著者

Hiroshige Itakura Mitsuhiro Yokoyama Masunori Matsuzaki Yasushi Saito Hideki Origasa Yuichi Ishikawa Shinichi Oikawa Jun Sasaki Hitoshi Hishida Toru Kita Akira Kitabatake Noriaki Nakaya Toshiie Sakata Kazuyuki Shimada Kunio Shirato Yuji Matsuzawa

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.18, no.2, pp.99-107, 2011 (Released:2011-02-24)

参考文献数

32

被引用文献数

98 191 39

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Aim: The Japan EPA Lipid Intervention Study (JELIS) was the first prospective randomized clinical trial to demonstrate prevention of coronary events by pure eicosapentaenoic acid (EPA). The aim of this study was to examine the relationships between various plasma fatty acid concentrations and the risk of coronary events in JELIS participants.Methods: In 15,534 participants, we calculated the hazard ratio for major coronary events (sudden cardiac death, fatal or nonfatal myocardial infarction, unstable angina pectoris, and angioplasty/stenting or coronary artery bypass grafting) relative to the on-treatment average level of plasma fatty acids with the Cox proportional hazard model.Results: As a result of EPA intervention, the plasma EPA concentration increased, but the docosahexaenoic acid (DHA) concentration did not. The other fatty acids measured decreased slightly. The higher plasma level of EPA (hazard ratio=0.83, p=0.049, in all participants and hazard ratio=0.71, p=0.018, in the EPA intervention group), but not of DHA, was inversely associated with the risk of major coronary events. The associations between other fatty acids and the risk of major coronary events were not significant. In all JELIS participants, the risk of major coronary events was significantly decreased (20%) in the group with high (150 µg/mL or more) on-treatment plasma EPA concentration compared with that in the low (less than 87 µg/mL) group.Conclusion: The risk of coronary artery disease is influenced by variations in plasma fatty acid composition. Among n-3 polyunsaturated fatty acids, EPA and DHA exhibited differences in the correlation with the risk of major coronary events.

著者

Yoko Yoshida Hideki Kato Yoichiro Ikeda Masaomi Nangaku

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.RV17026, (Released:2018-11-02)

参考文献数

98

被引用文献数

52

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Atypical hemolytic uremic syndrome (aHUS) is a type of thrombotic microangiopathy (TMA) defined by thrombocytopenia, microangiopathic hemolytic anemia, and renal failure. aHUS is caused by uncontrolled complement activation in the alternative pathway (AP). A variety of genetic defects in complement-related factors or acquired autoantibodies to the complement regulators have been found in 50 to 60% of all cases. Recently, however, the classification and diagnosis of aHUS are becoming more complicated. One reason for this is that some factors, which have not been regarded as complement-related factors, have been reported as predisposing factors for phenotypic aHUS. Given that genotype is highly correlated with the phenotype of aHUS, careful analysis of underlying genetic abnormalities or acquired factors is needed to predict the prognosis or to decide an optimal treatment for the disease. Another reason is that complement dysregulation in the AP have also been found in a part of other types of TMA such as transplantation-related TMA and pregnancy-related complication. Based on these findings, it is now time to redefine aHUS according to the genetic or acquired background of abnormalities.Here, we review the pathogeneses and the corresponding phenotypes of aHUS and complement-related TMAs.

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 19

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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

Claudine A Feio Maria C Izar Silvia S Ihara Soraia H Kasmas Celma M Martins Max N Feio Luís A Maués Ney C Borges Ronilson A Moreno Rui M Póvoa Francisco A Fonseca

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.1112010447, (Released:2011-12-03)

参考文献数

29

被引用文献数

18 32

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Aim: Euterpe Oleracea (açai) is a fruit from the Amazon region whose chemical composition may be beneficial for individuals with atherosclerosis. We hypothesized that consumption of Euterpe Oleracea would reduce atherosclerosis development by decreasing cholesterol absorption and synthesis.Methods: Male New Zealand rabbits were fed a cholesterol-enriched diet (0.5%) for 12 weeks, when they were randomized to receive Euterpe Oleracea extract (n = 15) or water (n = 12) plus a 0.05% cholesterol-enriched diet for an additional 12 weeks. Plasma phytosterols and desmosterol were determined by ultra-performance liquid chromatography and mass spectrometry. Atherosclerotic lesions were estimated by computerized planimetry and histomorphometry.Results: At sacrifice, animals treated with Euterpe Oleracea had lower levels of total cholesterol (p =0.03), non-HDL-cholesterol (p = 0.03) and triglycerides (p = 0.02) than controls. These animals had smaller atherosclerotic plaque area in their aortas (p = 0.001) and a smaller intima/media ratio (p = 0.002) than controls, without differences in plaque composition. At the end of the study, campesterol, β-sitosterol, and desmosterol plasma levels did not differ between groups; however, animals treated with Euterpe Oleracea showed lower desmosterol/campesterol (p = 0.026) and desmosterol/ β-sitosterol (p =0.006) ratios than controls.Conclusions: Consumption of Euterpe Oleracea extract markedly improved the lipid profile and attenuated atherosclerosis. These effects were related in part to a better balance in the synthesis and absorption of sterols.

著者

Jia-Ling Lin Po-Sheng Chen Hui-Wen Lin Liang-Miin Tsai Sheng-Hsiang Lin Yi-Heng Li

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.29, no.8, pp.1213-1225, 2022-08-01 (Released:2022-08-01)

参考文献数

39

被引用文献数

1 5

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Aim: The safety concern of statins is still a major issue for Asians. The aim of this study is to compare the risk of statin-associated adverse events among potent statins.Methods: We included patients from the Taiwan National Health Insurance Research Database who had been treated with atorvastatin, rosuvastatin, or pitavastatin and were without diabetes at baseline. They were classified into three groups: usual-dose statin (atorvastatin 10 mg/d or rosuvastatin 5–10 mg/d), high-dose statin (atorvastatin 20–40 mg/d and rosuvastatin 20 mg/d), and pitavastatin (2–4 mg/d). The primary endpoint is a composite of safety events, including hepatitis, myopathy, and new-onset diabetes mellitus (NODM). We matched age, sex, and year of recruitment among the three groups (n=50,935 in each group) and then used the multivariate Cox proportional hazards model to evaluate the relation between the safety endpoint and different statin groups.Results: After a mean follow-up of 3.08±0.83 years, the safety events occurred in 9.84% in the pitavastatin group, 10.88% in the usual-dose statin group, and 10.49% in high-dose statin group. The multivariate Cox proportional hazards model indicated that usual-dose statin and high-dose statin were associated with a higher risk of the composite safety events compared with pitavastatin (adjusted hazard ratio [aHR]: 1.12, 95% confidence interval [CI]: 1.08–1.17 for usual-dose statin and aHR: 1.06, 95% CI: 1.02–1.10 for high-dose statin). The risks of hepatitis requiring hospitalization and NODM were especially lower in pitavastatin group. Conclusions: Compared with atorvastatin and rosuvastatin, pitavastatin might be associated with a lower risk of safety events in Asians.

著者

Tamami Iwamoto Kazuaki Hosoda Reiko Hirano Hideaki Kurata Akiyo Matsumoto Wataru Miki Masumi Kamiyama Hiroshige Itakura Shigeru Yamamoto Kazuo Kondo

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.7, no.4, pp.216-222, 2000 (Released:2011-09-20)

参考文献数

42

被引用文献数

185 224

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Marine animals produce astaxanthin which is a carotenoid and antioxidant. In this study we determined the in vitro and ex vivo effects of astaxanthin on LDL oxidation. The oxidation of LDL was measured in a 1 ml reaction system consisting of increasing concentrations of astaxanthin (12.5, 25.0, 50.0 μg/ml), 400 μM V-70 (2, 2'-azobis (4-methoxy-2, 4-dimethylvaleronitrile)), and LDL (70 μg/ml protein). Astaxanthin dose, dependently significantly prolonged the oxidation lag time (31.5, 45.4, 65.0 min) compared with the control (19.9 min). For the ex vivo study 24 volunteers (mean age 28.2 [SD 7.8] years) consumed astaxanthin at doses of 1.8, 3.6, 14.4 and 21.6 mg per day for 14 days. No other changes were made in the diet. Fasting venous blood samples were taken at days 0, +14. LDL lag time was longer (5.0, 26.2, 42.3 and 30.7% respectively) compared with day O after consuming astaxanthin at doses of 1.8, 3.6, 14.4 and 21.6 mg for 14 days compared with day O, but there was no difference in oxidation of LDL between day O (lag time 59.9 + 7.2 min) and day 14 (57.2 ± 6.0 min) in the control group. Our results provide evidence that consumption of marine animals producing astaxanthin inhibits LDL oxidation and possibly therefore contributes to the prevention of atherosclerosis.

著者

Hironobu Mitani Kota Suzuki Junya Ako Kazuma Iekushi Renata Majewska Salsabil Touzeni Shizuya Yamashita

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.30, no.11, pp.1622-1634, 2023-11-01 (Released:2023-11-01)

参考文献数

32

被引用文献数

6

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Aims: The study aimed to investigate low-density lipoprotein cholesterol (LDL-C) goal achievement rates in patients receiving LDL-C-lowering therapy using recent real-world data, following the 2017 revision of the Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases (JAS GL2017). Methods: Patients with documented LDL-C test results were extracted from the Medical Data Vision claims database between July 2018 and June 2021 and divided into three groups according to JAS GL2017: primary prevention high risk (Group I, LDL-C goal <120 mg/dL), secondary prevention (Group II, LDL-C goal <100 mg/dL), and secondary prevention high risk (Group III, LDL-C goal <70 mg/dL). Results: The mean LDL-C value was 108.7 mg/dL (n=125,235), 94.4 mg/dL (n=57,910), and 90.6 mg/dL (n=33,850) in Groups I, II, and III, respectively. Intensive statin monotherapy (pitavastatin, rosuvastatin, or atorvastatin) was the most frequently prescribed lipid-lowering treatment (21.6%, 30.8%, and 42.7% in Groups I, II, and III, respectively), followed by ezetimibe (2.5%, 7.1%, and 8.5% in Groups I, II, and III, respectively). LDL-C goals were achieved by 65.5%, 60.6%, and 25.4% of patients overall in Groups I, II, and III, respectively. Achievement rates were 83.9%, 75.3%, and 29.5% in patients prescribed intensive statin monotherapy and 82.3%, 86.4%, and 46.4% in those prescribed statin and ezetimibe combinations in Groups I, II, and III, respectively. In Group III, the proportion of patients with familial hypercholesterolemia prescribed statin and ezetimibe combinations achieving LDL-C goals was low (32.5%). Conclusions: The proportion of patients achieving LDL-C goals for secondary prevention in the high-risk group remains low even with statin and ezetimibe combination therapy.

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

vol.28, no.4, pp.329-337, 2021-04-01 (Released:2021-04-01)

参考文献数

38

被引用文献数

17 16

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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

Keiichiro Yamane Yoshihiro Kato Junichi Tazaki Tomohisa Tada Takeru Makiyama Masao Imai Toshikazu Jinnai Tomoyuki Ikeda Ryutaro Shirakawa Takeshi Kimura Hisanori Horiuchi

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.19, no.6, pp.559-569, 2012 (Released:2012-06-28)

参考文献数

30

被引用文献数

23 23

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Aim: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is essential after percutaneous coronary intervention (PCI). Clopidogrel is a prodrug and changed into active metabolite by cytochrome p450 enzymes (CYPs), especially CYP2C19. Proton pump inhibitors (PPIs) are used for the prevention of aspirin-induced gastrointestinal bleeding. PPIs are also metabolized by CYP2C19, although the degree of its contribution is dependent on the kind of PPI. Omeprazole, a PPI, has been reported to weaken the antiplatelet effects of clopidogrel. Famotidine, a histamine receptor type 2 (H2) blocker, could also be an alternative to PPIs. The aim of this study was to evaluate the effects of PPIs and an H2 blocker on the antiplatelet function of clopidogrel.Methods: Patients receiving DAPT due to prior PCI, who took either omeprazole or rabeprazole, were enrolled (n=25). The initial PPI was changed to the other PPI as a crossover study. In another study, patients undergoing DAPT without taking PPIs or H2 blockers were enrolled (n=30) and famotidine was added.Results: Platelet aggregability when taking omeprazole was higher than when taking rabeprazole, evaluated by an optical aggregometer using collagen as a stimulus (p=0.0051) and by the VerifyNow P2Y12 assay (p=0.0060). Platelet aggregability when taking rabeprazole was comparable to that in control patients (n=15). Concomitant use of famotidine had no effect.Conclusion: Omeprazole significantly reduced the antiplatelet effect of clopidogrel and this effect on clopidogrel was stronger than that of rabeprazole. Concomitant use of famotidine had no effect on the antiplatelet effect of clopidogrel.

著者

Keiji Matsunaga Asako Mizobuchi Hai Ying Fu Shohei Ishikawa Hayato Tada Masa-aki Kawashiri Ichiro Yokota Tsuyoshi Sasaki Shigeru Ito Jun Kunikata Takashi Iwase Tomohiro Hirao Katsunori Yokoyama Yoichi Hoshikawa Takuji Fujisawa Kazushige Dobashi Takashi Kusaka Tetsuo Minamino

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.29, no.6, pp.839-849, 2022-06-01 (Released:2022-06-01)

参考文献数

21

被引用文献数

6 20

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Aim: Familial hypercholesterolemia (FH) is an underdiagnosed autosomal dominant genetic disorder characterized by high levels of plasma low-density lipoprotein cholesterol (LDL-C) from birth. This study aimed to assess the genetic identification of FH in children with high LDL-C levels who are identified in a universal pediatric FH screening in Kagawa, Japan.Method: In 2018 and 2019, 15,665 children aged 9 or 10 years underwent the universal lipid screening as part of the annual health checkups for the prevention of lifestyle-related diseases in the Kagawa prefecture. After excluding secondary hyper-LDL cholesterolemia at the local medical institutions, 67 children with LDL-C levels of ≥ 140 mg/dL underwent genetic testing to detect FH causative mutations at four designated hospitals.Results: The LDL-C levels of 140 and 180 mg/dL in 15,665 children corresponded to the 96.3 and 99.7 percentile values, respectively. Among 67 children who underwent genetic testing, 41 had FH causative mutations (36 in the LDL-receptor, 4 in proprotein convertase subtilisin/kexin type 9, and 1 in apolipoprotein B). The area under the curve of receiver operating characteristic curve predicting the presence of FH causative mutation by LDL-C level was 0.705, and FH causative mutations were found in all children with LDL-C levels of ≥ 250 mg/dL.Conclusion: FH causative mutations were confirmed in almost 60% of the referred children, who were identified through the combination of the lipid universal screening as a part of the health checkup system and the exclusion of secondary hyper-LDL cholesterolemia at the local medical institutions.

著者

Gantsetseg Ganbaatar Yukiko Okami Aya Kadota Namuun Ganbaatar Yuichiro Yano Keiko Kondo Akiko Harada Nagako Okuda Katsushi Yoshita Tomonori Okamura Akira Okayama Hirotsugu Ueshima Katsuyuki Miura for the NIPPON DATA80 Research Group

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.64330, (Released:2023-10-06)

参考文献数

53

被引用文献数

2

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Aim: A pro-inflammatory diet may increase the risk of cardiovascular disease (CVD) and all-cause mortality. However, this remains inconclusive as there is yet no study using a dietary record method that has been conducted in a large general population. Furthermore, an underestimation of the pro-inflammatory diet may exist due to the unmeasured effect of salt intake. Thus, in this study, we aimed to examine how pro-inflammatory diet is associated with the long-term risk of all-cause and CVD mortality in a representative Japanese population. Methods: A national nutrition survey was conducted throughout Japan in 1980. After considering the exclusion criteria, 9284 individuals (56% women aged 30-92 years) were included in this study. In total, 20 dietary parameters derived from 3-day weighed dietary records were used to calculate the dietary inflammatory index (DII). The causes of death were monitored until 2009. The Cox proportional hazards model was used to determine multivariable-adjusted hazard ratios (HRs). Stratified analysis according to salt intake level was also performed. Results: Compared with the lowest quartile of DII, multivariable-adjusted HRs (95% confidence intervals) in the highest quartile were 1.28 (1.15, 1.41), 1.35 (1.14, 1.60), 1.48 (1.15, 1.92), 1.62 (1.11, 2.38), and 1.34 (1.03, 1.75) for all-cause mortality, CVD mortality, atherosclerotic CVD mortality, coronary heart disease mortality, and stroke mortality, respectively. Stratified analysis revealed stronger associations among individuals with higher salt intake. Conclusions: As per our findings, a pro-inflammatory diet was determined to be positively associated with the long-term risk of all-cause and CVD mortality in a representative Japanese population. Thus, considering both salt intake and pro-inflammatory diet is deemed crucial for a comprehensive assessment of CVD risk.

著者

Masato Takase Naoki Nakaya Tomohiro Nakamura Mana Kogure Rieko Hatanaka Kumi Nakaya Ippei Chiba Ikumi Kanno Kotaro Nochioka Naho Tsuchiya Takumi Hirata Akira Narita Taku Obara Mami Ishikuro Akira Uruno Tomoko Kobayashi Eiichi N Kodama Yohei Hamanaka Masatsugu Orui Soichi Ogishima Satoshi Nagaie Nobuo Fuse Junichi Sugawara Shinichi Kuriyama Ichiro Tsuji Gen Tamiya Atsushi Hozawa Masayuki Yamamoto the ToMMo investigators

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.64425, (Released:2023-10-06)

参考文献数

42

被引用文献数

1

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Aim: The influence of family history of diabetes, probably reflecting genetic and lifestyle factors, on the association of combined genetic and lifestyle risks with diabetes is unknown. We examined these associations. Methods: This cross-sectional study included 9,681 participants in the Tohoku Medical Megabank Community-based Cohort Study. A lifestyle score, which was categorized into ideal, intermediate, and poor lifestyles, was given. Family history was obtained through a self-reported questionnaire. A polygenic risk score (PRS) was constructed in the target data (n=1,936) using publicly available genome-wide association study summary statistics from BioBank Japan. For test data (n=7,745), we evaluated PRS performance and examined the associations of combined family history and genetic and lifestyle risks with diabetes. Diabetes was defined as non-fasting blood glucose ≥ 200 mmHg, HbA1c ≥ 6.5%, and/or self-reported diabetes treatment. Results: In test data, 467 (6.0%) participants had diabetes. Compared with a low genetic risk and an ideal lifestyle without a family history, the odds ratio (OR) was 3.73 (95% confidence interval [CI], 1.92–7.00) for a lower genetic risk and a poor lifestyle without a family history. Family history was significantly associated with diabetes (OR, 3.58 [95% CI, 1.73–6.98]), even in those with a low genetic risk and an ideal lifestyle. Even among participants who had an ideal lifestyle without a family history, a high genetic risk was associated with diabetes (OR, 2.49 [95% CI, 1.65–3.85]). Adding PRS to family history and conventional lifestyle risk factors improved the prediction ability for diabetes. Conclusions: Our findings support the notion that a healthy lifestyle is important to prevent diabetes regardless of genetic risk.

著者

Tsuyoshi Nozue Ichiro Michishita Yasuki Ito Tsutomu Hirano

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.15, no.3, pp.146-153, 2008 (Released:2008-07-07)

参考文献数

44

被引用文献数

25 25

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Aim: The effects of statin on small dense low-density lipoprotein cholesterol (sd-LDL-C) and remnant-like particle cholesterol (RLP-C) levels in heterozygous familial hypercholesterolemia (FH) have not been examined. This study aimed to clarify the effects of statin on sd-LDL-C and RLP-C levels in heterozygous FH.Methods: Seventeen patients with heterozygous FH were randomly assigned to 2 mg/day pitavastatin or 10 mg/day atorvastatin. At baseline and 12 weeks after treatment with statin, we measured sd-LDL-C and RLP-C levels.Results: Sd-LDL-C levels significantly decreased from 43 ± 24 to 16 ± 10 mg/dL (−63%, p=0.001) in the pitavastatin group, and from 44 ± 17 to 19 ± 10 mg/dL (−55%, p<0.001) in the atorvastatin group. RLP-C levels decreased from 8.4 ± 2.8 to 6.6 ± 2.7 mg/dL (−16%, p=0.156) in the pitava-statin group, and from 9.8 ± 4.7 to 5.9 ± 5.4 mg/dL (−45%, p=0.044) in the atorvastatin group. There were no significant differences in percent changes of sd-LDL-C (p=0.370) and RLP-C levels (p=0.097) between the two groups.Conclusions: Sd-LDL-C measured by the heparin-magnesium precipitation method and RLP-C levels in heterozygous FH were decreased by 12 weeks of statin therapy. Statin might have additional anti-atherogenic effects by reducing not only LDL-C but also sd-LDL-C and RLP-C.

著者

Michio Shimabukuro

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.30, no.8, pp.853-854, 2023-08-01 (Released:2023-08-01)

参考文献数

10

著者

Michio Shimabukuro

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.ED226, (Released:2023-01-21)

参考文献数

10

著者

Michio Shimabukuro

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.ED235, (Released:2023-05-26)

参考文献数

10

被引用文献数

1

著者

Masahito Michikura Masatsune Ogura Mika Hori Kota Matsuki Hisashi Makino Kiminori Hosoda Mariko Harada-Shiba

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.1603-1612, 2022-11-01 (Released:2022-11-01)

参考文献数

25

被引用文献数

4 10

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Aims: Achilles tendon (AT) xanthomas are a specific physical finding of familial hypercholesterolemia (FH) and AT thickness has been used for its diagnosis and evaluation of its severity. Recently, we reported that the AT of FH patients was softer than that of non-FH patients and the combined use of a cut-off value for AT softness with that for AT thickness improved diagnostic accuracy. However, an association between AT softness and severity of atherosclerosis has not been reported. Accordingly, the present study aimed to investigate whether AT softness was associated with carotid atherosclerosis and presence of atherosclerotic cardiovascular disease (ASCVD) in FH.Methods: The AT of 176 genetically diagnosed FH patients and 98 non-FH patients was examined to measure AT thickness and the elasticity index (EI) as an indicator for assessing AT softness using ultrasonography.Results: Increased age was associated with AT softness, and overweight was negatively related to AT softness. There were significant inverse correlations between EI and maximum and mean intima-media thickness (IMT) within the common carotid artery only among FH patients. In multiple linear regression analysis, although the relationship between EI and mean IMT was attenuated, the association between EI and maximum IMT remained robust. In logistic regression analysis adjusted for age, sex and traditional cardiovascular risk factors (smoking history, presence of hypertension, presence of diabetes mellitus, overweight, LDL-cholesterol, HDL-cholesterol, and Log triglycerides), EI was associated with presence of ASCVD (Odds ratio per 1-SD increase, 0.37; 95% CI, 0.15 – 0.86; P=0.0252).Conclusion: The degree of lipid deposition in the AT of FH patients could be assessed by its thickness as well as its softness. AT softness is not only useful in diagnosing FH but is also associated with the severity of carotid atherosclerosis and presence of ASCVD. In addition, these findings suggest that AT softness would be helpful in risk assessment for FH patients.

著者

Mariko Harada-Shiba Junya Ako Atsushi Hirayama Masato Nakamura Atsushi Nohara Kayoko Sato Yoshitaka Murakami Ryusuke Koshida Asuka Ozaki Hidenori Arai

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.29, no.8, pp.1201-1212, 2022-08-01 (Released:2022-08-01)

参考文献数

32

被引用文献数

3 7

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Aim: Genetic testing can provide a definitive diagnosis of familial hypercholesterolemia (FH). However, accessibility of genetic testing may be limited in certain countries where it is not considered “standard of care,” including Japan. In addition, mutations responsible for FH cannot be identified in approximately 30% of patients. Methods: EXPLORE-J is a multicenter, prospective, observational study of patients presenting with acute coronary syndrome (ACS). The genetic data were analyzed and adjudicated as pathogenic, indeterminate, or nondetectable pathogenic variant.Results: Of 1,944 patients, 431 underwent genetic screening. Overall, most patients had nonpathogenic variants of LDLR, LDLRAP1, or PCSK9 (n=396, 91.9%). Of the 25 (5.8%) patients with pathogenic variants, variants of the LDLR gene and the PCSK9 gene were seen in 10 and 15 patients, respectively. Indeterminate variants were observed in 10 (2.3%) patients. Of the 431 patients, eight (1.9%) met the criteria for a diagnosis of FH using the Japanese Atherosclerosis Society (JAS) 2017 guidelines. When genetic data were incorporated, 33 (7.7%) patients met the JAS guidelines. No patients with FH pathogenic variants satisfied the JAS clinical criteria for a diagnosis of FH.Conclusions: The results revealed a higher prevalence of genetic mutations of FH among Japanese patients with ACS and a low sensitivity of the FH diagnostic criteria of the JAS 2017 guidelines. These findings highlight the difficulties of FH diagnosis in patients with ACS in the acute phase and suggest the importance of genetic testing and family history.

著者

Mariko Harada-Shiba Hidenori Arai Shinichi Oikawa Takao Ohta Tomoo Okada Tomonori Okamura Atsushi Nohara Hideaki Bujo Koutaro Yokote Akihiko Wakatsuki Shun Ishibashi Shizuya Yamashita

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.19, no.12, pp.1043-1060, 2012 (Released:2012-12-20)

参考文献数

85

被引用文献数

144 146

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Familial hypercholesterolemia (FH) is a highly prevalent autosomal dominant hereditary disease, generally characterized by three major signs, hyper-low-density-lipoprotein (LDL) cholesterolemia, tendon/skin xanthomas and premature coronary artery disease (CAD). Because the risk of CAD is very high in these patients, they should be identified at an early stage of their lives and started on intensive treatment to control LDL-cholesterol. We here introduce a new guideline for the management of FH patients in Japan intending to achieve better control to prevent CAD. Diagnostic criteria for heterozygous FH are 2 or more of 1) LDL-cholesterol ≥180 mg/dL, 2) tendon/skin xanthoma(s), and 3) family history of FH or premature CAD within second degree relatives, for adults; and to have both 1) LDL-cholesterol ≥140 mg/dL and 2) family history of FH or premature CAD within second degree relatives, for children. For the treatment of adult heterozygous FH, intensive lipid control with statins and other drugs is necessary. Other risks of CAD, such as smoking, diabetes mellitus, hypertension etc., should also be controlled strictly. Atherosclerosis in coronary, carotid, or peripheral arteries, the aorta and aortic valve should be screened periodically. FH in children, pregnant women, and women who wish to bear a child should be referred to specialists. For homozygotes and severe heterozygotes resistant to drug therapies, LDL apheresis should be performed. The treatment cost of homozygous FH is authorized to be covered under the program of Research on Measures against Intractable Diseases by the Japanese Ministry of Health, Labour, and Welfare.

著者

Aya Hirata

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.30, no.2, pp.105-106, 2023-02-01 (Released:2023-02-01)

参考文献数

9