著者
Mariko Harada-Shiba Takao Ohta Akira Ohtake Masatsune Ogura Kazushige Dobashi Atsushi Nohara Shizuya Yamashita Koutaro Yokote Joint Working Group by Japan Pediatric Society and Japan Atherosclerosis Society for Making Guidance of Pediatric Familial Hypercholesterolemia
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.CR002, (Released:2018-02-06)
参考文献数
49
被引用文献数
4

This paper describes consensus statement by Joint Working Group by Japan Pediatric Society and Japan Atherosclerosis Society for Making Guidance of Pediatric Familial Hypercholesterolemia (FH) in order to improve prognosis of FH.FH is a common genetic disease caused by mutations in genes related to low density lipoprotein (LDL) receptor pathway. Because patients with FH have high LDL cholesterol (LDL-C) levels from the birth, atherosclerosis begins and develops during childhood which determines the prognosis. Therefore, in order to reduce their lifetime risk for cardiovascular disease, patients with FH need to be diagnosed as early as possible and appropriate treatment should be started.Diagnosis of pediatric heterozygous FH patients is made by LDL-C ≥140 mg/dL, and family history of FH or premature CAD. When the diagnosis is made, they need to improve their lifestyle including diet and exercise which sometimes are not enough to reduce LDL-C levels. For pediatric FH aged ≥10 years, pharmacotherapy needs to be considered if the LDL-C level is persistently above 180 mg/dL. Statins are the first line drugs starting from the lowest dose and are increased if necessary. The target LDL-C level should ideally be <140 mg/dL. Assessment of atherosclerosis is mainly performed by noninvasive methods such as ultrasound.For homozygous FH patients, the diagnosis is made by existence of skin xanthomas or tendon xanthomas from infancy, and untreated LDL-C levels are approximately twice those of heterozygous FH parents. The responsiveness to pharmacotherapy should be ascertained promptly and if the effect of treatment is not enough, LDL apheresis needs to be immediately initiated.
著者
Shen Gao Dong Zhao Yue Qi Wei Wang Miao Wang Jiayi Sun Jun Liu Yan Li Jing Liu
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.43299, (Released:2018-03-07)
参考文献数
34
被引用文献数
1

Aims: To investigate the association between circulating oxidized low-density lipoprotein (ox-LDL) levels and progression of subclinical atherosclerosis and to examine whether this link is independent of other low-density lipoprotein (LDL)-related parameters.Methods: Totally, 804 subjects who were free of cardiovascular disease at baseline completed risk factor surveys and carotid ultrasound measurements in 2002 and 2012. Modified Poisson regression was performed to examine the association between baseline serum ox-LDL levels and the 10-year risk of progression of carotid atherosclerosis which was defined as the development of at least one new plaque in a previously plaque-free carotid segment at re-examination.Results: The mean age of the subjects was 58.6±7.7 years at baseline and 43.3% were men. A total of 504 (62.7%) subjects had carotid plaque progression at re-examination. Subjects in the intermediate and highest tertiles of ox-LDL had a significantly higher adjusted risk of atherosclerosis progression than those in the lowest tertile [relative risk (95% confidence interval) 1.17 (1.01–1.34) for the intermediate tertile and 1.23 (1.07–1.42) for the highest tertile]. This association was independent of baseline levels of LDL-C, total LDL particle number, and small LDL particle number.Conclusion: This study demonstrates that serum ox-LDL levels predict 10-year progression of subclinical atherosclerosis. Moreover, this effect is independent of the cholesterol content, the number, and the size of LDL particles.
著者
Mariko Harada-Shiba Hidenori Arai Yasushi Ishigaki Shun Ishibashi Tomonori Okamura Masatsune Ogura Kazushige Dobashi Atsushi Nohara Hideaki Bujo Katsumi Miyauchi Shizuya Yamashita Koutaro Yokote Working Group by Japan Atherosclerosis Society for Making Guidance of Familial Hypercholesterolemia
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.CR003, (Released:2018-06-07)
参考文献数
74
被引用文献数
1

Statement1. Familial hypercholesterolemia (FH) is an autosomal hereditary disease with the 3 major clinical features of hyper-LDL-cholesterolemia, premature coronary artery disease and tendon and skin xanthomas. As there is a considerably high risk of coronary artery disease, in addition to early diagnosis and intensive treatment, family screening (cascade screening) is required (Recommendation level A)2.For a diagnosis of FH, at least 2 of the following criteria should be satisfied:① LDL-C ≥180 mg/dL, ② Tendon/skin xanthomas, ③ History of FH or premature coronary artery disease (CAD) within 2nd degree blood relatives (Recommendation level A)3. Intensive lipid-lowering therapy is necessary for the treatment of FH. First-line drug should be statin. (Recommendation level A, evidence level 3)4.Screening for coronary artery disease as well as asymptomatic atherosclerosis should be conducted periodically in FH patients. (Recommendation level A)5. For homozygous FH, consider LDL apheresis and treatment with PCSK9 inhibitors or MTP inhibitors. (Recommendation level A)6.For severe forms of heterozygous FH who have resistant to drug therapy, consider PCSK9 inhibitors and LDL apheresis. (Recommendation level A)7.Refer FH homozygotes as well as heterozygotes who are resistant to drug therapy, who are children or are pregnant or have the desire to bear children to a specialist. (Recommendation level A)
著者
Haruo Ohnishi Yasushi Saito
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
vol.20, no.12, pp.861-877, 2013-12-19 (Released:2013-12-19)
参考文献数
101
被引用文献数
37 37

The clinical efficacy of fish oil and high-purity eicosapentaenoic acid ethyl ester (hp-EPA-E) for treating cardiovascular disease (CVD) has been reported. Fish oil contains saturated and monounsaturated fatty acids that have pharmacological effects opposite to those of ω3 fatty acids (ω3). Moreover, ω3, such as EPA and docosahexaenoic acid (DHA), do not necessarily have the same metabolic and biological actions. This has obscured the clinical efficacy of ω3. Recently, the Japan EPA Lipid Intervention Study (JELIS) of hp-EPA-E established the clinical efficacy of EPA for CVD, and higher levels of blood EPA, not DHA, were found to be associated with a lower incidence of major coronary events. A significant reduction in the risk of coronary events was observed when the ratio of EPA to arachidonic acid (AA) (EPA/AA) was >0.75. Furthermore, the ratio of prostaglandin (PG) I3 and PGI2 to thromboxane A2 (TXA2) ([PGI2+PGI3]/TXA2) was determined to have a linear relationship with the EPA/AA ratio as follows: (PGI2+PGI3)/TXA2 =λ+π* (EPA/AA). Like PGI2, PGI3 not only inhibits platelet aggregation and vasoconstriction, but also is assumed to reduce cardiac ischemic injury and arteriosclerosis and promote angiogenesis. Thus, the effects of EPA in reducing the risk of CVD could be mediated by biological action of PGI3 in addition to hypotriglyceridemic action of EPA. Compared with DHA, EPA administration increases the EPA/AA ratio and the (PGI2+PGI3)/TXA2 balance to a state that inhibits the onset and/or progression of CVD.
著者
Mariko Harada-Shiba John J.P. Kastelein G. Kees Hovingh Kausik K. Ray Akira Ohtake Osamu Arisaka Takao Ohta Tomoo Okada Hideki Suganami Albert Wiegman
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.42242, (Released:2017-11-29)
参考文献数
24

Aim: Children with Familial Hypercholesterolemia (FH) are widely prescribed statins, and it has been suggested that the effects of statins differ among ethnicities. We compared the efficacy and safety of pitavastatin in children and adolescents with FH in clinical trials conducted in Japan and Europe.
著者
Tamio Teramoto Makiko Usami Yoshiharu Takagi Marie T. Baccara-Dinet for the ODYSSEY Japan Investigators
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.45070, (Released:2018-08-01)
参考文献数
39

Aim: To examine the efficacy and safety of alirocumab in Japanese patients with dyslipidemia with or without diabetes mellitus (DM).Methods: Patients (n=216) with heterozygous familial hypercholesterolemia (heFH), non-FH at high cardiovascular risk with coronary artery disease (CAD), or category III (primary prevention) were enrolled; 148 (68.5%) patients had a diagnosis of DM at baseline. Patients were randomized (2:1), with stratification factor (heFH, non-FH), to alirocumab (75 mg every 2 weeks [Q2W] with increase to 150 mg if week 8 LDL-C was above predefined limits) or placebo subcutaneously for 52 weeks on top of stable statin therapy.Results: At Week 24, least square (LS) mean±standard error changes in low-density lipoprotein cholesterol (LDL-C) concentration from baseline in alirocumab-treated patients were -63.1±1.6% and -60.8±2.7% in those with and without DM. These LDL-C reductions were maintained to Week 52: -63.0±1.6% (LS mean difference vs placebo -62.4±3.0%; P<0.0001) with DM and -61.3±2.8% (LS mean difference vs placebo -53.4±4.0%; P<0.0001) without DM. The most common adverse events in the alirocumab group were nasopharyngitis, back pain, injection site reaction, and fall. No particular safety signals or concerns were noted between DM and non-DM groups at 52 weeks. A dose-increase in alirocumab from 75 to 150 mg Q2W was necessary in two heFH patients, neither of whom had DM.Conclusions: In high-cardiovascular-risk Japanese patients with hypercholesterolemia on stable statin therapy, alirocumab produced substantial and sustained LDL-C reductions throughout the 52-week study regardless of DM status at baseline, with a similar safety profile to placebo.
著者
Mikio Mukai Keiko Komori Toru Oka
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.RV17027, (Released:2018-09-14)
参考文献数
52

The advent of new chemotherapeutic and immunotherapeutic treatments has markedly improved outcomes in patients with cancer. However, increasing numbers of elderly patients with cancer and prolonged periods of treatment have made the management of cardiovascular complications and treatment-induced cardiotoxicity an important concern, and onco-cardiology has received increasing attention. The number of patients with cardiotoxicity, particularly atherosclerotic lesions, and the usage of angiogenesis inhibitors have increased, making the involvement of onco-cardiologists essential for effective disease management. A paradigm shift in immunotherapy was caused by the development of immune checkpoint inhibitors. Because vascular endothelial growth factors (VEGF) in the cancer microenvironment and cancer immune function are interrelated angiogenesis inhibitors will most likely play an increasingly important role in combined immunotherapy. To ensure the optimal long-term diagnosis and long-term treatment of cancer and the effective management of treatment-related atherosclerotic diseases, the long-term continuous participation of onco-cardiologists is essential.
著者
Ken Harada Hitomi Suzuki Shun Matsunaga Tomohiro Onishi Yoshinori Nishikawa Hiroshi Funakubo Kumiko Mamiya Tomoyuki Nagao Norihiro Shinoda Shinichi Sakai Masataka Kato Nobuyuki Marui Hideki Ishii Tetsuya Amano Tatsuaki Matsubara Toyoaki Murohara
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.42663, (Released:2018-02-01)
参考文献数
30

Aim: Increased epicardial fat volume (EFV) is an independent risk factor for acute coronary syndrome (ACS). Although EFV increases with body mass index (BMI), some ACS patients have an increased EFV but normal BMI. We here investigated the clinical characteristics of nonobese ACS patients with an increased EFV.Methods: A total of 197 Japanese patients hospitalized for ACS was evaluated for EFV, abdominal visceral fat area (VFA), and lipid and glucose profiles. Control subjects comprised 141 individuals who were suspected of having ACS but whose coronary computed tomography findings were normal.Results: EFV was increased in ACS patients compared with control subjects (120±47 versus 95±45 mL, P<0.01). ACS patients were divided into four groups based on average EFV (120 mL) and a BMI obesity cutoff of 25 kg/m2. For the 30 nonobese ACS patients with an above-average EFV, EFV was positively correlated with VFA (r=0.23, P=0.031). These individuals were significantly older (74±10 years) and tended to have a higher homeostasis model assessment–insulin resistance value (5.5±3.8) compared with other ACS patients. Among nonobese study subjects, EFV was independently associated with ACS (odds ratio=2.01, P=0.021) and correlated with abdominal circumference (r=0.26, P=0.017).Conclusion: Nonobese ACS patients with an increased EFV were elderly and tended to manifest insulin resistance. Measurement of EFV may prove informative for evaluation of ACS risk among elderly nonobese individuals with an increased abdominal girth.
著者
Ehimen C Aneni Chukwuemeka U Osondu Javier De La Cruz Seth S Martin Michael J Blaha Adnan Younus Theodore Feldman Arthur S Agatston Emir Veledar Khurram Nasir
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.40741, (Released:2018-09-14)
参考文献数
27

Aims: There is limited knowledge about the association of lipoprotein particles and markers of coronary atherosclerosis such as coronary artery calcification (CAC) in relatively young high-risk persons. This study examines the association of lipoprotein subfractions and CAC in high cardiometabolic risk individuals.Methods: The study presents analysis from baseline data of a randomized trial targeted at high-risk workers. Employees of Baptist Health South Florida with metabolic syndrome or diabetes were recruited. At baseline, all 182 participants had lipoprotein subfraction analysis using the ion mobility technique and participants above 35 years (N=170) had CAC test done. Principal components (PC) were computed for the combination of lipoprotein subclasses. Multiple bootstrapped regression analyses (BSA) were conducted to assess the relationship between lipoprotein subfractions and CAC.Results: The study population (N=170) was largely female (84%) with a mean age of 58 years. Three PCs accounted for 88% variation in the sample. PC2, with main contributions from VLDL particles in the positive direction and large LDL particles in the negative direction was associated with a 22% increase in CAC odds (P value <0.05 in 100% of BSA). PC3, with main contributions from HDL lipoprotein particles in the positive direction and small/medium LDL and large IDL particles in the negative direction, was associated with a 9% reduction in CAC odds (P<0.05 in 88% of BSA). PC1, which had approximately even contributions from HDL, LDL, IDL and VLDL lipoprotein subfractions in the positive direction, was not associated with CAC.Conclusion: In a relatively young but high-risk population, a lipoprotein profile predominated by triglyceride-rich lipoproteins was associated with increased risk of CAC, while one predominated by HDL lipoproteins offered modest protection. Lipoprotein sub-fraction analysis may help to further discriminate patients who require more intensive cardiovascular work-up and treatment.
著者
Ayako Kurihara Tomonori Okamura Daisuke Sugiyama Aya Higashiyama Makoto Watanabe Nagako Okuda Aya Kadota Naoko Miyagawa Akira Fujiyoshi Katsushi Yoshita Takayoshi Ohkubo Akira Okayama Katsuyuki Miura Hirotsugu Ueshima for the NIPPON DATA90 Research Group
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.44172, (Released:2018-08-09)
参考文献数
36

Aim: To examine the relationship between the intake of dietary vegetable protein and CVD mortality in a 15-year follow-up study of a representative sample of the Japanese population.Methods: A total of 7,744 participants aged 30 years or older (3,224 males and 4,520 females) who were free of CVD at baseline were included in this analysis. Vegetable protein intake (% energy) was assessed using a three-day semi-weighed dietary record at baseline. Multivariable-adjusted hazard ratios (HRs) were calculated using Cox's proportional hazards model after adjusting for confounding factors.Results: The total person-years studied were 107,988 with a mean follow-up period of 13.9 years. There were 1,213 deaths during the follow-up period, among which 354 (29.2%) were due to CVD. Vegetable protein intake was associated inversely with CVD and cerebral hemorrhage mortality, with the HRs for a 1% energy increment in vegetable protein intake being 0.86 (95% CI, 0.75–0.99) and 0.58 (95% CI, 0.35–0.95), respectively. In the subgroup analysis of participants with or without hypertension, the inverse association between vegetable protein intake and CVD mortality was more evident in the nonhypertensive group, with the HRs for CVD and stroke being 0.68 (95% CI, 0.50–0.94) and 0.50 (95% CI, 0.30–0.84), respectively.Conclusions: Vegetable protein intake may prevent future CVD, particularly in nonhypertensive subjects in the Japanese population. However, further studies are necessary to examine the biological mechanisms of this effect.
著者
Maki Yamashita Naoki Tamasawa Kota Matsuki Jutaro Tanabe Hiroshi Murakami Jun Matsui Toshihiro Suda
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
vol.17, no.11, pp.1183-1189, 2010 (Released:2010-11-27)
参考文献数
37
被引用文献数
8 9

Aims: We studied the effect of insulin on HDL-mediated cholesterol efflux from macrophages. The potential involvement of cholesteryl ester hydrolysis and membrane cholesterol transport was also addressed.Methods: Human monocyte-derived THP-1 cells were developed into macrophages. Cholesterol efflux was measured by incubating macrophages, labeled with [3H]-cholesterol, with HDL for 24 h. The cells were treated with insulin (0-500 nM) for 30 min prior to the addition of HDL. To investigate the molecular mechanisms of the effect of insulin, the expressions of neutral cholesteryl ester hydrolase (nCEH) and ATP-binding cassette transporter (ABC) G1 were analyzed.Results: Insulin inhibited, in a concentration-dependent manner, HDL-mediated cholesterol efflux from macrophages. Insulin also inhibited the enzyme activity of nCEH and its mRNA and protein expression in cells. Insulin also suppressed the expressions of mRNA and protein for ABCG1.Conclusions: Insulin inhibits HDL-mediated cholesterol efflux from macrophages, which may result from the suppression of nCEH and ABCG1 expressions. Our findings show part of the potential molecular mechanism of atherogenesis in type 2 diabetes with hyperinsulinemia.
著者
Chika Okada Hironori Imano Kazumasa Yamagishi Renzhe Cui Mitsumasa Umesawa Koutatsu Maruyama Isao Muraki Mina Hayama-Terada Yuji Shimizu Tomoko Sankai Takeo Okada Masahiko Kiyama Akihiko Kitamura 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.44438, (Released:2018-06-13)
参考文献数
25
被引用文献数
1

Aims: The frequency of breakfast intake has been reported to be inversely associated with the risk of cardiovascular events; however, it is uncertain what the impact of the energy and nutrient intakes from breakfast are. We assessed the association between these intakes from breakfast and the risk of stroke prospectively.Methods: In a baseline survey of four Japanese communities between 1981 and 1990, we enrolled 3 248 residents (1 662 men and 1 586 women) aged 40–59 years who were free from stroke and heart disease and who responded to the 24-hour dietary recall survey. We assessed the dietary intake at breakfast, lunch, dinner, and other times separately.Results: During the median 25-year follow-up, 230 individuals (147 men and 83 women) developed stroke. After adjustment for age, community, other dietary intakes, and lifestyle and physiological factors, the multivariable-adjusted hazard ratios (95% confidence intervals) of intracerebral hemorrhage for the highest versus lowest quartiles of energy intake from breakfast were 0.38 (0.15–0.99) in men and 1.36 (0.36–5.10) in women. For the major nutrients, a higher saturated or monounsaturated fat intake at breakfast was associated with a reduced risk of intracerebral hemorrhage in men, and remained statistically significant after further adjustment for intake of other major nutrients from breakfast.Conclusions: A higher intake of energy from breakfast, primarily saturated or monounsaturated fat, was associated with a reduced risk of intracerebral hemorrhage in Japanese men.
著者
Kenji Sakata Tadatsugu Gamou Hayato Tada Kenshi Hayashi Hidekazu Ino Masakazu Yamagishi Masa-aki Kawashiri behalf of the MILLION Study Group
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.44255, (Released:2018-09-21)
参考文献数
25

Aim: The prospective, randomized, multicenter Myocardial Ischemia Treated with Percutaneous Coronary Intervention and Plaque Regression by Lipid Lowering & Blood Pressure Controlling assessed by Intravascular Ultrasonography (MILLION) study demonstrated that combined treatment with atorvastatin and amlodipine enhanced coronary artery plaque regression. Although the baseline high-sensitive C-reactive protein (hs-CRP) reportedly plays an important role in atherogenesis, few data exist regarding the relationship between hs-CRP and plaque regression in patients receiving a combined atorvastatin and amlodipine therapy.Methods: A total of 68 patients (male, 55; mean age, 64.2 years) with baseline and follow-up 3-dimensional intravascular ultrasound examinations in the MILLION study were stratified by baseline hs-CRP level quartiles. The serial measurements of lipid, blood pressure, and percentage changes in the plaque volume were compared between the groups, and the factors associated with the percentage change in the plaque volume were assessed.Results: There were no significant between-group differences in the extent of change in low-density lipoprotein cholesterol (LDL-C) or systolic and diastolic blood pressure after 18–24 months of treatment. The percentage change in the plaque volume showed a linear association with the baseline hs-CRP (p for trend <0.05); however, there was no correlation with changes in LDL-C or systolic and diastolic blood pressure. In the multiple regression analysis, the baseline hs-CRP level was independently associated with the percentage change in the plaque volume (β=0.29, p=0.022).Conclusions: Coronary plaque regression was associated with the baseline hs-CRP level in patients treated with a combined lipid- and blood pressure-lowering therapy.
著者
Yasuyuki Sasaguri Akihide Tanimoto
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
vol.11, no.3, pp.122-130, 2004 (Released:2004-07-09)
参考文献数
73
被引用文献数
30 30

The atherosclerotic intimal lesion contains endothelial cells, smooth muscle cells, monocytes/macrophages and T lymphocytes, which constitute a histamine-cytokine network that participates in chronic inflammatory responses. Monocytes/macrophages and T lymphocytes express the histamine-producing enzyme histidine decarboxylase (HDC), and specific histamine receptors (HHR), which are switched from HH2R to HHR1 during macrophage differentiation. Endothelial and smooth muscle cells also express HHR in response to histamine. The effects of histamine on these cells include a regulation of atherosclerosis-related events such as cell proliferation, expression of matrix metalloproteinase, adhesion molecules and cytokines. Furthermore, recent studies have indicated that histamine and the activation of its specific receptors modulate the Th1/Th2 balance in inflammatory lesions through the regulation of cytokine production from inflammatory cells. The histamine-cytokine network in the atherosclerotic intima could regulate inflammatory and immune responses, including Th1/Th2 balance, and contribute to atherogenesis.
著者
Momoko Muto Osamu Ezaki
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
vol.25, no.5, pp.375-392, 2018-05-01 (Released:2018-05-01)
参考文献数
44
被引用文献数
2

Aim: The associations between dietary saturated fatty acids and the risks of stroke subtypes in cohort studies were examined by a meta-analysis of separate ethnic Japanese and non-Japanese cohorts, and causes of their difference were elucidated.Method: Log hazard ratio (HR) with 95% confidence interval (CI) of the highest versus the lowest saturated fat intake from cohort studies were weighed by an inverse variance method to combine HRs.Results: Five studies of intracerebral hemorrhage and 11 studies/comparisons of ischemic stroke were selected. A meta-analysis of intracerebral hemorrhage excluding subarachnoid hemorrhage showed a strong inverse association in Japanese (n=3, HR=0.55, 95% CI 0.32–0.94) but not in non-Japanese (n=2, HR=0.98, 95% CI 0.62–1.53). A meta-analysis of ischemic stroke showed a mild inverse association in Japanese (n=4, HR=0.82, 95% CI 0.71–0.93) but not in non-Japanese (n=7, HR= 0.93, 95% CI 0.84–1.03). The effect size of saturated fat in reducing the risk of stroke in Japanese was stronger for intracerebral hemorrhage (45% reduction) than for ischemic stroke (18% reduction).Conclusions: In Japanese but not in non-Japanese, a diet high in saturated fat is associated with a low risk of intracerebral hemorrhage and ischemic stroke. This may be due to differences in the range of intake of saturated fat, genetic susceptibility, incidence of lacunar infarction, and/or confounding factors such as dietary proteins. An intervention study targeting Japanese will be required to verify the causality.
著者
Hayato Tada Atsushi Nohara Akihiro Inazu Nagahiko Sakuma Hiroshi Mabuchi Masa-aki Kawashiri
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.RV17024, (Released:2018-07-20)
参考文献数
31

Sitosterolemia is a rare inherited disease characterized by increased levels of plant sterols, such as sitosterol. The cause of this disease is ATP-binding cassette (ABC) subfamily G member 5 or member 8 (ABCG5 or ABCG8, respectively) gene mutations. Recent advances in genetics have revealed that the prevalence of subjects with deleterious mutations in ABCG5 and/or ABCG8 genes could be more than 1 in ~200,000 individuals among the general population. Furthermore, accumulated evidence, including infantile cases exhibiting progression/regression of systemic xanthomas associated with LDL cholesterol levels, have shown that the elevation of LDL cholesterol seems to be the major cause of development of atherosclerosis and not the elevation of sitosterol. Regarding therapies, LDL apheresis, as well as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, could be useful for sitosterolemia, in addition to ezetimibe and/or colestimide. In this study, we provide the current understanding and future perspectives of sitosterolemia, which is currently considered an extremely rare disorder but is expected to be much more prevalent in clinical settings.
著者
Yusuke Takahara Tomotake Tokunou Toshihiro Ichiki
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
vol.25, no.8, pp.698-708, 2018-08-01 (Released:2018-08-01)
参考文献数
38

Aim: Dipeptidyl peptidase-4 (DPP-4) inhibitors lower blood glucose levels through inhibition of incretin degradation, which stimulates insulin secretion. Recent studies reported that DPP-4 inhibitors suppressed atherogenesis in apolipoprotein E-knockout (ApoEKO) mice. In this study, we investigated whether teneligliptin, a DPP-4 inhibitor, affects the development of abdominal aortic aneurysms (AAA) in ApoEKO mice.Methods: ApoEKO mice were fed a high-fat diet (HFD) and infused with angiotensin (Ang) II by osmotic mini pumps for 4 weeks to induce AAA with (DPP-4i group) or without (control group) teneligliptin administered orally from 1 week before HFD and Ang II infusion to the end of the experiment. Confluent rat vascular smooth muscle cells (VSMCs) were serum-starved for 48 hours, then incubated with or without teneligliptin for another 24 hours and stimulated with Ang II.Results: Treatment with teneligliptin significantly reduced the AAA formation rate (30.7% vs. 71.4% vs. control, P<0.05), aortic dilatation (1.32±0.09 mm vs. 1.76±0.18 mm in the control, P<0.05) and severity score (0.75±0.28 vs. 1.91±0.4 in the control, P<0.05). Elastin degradation grade was also attenuated in DPP-4i group (2.83±0.17 vs. 3.45±0.16 in the control, P<0.05). The number of macrophages infiltrating into the abdominal aorta was decreased in the DPP-4i group (51.8± 29.8/section vs. 219.5±78.5/section in the control, P<0.05). Teneligliptin attenuated Ang II-induced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt, and mRNA expression of monocyte chemoattractant protein-1 in VSMCs.Conclusion: Treatment with teneligliptin suppressed AAA formation in ApoEKO mice with HFD and Ang II infusion. Suppression of macrophage infiltration by teneligliptin may be involved in the inhibition of AAA formation.
著者
Hoichi Amano Yoshiharu Fukuda Takashi Yokoo Kazue Yamaoka
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.42036, (Released:2018-03-27)
参考文献数
24

Aim: Shift workers have a high risk of cardiovascular disease (CVD). Systemic inflammation measured has been associated with the risk of CVD onset, in addition to classical risk factors. However, the association between work schedule and inflammatory cytokine levels remains unclear. The purpose of this study was to examine the association between work schedule and interleukin-6 (IL-6)/high-sensitivity C-reactive protein (hs-CRP) levels among Japanese workers.Methods: The present cross-sectional study was a part of the Japanese Study of Health, Occupation and Psychosocial Factors Related Equity (J-HOPE). A total of 5259 persons who measured inflammatory cytokine were analyzed in this study. One-way analysis of variance was used to test log-transformed IL-6/hs-CRP differences by work schedule. Multiple regression analysis was used to examine the difference adjusted for other possible CVD risk factors.Results: There were 3660 participants who had a regular work schedule; the remaining schedules were shift work without night work for 181 participants, shift work with night work for 1276 participants, and only night work for 142 participants. The unadjusted model showed that only night workers were significantly related to high levels of IL-6 compared with regular workers. Even in the multiple regression analysis, the higher level of IL-6 among only night workers remained significant (β=0.058, P=0.01). On the contrary, hs-CRP was not.Conclusion: The present study revealed that only night shift work is significantly associated with high levels of IL-6 in Japanese workers. These observations help us understand the mechanism for the association between work schedule and CVD onset.
著者
Hideyuki Kanda Peiyu Wang Tomonori Okamura GaoWa Wuyun HePing Wu Xiulan Su Takehito Hayakawa Kenji Amamoto Hirotsugu Ueshima
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.1012090325-1012090325, (Released:2010-12-10)
参考文献数
25

Aim: The World Health Organization (WHO) includes insulin resistance among its criteria for diagnosing metabolic syndrome (MetS); however, previous epidemiologic studies have limited their research to settled populations only. This study aims to clarify the relationship between plasma insulin and metabolic factors on a broader scale by studying data obtained from nomadic and settled Mongolian populations.Methods: A cross-sectional epidemiologic study of 200 nomads and 256 farmers was performed in Inner Mongolia, Republic of China. Plasma insulin levels and other metabolic factors, such as blood pressure, serum lipids and obesity, were measured. Participants were classified into 3 categories according to their plasma insulin levels.Results: Cut-off values grouped into tertiles of fasting insulin for all participants were 6.73 nmol/L and 10.33 nmol/L. The mean number of metabolic risk factors, waist circumference, fasting plasma glucose and triglyceride were higher, and the mean HDL cholesterol was lower in the higher fasting insulin tertile among farmers after adjusting for age, gender, smoking, alcohol drinking and total cholesterol. However, no MetS factors were statistically related with fasting insulin tertile levels among nomads.Conclusions: In nomads, hyperinsulinemia may not be an indicator of MetS due to their specific life-style.