- 著者
- Masunori Matsuzaki Toru Kita Hiroshi Mabuchi Yuji Matsuzawa Noriaki Nakaya Shinichi Oikawa Yasushi Saito Jun Sasaki Kazuaki Shimamoto Hiroshige Itakura the J-LIT Study Group
- 出版者
- The Japanese Circulation Society
- 雑誌
- Circulation Journal (ISSN:13469843)
- 巻号頁・発行日
- vol.66, no.12, pp.1087-1095, 2002 (Released:2002-11-25)
- 参考文献数
- 52
- 被引用文献数
- 172 196
Hyperlipidemia is a well-established risk factor for primary coronary heart disease (CHD). Although simvastatin is known to lower serum lipid concentrations, the protective effect of such lipid-lowering therapy against primary CHD has not been established in Japanese patients with hypercholesterolemia. The Japan Lipid Intervention Trial was a 6-year, nationwide cohort study of 47,294 patients treated with open-labeled simvastatin (5-10 mg/day) and monitored by physicians under standard clinical conditions. The aim of the study was to determine the relationship between the occurrence of CHD and the serum lipid concentrations during low-dose simvastatin treatment. Simvastatin reduced serum concentrations of total cholesterol (TC), low-density lipoprotein- cholesterol (LDL-C) and triglyceride (TG), by 18.4%, 26.8% and 16.1% on average, respectively, during the treatment period. The risk of coronary events was higher when the average TC concentration was ≥240 mg/dl and the average LDL-C concentration was ≥160 mg/dl. The incidence of coronary events increased in the patients with TG concentration ≥300 mg/dl compared with patients with TG concentration <150 mg/dl. The high-density lipoprotein cholesterol (HDL-C) inversely correlated with the risk of coronary events. The J-curve association was observed between average TC or LDL-C concentrations and total mortality. Malignancy was the most prevalent cause of death. The health of patients should be monitored closely when there is a remarkable decrease in TC and LDL-C concentrations with low-dose statin. A reasonable strategy to prevent coronary events in Japanese hypercholesterolemic patients without prior CHD under low-dose statin treatment might be regulating the serum lipid concentrations to at least <240 mg/dl for TC, <160 mg/dl for LDL-C, <300 mg/dl for TG, and >40 mg/dl for HDL-C. (Circ J 2002; 66: 1087 - 1095)
- 著者
- Hidenori Arai Akira Yamamoto Yuji Matsuzawa Yasushi Saito Nobuhiro Yamada Shinichi Oikawa Hiroshi Mabuchi Tamio Teramoto Jun Sasaki Noriaki Nakaya Hiroshige Itakura Yuichi Ishikawa Yasuyoshi Ouchi Hiroshi Horibe Nobuo Shirahashi Toru Kita
- 出版者
- 一般社団法人 日本動脈硬化学会
- 雑誌
- Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
- 巻号頁・発行日
- vol.13, no.4, pp.202-208, 2006 (Released:2006-08-15)
- 参考文献数
- 15
- 被引用文献数
- 87 126
To determine the prevalence of metabolic syndrome in the Japanese general population, we analyzed data from a nationwide survey conducted in 2000. According to the Japanese new diagnostic criteria for metabolic syndrome in 2005, we analyzed 3,264 people aged from 20 to 79 (men, 1,917; women, 1,347) from the total participants. The incidence of metabolic syndrome was 7.8%. Men had a higher incidence (12.1%) than women (1.7%). Most of the women satisfying the criteria were 50 years old or over, while the incidence in men started to rise from their 30s. When we applied the criteria of Adult Treatment Panel III, the incidence was about 3-fold higher. In this population visceral obesity was associated with metabolic abnormalities, such as higher LDL-cholesterol, triglyceride, glucose, and blood pressure and lower HDL-cholesterol. Thus we determined the incidence of metabolic syndrome and each metabolic abnormality in the Japanese general population in 2000 and found an association of visceral obesity with metabolic abnormalities. Intervention to reduce the incidence of metabolic syndrome in Japan is necessary to reduce the risk of cardiovascular disease.
- 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
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
- Hidenori Arai Akira Yamamoto Yuji Matsuzawa Yasushi Saito Nobuhiro Yamada Shinichi Oikawa Hiroshi Mabuchi Tamio Teramoto Jun Sasaki Noriaki Nakaya Hiroshige Itakura Yuichi Ishikawa Yasuyoshi Ouchi Hiroshi Horibe Tohru Egashira Hiroaki Hattori Nobuo Shirahashi Toru Kita
- 出版者
- 一般社団法人 日本動脈硬化学会
- 雑誌
- Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
- 巻号頁・発行日
- vol.12, no.5, pp.240-250, 2005 (Released:2005-10-05)
- 参考文献数
- 53
- 被引用文献数
- 27 31
We studied the association of six common polymorphisms of four genes related to lipid metabolism with serum lipid levels. We selected single-nucleotide polymorphisms (SNPs) in the genes for cholesteryl ester transfer protein (CETP), lipoprotein lipase (LPL), hepatic lipase (LIPC), and apolipoprotein CIII (APOC3), and studied 2267 individuals randomly selected from the participants of Serum Lipid Survey 2000. There was a significant association of CETP polymorphism (D442G, Int14 +1 G → A, and TaqIB), LPL polymorphism (S447X), and LIPC polymorphism (−514 → CT) with HDL-cholesterol levels. We also found a significant association of LPL polymorphism (S447X) and APOC3 polymorphism (SstI) with triglyceride levels. This is the largest database showing the association of common genetic variants in lipid metabolism with serum lipid levels in the general Japanese population. Further study is necessary to elucidate the role of these gene polymorphisms in cardiovascular events.
- 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
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
- Mototsugu Nagao Akira Asai Lena Eliasson Shinichi Oikawa
- 出版者
- The Japan Endocrine Society
- 雑誌
- Endocrine Journal (ISSN:09188959)
- 巻号頁・発行日
- pp.EJ22-0253, (Released:2022-12-07)
Type 2 diabetes (T2D) is a polygenic disease and studies to understand the etiology of the disease have required selectively bred animal models with polygenic background. In this review, we present two models; the Goto-Kakizaki (GK) rat and the Oikawa-Nagao Diabetes-Prone (ON-DP) and Diabetes-Resistant (ON-DR) mouse. The GK rat was developed by continuous selective breeding for glucose tolerance from the outbred Wistar rat around 50 years ago. The main cause of spontaneous hyperglycemia in this model is insulin secretion deficiency from pancreatic β-cells and mild insulin resistance in insulin target organs. A disadvantage of the GK rat is that environmental factors have not been considered in the selective breeding. Hence, the GK rat may not be suitable for elucidating predisposition to diabetes under certain environmental conditions, such as a high-fat diet. Therefore, we recently established two mouse lines with different susceptibilities to diet-induced diabetes, which are prone and resistant to the development of diabetes, designated as the ON-DP and ON-DR mouse, respectively. The two ON mouse lines were established by continuous selective breeding for inferior and superior glucose tolerance after high-fat diet feeding in hybrid mice of three inbred strains. Studies of phenotypic differences between ON-DP and ON-DR mice and their underlying molecular mechanisms will shed light on predisposing factors for the development of T2D in the modern obesogenic environment. This review summarizes the background and the phenotypic differences and similarities of GK rats and ON mice and highlights the advantages of using selectively bred rodent models in diabetes research.
- 著者
- Hiroshi Mabuchi Toru Kita Masunori Matsuzaki Yuji Matsuzawa Noriaki Nakaya Shinichi Oikawa Yasushi Saito Jun Sasaki Kazuaki Shimamoto Hiroshige Itakura the J-LIT Study Group
- 出版者
- The Japanese Circulation Society
- 雑誌
- Circulation Journal (ISSN:13469843)
- 巻号頁・発行日
- vol.66, no.12, pp.1096-1100, 2002 (Released:2002-11-25)
- 参考文献数
- 26
- 被引用文献数
- 84 103
Hyperlipidemia is primarily implicated in the progression of coronary heart disease (CHD) and its treatment is essential for patients with a history of CHD. Statins such as simvastatin, the lipid-lowering agents, are well-known for their ability to normalize patient's serum lipid levels. The Japan Lipid Intervention Trial study of simvastatin is the first nationwide investigation of the relationship between serum lipid levels and the development of CHD in Japanese patients with hypercholesterolemia. Of 5,127 patients, exclusively with a history of documented CHD at enrollment, 4,673 were treated with open-labeled simvastatin at an initial dose of 5-10 mg/day and were monitored for 6 years. The risk of coronary events tended to be higher in patients with a serum total cholesterol (TC) ≥240 mg/dl compared with total cholesterol <240 mg/dl. The concentration of low-density lipoprotein cholesterol (LDL-C) positively correlated and that of high-density lipoprotein cholesterol (HDL-C) inversely correlated with the risk of CHD. Each 10 mg/dl decrease in LDL-C and each 10 mg/dl increase in HDL-C concentration reduced the risk of CHD by 8.0% (95% confidence interval 3.8-12.0) and 28.3% (95% CI 13.9-40.3), respectively. A reasonable therapeutic strategy to reduce CHD progression in patients with prior CHD under low-dose statin treatment might be regulating the serum LDL-C concentration to at least <120 mg/dl and HDL-C >40 mg/dl, respectively. (Circ J 2002; 66: 1096 - 1100)