to the primary endpoint, which occurred in 14.1% (95% confidence interval [CI]: 6.0-22.2) and in 13.7% (95%CI: 5.8-21.6) of patients, respectively (non-inferiority margin, 15.0%; P for non-inferiority <0.001). There were no significant between-group differences in the rate of TVF (10.0% vs. 17.5%; P=0.168) nor in the rate of ST (0.0% vs. 1.3%; P=0.316) during the 12-month clinical follow-up. Conclusions: The effectiveness and safety of ZES are similar to those of SES and therefore it is a good treatment option in patients undergoing PCI for CTO with DESs. (Circ J 2012; 76: 868-875)
著者
Yi Yen Kuo-Chun Hung Yi-Hsin Chan Victor Chien-Chia Wu Yu-Ting Cheng Chia-Pin Lin Jih-Kai Yeh Pao-Hsien Chu Shao-Wei Chen
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-22-0718, (Released:2023-04-06)
参考文献数
38

Background: Studies of the influence of smaller body type on the severity of prosthesis-patient mismatch (PPM) after small-sized surgical aortic valve replacement (SAVR) are few, but the issue is particularly relevant for Asian patients.Methods and Results: 695 patients who underwent SAVR with bioprosthetic valves had their hemodynamic valve performance analyzed at 3 months, 1 year, 3 years, and 5 years after operation, and clinical outcomes were assessed. The patients were stratified into 3 valve size groups: 19/21, 23, and 25/27 mm. A smaller valve was associated with higher mean pressure gradients at the 4 time points after operation (P trend <0.05). However, the 3 valve size groups demonstrated no significant differences in the risk of clinical events. At none of the time points did patients with projected PPM show increased mean pressure gradients (P>0.05), whereas patients with measured PPM did (P<0.05). Compared with patients with projected PPM, those with measured PPM demonstrated higher rates of infective endocarditis readmission (adjusted hazard ratio [aHR] 3.31, 95% confidence interval [CI] 1.06–10.39) and a higher risk of composite outcomes (aHR 1.45, 95% CI 0.95–2.22, P=0.087).Conclusions: Relative to those receiving larger valves, patients receiving small bioprosthetic valves had poorer hemodynamic performance but did not demonstrate differences in clinical events in long-term follow-up.
著者
Hayato Tada Hirofumi Okada Akihiro Nomura Satoshi Yashiro Atsushi Nohara Yasushi Ishigaki Masayuki Takamura Masa-aki Kawashiri
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.83, no.9, pp.1917-1924, 2019-08-23 (Released:2019-08-23)
参考文献数
21
被引用文献数
55 55

Background:A substantial proportion of patients clinically diagnosed as having familial hypercholesterolemia (FH) do not manifest causative mutation(s) in the FH genes such asLDLR,APOB, andPCSK9. We aimed to evaluate the effect of rare and deleterious mutation(s) inABCG5/ABCG8on hyper-low-density lipoprotein (LDL) cholesterolemia in individuals who meet the clinical criteria for FH.Methods and Results:We compared the LDL cholesterol (LDL-C) values among 487 subjects with FH; the subjects were grouped according to the presence of mutation(s) in FH andABCG5/ABCG8genes. We identified 276 individuals with a deleterious mutation in 1 FH gene (57%, monogenic FH), but found no causative mutations in 156 individuals (32%, mutation-negative). A total of 37 individuals had deleterious mutations inABCG5orABCG8, but not in FH genes (8%,ABCG5/ABCG8mutation carriers). Among these, 3 individuals had sitosterolemia (0.6%) with double mutations. We also identified 18 individuals with deleterious mutations in an FH gene andABCG5orABCG8(4%,ABCG5/ABCG8-oligogenic FH). Subjects without mutations had significantly higher polygenic scores than those in any other groups. LDL-C levels in oligogenic FH subjects were significantly higher than in the monogenic FH subjects. Moreover, sitosterol/lathosterol levels were significantly affected by those mutations.Conclusions:The results suggested that rare and deleterious mutations inABCG5/ABCG8contribute substantially to mimicking and exacerbation of the FH phenotype.
著者
Takahiro Tokuhisa Masafumi Yano Masakazu Obayashi Toshiyuki Noma Mamoru Mochizuki Tetsuro Oda Shinichi Okuda Masahiro Doi Jinyao Liu Yasuhiro Ikeda Takeshi Yamamoto Tomoko Ohkusa Masunori Matsuzaki
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.70, no.6, pp.777-786, 2006 (Released:2006-05-25)
参考文献数
42
被引用文献数
18 20

Background The Ca2+ regulatory proteins in the sarcoplasmic reticulum (SR) play a key role in the pathogenesis of heart failure. In the present study the effect of chronic β-receptor-stimulation on cardiac and SR functions was assessed, with or without angiotensin-II receptor antagonist treatment recently reported to have anti-β-adrenergic activity. Methods and Results Rats were treated with isoproterenol with (+) or without (-) candesartan (CAN) and then SR vesicles were isolated from the left ventricular muscle. Both Ca2+-uptake and the amount of SR Ca2+-ATPase were significantly lower in the CAN (-) group than in the shams, but those were almost normally restored in the CAN (+). Although the level of the protein kinase A (PKA)-phosphorylation of the SR Ca2+ release channel, known as the ryanodine receptor (RyR2), was elevated in the CAN (-), no Ca2+-leak was detected. However, SIN-1 (O2 - donor) induced Ca2+-leak in the CAN (-) at a 10-fold lower dose than in the sham and CAN (+). In cardiomyocytes, SIN-1 decreased cell shortening and the peak Ca2+ transient and prolonged time from peak to 70% decline in CAN (-), again at 10-fold lower dose than in the sham and CAN (+). Conclusion Chronic β-receptor-stimulation did not induce any Ca2+-leak from the SR, whereas Ca2+-leak was easily induced when oxidative stress was applied to the PKA-phosphorylated RyR2. Candesartan not only improved Ca2+-uptake, but also prevented PKA-phosphorylation, rendering the SR less susceptible to Ca2+-leak. (Circ J 2006; 70: 777 - 786)
著者
Hiroki Mori Tadahiro Yoshikawa Hitomi Kimura Hiroshi Ono Hitoshi Kato Yasuo Ono Masaki Nii Takahiro Shindo Ryo Inuzuka Hitoshi Horigome Masaru Miura Shunichi Ogawa Junko Shiono Yoshiyuki Furutani Mikiko Ishido Toshio Nakanishi
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.86, no.1, pp.109-115, 2021-12-24 (Released:2021-12-24)
参考文献数
21
被引用文献数
1 4

Background:There has been no nationwide survey on the prognosis of pediatric dilated cardiomyopathy (DCM) in Japan. Therefore, we designed this retrospective multicenter study to investigate the long-term survival rate in pediatric patients with DCM in Japan.Methods and Results:In this multicenter retrospective observational study, data were reviewed for 106 patients aged <18 years who had been diagnosed with DCM at any 1 of 18 Japanese institutions between 1990 and 2014. The median age at diagnosis was 2.0 years and the median duration of observation was 3.3 years. Most DCM patients were diagnosed because of symptoms of heart failure. On echocardiography, the median left ventricular end-diastolic dimension z score was 5.4 and fractional shortening was 0.10. Freedom from death or transplantation rates at 1, 3, 5, 10, and 20 years after diagnosis were 76%, 66%, 64%, 58%, and 43%, respectively. Freedom from death rates at 1, 5, 10, and 20 years after diagnosis were 81%, 75%, 72%, and 53%, respectively. The incidence of heart transplantation at 1, 5, 10, and 20 years after diagnosis was 6%, 15%, 20%, and 20%, respectively, suggesting that only 15% of patients in Japan underwent heart transplantation within 5 years of diagnosis.Conclusions:In Japan, the prognosis of pediatric DCM is poor and the rate of heart transplantation is low.
著者
Kenji Suda Yoshiyuki Kudo Takashi Higaki Yuichi Nomura Masaru Miura Masahiko Matsumura Mamoru Ayusawa Shunichi Ogawa Toyojiro Matsuishi
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.73, no.7, pp.1319-1323, 2009 (Released:2009-06-25)
参考文献数
17
被引用文献数
48 57

Background: To determine the prognosis of patients with giant coronary aneurysms (GA) caused by Kawasaki disease (KD) treated with combined oral warfarin and aspirin. Methods and Results: A multicenter follow-up study of 83 patients (65 males, 18 females) with GA who had been treated for ≥3 months with warfarin. Most patients were placed on the combination therapy as soon as the GA was detected and remained on it for 6.0 ±5.3 years, giving a total of 482 patient-years. Target international normalized ratio of prothrombin time ranged from 1.5 to ≥2.5. During this observational period, 5 patients suffered from 8 episodes of acute myocardial infarction and 1 died. Coronary thrombus formation enforced 6 courses of intracoronary thrombolysis in 3 patients (1-4 times). Consequently, freedom of cardiac events was 92.5% at 1 year and 91% at 10 years and the linearized cardiac event rate was 2.9% patient-year. Hemorrhagic complications occurred on 8 occasions (1 subdural hematoma) in 5 patients, giving 1.7% patient-year. Conclusions: The combination of warfarin and aspirin has an acceptably high cardiac-event-free survival in patients with GA caused by KD, though it has a certain risk of hemorrhagic complications. (Circ J 2009; 73: 1319-1323)