著者

佐野 隆一 阿部 隆三 及川 真一 藤井 豊 後藤 由夫 高瀬 貞夫

出版者

Japan Atherosclerosis Society

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.15, no.4, pp.1005-1008, 1987

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The lipid levels of serum and lipoproteins were examined in eleven patients with myotonic dystrophy (MD) and ten normal subjects. Hyperlipoproteinemia was seen in six patients, including type IIb of three patients, type IIa of two and type V of one. Total cholesterol (C) and triglyceride (TG) levels of serum and lipoproteins in MD were not significant. TG/C ratio of lipoproteins in MD were not so high compared with normals.<br>The mean age of the patients with hyperlipoproteinemia was significantly higher than that of normolipoproteinemia. The correlation coefficients between age and lipid levels of serum and lipoproteins were examined. The age was positively correlated to serum C and VLDL-TG levels. Further, in the MD patients except for case 1 with type V hyperlipoproteinemia, the age was positively correlated to LDL-TG and LDL-C levels, and negatively correlated to HDL-TG levels.<br>In conclusion, the LDL levels increased and the HDL levels decreased with age in MD. These results suggest that the abnormalities of serum lipid metabolism is one of the characteristic changes in MD.

著者

Takashi Nomiyama

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.ED130, (Released:2020-06-05)

参考文献数

10

著者

Shinichiro Uchiyama Takao Hoshino Hugo Charles Kenji Kamiyama Taizen Nakase Kazuo Kitagawa Kazuo Minematsu Kenichi Todo Yasushi Okada Jyoji Nakagawara Ken Nagata Hiroshi Yamagami Takenori Yamaguchi Pierre Amarenco

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.58552, (Released:2020-09-17)

参考文献数

22

被引用文献数

4

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Aims: We have previously reported 5-year follow-up data on the TIAregistry.org, an international prospective cohort in patients with transient ischemic attack (TIA) or minor stroke. We conducted a Japanese subgroup analysis because outcomes and predictors might differ according to ethnicities and regions. In this study, we compared the baseline and 5-year follow-up data of Japanese and non-Japanese patients with TIA or minor stroke.Methods: Patients with TIA or minor ischemic stroke within 7 days after the onset were classified into two groups based on ethnicity, Japanese (n=345) and non-Japanese (n=3502); further, 5-year event rates were compared between the two groups. We also determined predictors of 5-year stroke for both groups. Results: Vascular death and death from any cause were identified to be less prevalent, unlike stroke and intracranial hemorrhage, which was determined to be more prevalent in Japanese than in non-Japanese patients. Five-year rate of stroke was significantly higher in Japanese patients. Cumulative stroke and major cardiovascular event rates did not decline but instead linearly increased from 1 to 5 years in both groups. Baseline risk factors for 5-year stroke were as follows: age, diabetes, history of stroke or TIA, and congestive heart failure in Japanese patients. Independent predictors of 5-year stroke were large artery atherosclerosis, congestive heart failure, diabetes, and age in Japanese patients. Conclusions: Recurrent stroke and intracranial hemorrhage were determined to be more prevalent at 5 years after TIA or minor stroke in Japanese patients than in non-Japanese patients. Strategies to mitigate the long-term risks of stroke, aside from adherence to current guidelines, should take Japanese-patient-specific residual risks into account.

著者

松田 保 山之内 博

出版者

Japan Atherosclerosis Society

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.9, no.4, pp.543-549, 1981

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Hypothesis, firstly proposed by Rokitansky in 1852 and revived by Duguid in 1946, that atherosclerotic plaques result, at least partly, from organization of fibrin thrombi, is fascinating from view point of blood coagulation, although direct evidences have been lacking. Authors have demonstrated that levels of β-thromboglobulin and platelet factor 4 decreased following administration of antiplatelet agents and that concentration of antithrombin III in plasma lowered following decrease in levels of vitamin K dependent procoagulants by administration of warfarin. These results support Astrup's hypothesis that minimal fibrin deposition and its lysis continuously occurrs on vascular intima in normal subjects. Assuming that these hypotheses are true, hypercoagulability of blood in a broad sence may accelerate deposition of fibrin on vascular wall and may lead to progression of atherosclerosis.<br>Purpose of this study is to elucidate this problem from investigation of blood constituents which affect removal of activated clotting factors which are most important in formation of fibrin. Two major parameters which affect blood viscosity, namely hematocrit values and fibrinogen content, and two most important inhibitors of activated procoagulants, namely antithrombin III and α₂-macroglobulin, were compared to grade of atherosclerosis of coronary and cerebral arteries classified grossly with naked eyes in serial 537 autopsied cases without cancer or DIC.<br>Following results were obtained: Hematocrit values were significantly higher in patients with marked atherosclerosis of cerebral artery. There were no statistically significant correlations between levels of inhibitors or fibrinogen and the grade of atherosclerosis, although total antithrombin levels, which were generally lower in males because of higher content of α₂-macroglobulin in females, decreased in females with severe atherosclerosis. However, a 54-years old male with congenital dysfibrinogenemia, in whom delayed convertion rate of fibrinogen into fibrin and impaired platelet aggregability induced thrombin and angiographically marked sclerosis of cerebral artery were demonstrated, had repeated attack of cerebral infarction, although risk factor of arteriosclerosis was lacking but hypertension.<br>From these results, it is concluded that evidences in favor of the thrombogenic theory of atherosclerosis is insufficient and that mild suppression of blood clotting system is not enough to protect one from arteriosclerosis.

著者

松田 保 村上 元孝

出版者

Japan Atherosclerosis Society

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.3, no.4, pp.447-455, 1976

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Coagulability of blood was measured in 80 cases of acute myocardial infarction, 98 cases of acute cerebral infarction and 33 cases of acute cerebral hemorrhage. Platelet counts, activated partial thromboplastin times, prothrombin times, plasma fibrinogen content, levels of plasma antithrombin III, α₂-macroglobulin and fibrin degradation products (FDP) determined within 1 month before the attack of myocardial infarction or stroke, and those measured within 48 hours or 3 to 7 days following the onset of these diseases were compared with data obtained from 370 healthy subjects over age sixty.<br>Concentrations of plasma antithrombin III were apparently decreased before and after the development of myocardial infarction. In ten autopsied patients with acute myocardial infarction, three cases with extremely low levels of plasma antithrombin III (less than 2 mg/d<i>l</i>) were complicated with disseminated intravascular coagulation (DIC), acute cerebral infarction and/or thromboembolism of lower extremities, while no thromboembolic episodes following myocardial infarction were observed in the other seven cases in whom plasma antithrombin III concentrations were more than 20mg/d<i>l</i>. Levels of the other thrombin inhibitor in plasma than antithrombin III, i. e. α₂-macroglobulin, were increased immediately after the occurrence of cerebral hemorrhage. Plasma fibrinogen content was markedly increased after the development of myocardial infarction or cerebrovascular diseases. Activated partial thromboplastin times, prothrombin times and FDP did not significantly change before and after the development of these diseases. These data suggest that there may be a relation between development of myocardial infarction and the low levels of plasma antithrombin III. Increased levels of plasma fibrinogen, as a result of myocardial infarction or stroke, may not accelerate coagulation mechanism but act disadvantageously by elevating blood viscosity.<br>Relationship between activated partial thromboplastin times, prothrombin times, plasma fibrinogen content, levels of plasma antithrombin III, α₂-niacroglobulin or FDP, determined within 1 month before death, and grade of atherosclerosis of aorta, cerebral, coronary or femoral artery, classified grossly with the naked eye, was investigated in 186 autopsied cases without cancer or DIC, retrospectively. There were no correlations between these parameters and the grade of atherosclerosis, except that levels of FDP were significantly increased in cases with severe atherosclerosis of femoral artery. From these results, direct evidences supporting thrombogenic hypothesis of atherosclerosis suggested by Duguid were not obtained. However, atherosclerotic lesion of peripheral artery may activate clotting processes and increase FDP.

著者

Hitoshi Hamamura Hisashi Adachi Mika Enomoto Ako Fukami Sachiko Nakamura Yume Nohara Nagisa Morikawa Akiko Sakaue Kenta Toyomasu Maki Yamamoto Yoshihiro Fukumoto

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.56390, (Released:2020-07-04)

参考文献数

38

被引用文献数

14

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Aim: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been identified as an important regulator of low-density lipoprotein (LDL) receptor processing. Evolocumab and alirocumab are PCSK9 inhibitors; however, little is known about the association between PCSK9 levels and lipid profiles in a general population. Because PCSK9 inhibitors have LDL-C lowering effects, we investigated whether there is a positive correlation between serum PCSK9 levels and LDL-C or lipoprotein(a) [Lp(a)]. Methods: In Uku town, 674 residents (mean age; 69.2±8.3 years) received health check-ups. The participants underwent a physical examination and blood tests, including PCSK9 and Lp(a). Serum PCSK9 and Lp(a) were measured by ELISA and Latex methods, respectively. HOMA-IR was calculated by fasting plasma glucose×insulin levels/405. Results: The mean (range) of PCSK9 and Lp(a) were 211.2 (49-601) ng/mL and 60 (1-107) mg/dL, respectively. Because of a skewed distribution, the log-transformed values were used. With univariate linear regression analysis, PCSK9 levels were associated with Lp(a) (p=0.028), triglycerides (p<0.001), and HOMA-IR (p<0.001), but not with LDL-C (p=0.138) levels. Multiple stepwise regression analysis revealed that serum PCSK9 levels were independently associated with triglycerides (p<0.001), Lp(a) (p=0.033) and HOMA-IR (p=0.041). Conclusions: PCSK-9 is independently associated with triglycerides, Lp(a) levels, and HOMA-IR, but not LDL-C, in a relatively large general population sample.

著者

Mari Tanaka Hironori Imano Yasuhiko Kubota Kazumasa Yamagishi Mitsumasa Umesawa Isao Muraki Renzhe Cui Mina Hayama-Terada Yuji Shimizu Takeo Okada Tetsuya Ohira Tomoko Sankai Takeshi Tanigawa Shinichi Sato Akihiko Kitamura Masahiko Kiyama Hiroyasu Iso and the CIRCS Investigators

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.54064, (Released:2020-06-10)

参考文献数

30

被引用文献数

11

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Aim: This study aimed to investigate the association between the serum high-sensitivity C-reactive protein (hs-CRP) levels and incident atrial fibrillation risk in the general Japanese population, who have lower hs-CRP levels than the Western population, and assess whether the association is modified by sex, overweight, hypertension, and smoking status. Methods: We conducted a prospective study in 6517 Japanese men and women aged 40–79 years without atrial fibrillation at baseline and enrolled in the Circulatory Risk in Communities Study (2002–2008). The hs-CRP levels were measured using the latex particle-enhanced immunonephelometric assay. Atrial fibrillation was identified using standard 12-lead electrocardiograms and information on physician-diagnosed atrial fibrillation history from the follow-up surveys. We used a Cox proportional hazard regression stratified by community. Results: During a median follow-up of 11 years, 127 new cases of atrial fibrillation (74 and 53 cases among men and women, respectively) were found. Compared to the lowest quintile of hs-CRP levels, the multivariable hazard ratios (95% confidence intervals) were 2.54 (1.17–5.50), 2.28 (1.06–4.93), 2.92 (1.37–6.23), and 2.77 (1.30–5.91) for the second, third, fourth, and fifth (highest) quintiles, respectively. There was no significant effect modification by sex, overweight, hypertension, and smoking status (P for interaction >0.05). Conclusions: Elevated hs-CRP levels were significantly associated with increased risk of atrial fibrillation in the Japanese population. The association of hs-CRP levels with incident atrial fibrillation did not vary according to sex, overweight, hypertension status, or smoking status.

著者

Shuaibo Huang Ru Ding Yi Lin Zhiqing He Feng Wu Xianliang Dai Yihong Chen Yanping Gui Zhigang Huang Zonggui Wu Chun Liang

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.23, no.5, pp.632-643, 2016-05-02 (Released:2016-05-02)

参考文献数

59

被引用文献数

5 13

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Aim: Immunologic dysfunction was recently found to be one of the most important mechanisms underlying the initiation and development of atherosclerosis. Thymus involution can contribute to immune disturbance and disequilibrium of T-cell subsets. This study aimed to explore whether recent thymic emigration (RTE) is impaired in patients with coronary artery disease (CAD).Methods: Content of signal-joint T cell receptor excision circles (sj-TREC) in T lymphocytes, a molecular marker of RTE, was assessed among CAD patients and age-matched controls. Monochrome multiplex quantitative PCR method was used to assess the samples' telomere length in order to exclude the potential influence of T cell proliferation on the dilution of sj-TREC. Patients were grouped according to Gensini score (GS) (low, GS <18; intermediate, GS 18–41; high, GS >41). Ordinary logistic regression models were used to determine potential risk factors for CAD and GS tertiles.Results: Average copy numbers of sj-TREC per 106 T lymphocytes among patients with unstable angina, stable angina, and controls were 726±429, 1213±465, and 1795±838, respectively (P<0.001). However, there was no significant difference in telomere length among groups. Moreover, the content of sj-TREC in the high GS group was most significantly reduced than the low GS group (P<0.001). Multivariate logistic regression analysis revealed that lower sj-TREC was independently associated with the progression of CAD (OR=0.44, P<0.001) and higher GS (OR=0.4, P<0.001).Conclusion: Impaired RTE could be partly responsible for CAD development. Mechanisms may be involved in the disturbance of T lymphocyte compartment and interruption of maintained immune tolerance resulting from thymus involution.

著者

Shizuya Yamashita Hidenori Arai Hideaki Bujo Daisaku Masuda Tohru Ohama Toshiyuki Ishibashi Koji Yanagi Yasuji Doi Satoshi Nakagawa Koichi Yamashiro Kenichiro Tanabe Toru Kita Masunori Matsuzaki Yasushi Saito Masanori Fukushima Yuji Matsuzawa on Behalf of the PROSPECTIVE Study Group

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.55327, (Released:2020-04-24)

参考文献数

50

被引用文献数

24

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Aims: Although intensive statin therapy reduced cardiovascular risks, cardiovascular events have not been completely prevented. Probucol is a potent antioxidant and reduces tendon xanthomas in familial hypercholesterolemia patients despite reduction of high-density lipoprotein (HDL)-cholesterol (HDL-C). We investigated whether probucol can reduce cardiovascular events on top of conventional lipid-lowering therapy in patients with coronary heart disease (CHD). Methods: PROSPECTIVE is a multicenter, randomized, prospective study that recruited 876 Japanese patients with CHD and dyslipidemia with an low-density lipoprotein (LDL)-cholesterol (HDL-C) level of ≥ 140 mg/dL without medication or those treated with lipid-lowering drugs. Lipid-lowering agents were administered during the study period in the control group (n=438), and probucol 500 mg/day was added to lipid-lowering therapy in the probucol group (n=438). Patients were randomly assigned to two treatment groups by adjusting the LDL-C level and presence of diabetes and hypertension and followed up for more than 3 years. The primary end point was a composite of cerebrovascular and cardiovascular events (cardiovascular disease death including sudden death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, hospitalization for heart failure, or coronary revascularization). The secondary end point was carotid intima–media thickness in a subset of patients. Results: The incidence of the primary end point showed a trend to be lower in the probucol group compared with that in the control group despite reduced HDL-C without serious adverse events. Anti-atherogenic effects of probucol may be attributed to its potent antioxidative function and enhancement of reverse cholesterol transport. Conclusion: Since there was no statistical significance between the probucol and control groups despite a marked reduction of HDL-C, further studies on the clinical outcomes of probucol on top of conventional therapy may be necessary in the future (UMIN000003307).

著者

Hiroaki Ikezaki Norihiro Furusyo Yuya Yokota Masumi Ai Bela F Asztalos Masayuki Murata Jun Hayashi Ernst J Schaefer

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.54130, (Released:2020-04-10)

参考文献数

46

被引用文献数

13

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Aim: The association between small dense low-density lipoprotein cholesterol (sdLDL-C) levels and carotid intimal medial thickness (cIMT) progression has not been evaluated fully. We assessed specialized lipoproteins, including sdLDL-C, with regard to cIMT progression in a prospective observational study in Japan. Methods: Plasma total cholesterol, direct LDL-C, sdLDL-C, LDL-triglycerides (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, triglycerides, Lp(a), and adiponectin were measured in 2,030 men and women (median age 59 years, free of cardiovascular disease (CVD) and off cholesterol lowering medication). At both baseline and after a five-year follow-up, cIMT was assessed. Univariate, multivariate regression, and least square analyses were performed to examine the relationships between direct LDL-C, sdLDL-C, and other lipoproteins with cIMT progression. Results: The median cIMT at baseline was 0.63 mm and five-year progression was 0.18 mm. After adjustment for standard CVD risk factors, including age, gender, systolic blood pressure, total cholesterol, HDL-C, smoking, diabetes, and hypertension treatment, only direct LDL-C, sdLDL-C, and the sdLDL-C/LDL-C ratio were associated with cIMT progression. Even in subjects with direct LDL-C <100 mg/dL, who were considered at low CVD risk, elevated sdLDL-C were associated with cIMT progression (P for trend=0.009) in a model with established CVD risk factors, although the sdLDL-C/LDL-C ratio did not. Those correlations did not change by including triglycerides as a controlling factor or excluding premenopausal women from the analyzed population. Conclusions: Small dense LDL-C has a stronger relationship with cIMT progression than LDL-C does; therefore, measuring sdLDL-C may allow for the formulation of optimal therapy for CVD prevention.

著者

Kazuyuki Ozaki Takaaki Kubo Ryuta Imaki Hisahito Shinagawa Hidehira Fukaya Keita Ohtaki Seiga Ozaki Tohru Izumi Yoshifusa Aizawa

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.13, no.4, pp.216-219, 2006 (Released:2006-08-15)

参考文献数

22

被引用文献数

32 38

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We investigated the lipid lowering and anti-atherosclerotic effects of atorvastatin in patients with hypercholesterolemia. Thirty patients were given atorvastatin 10 mg daily, and assessed for serum lipids, intima-media thickness (IMT), and brachial-ankle pulse wave velocity (ba-PWV) at the baseline, 6 months, and 12 months. Remnant-like particle-cholesterol (RLP-C), lipoprotein (a)(Lp(a)), and high-sensitivity C-reactive protein (hs-CRP) were measured in some patients at the baseline and at 6 months. Total cholesterol, triglyceride and low-density lipoprotein cholesterol were significantly decreased by 32%, 23% and 44% at 6 months, respectively, and these effects were sustained at 12 months. There was no change in high-density lipoprotein cholesterol. IMT at the baseline was 0.88 ± 0.16 mm and decreased to 0.76 ± 0.13 mm at 6 months, remaining at 0.75 ± 0.12 mm at 12 months. We did not observe any significant changes in ba-PWV. RLP-C and hs-CRP were significantly reduced from 7.3 ± 10.8 mg/dL to 4.3 ± 5.3 mg/dL and 0.075 ± 0.065 mg/dL to 0.039 ± 0.043 mg/dL at 6 months, respectively. There was no change in Lp(a). The observed decrease in IMT suggests that atorvastatin possibly improves atherosclerosis, in addition to the significant reduction of serum lipids.

著者

Yuya Nakano

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.RV17039, (Released:2019-12-20)

参考文献数

84

被引用文献数

23

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Low birth weight (LBW) infants have higher risk of developing insulin resistance and its comorbidities later in life. The concept of “developmental origins of health and disease” suggests that intrauterine and postnatal environments have an important role in increasing these risks. The risk of such adult-onset diseases in LBW infants might be associated with adipose tissue maldevelopment including altered body composition and increased amount of visceral fat, which is the same mechanism as that in children and adults with metabolic syndrome. However, LBW infants often have different characteristics: they are not always overweight or obese over their life course. The inconsistency might be associated with the thrifty phenotype, which is produced in response to impaired growth potential and decreased lean body mass. LBW infants tend to be obese within the limits of impaired growth potential. Through our previous investigations evaluating longitudinal changes in adiponectin levels at an early stage of life, we speculated that probably, the intrauterine life of term infants or the period up to term-equivalent age in preterm infants might be the key age for the development of adipose tissues including fat cells. Because of that, we hypothesized that the smaller number of adipocytes in LBW infants might be associated with overloading of single adipocytes and impaired adipose tissue expandability. The possible mechanisms are discussed from the perspective of adipose tissue maldevelopment in LBW infants.

著者

Kazuo Omori Naoto Katakami Shoya Arakawa Yuichi Yamamoto Hiroyo Ninomiya Mitsuyoshi Takahara Taka-aki Matsuoka Hiroshi Tsugawa Masahiro Furuno Takeshi Bamba Eiichiro Fukusaki Iichiro Shimomura

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.52506, (Released:2020-01-25)

参考文献数

32

被引用文献数

15

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Aim: An identification of the high-risk group of atherosclerotic cardiovascular disease (CVD) is important in the management of patients with diabetes. Metabolomics is a potential tool for the discovery of new biomarkers. With this background, we aimed to identify metabolites associated with atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 176 patients with T2DM who have never had a CVD event and 40 who were survivors of coronary artery disease (CAD) events were enrolled. Non-targeted metabolome analysis of fasting plasma samples was performed using gas chromatography coupled with mass spectrometry (GC/MS) highly optimized for multiple measurement of blood samples. First, metabolites were screened by analyzing the association with the established markers of subclinical atherosclerosis (i.e., carotid maximal intima-media thickness (max-IMT) and flow-mediated vasodilation (FMD)) in the non-CVD subjects. Then, the associations between the metabolites detected and the history of CAD were investigated. Result: A total of 65 annotated metabolites were detected. Non-parametric univariate analysis identified inositol and indoxyl sulfate as significantly (p<0.05) associated with both max-IMT and FMD. These metabolites were also significantly associated with CAD. Moreover, inositol remained to be associated with CAD even after adjustments for traditional coronary risk factors. Conclusions: We identified novel biomarker candidates for atherosclerosis in Japanese patients with T2DM using GC/MS-based non-targeted metabolomics.

著者

Kenji Ebihara Kazumasa Yamagishi Mitsumasa Umesawa Isao Muraki Renzhe Cui Hironori Imano Yasuhiko Kubota Mina Hayama-Terada Yuji Shimizu Tetsuya Ohira Tomoko Sankai Takeo Okada Akihiko Kitamura Masahiko Kiyama Hiroyasu Iso for the CIRCS Investigators

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.52241, (Released:2020-01-11)

参考文献数

30

被引用文献数

3

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Aim: N-terminal pro-B-type natriuretic peptide (NT-proBNP), frequently used as a biochemical marker for detecting and monitoring heart failure, is also a risk marker for development of coronary heart disease and total stroke. However, studies that explore subtypes of ischemic stroke with regard to NT-proBNP are scarce. Here, we examined NT-proBNP and its impact upon subtypes of ischemic stroke (lacunar stroke, large-artery occlusive stroke and embolic stroke) among Japanese. Methods: We measured NT-proBNP and categorized 4,393 participants of the Circulatory Risk in Communities Study into four groups (<55, 55-124, 125-399, and ≥ 400 pg/ml). We used a multivariable Cox proportional hazards model to examine association with risks of stroke and subtypes. Results: During 4.7 years of follow-up, we identified 50 strokes, including 35 ischemic (15 lacunar, 6 largeartery occlusive, 10 embolic strokes) and 14 hemorrhagic strokes. NT-proBNP was associated with stroke risk: the multivariable hazard ratio of total strokes was 7.29 (2.82-18.9) for the highest and 2.78 (1.25-6.16) for the second highest NT-proBNP groups compared with the lowest group. The respective hazard ratios for the highest NT-proBNP group were 9.37 (3.14–28.0) for ischemic stroke and 6.81 (1.11–41.7) for lacunar stroke. Further adjustment for atrial fibrillation did not attenuate these associations. The associations were similarly observed for large-artery occlusive and embolic strokes. Conclusion: We found that even moderate serum levels of NT-proBNP were associated with the risk of total and ischemic strokes among Japanese whose NT-proBNP levels were relatively low compared with Westerners.

著者

Shusaku Maeda Shuhei Nakanishi Masayasu Yoneda Tomokazu Awaya Kiminori Yamane Tsutomu Hirano Nobuoki Kohno

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.1112200459, (Released:2011-12-21)

参考文献数

34

被引用文献数

37 55

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Aim: Small dense low-density lipoprotein (sdLDL) has been suggested to be more atherogenic than large buoyant LDL. High-density lipoprotein (HDL) consists of two major subfractions (HDL2, HDL3), and just as controversy remains regarding which of the two is the more powerful negative risk factor for atherosclerosis, associations between sdLDL and these HDL subfractions are unclear.Methods: We measured sdLDL cholesterol (sdLDL-C), HDL2 cholesterol (HDL2-C) and HDL3 cholesterol (HDL3-C) by a newly developed method in 481 Japanese-Americans who were not using lipid-lowering medication, and examined the associations of these cholesterol concentrations with variables related to atherosclerosis.Results: In multivariate analysis, sdLDL-C was positively correlated with the body mass index (BMI), fasting glucose and insulin, 2-h glucose, HOMA-IR, high sensitivity C-reactive protein (hsCRP), and carotid artery intima-media thickness (IMT) after adjustment for age and sex. In particular, sdLDL-C was positively correlated with IMT, even after adjustment for sex, age, smoking status, hypertension, diabetes mellitus and hsCRP. HDL2-C was more closely inversely correlated than total HDL-C with BMI, fasting glucose and insulin, 2-h glucose, HOMA-IR, and hsCRP, whereas HDL3-C was not correlated with these factors. Additionally, HDL2-C was more closely correlated than total HDL-C or HDL3-C with sdLDL-C, LDL-C, triglycerides (TG), and apolipoprotein B (apoB).Conclusions: SdLDL-C was closely associated with insulin resistance and glucose tolerance, lending credence to its potential as a useful risk marker in assessing carotid artery IMT and the present degree of atherosclerosis in Japanese-Americans. The findings also suggest that subjects with higher HDL2-C levels were better protected from atherosclerosis.

著者

Jin Kirigaya Noriaki Iwahashi Hironori Tahakashi Yugo Minamimoto Masaomi Gohbara Takeru Abe Eiichi Akiyama Kozo Okada Yasushi Matsuzawa Nobuhiko Maejima Kiyoshi Hibi Masami Kosuge Toshiaki Ebina Kouichi Tamura Kazuo Kimura

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.51409, (Released:2019-10-18)

参考文献数

32

被引用文献数

26

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Aim: The purpose of this study is to investigate the impact of arterial stiffness assessed using Cardio-ankle Vascular Index (CAVI) on long-term outcome after acute coronary syndrome (ACS). Methods: A total of 387 consecutive patients (324 males; age, 64±11 years) with ACS were enrolled. We examined CAVI and brachial-ankle pulse wave velocity (ba PWV) as the parameters of arterial stiffness. The patients were divided into two groups according to the cut-off value of CAVI determined using the receiver operating characteristic curve for the prediction of major adverse cardiovascular events (MACE): low-CAVI group, 177 patients with CAVI <8.35; high-CAVI group, 210 patients with CAVI ≥ 8.35. The primary endpoint was the incidence of MACE (cardiovascular death, recurrence of ACS, heart failure requiring hospitalization, or stroke). Results: A total of 62 patients had MACE. Kaplan–Meier analysis demonstrated a significantly higher probability of MACE in the high-CAVI group than in the low-CAVI group (median follow-up: 62 months; log-rank, p<0.001). Multivariate analysis suggested that CAVI was an independent predictor of MACE (hazard ratio [HR], 1.496; p=0.02) and cardiovascular death (HR, 2.204; p=0.025), but ba PWV was not. We investigated the incremental predictive value of adding CAVI to the GRACE score (GRS), a validated scoring system for risk assessment in ACS. Stratified by CAVI and GRS, a significantly higher rate of MACE was seen in patients with both higher CAVI and higher GRS than the other groups (p<0.001). Furthermore, the addition of CAVI to GRS enhanced net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI, 0.337, p=0.034; and IDI, 0.028, p=0.004). Conclusion: CAVI was an independent long-term predictor of MACE, especially cardiovascular death, adding incremental clinical significance for risk stratification in patients with ACS.

著者

Yasumichi Arai Michiyo Takayama Yukiko Abe Nobuyoshi Hirose

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.18, no.7, pp.545-550, 2011 (Released:2011-07-22)

参考文献数

47

被引用文献数

44 61

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Dysregulation of adipose tissue-derived bioactive molecules, termed adipokines, is recognized as common ground for insulin resistance and metabolic syndrome associated with obesity. However, adipokine dysregulation is paradoxically associated with lipodystrophy and lipoatrophy with aging. In familial partial lipodystrophic syndromes and Hutchinson-Gilford progeria syndrome, both of which are caused by mutations in the LMNA gene, loss of adipose tissue is associated with adipokine dysregulation, insulin resistance, and atherosclerosis, suggesting a critical role of adipose tissue function in controlling whole body energy metabolism, age-related pathologies, and longevity. Centenarians, a model of healthy aging and longevity, are reported to exhibit preserved insulin sensitivity as well as favorable adipokine profiles, particularly high levels of circulating adiponectin. Furthermore, adipose tissue dysfunction indicated by dysregulation of leptin, tumor necrosis factor-α, and adiponectin is associated with poor prognosis in centenarians. In contrast to results obtained for obesity, adipokine dysregulation in centenarians is associated with very low leptin levels, suggesting that age-related lipoatrophy is the major factor for adipose tissue dysfunction at an advanced age. These observations suggest that adipose tissue excess as well as its aging is implicated in the regulation of adipokines, insulin sensitivity, and lifespan in humans.

著者

Yuta Sato Daiji Nagayama Atsuhito Saiki Rena Watanabe Yasuhiro Watanabe Haruki Imamura Takashi Yamaguchi Noriko Ban Hidetoshi Kawana Ayako Nagumo Masahiro Ohira Kei Endo Takumi Kurosu Takanobu Tomaru Kohji Shirai Ichiro Tatsuno

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.31385, (Released:2015-12-02)

参考文献数

41

被引用文献数

34 81

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Aim: We investigated whether cardio-ankle vascular index (CAVI), an arterial stiffness marker, independently predicts future cardiovascular events in subjects with metabolic disorders.Methods: 1562 outpatients underwent CAVI between April 2004 and March 2006 at Toho University, Sakura Medical Center in Chiba, Japan. Patients who already had cardiovascular events at baseline, patients with low ankle brachial index (<0.9), and patients with atrial fibrillation were excluded. After exclusion, 1080 subjects with metabolic disorders including diabetes mellitus, hypertension and dyslipidemia were screened and followed prospectively.Results: Eventually, 1003 subjects (92.9% of 1,080 subjects) followed until March 2012 (follow-up duration 6.7±1.6 years) were analyzed. During the observation period, 90 subjects had new-onset myocardial infarction or angina pectoris confirmed by angiography. All subjects were stratified into quartiles by baseline CAVI (Q1: CAVI ≤8.27, Q2: CAVI 8.28-9.19, Q3: CAVI 9.20-10.08, Q4: CAVI ≥10.09). Age, male ratio and future cardiovascular events increased as CAVI quartile became higher. In Cox proportional hazards regression analysis, the factors independently associated with higher risk of future cardiovascular events were every 1.0 increment of CAVI [hazard ratio (HR) 1.126, p= 0.039], male gender (HR 2.276, p=0.001), smoking (HR 1.846, p=0.007), diabetes mellitus (HR 1.702,p=0.020), and hypertension (HR 1.682, p=0.023).Conclusion: In individuals with metabolic disorders, CAVI was a predictor of future cardiovascular events, independent of traditional coronary risk factors. CAVI is a potentially valuable tool to identify persons likely to benefit from more intensive therapeutic approaches.

著者

Hiroshi Yoshida Hayato Tada Kumie Ito Yoshimi Kishimoto Hidekatsu Yanai Tomonori Okamura Katsunori Ikewaki Kyoko Inagaki Tetsuo Shoji Hideaki Bujo Takashi Miida Masayuki Yoshida Masafumi Kuzuya Shizuya Yamashita

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.50187, (Released:2019-09-05)

参考文献数

26

被引用文献数

27

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Aims: The present study was conducted to establish a practical method for measuring non-cholesterol sterols and reference intervals of serum levels.Methods: Healthy subjects (109 men and 151 women), four patients with sitosterolemia, and 10 heterozygous mutation carriers of ABCG5/ABCG8 genes were investigated. Then, three non-cholesterol sterols (sitosterol, campesterol, and lathosterol) of fasting serum samples were measured via a practical and highly sensitive gas chromatography (GC) method with 0.2 µg/mL as the lower limit of quantification. The coefficient of variation (CV) values for within-run reproducibility were 3.06%, 1.89%, and 1.77% for lathosterol, campesterol, and sitosterol, respectively. The CV values for between-run reproducibility were 2.81%, 2.06%, and 2.10% for lathosterol, campesterol, and sitosterol, respectively.Results: The serum levels of sitosterol and campesterol were significantly higher in women than in men, whereas the serum levels of lathosterol were significantly higher in men than in women. Because of these gender difference, the determination of reference intervals of the three sterol values was performed by considering gender. The reference intervals of sitosterol, campesterol, and lathosterol were 0.99–3.88, 2.14–7.43, and 0.77–3.60 µg/mL in men and 1.03–4.45, 2.19–8.34, and 0.64–2.78 µg/mL in women, respectively. The serum levels of sitosterol and campesterol were higher in patients with sitosterolemia (94.3±47.3 and 66.3±36.6 µg/mL, respectively) than in healthy subjects.Conclusion: These results demonstrate a practical and highly sensitive GC method to measure non-cholesterol sterol levels and gender-segregated reference intervals of sitosterol, campesterol, and lathosterol in Japanese healthy subjects.

著者

Jiancong Ren Yanshuo Han Tongming Ren Hong Fang Xiaohan Xu Yu Lun Han Jiang Shijie Xin Jian Zhang

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.49106, (Released:2019-08-28)

参考文献数

47

被引用文献数

15

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Aim: Inflammation plays a significant role in the pathogenesis of human abdominal aortic aneurysm (AAA). AEBP1 can promote activation of the NF-κB pathway, subsequently affecting the expression of NF-κB target genes, including inflammatory cytokines and matrix metalloproteinases (MMPs). Our objective was to examine the role of AEBP1 in the development of AAA and characterize the underlying mechanism. Methods: ITRAQ, RT-PCR, western blot, immunohistochemistry, and ELISA were used to compare different experimental groups with the controls and to determine the differentially expressed genes. We generated an AAA model using porcine pancreatic elastase in Sprague–Dawley rats and silenced their AEBP1 in vivo by adenoviruses injected intra-adventitially. We also silenced or overexpressed AEBP1 in human vascular smooth muscle cells in vitro in the presence and in the absence of NF-κB inhibitor BAY 11-7082. Results: Proteome iTRAQ revealed a high expression of AEBP1 in AAA patients, which was verified by qRT-PCR, western blot, immunohistochemistry, and ELISA. The mean expression level of AEBP1 in AAA patients was higher than that in controls. Along with AEBP1 upregulation, we also verified mis-activation of NF-κB in human AAA samples. The in vivo studies indicated that AEBP1 knockdown suppressed AAA progression. Finally, the in vitro studies illustrated that AEBP1 promotes activation of the NF-κB pathway, subsequently upregulating pro-inflammatory factors and MMPs. Conclusions: Our results indicate a role of AEBP1 in the pathogenesis of AAA and provide a novel insight into how AEBP1 causes the development of AAA by activating the NF-κB pathway.