著者

Hirofumi Tomiyama Kazuki Shiina

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.27, no.7, pp.621-636, 2020-07-01 (Released:2020-07-01)

参考文献数

156

被引用文献数

38 53

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The brachial-ankle pulse wave velocity (brachial-ankle PWV), which is measured simply by wrapping pressure cuffs around the four extremities, is a simple marker to assess the stiffness of the medium- to large- sized arteries. The accuracy and reproducibility of its measurement have been confirmed to be acceptable. Risk factors for cardiovascular disease, especially advanced age and high blood pressure, are reported to be associated with an increase of the arterial stiffness. Furthermore, arterial stiffness might be involved in a vicious cycle with the development/progression of hypertension, diabetes mellitus and chronic kidney disease. Increase in the arterial stiffness is thought to contribute to the development of cardiovascular disease via pathophysiological abnormalities induced in the heart, brain, kidney, and also the arteries themselves. A recent independent participant data meta-analysis conducted in Japan demonstrated that the brachial-ankle PWV is a useful marker to predict future cardiovascular events in Japanese subjects without a previous history of cardiovascular disease, independent of the conventional model for the risk assessment. The cutoff point may be 16.0 m/s in individuals with a low risk of cardiovascular disease (CVD), and 18.0 m/s in individuals with a high risk of CVD and subjects with hypertension. In addition, the method of measurement of the brachial-ankle PWV can also be used to calculate the inter-arm systolic blood pressure difference and ankle-brachial pressure index, which are also useful markers for cardiovascular risk assessment.

著者

Hirofumi Tomiyama Chisa Matsumoto Kazuki Shiina Akira Yamashina

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.23, no.2, pp.128-146, 2016-02-01 (Released:2016-02-01)

参考文献数

120

被引用文献数

72 71

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Since 2001, brachial-ankle pulse wave velocity (brachial-ankle PWV) measurement has been applied for risk stratification of patients with atherosclerotic cardiovascular disease and/or its risk factors in Japan. Measurement of the brachial-ankle PWV is simple and well standardized, and its reproducibility and accuracy are acceptable. Several cross-sectional studies have demonstrated a significant correlation between the brachial-ankle PWV and known risk factors for cardiovascular disease; the correlation is stronger in subjects with cardiovascular disease than in those without cardiovascular disease. We conducted a meta-analysis, which demonstrated that the brachial-ankle PWV is an independent predictor of future cardiovascular events. Furthermore, the treatment of cardiovascular risk factors and lifestyle modifications have been shown to improve the brachial-ankle PWV. Thus, at present, brachial-ankle PWV is close to being considered as a useful marker in the management of atherosclerotic cardiovascular disease and/or its risk factors.

著者

Toru Miyoshi Satoko Naoe Hiroyuki Wakabayashi Takashi Yano Takuya Mori Shingo Kanda Makoto Arita Hiroshi Ito

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.64135, (Released:2023-08-02)

参考文献数

39

被引用文献数

2

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Aims: MND-2119 is a novel once-daily dose self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester (EPA-E) and is approved as an antihyperlipidemia agent in Japan. It has improved absorption and achieves higher plasma EPA concentrations at Cmax than conventional EPA-E. In the JELIS trial, concomitant use of EPA-E with statin therapy significantly reduced atherosclerotic cardiovascular disease (ASCVD) risks. As a potential mechanism of action of EPA, endogenous formation of EPA-derived anti-inflammatory metabolites is receiving greater attention. This study aims to investigate the endogenous formation of EPA-derived anti-inflammatory metabolites following single and multiple administrations of MND-2119. Methods: Healthy adult male subjects were randomly assigned to a nonintervention (control) group, MND-2119 2-g/day group, MND-2119 4-g/day group, or EPA-E 1.8-g/day group for 7 days (N=8 per group). Plasma fatty acids and EPA-derived metabolites were evaluated. Peripheral blood neutrophils were isolated, and the production of EPA-derived metabolites from in vitro stimulated neutrophils was evaluated. Results: After single and multiple administrations of MND-2119 2 g/day, there were significant increases in plasma EPA concentration, 18-hydroxyeicosapentaenoic acid (18-HEPE), and 17,18-epoxyeicosatetraenoic acid compared with those of EPA-E 1.8 g/day. They were further increased with MND-2119 4 g/day administration. In neutrophils, the EPA concentration in the MND-2119 2-g/day group was significantly higher compared with that in the EPA-E 1.8-g/day group after multiple administration, and 18-HEPE production was positively correlated with EPA concentration. No safety issues were noted. Conclusions: These results demonstrate that MND-2119 increases the plasma and cellular concentrations of EPA and EPA-derived metabolites to a greater extent than conventional EPA-E formulations.

著者

Junnichi Ishii Kosuke Kashiwabara Yukio Ozaki Hiroshi Takahashi Fumihiko Kitagawa Hideto Nishimura Hideki Ishii Satoshi Iimuro Hideki Kawai Takashi Muramatsu Hiroyuki Naruse Hiroshi Iwata Sadako Tanizawa-Motoyama Hiroyasu Ito Eiichi Watanabe Yutaka Matsuyama Yoshihiro Fukumoto Ichiro Sakuma Yoshihisa Nakagawa Kiyoshi Hibi Takafumi Hiro Seiji Hokimoto Katsumi Miyauchi Hiroshi Ohtsu Hideo Izawa Hisao Ogawa Hiroyuki Daida Hiroaki Shimokawa Yasushi Saito Takeshi Kimura Masunori Matsuzaki Ryozo Nagai

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.29, no.10, pp.1458-1474, 2022-10-01 (Released:2022-10-01)

参考文献数

33

被引用文献数

1 11

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Aim: We investigated the relationship between small dense low-density cholesterol (sdLDL-C) and risk of major adverse cardiovascular events (MACE) in patients treated with high- or low-dose statin therapy.Methods: This was a prospective case-cohort study within the Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study, a randomized trial of high- or low-dose (4 or 1 mg/d pitavastatin, respectively) statin therapy, in patients with stable coronary artery disease (CAD). Serum sdLDL-C was determined using an automated homogenous assay at baseline (randomization after a rule-in period, >1 month with 1 mg/d pitavastatin) and 6 months after randomization, in 497 MACE cases, and 1543 participants randomly selected from the REAL-CAD study population.Results: High-dose pitavastatin reduced sdLDL-C by 20% than low-dose pitavastatin (p for interaction <0.001). Among patients receiving low-dose pitavastatin, baseline sdLDL-C demonstrated higher MACE risk independent of LDL-C (hazard ratio [95% confidence interval], 4th versus 1st quartile, 1.67 [1.04–2.68]; p for trend=0.034). High-dose (versus low-dose) pitavastatin reduced MACE risk by 46% in patients in the highest baseline sdLDL-C quartile (>34.3 mg/dL; 0.54 [0.36–0.81]; p=0.003), but increased relative risk by 40% in patients with 1st quartile (≤ 19.5 mg/dL; 1.40 [0.94–2.09]; p=0.099) and did not alter risk in those in 2nd and 3rd quartiles (p for interaction=0.002).Conclusions: These findings associate sdLDL-C and cardiovascular risk, independent of LDL-C, in statin-treated CAD patients. Notably, high-dose statin therapy reduces this risk in those with the highest baseline sdLDL-C.

著者

Akihiro Nakagomi Toshiyuki Shibui Keiichi Kohashi Munenori Kosugi Yoshiki Kusama Hirotsugu Atarashi Wataru Shimizu

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.22, no.11, pp.1158-1171, 2015-11-02 (Released:2015-11-02)

参考文献数

40

被引用文献数

27 25

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Aims: 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have multiple pleiotropic effects, such as anti-inflammatory and vascular endothelium protection, that are independent of their low-density-lipoprotein (LDL) cholesterol lowering effects. However, whether different statins exert diverse effects on inflammation, insulin resistance, and the progression of carotid atherosclerosis [as indicated by the intima-media thickness (CIMT)] in patients with dyslipidemia remains unclear.Methods: A total of 146 patients with hypercholesterolemia without known cardiovascular disease were randomly assigned to receive 5 mg/day of atorvastatin (n=73) or 1 mg/day of pitavastatin (n=73).Results: At baseline, age, gender, blood pressure, lipid profiles, and the serum monocyte chemoattractant protein (MCP)-1, homeostasis model assessment of insulin resistance (HOMA-IR) and CIMT values were comparable between the groups. After 12 months of treatment, atorvastatin and pitavastatin equally reduced the LDL cholesterol levels; however, atorvastatin increased the HOMA-IR by +26% and pitavastatin decreased this parameter by -13% (p<0.001). The MCP-1 values were reduced by -28% in the patients treated with pitavastatin and only -11% in those treated with atorvastatin (p=0.016). A greater percent decrease in the mean CIMT from baseline was observed in the patients treated with pitavastatin than in those treated with atorvastatin (-4.9% vs. -0.5%, p=0.020).Conclusions: These data indicate that, while these agents significantly and equally reduce the LDL cholesterol levels, atorvastatin and pitavastatin have different effects on inflammation, insulin resistance, and the progression of carotid atherosclerosis in patients with dyslipidemia.

著者

Stefano A. Santini Cinzia Carrozza Paola Lulli Cecilia Zuppi Gian Carlo Tonolo Salvatore Musumeci

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.10, no.3, pp.160-164, 2003 (Released:2004-02-18)

参考文献数

21

被引用文献数

26 30

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Atorvastatin, a second generation synthetic 3-hydroxy 3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor used in the treatment of hypercholesterolemia, reduces both intracellular cholesterol synthesis and serum cholesterol levels, and this could have a potential negative impact on gonadal and adrenal steroidogenesis. Hypercholesterolemia in type 2 diabetes, even when mild, must be treated in an aggressive way, due to the more strict therapeutic goals than in the non diabetic population. Since the wide use of 3-hydroxy 3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor (statins) in type 2 diabetes, the main aim of our study was to evaluate the effects of “therapeutic” doses of atorvastatin on gonadal and adrenal hormones in 24 type 2 diabetic patients (16 males and 8 postmenopausal females), with mild to moderate hypercholesterolemia (LDL-cholesterol = 150.1 ± 32.0 and 189.9 ± 32.9 mg/dl, respectively) studied before and after a 3 months treatment with atorvastatin (20 mg/day). In all patients, lipids and serum cortisol, dehydroepiandrosterone sulphate (DHEA-S), androstendione and sex hormone binding globulin (SHBG) were measured, with the addition, only in males, of testosterone and free testosterone index. After atorvastatin treatment a significant decrease in total and LDL cholesterol was observed (p < 0.05), while HDL-cholesterol did not significantly change ( p = N.S.), as no significant difference was found between steroid hormones measured before and after atorvastatin either in male and females. In conclusion, our data suggest that, in type 2 diabetic patients, the use of atorvastatin has no clinically important effects on either gonadal or adrenal steroid hormones.

著者

Xiaomin Sun Zhen-Bo Cao Kumpei Tanisawa Tomoko Ito Satomi Oshima Yoshiko Ishimi Izumi Tabata Mitsuru Higuchi

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.22, no.4, pp.355-362, 2015-04-21 (Released:2015-04-21)

参考文献数

35

被引用文献数

24 26

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Aim: Low circulating 25-hydroxyvitamin D [25(OH)D] concentration has been linked to a high prevalence of cardiovascular disease. One explanation for this phenomenon is that there is an association between the serum 25(OH)D level and lipid profiles. However, studies examining this relationship are limited and have yielded inconsistent results. We thus aimed to evaluate the association between the serum 25(OH)D concentration and lipid profiles in Japanese men taking into consideration confounding factors, including the visceral fat area (VFA) and cardiorespiratory fitness.Methods: A total of 136 men (age range: 20-79 years) participated in our study. Fasting blood samples were analyzed to determine the 25(OH)D, oxidized low-density lipoprotein (oxLDL), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein (Apo)A-1 and ApoB levels. The VFA was evaluated on magnetic resonance imaging (MRI), and cardiorespiratory fitness was assessed by measuring the peak oxygen uptake (O2 peak).Results: The median 25(OH)D concentration was 35.6 nmol/L, and the prevalence of 25(OH)D deficiency was 78.7%. A multiple linear regression analysis revealed that the serum 25(OH)D concentration was inversely related to the LDL-C/HDL-C, TG, ApoB and ApoB/ApoA-1 values, even after adjusting for age, season, smoking status, alcohol consumption, medication use, vitamin D intake, calcium intake, VFA and cardiorespiratory fitness.Conclusions: Serum 25(OH)D level is inversely correlated with the LDL-C/HDL-C, TG, ApoB and ApoB/ApoA-1 values in Japanese men, independent of the VFA and cardiorespiratory fitness.

著者

Tsutomu Hirano Noriyuki Satoh Yasuki Ito

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.64271, (Released:2023-07-11)

参考文献数

32

被引用文献数

2

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Aims: Small dense (sd) low-density lipoprotein (LDL)-cholesterol (C) is the most powerful predictor of cardiovascular (CV) disease among lipid biomarkers and is generated by hypertriglyceridemia and insulin resistance. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly proposed liver disease with a high CV risk. We investigated the specific association of sdLDL-C with MAFLD beyond triglycerides (TG) and obesity. Methods: Participants were 839 non-alcoholic drinkers with type 2 diabetes enrolled in a regional diabetes cohort. Fatty liver (FL) and visceral fat area (VFA) was detected by computed tomography scan. sdLDL-C and LDL-TG were measured by our established homogeneous assay. TG rich lipoprotein (TRL) was calculated by subtracting LDL-C plus HDL-C from total-C. Grade of sdLDL-C (≤ 24, 25–34, 35–44, and ≥ 45 mg/dL) was classified according to the Hisayama study. Results: Compared to non-FL counterparts, FL subjects were younger, predominantly male and smokers; and had higher body mass index (BMI), VFA, hemoglobin A1c, C-peptide, TG, and sdLDL-C, while had similar levels of LDL-C, LDL-TG, and TRL-C. Multivariate logistic analysis revealed that sdLDL-C was the most powerful lipid parameter for identifying FL, independent of TG, HDL-C, BMI, and VFA. The independent association between TG and FL was lost when sdLDL-C was added to the analysis. These results remained the same when lipid-lowering drug users were excluded. After adjustment for confounders, the odds ratio for FL was 2.4–2.7 at sdLDL ≥ 35 mg/dL based on sdLDL ≤ 24 mg/dL. Conclusions: sdLDL-C levels are specifically elevated in patients with diabetes and MAFLD, independent of TG and VFA, suggesting liver-centered metabolic abnormalities.

著者

Kuniyuki Nakamura Tetsuro Ago

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.RV22007, (Released:2023-06-30)

参考文献数

80

被引用文献数

1

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There are still many patients suffering from ischemic stroke and related disabilities worldwide. To develop a treatment that promotes functional recovery after acute ischemic stroke, we need to elucidate endogenous tissue repair mechanisms. The concept of a neurovascular unit (NVU) indicates the importance of a complex orchestration of cell-cell interactions and their microenvironment in the physiology and pathophysiology of various central nervous system diseases, particularly ischemic stroke. In this concept, microvascular pericytes play a crucial role in regulating the blood-brain barrier integrity, cerebral blood flow (CBF), and vascular stability. Recent evidence suggests that pericytes are also involved in the tissue repair leading to functional recovery following acute ischemic stroke through the interaction with other cell types constituting the NVU; pericytes may organize CBF recovery, macrophage-mediated clearance of myelin debris, intrainfarct fibrosis, and periinfarct astrogliosis and remyelination. In this review, we will discuss the physiological and pathophysiological functions of pericytes, their involvement in the molecular mechanisms underlying tissue repair and functional recovery after ischemic stroke, and a therapeutic strategy to promote endogenous regeneration.

著者

Rie Kishida Kazumasa Yamagishi Isao Muraki Mizuki Sata Akiko Tamakoshi Hiroyasu Iso for the JACC Study Group

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.27, no.12, pp.1340-1347, 2020-12-01 (Released:2020-12-01)

参考文献数

39

被引用文献数

16 25

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Aim: Seaweed is a popular traditional foodstuff in Asian countries. To our knowledge, few studies have examined the association of seaweed intake with mortality from cardiovascular disease. We examined the association of frequency of seaweed intake with total and specific cardiovascular disease mortality. Methods: We examined the association of seaweed intake with mortality from cardiovascular disease among 40,234 men and 55,981 women who participated in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. Sex-specific hazard ratios for mortality from cardiovascular disease (stroke, stroke subtypes, and coronary heart disease) according to the frequency of seaweed intake were calculated stratified by study area and adjusted for potential cardiovascular risk factors and dietary factors. Results: During the 1,580,996 person-year follow-up, 6,525 cardiovascular deaths occurred, of which 2,820 were due to stroke, and 1,378, to coronary heart disease. Among men, the multivariable analysis showed that participants who ate seaweed almost every day compared with those who never ate seaweed had hazard ratios (95% confidence interval; P for trend) of 0.79 (0.62–1.01; 0.72) for total cardiovascular disease, 0.70 (0.49–0.99; 0.47) for total stroke, 0.69 (0.41–1.16; 0.11) for cerebral infarction. Among women, the multivariable-adjusted hazard ratios were 0.72 (0.55–0.95; 0.001) for total cardiovascular disease, 0.70 (0.46–1.06; 0.01) for total stroke, and 0.49 (0.27–0.90; 0.22) for cerebral infarction. No associations were observed between seaweed intake and risk of intraparenchymal hemorrhage and coronary heart disease among either men or women. Conclusions: We found an inverse association between seaweed intake and cardiovascular mortality among Japanese men and women, especially that from cerebral infarction.

著者

Saki Teramura Kazumasa Yamagishi Mitsumasa Umesawa Mina Hayama-Terada Isao Muraki Koutatsu Maruyama Mari Tanaka Rie Kishida Tomomi Kihara Midori Takada Tetsuya Ohira Hironori Imano Yuji Shimizu Tomoko Sankai Takeo Okada Akihiko Kitamura Masahiko Kiyama Hiroyasu Iso

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.63907, (Released:2023-03-03)

参考文献数

40

被引用文献数

6

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Aim: We aimed to examine sex-specific risk factors for hyperuricemia or gout in Japanese cohorts. Methods: We followed up 3,188 men (mean age, 55.6 years) and 6,346 women (mean age, 54.1 years) without hyperuricemia, gout, or elevated liver enzymes at baseline from 1986 to 1990 for a median of 14.6 years. The participants were considered as having hyperuricemia or gout if their serum uric acid levels were ≥ 7.0 mg/dL or they were receiving treatment for hyperuricemia or gout during annual health checkups. The sex-specific multivariable hazard ratios (HRs) of hyperuricemia or gout incidence were calculated after adjustment for smoking and drinking status, body mass index, hypertension, diabetes, hypercholesterolemia, and hypertriglyceridemia using the Cox proportional-hazard model. Results: During follow-up, 733 men and 355 women had hyperuricemia or gout. Among men, the multivariable HRs (95% confidence intervals) of hyperuricemia or gout were 1.23 (1.00–1.52) and 1.41 (1.13–1.75) for drinkers of <46 and ≥ 46 g ethanol/day, respectively, compared with non-drinkers; 1.00 (0.81–1.24) and 1.18 (0.93–1.50) for smokers of 1–19 and ≥ 20 cigarettes/day, respectively, compared with never smokers; and 1.41 (1.20–1.65) for hypertensive compared with non-hypertensive participants. The HRs for women were 1.02 (0.70–1.48), 1.66 (1.05–2.63), and 1.12 (0.88–1.42) for current drinkers, current smokers, and hypertensive participants, respectively. For both men and women, body mass index, diabetes, hypercholesterolemia, and hypertriglyceridemia were not associated with hyperuricemia or gout incidence. Conclusions: Hypertension and alcohol drinking are risk factors for hyperuricemia or gout among men and smoking among women.

著者

Yuki Ishinoda Nobuyuki Masaki Yasuhiro Hitomi Akira Taruoka Akane Kawai Midori Iwashita Yusuke Yumita Kazuki Kagami Risako Yasuda Yasuo Ido Takumi Toya Yukinori Ikegami Takayuki Namba Yuji Nagatomo Koji Miyazaki Bonpei Takase Takeshi Adachi

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.63779, (Released:2023-02-11)

参考文献数

55

被引用文献数

4

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Aims: The long-term prognostic value of the bioavailability of L-arginine, an important source of nitric oxide for the maintenance of vascular endothelial function, has not been investigated fully. We therefore investigated the relationship between amino acid profile and long-term prognosis in patients with a history of standby coronary angiography. Methods: We measured the serum concentrations of L-arginine, L-citrulline, and L-ornithine by high-speed liquid chromatography. We examined the relationship between the L-arginine/L-ornithine ratio and the incidence of all-cause death, cardiovascular death, and major adverse cardiovascular events (MACEs) in 262 patients (202 men and 60 women, age 65±13 years) who underwent coronary angiography over a period of ≤ 10 years.Results: During the observation period of 5.5±3.2 years, 31 (12%) patients died, including 20 (8%) of cardiovascular death, while 32 (12%) had MACEs. Cox regression analysis revealed that L-arginine/L-ornithine ratio was associated with an increased risk for all-cause death (unadjusted hazard ratio, 95% confidence interval) (0.940, 0.888–0.995) and cardiovascular death (0.895, 0.821–0.965) (p<0.05 for all). In a mod el adjusted for age, sex, hypertension, hyperlipidemia, diabetes, current smoking, renal function, and log10-transformed brain natriuretic peptide level, cardiovascular death (0.911, 0.839–0.990, p=0.028) retained an association with a low L-arginine/ L-ornithine ratio. When the patients were grouped according to an L-arginine/L-ornithine ratio of 1.16, the lower L-arginine/L-ornithine ratio group had significantly higher incidence of all-cause death, cardiovascular death, and MACEs. Conclusion: A low L-arginine/L-ornithine ratio may be associated with increased 10-year cardiac mortality.

著者

Hiroaki Shiraishi Kazuhisa Ikemoto Shin Tada Yasuhiro Udagawa Masatsugu Ohtsuki Chiho Sumi-Ichinose Kazunao Kondo Takahide Nomura

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.18, no.4, pp.312-317, 2011 (Released:2011-04-27)

参考文献数

25

被引用文献数

5 5

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Aims: Cilostazol, a type III phosphodiesterase inhibitor, is utilized for the treatment of intermittent claudication and is considered to have the beneficial effects against the atherogenic process. In the present study, we examined the effects of cilostazol on BH4 biosynthesis in HUVEC treated with a mixture of the pro-inflammatory cytokines IFN-γ and TNF-α.Methods: Isolated HUVECs were grown to confluence and treated with IFN-γ (300 units/mL) and TNF-α (300 units/mL) for 16 h in order to stimulate BH4 biosynthesis. The BH4 levels were mea-sured by HPLC. The mRNA expression of GTP cyclohydrolase I (GTPCH), the rate-limiting enzyme of BH4 biosynthesis, and GTPCH feedback regulatory protein (GFRP) were quantified by real-time PCR. The GTPCH protein expression was assessed by western blot analysis.Results: Cilostazol significantly reduced the BH4 levels in cytokine-stimulated HUVEC. Cilostazol produced a concomitant increase in the cAMP levels in HUVEC. Cilostazol decreased the GTPCH activity as well as the expression of GTPCH mRNA and protein. 8-bromo-cAMP (8Br-cAMP), a cell-permeable cAMP analogue, did not reproduce the effects of cilostazol. Cilostazol did not affect the cytokine-induced inhibition of GFRP mRNA expression.Conclusions: We conclude that cilostazol inhibited cytokine-stimulated BH4 biosynthesis via a cAMP-independent mechanism in HUVEC. Our data indicate that cilostazol reduced GTPCH activity and did so by suppressing the GTPCH protein levels.

著者

Masato Takase Naoki Nakaya Tomohiro Nakamura Mana Kogure Rieko Hatanaka Kumi Nakaya Ippei Chiba Ikumi Kanno Kotaro Nochioka Naho Tsuchiya Takumi Hirata Yohei Hamanaka Junichi Sugawara Tomoko Kobayashi Nobuo Fuse Akira Uruno Eiichi N Kodama Shinichi Kuriyama Ichiro Tsuji Atsushi Hozawa

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.64039, (Released:2023-02-11)

参考文献数

56

被引用文献数

2

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Aim: We examined the association between the carotid intima medica thickness (cIMT) and risk factors for atherosclerosis based on the Japan Atherosclerosis Society 2022 Atherosclerosis Prevention Guideline. Methods: Using data from the Tohoku Medical Megabank Community-based Cohort Study, we performed a cross-sectional study that enrolled 13,366 participants (age ≥ 20 years) with an analysis of covariance to assess associations between cIMT and risk factors for atherosclerosis. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. Analysis was conducted in the model adjusted for age, sex, smoking status, drinking status, body mass index (BMI), systolic blood pressure (SBP), glycated hemoglobin (HbA1c), high-density lipoprotein-cholesterol (HDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), and height. Results: In this study cohort, the average age and cIMT were 57.3 (13.8) years and 0.61 (0.13) mm, respectively, which included 3,988 males (29.8%). Males had a higher cIMT than did the females. Age, height, BMI, SBP, HbA1c, and non-HDL-C were positively associated with cIMT. HDL-C was inversely associated with cIMT. Compared with never drinkers, current drinkers (≥ 46.0 g/day) had a significantly decreased cIMT. Conclusions: The cIMT was associated with atherosclerosis risk factors including age, sex, BMI, SBP, HbA1c, non-HDL-C, and HDL-C, and adequate control of risks in high-risk individuals might be required to prevent atherosclerotic cardiovascular diseases.

著者

Mengjin Hu Zhaoting Gong Yuejin Yang

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.63924, (Released:2022-12-16)

参考文献数

28

被引用文献数

2

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Aim: Some observational studies suggested that atherosclerosis increased the risk of venous thromboembolism (VTE), and vice versa. However, the results were conflicting, and the causal relationship is yet to be established. Therefore, we applied Mendelian randomization (MR) analyses to assess the bidirectional causality between coronary heart disease (CHD) and VTE, deep venous thrombosis (DVT), and pulmonary embolism (PE). Methods: A total of 184,305 individuals with CHD were included from the CARDIoGRAMplusC4D Consortium. Information on VTE, DVT, and PE were obtained from the FinnGen biobank. Genetic instruments for CHD and VTE were constructed using 37 and 12 single-nucleotide polymorphisms, respectively. Inverse-variance weighted meta-analysis under a random-effect model was used as the preliminary estimate. Five complementary MR methods were also used, including weighted median, MR-Egger, multivariable MR (adjusted for the body mass index), simple mode, and weighted mode methods. Results: The genetically instrumented VTE (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.00-1.11; P=0.06), DVT (OR: 1.03; 95% CI: 0.99-1.08; P=0.19), or PE (OR: 1.07; 95% CI: 0.98-1.16; P=0.11) showed no causal relationships with CHD. There was also no clear evidence showing the causal effects of CHD on VTE (OR: 1.00; 95% CI: 0.82-1.22; P=0.98), DVT (OR: 1.00; 95% CI: 0.79-1.27; P=0.97), or PE (OR: 0.98; 95% CI: 0.82-1.18; P=0.87). No pleiotropic bias was found in the MR analyses. As heterogeneity was significant, a random model was used to minimize the effect of heterogeneity. Conclusions: No causal associations existed between CHD and VTE. Arterial and venous thromboses may represent separate entities.

著者

Masahito Iioka Shiro Fukuda Norikazu Maeda Tomoaki Natsukawa Shunbun Kita Yuya Fujishima Hirotaka Sawano Hitoshi Nishizawa Iichiro Shimomura

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.29, no.12, pp.1823-1834, 2022-12-01 (Released:2022-12-01)

参考文献数

44

被引用文献数

1

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Aims: T-cadherin (T-cad) is a specific binding partner of adiponectin (APN), adipocyte-specific secretory protein. APN exhibits organ protection via the T-cad-dependent accumulation onto several tissues such as the aorta, heart, and muscle. Recently, for the first time, we showed that three forms (130, 100, and 30 kDa) of soluble T-cad existed in human serum and correlated with several clinical parameters in patients with type 2 diabetes. Nevertheless, the significance of soluble T-cad has not been elucidated in the acute stage of cardiovascular diseases. We herein examined soluble T-cad concentrations and investigated their clinical significance in patients with emergency hospital admission due to ST-segment elevation myocardial infarction (STEMI).Methods: This observational study enrolled 47 patients with STEMI who were treated via primary percutaneous coronary intervention (PCI). Soluble T-cad and APN concentrations were measured by using an enzyme-linked immunosorbent assay. This study is registered with the University Hospital Medical Information Network (Number: UMIN 000014418).Results: Serum concentrations of soluble 130 and 100 kDa T-cad rapidly and significantly decreased after hospitalization and reached the bottom at 72 h after admission (p<0.001 and p<0.001, respectively). The patients with high soluble T-cad and low APN concentrations on admission showed a significantly higher area under the curve of serum creatine kinase-MB (p<0.01).Conclusion: Serum soluble T-cad concentration changed dramatically in patients with STEMI, and the high T-cad and low APN concentrations on admission were associated with the myocardial infarction size. Further study is needed to investigate the usefulness of categorizing patients with STEMI by serum T-cad and APN for the prediction of severe prognoses.

著者

Takafumi Mizuno Takao Hoshino Kentaro Ishizuka Sono Toi Shuntaro Takahashi Sho Wako Satoko Arai Kazuo Kitagawa

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.63849, (Released:2022-11-26)

参考文献数

35

被引用文献数

4

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Aims: We aimed to assess the prognostic impact of hyperhomocysteinemia (HHcy) on the recurrent vascular event risk in stroke patients with or without chronic kidney disease (CKD). Methods: In this prospective observational study, 621 patients (mean age, 69.5 years; male, 62.2%) with ischemic stroke or transient ischemic attack were consecutively enrolled within 1 week of onset and followed-up for 1 year. HHcy was defined as elevated levels of fasting total homocysteine >15 µmol/L. CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2 or a history of renal replacement therapy. The primary outcome was a composite of major adverse cardiovascular events (MACEs), including nonfatal stroke, nonfatal acute coronary syndrome, major peripheral artery disease, and vascular death. Results: The prevalence of HHcy was 18.5%. Patients with HHcy were more likely to have intracranial (37.4% versus 24.8%; p=0.008) and extracranial (20.9% versus 13.0%; p=0.037) artery stenosis than were those without HHcy. At 1 year, patients with HHcy were at a greater risk of MACE than were those without HHcy (annual rate, 17.8% versus 10.4%; log-rank p=0.033). In the Cox proportional hazard regression models, HHcy was independently associated with an increased risk of MACE in patients with CKD (adjusted hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.02-4.20), whereas HHcy was not predictive of MACE in those without CKD (adjusted HR, 1.00; 95% CI, 0.30-3.32). Conclusions: Elevated levels of serum homocysteine can be an important modifiable risk factor in stroke patients with CKD, but not in those without CKD.

著者

Mohammad Moniruzzaman Aya Kadota Takashi Hisamatsu Hiroyoshi Segawa Keiko Kondo Sayuki Torii Naoko Miyagawa Akira Fujiyoshi Yuichiro Yano Yoshiyuki Watanabe Akihiko Shiino Kazuhiko Nozaki Hirotsugu Ueshima Katsuyuki Miura on behalf of the SESSA Research Group

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.63824, (Released:2022-11-15)

参考文献数

42

被引用文献数

1

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Aim: Irisin, an exercise-induced myokine, is a potential neurotrophic factor; however, its relationship with cerebral small vessel disease (CSVD) remains unknown. Therefore, we investigated whether serum irisin levels are associated with CSVD in healthy Japanese men. Methods: We analyzed data from 720 men free of stroke and participated in this observational study. Serum irisin levels were measured by enzyme-linked immunosorbent assay. CSVD was assessed on deep and subcortical white matter hyperintensities (DSWMHs), periventricular hyperintensities (PVHs), lacunar infarcts (LIs), and cerebral microbleeds (CMBs) on brain magnetic resonance imaging. We calculated the total CSVD score (ranges 0–4) to express the total CSVD burden. We computed the adjusted odds ratios (ORs), with 95% confidence intervals (CIs), of the total CSVD score and individual CSVD features using logistic regression models according to the quartiles of irisin (reference: Q1). Results: Serum irisin levels were associated with lower ORs of higher (vs. zero or lower score) total CSVD score, with the lowest risk (OR, 0.63; 95% CI, 0.41–0.97) being observed in Q3 compared to Q1 after adjustment of potential covariates. Similar results were obtained for younger adults (<65 years). Among individual CSVD features, irisin was associated with a reduced risk of LIs in the total sample and PVHs, LIs, and CMBs in younger adults. No relationship was observed in older adults (≥ 65 years). Conclusions: Serum irisin levels were associated with less burden of total CSVD in healthy Japanese men. Serum irisin levels were also related with a reduced risk of PVHs, LIs, and CMBs, but not DSWMHs.

著者

Daisuke Kanai Hideki Fujii Kentaro Nakai Keiji Kono Kentaro Watanabe Shunsuke Goto Shinichi Nishi

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.29, no.11, pp.1646-1654, 2022-11-01 (Released:2022-11-01)

参考文献数

39

被引用文献数

1

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Aim: Acute kidney injury (AKI) is an important clinical issue in the diagnosis and treatment of cardiovascular diseases. The association between pretreatment by statins and the occurrence of AKI in patients with peripheral arterial diseases (PAD) remains unclear. Therefore, we examined the association between statin therapy and the occurrence of AKI in patients with PAD.Methods: We retrospectively analyzed data from the endovascular treatment (EVT) database in our hospital. A total of 295 patients who underwent angiography and/or intervention for PAD between October 2011 and March 2016 were enrolled and divided into two groups: those without statins (control group; N=157) and those with statins (statin group; N=138) for at least 1 month before admission. We examined the occurrence of AKI and its related factors in these patients.Results: The serum creatinine levels, dose of contrast medium, use of a renin-angiotensin system inhibitor, smoking habit, and blood pressure were similar in both groups. The statin group had more diabetes patients, had patients who were significantly younger, had patients with a higher body mass index (BMI), and had patients with lower low-density lipoprotein cholesterol than the control group. With regard to the occurrence of AKI, there was a significantly lower incidence in the statin group compared with the control group (5% vs. 16%, p<0.05). The result of the multivariate analysis indicated that statin therapy was significantly correlated with lower occurrence rates of AKI (p<0.05).Conclusions: Our study suggests that statin therapy might prevent the occurrence of AKI after angiography and/or intervention for PAD.

著者

Masato Takase Mitsuhiro Yamada Tomohiro Nakamura Naoki Nakaya Mana Kogure Rieko Hatanaka Kumi Nakaya Ikumi Kanno Kotaro Nochioka Naho Tsuchiya Takumi Hirata Yohei Hamanaka Junichi Sugawara Tomoko Kobayashi Nobuo Fuse Akira Uruno Eiichi N Kodama Shinichi Kuriyama Ichiro Tsuji Atsushi Hozawa

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.63826, (Released:2022-11-04)

参考文献数

54

被引用文献数

2

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Aim: Impaired lung function is associated with atherosclerotic vascular events. Carotid intima-media thickness (cIMT) is a marker for subclinical atherosclerosis. However, few studies have examined the association between lung function and cIMT among never smokers or individuals stratified by age. We investigated the association between lung function and cIMT in the Japanese population. Methods: We conducted a cross-sectional study of 3,716 men and 8,765 women aged 20 years or older living in Miyagi Prefecture, Japan. Lung function was evaluated using forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC) was measured using spirometry. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. An analysis of covariance was used to assess associations between lung function and cIMT and adjusted for potential confounders. A linear trend test was conducted by scoring the categories from 1 (lowest) to 4 (highest) and entering the score as a continuous term in the regression model. Results: After adjusting for potential confounders including passive smoking, lower FEV1 and FVC were associated with higher cIMT in both men and women (P<0.001 for linear trend). This association was confirmed even when we restricted our study to never smokers. Furthermore, even when we stratified by age, an inverse association between lung function and cIMT was confirmed in middle-aged (40-64 years) and elderly participants (65-74 years). Conclusions: Lower lung function was associated with higher cIMT in the Japanese population independent of age and smoking. Assessment of atherosclerosis or lung function may be required for individuals with lower lung function or atherosclerosis.