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editors, Valentin Fuster, Eric J. Topol, Elizabeth G. Nabel
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論文
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Matsui, Nobumasa ; Washida, Kei ; Shoji, Morio ; Terada, Shigeru ; Miaki, Hiroichi ; 松井, 伸公 ; 鷲田, 恵 ; 正司, 守生 ; 寺田, 茂 ; 三秋, 泰一
概要:
Foot ulcers cause gait disturbances, decreased quality of life, and high rates of mortality in diabetic patients. High p
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lantar pressure and failure of peripheral circulation dynamics have been mentioned as risk factors for diabetic foot ulcers. It has been reported that plantar pressure is affected by the limited joint mobility （LJM） of foot joints. Therefore, preventing LJM of foot joints is important for prevention of diabetic foot ulcers. Failure of peripheral circulation dynamics can be evaluated by measuring brachial-ankle pulse wave velocity （baPWV）. The LJM of foot joints and arteriosclerosis are involved in the etiology of diabetic foot ulcers, but there have been no studies regarding the relationship between these two factors. We investigated the relationship between the range of motion （ROM） of foot joints and baPWV in diabetic patients.The study population consisted of 48 diabetic patients admitted to hospital for glycemic control and diabetes education. The LJM parameters measured were passive ROM of plantar flexion and dorsiflexion of the ankle joint, flexion and extension of the first metatarsophalangeal joint, and pronation and supination of the subtalar joint. baPWV was measured using an automated device. Pearsonʼs and partial correlation coefficients of patientsʼ baPWV and ROM values were calculated. The control conditions were age, gender, diabetes condition （diabetes duration, HbA1c levels, and diabetic polyneuropathy）, and arteriosclerosis status （systolic and diastolic blood pressure）.The mean age of the subjects was 57.4±11.8 years. ROM values for ankle, first metatarsophalangeal, and subtalar joints were 56.9°±8.8°, 89.7°±11.8°, and 27.0°±7.1°, respectively. Partial correlation analysis revealed a negative correlation between baPWV and ankle ROM （r=－0.35, p=0.03） after controlling for age, sex, systolic and diastolic blood pressure, diabetes duration, HbA1c level, and diabetic polyneuropathy. No significant associations of these outcomes were found in other joints.In diabetic patients, baPWV and ankle ROM were significantly negatively correlated when controlling for factors such as age, systolic and diastolic blood pressure, diabetes duration, HbA1c level, and diabetic polyneuropathy. However, additional studies are needed to draw clinical conclusions.<br />糖尿病性足部潰瘍は歩行障害、QOL の低下、死亡率の上昇を引き起こす。糖尿病性足部潰瘍の危険因子として高すぎる足底圧と末梢循環動態の障害が報告されている。足底圧は、足部関節の可動域制限の影響を受けることが示されている。従って、足部関節の関節可動域制限を予防することは、糖尿病性足部潰瘍の予防において重要である。末梢循環動態は、上腕 ‐ 足首脈波速度（baPWV）で評価できる。足部関節の可動域制限および動脈硬化は糖尿病性足部潰瘍に個々に関与しているが、両者の関係は不明である。そこで本研究の目的は、糖尿病患者の足部関節の関節可動域と baPWV の関係を調べることとした。対象は、血糖コントロールと糖尿病教育のために入院した 48 人の糖尿病患者とした。測定された関節可動域は、足関節の背屈および底屈、第1中足趾節間関節の屈曲および伸展、および距骨下関節の回内および回外方向の他動関節可動域とした。baPWV は専用の自動計測装置で測定した。対象の baPWV および各関節の関節可動域のピアソンおよび偏相関係数を計算した。偏相関係数の統制条件は、年齢、性別、糖尿病の状態（糖尿病罹病期間、 HbA1c 値および糖尿病性多発性神経障害）および動脈硬化に関連する値（収縮期血圧および拡張期血圧）とした。対象の平均年齢は 57.4 ± 11.8 歳であった。足関節、第 1 中足趾節間関節、距骨下関節の関節可動域は、それぞれ 56.9 ± 8.8°、89.7 ± 11.8°、27.0 ± 7.1°であった。偏相関分析は、年齢、性別、収縮期血圧および拡張期血圧、糖尿病期間、HbA1c 値および糖尿病性多発性神経障害の有無で制御した後、baPWV と足関節の関節可動域との間に負の相関を示した（r = -0.35、p = 0.03）。他の関節では有意な関連は認められなかった。糖尿病患者では、年齢、収縮期および拡張期血圧、糖尿病期間、HbA1c 値および糖尿病性多発性神経障害の因子で統制しても、baPWV および足関節の関節可動域は有意に負の相関関係を認めた。しかしながら、臨床的結論を引き出すためにはさらなる研究が必要である。
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Sakamoto, Aiji ; Sugamoto, Yuka ; Tokunaga, Y. ; Yoshimuta, Tsuyoshi ; Hayashi, Kenshi ; Konno, Tetsuo ; Kawashiri, Masa-aki ; Takeda, Yoshiyu ; Yamagishi, Masakazu ; 林, 研至 ; 今野, 哲雄 ; 川尻, 剛照 ; 武田, 仁勇 ; 山岸, 正和
概要:
金沢大学医薬保健研究域医学系<br />Ephrin B1 and its cognate receptor, Eph receptor B2, key regulators of embryogenesis, are expressed
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in human atherosclerotic plaque and inhibit adult human monocyte chemotaxis. Few data exist, however, regarding the gene expression profiles of the ephrin (EFN) and Eph receptor (EPH) family of genes in atherosclerosis-related human cells. Gene expression profiles were determined of all 21 members of this gene family in atherosclerosis-related cells by reverse transcription-polymerase chain reaction analysis. The following 17 members were detected in adult human peripheral blood monocytes: EFNA1 and EFNA3 - EFNA5 (coding for ephrins A1 and A3 - A5); EPHA1, EPHA2, EPHA4 - EPHA6 and EPHA8 (coding for Eph receptors A1, A2, A4 - A6 and A8); EFNB1 and EFNB2 (coding for ephrins B1 and B2); and EPHB1 - EPHB4 and EPHB6 (coding for Eph receptors B1 - B4 and B6). THP-1 monocytic cells, Jurkat T cells and adult arterial endothelial cells also expressed multiple EFN and EPH genes. These results indicate that a wide variety of ephrins and Eph receptors might affect monocyte chemotaxis, contributing to the development of atherosclerosis. Their pathological significance requires further study. © 2011 Field House Publishing LLP.
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Miyauchi, Katsumi ; Kimura, Takeshi ; Morimoto, Takeshi ; Nakagawa, Yoshihisa ; Yamagishi, Masakazu ; Ozaki, Yukio ; Hiro, Takafumi ; Daida, Hiroyuki ; Matsuzaki, Masunori ; 山岸, 正和
概要:
金沢大学医薬保健研究域医学系<br />Background: Many trials have shown that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase i
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nhibitors reduce the incidence of cardiovascular events and mortality. One method of decreasing the incidence of cardiovascular events could be to reduce the progression of coronary atherosclerosis, and a recent study found that atorvastatin can cause coronary plaque to regress. To generalize this finding, using conventional HMG-CoA reductase inhibitors at many Japanese centers, randomized trials of pitavastatin and atorvastatin will be conducted with patients with acute coronary syndrome (ACS). Methods and Results: Patients with ACS who have undergone successful percutaneous coronary intervention under intravascular ultrasound guidance will be studied. They will be randomly allocated to pitavastatin or atorvastatin groups and followed up for 8-12 months. The primary endpoint will be the percent change in coronary plaque volume, and secondary endpoints will include absolute changes in coronary plaque volume, serum lipid levels and inflammatory markers. The safety profile will also be evaluated. Conclusions: This study will examine the ability of HMG-CoA reductase inhibitors to regress coronary plaque in Japanese patients with ACS and the findings should help to improve the prognosis of such patients and clarify the involved mechanisms.<br />出版者照会後に全文公開
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Kobayashi, Junji ; Nohara, Atsushi ; Kawashiri, Masaaki ; Inazu, Akihiro ; Koizumi, Junji ; Nakajima, Katsuyuki ; Mabuchi, Hiroshi
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金沢大学大学院医学系研究科<br />Lipoprotein lipase (LPL) is a lipolytic enzyme involved in catalyzing hydrolysis of triglycerides (TG
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) in chylomicrons and very low-density lipoprotein (VLDL) particles. Over the last decade, increasing attention has been paid to the clinical significance of measuring serum LPL protein mass without heparin injection to the study subjects. In earlier studies, this marker was utilized to classify LPL deficient subjects, which is an extremely rare metabolic disorder with a frequency of one in one million. Later, researchers paid more attention to the clinical significance of measuring this parameter in more common metabolic disorders. Studies have shown that pre-heparin plasma or serum LPL mass has significant relationships with serum lipids and lipoproteins, visceral fat area, insulin resistance, and even the development of coronary atherosclerosis in cross-sectional studies, although this might be a metabolic surrogate marker with almost no catalytic activities, which does not appear to be involved in catalyzing hydrolysis of TG in TG-rich lipoproteins. Recently, a prospective study has demonstrated that low serum LPL concentration predicts future coronary events. Taken together, we suggest that pre-heparin LPL mass in plasma or sera provide us with useful and important information on the development of metabolic disorders leading to atherosclerotic disease. © 2006 Elsevier B.V. All rights reserved.
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Kawashiri, Masaaki ; Higashikata, Toshinori ; Takata, Mutsuko ; Katsuda, Shoji ; Miwa, Kenji ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Shimizu, Masami ; Koizumi, Junji ; Mabuchi, Hiroshi
概要:
金沢大学大学院医学系研究科 <br />A 38-year-old Japanese woman was admitted to hospital for further examination of systemic xanthomas.
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She had a past history of genital bleeding during her third delivery at the age of 21 years. She was diagnosed with Sheehan's syndrome. Her serum total cholesterol and triglyceride concentrations were 500 and 898 mg/dl, respectively. She was also diagnosed as having type III hyperlipoproteinemia on the basis of the presence of a broad-β-band on agarose gel electrophoresis and extremely high concentrations of very-low-density lipoprotein cholesterol (310 mg/dl). The diagnosis was later confirmed by her apolipoprotein E isoforms (E2/E2) and genotypes (epsilon2/epsilon2). Thyroid and corticosteroid hormone replacement therapy cured the xanthomas, but also elevated her blood pressure. The serum concentration of intermediate-density lipoprotein cholesterol was consistently high, whereas that of low-density lipoprotein cholesterol was relatively low during the follow-up. Coronary atherosclerosis had already developed by the age of 38 years, and progressed significantly over the following 28 years. Severe stenotic lesions were observed in the bilateral renal arteries and carotid arteries, and in the abdominal aorta when she was 66 years old. These findings suggest that the continuous elevation of intermediate-density lipoprotein cholesterol for a long period contributed to the development of the atherosclerotic lesions.
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Miyauchi, Katsumi ; Kimura, Takeshi ; Morimoto, Takeshi ; Nakaagawa, Yoshihisa ; Yamagishi, Masakazu ; Ozaki, Yukio ; Hiro, Takafumi ; Daida, Hiroyuki ; Matsuzaki, Masunori
概要:
Background Many trials have shown that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce the
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incidence of cardiovascular events and mortality. One method of decreasing the incidence of cardiovascular events could be to reduce the progression of coronary atherosclerosis, and a recent study found that atorvastatin can cause coronary plaque to regress. To generalize this finding, using conventional HMG-CoA reductase inhibitors at many Japanese centers, randomized trials of pitavastatin and atorvastatin will be conducted with patients with acute coronary syndrome (ACS). Methods and Results Patients with ACS who have undergone successful percutaneous coronary intervention under intravascular ultrasound guidance will be studied. They will be randomly allocated to pitavastatin or atorvastatin groups and followed up for 8-12 months. The primary endpoint will be the percent change in coronary plaque volume, and secondary endpoints will include absolute changes in coronary plaque volume, serum lipid levels and inflammatory markers. The safety profile will also be evaluated. Conclusions This study will examine the ability of HMG-CoA reductase inhibitors to regress coronary plaque in Japanese patients with ACS and the findings should help to improve the prognosis of such patients and clarify the involved mechanisms. (Circ J 2006; 70: 1624 - 1628)<br />出版者照会後に全文公開
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Takayama, Tadateru ; Hiro, Takafumi ; Yamagishi, Masakazu ; Daida, Hiroyuki ; Saito, Satoshi ; Yamaguchi, Tetsu ; Matsuzaki, Masunori
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http://www.j-circ.or.jp/english/<br />Background There have been few multicenter studies using intravascular ultrasound
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(IVUS) to assess the process of atherosclerosis in a Japanese population with hypercholesterolemia that is being treated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for control of low-density lipoprotein-cholesterol. Methods and Results An open-label multicenter study is planned to evaluate with IVUS whether treatment with rosuvastatin for 76 weeks results in regression of coronary artery atheroma volume in patients who have coronary heart disease (CHD) and hypercholesterolemia. Sample size is 200 subjects with CHD who are to undergo percutaneous coronary intervention. The planned duration is between October 2005 and October 2008. Conclusions The COSMOS study will be the first multicenter cardiovascular study in a Japanese population and may provide new evidence on the effects of rosuvastatin on the progression of coronary atherosclerotic lesions. (Circ J 2007; 71: 271 -275)<br />出版者照会後に全文公開
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Takayama, Tadateru ; Hiro, Takafumi ; Yamagishi, Masakazu ; Daida, Hiroyuki ; Hirayama, Atsushi ; Saito, Satoshi ; Yamaguchi, Tetsu ; Matsuzaki, Masunori ; The COSMOS Investigators ; 山岸, 正和
概要:
Background: It has been suggested that intensive lipid-lowering therapy using statins significantly decreases atheromato
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us plaque volume. The effect of rosuvastatin on plaque volume in patients with stable coronary artery disease (CAD), including those receiving prior lipid-lowering therapy, was examined in the present study. Methods and Results: A 76-week open-label trial was performed at 37 centers in Japan. Eligible patients began treatment with rosuvastatin 2.5 mg/day, which could be increased at 4-week intervals to ≤20 mg/day. A total of 214 patients underwent intravascular ultrasound (IVUS) at baseline; 126 patients had analyzable IVUS images at the end of the study. The change in the serum low-density lipoprotein-cholesterol level from baseline to end of follow-up was -38.6 ±16.9%, whereas that of high-density lipoprotein-cholesterol was +19.8 ±22.9% (both P<0.0001). Percent change of plaque volume, the primary endpoint, was -5.1 ±14.1% (P<0.0001). Conclusions: Rosuvastatin exerted significant regression of coronary plaque volume in Japanese patients with stable CAD, including those who had previously used other lipid-lowering drugs. Rosuvastatin might be useful in the setting of secondary prevention in patients with stable CAD. (Circ J 2009; 73: 2110-2117)<br />出版者照会後に全文公開
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Daida, Hiroyuki ; Takayama, Tadateru ; Hiro, Takafumi ; Yamagishi, Masakazu ; Hirayama, Atsushi ; Saito, Satoshi ; Yamaguchi, Tetsu
概要:
Background: The incidence of cardiac events is higher in patients with diabetes than in people without diabetes. The Cor
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onary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects (COSMOS) demonstrated significant plaque regression in Japanese patients with chronic coronary disease after 76 weeks of rosuvastatin (2.5 mg once daily, up-titrated to a maximum of 20 mg/day to achieve LDL cholesterol <80 mg/dl).Methods: In this subanalysis of COSMOS, we examined the association between HbA1c and plaque regression in 40 patients with HbA1c ≥6.5% (high group) and 86 patients with HbA1c <6.5% (low group).Results: In multivariate analyses, HbA1c and plaque volume at baseline were major determinants of plaque regression. LDL cholesterol decreased by 37% and 39% in the high and low groups, respectively, while HDL cholesterol increased by 16% and 22%, respectively. The reduction in plaque volume was significantly (p = 0.04) greater in the low group (from 71.0 ± 39.9 to 64.7 ± 34.7 mm3) than in the high group (from 74.3 ± 34.2 to 71.4 ± 32.3 mm3). Vessel volume increased in the high group but not in the low group (change from baseline: +4.2% vs -0.8%, p = 0.02). Change in plaque volume was significantly correlated with baseline HbA1c.Conclusions: Despite similar improvements in lipid levels, plaque regression was less pronounced in patients with high HbA1c levels compared with those with low levels. Tight glucose control during statin therapy may enhance plaque regression in patients with stable coronary disease.Trial registration: ClinicalTrials.gov, Identifier NCT00329160. © 2012 Daida et al.; licensee BioMed Central Ltd.
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