論文 - 海北 幸一
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Onoue Y., Tsujita K., Hokimoto S., Kaikita K., Sugiyama S., Ogawa H.
Journal of Cardiology Cases 4 ( 3 ) e163 - e167 2011年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Cardiology Cases
Fibromuscular dysplasia (FMD) is one of the etiologies of renal artery stenosis (RAS) and secondary hypertension. Balloon angioplasty has emerged as the mainstay of treatment because patients with FMD usually show substantial clinical and anatomic response to renal angioplasty without stenting. We report a 21-year-old male case of FMD-induced RAS treated with intravascular ultrasound- and pressure gradient-guided renal angioplasty. Ultrasonic imaging of the stenotic renal artery clearly visualized adventitial fibrotic band surrounding the negative remodeled renal artery and the accompanying atherosclerotic plaque. The findings suggest that atherosclerotic change can occur in young patients with renal FMD that is basically considered to be nonatherosclerotic. Pressure gradient measurement is also useful in confirming hemodynamic improvement during angioplasty. © 2011 Japanese College of Cardiology.
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Passive exercise using whole-body periodic acceleration enhances blood supply to ischemic hindlimb 査読あり
Rokutanda T., Izumiya Y., Miura M., Fukuda S., Shimada K., Izumi Y., Nakamura Y., Araki S., Hanatani S., Matsubara J., Nakamura T., Kataoka K., Yasuda O., Kaikita K., Sugiyama S., Kim-Mitsuyama S., Yoshikawa J., Fujita M., Yoshiyama M., Ogawa H.
Arteriosclerosis, Thrombosis, and Vascular Biology 31 ( 12 ) 2872 - 2880 2011年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Arteriosclerosis, Thrombosis, and Vascular Biology
Objective-Whole-body periodic acceleration (WBPA) has been developed as a passive exercise technique to improve endothelial function by increasing shear stress through repetitive movements in spinal axis direction. We investigated the effects of WBPA on blood flow recovery in a mouse model of hindlimb ischemia and in patients with peripheral arterial disease. Methods and results-After unilateral femoral artery excision, mice were assigned to either the WBPA (n=15) or the control (n=13) group. WBPA was applied at 150 cpm for 45 minutes under anesthesia once a day. WBPA significantly increased blood flow recovery after ischemic surgery, as determined by laser Doppler perfusion imaging. Sections of ischemic adductor muscle stained with anti-CD31 antibody showed a significant increase in capillary density in WBPA mice compared with control mice. WBPA increased the phosphorylation of endothelial nitric oxide synthase (eNOS) in skeletal muscle. The proangiogenic effect of WBPA on ischemic limb was blunted in eNOS-deficient mice, suggesting that the stimulatory effects of WBPA on revascularization are eNOS dependent. Quantitative real-time polymerase chain reaction analysis showed significant increases in angiogenic growth factor expression in ischemic hindlimb by WBPA. Facilitated blood flow recovery was observed in a mouse model of diabetes despite there being no changes in glucose tolerance and insulin sensitivity. Furthermore, both a single session and 7-day repeated sessions of WBPA significantly improved blood flow in the lower extremity of patients with peripheral arterial disease. Conclusion-WBPA increased blood supply to ischemic lower extremities through activation of eNOS signaling and upregulation of proangiogenic growth factor in ischemic skeletal muscle. WBPA is a potentially suitable noninvasive intervention to facilitate therapeutic angiogenesis. © 2011 American Heart Association, Inc.
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Repetitive early stent thrombosis in a patient with the CYP2C19<sup>*</sup>3/<sup>*</sup>3 genotype 査読あり
Takashio S., Hokimoto S., Kaikita K., Fujimoto K., Misumi I., Nakagawa K., Ogawa H.
Journal of Cardiology Cases 4 ( 1 ) e16 - e19 2011年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Cardiology Cases
A 45-year-old man presented with acute inferior myocardial infarction and underwent emergent coronary angiography (CAG). CAG revealed total occlusion of both the proximal right coronary artery (RCA) and distal left circumflex artery, and two bare-metal stents were deployed in the RCA. After the procedure, dual antiplatelet therapy (DAT) with 100 mg aspirin and 75 mg clopidogrel daily were given as usual, however, stent thrombosis occurred three times and he underwent repeat interventions. To investigate the cause of repeated stent thrombosis, the platelet function during DAT was measured. The result showed that he did not achieve an adequate antiplatelet effect. Clopidogrel is a prodrug that requires biotransformation by cytochrome P450 (CYP) enzyme in the liver. Recently, the carriers of CYP2C19 2 or 3 null-of-function allele, have been shown to demonstrate an increased risk of cardiovascular events, including stent thrombosis, compared with non-carriers. This patient carried the CYP2C19 3/ 3 genotype. This is the first report of repetitive stent thrombosis in a poor metabolizer carrying two loss-of-function alleles (CYP2C19 3/ 3). © 2011 Japanese College of Cardiology. * * * * * *
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Enomoto K., Yamabe H., Toyama K., Matsuzawa Y., Yamamuro M., Uemura T., Morihisa K., Iwashita S., Kaikita K., Sugiyama S., Ogawa H.
Journal of Cardiology 58 ( 1 ) 69 - 73 2011年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Cardiology
Background and purpose: Cardiac resynchronization therapy (CRT) is a beneficial strategy to improve severe cardiac dysfunction in patients with congestive heart failure (CHF). The improvement of endothelial function in CHF patients treated with CRT is reflected in the mortality risk reduction. However the precise mechanisms of the relationship between CRT and vascular endothelial function have not been well discussed. Methods and subjects: Twenty-two severe consecutive CHF patients associated with dilated cardiomyopathy [New York Heart Association (NYHA) class 3.3 ± 0.5, left ventricular ejection fraction (LVEF) 24.4 ± 5.9%] were included in this study. We evaluated endothelial function, measured by reactive hyperemia peripheral arterial tonometry (RH-PAT), between optimal medical therapy alone group (medical therapy group: n = 10) and CRT group (n = 12) at the study enrolment and 12 weeks later. Furthermore we analyzed the association between the RH-PAT and cardiac function. Essential results: Both therapies significantly and equally improved NYHA class, LVEF, end-diastolic left ventricular dimension and plasma levels of brain natriuretic peptide (BNP). CRT significantly increased RH-PAT index (medical therapy group: 1.5 ± 0.2 to 1.5 ± 0.3, p = 0.824; CRT group: 1.4 ± 0.2 to 1.7 ± 0.4, p = 0.003) and cardiac output (medical therapy group: 3.3 ± 1.1 to 3.5 ± 1.0, p = 0.600; CRT group: 2.7 ± 0.6 to 4.3 ± 1.5, p = 0.001), compared to the medical therapy group. There was significant positive correlation between the change in RH-PAT index and cardiac output (r = 0.600, p = 0.003). Conclusions: CRT significantly improved endothelial function through the improvement of cardiac output in CHF patients, compared to optimal medical therapy. © 2011 Japanese College of Cardiology.
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Miyazaki Y., Kaikita K., Endo M., Horio E., Miura M., Tsujita K., Hokimoto S., Yamamuro M., Iwawaki T., Gotoh T., Ogawa H., Oike Y.
Arteriosclerosis, Thrombosis, and Vascular Biology 31 ( 5 ) 1124 - 1132 2011年5月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Arteriosclerosis, Thrombosis, and Vascular Biology
Objective- To investigate whether and how the endoplasmic reticulum (ER) stress-induced, CCAAT/enhancer-binding protein-homologous protein (CHOP)-mediated pathway regulates myocardial ischemia/reperfusion injury. Methods and Results- Wild-type and chop-deficient mice underwent 50 minutes of left coronary artery occlusion followed by reperfusion. Expression of chop and spliced x-box binding protein-1 (sxbp1) mRNA was rapidly and significantly increased in reperfused myocardium of wild-type mice. chop-deficient mice exhibited markedly reduced injury size after reperfusion compared with wild-type mice, accompanied by a decreasing number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cardiomyocytes. Interestingly, myocardial inflammation, as assessed by expression of inflammatory cytokines and chemokines and numbers of infiltrated inflammatory cells, was also attenuated in chop-deficient mice. Moreover, expression of interleukin-6 mRNA in response to lipopolysaccharide was enhanced by simultaneous stimulation with thapsigargin, a potent ER stressor, in wild-type cardiomyocytes but not in chop-deficient cardiomyocytes. Finally, we found that superoxide was produced in reperfused myocardium and that intravenous administration of edaravone, a free radical scavenger, immediately before reperfusion significantly suppressed the superoxide overproduction and subsequent expression of sxbp1 and chop mRNA, followed by reduced injury size in wild-type mice. Conclusion- The ER stress-induced, CHOP-mediated pathway, which is activated in part by superoxide overproduction after reperfusion, exacerbates myocardial ischemia/reperfusion injury by inducing cardiomyocyte apoptosis and myocardial inflammation. Copyright © 2011 American Heart Association. All rights reserved.
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Hypercholesterolemia and hypoadiponectinemia are associated with necrotic core-rich coronary plaque 査読あり
Kojima S., Kojima S., Maruyoshi H., Nagayoshi Y., Kaikita K., Sumida H., Sugiyama S., Funahashi T., Ogawa H.
International Journal of Cardiology 147 ( 3 ) 371 - 376 2011年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Cardiology
Background: Hypercholesterolemia is a risk factor for coronary artery disease and closely linked to unstable plaque. Hypoadiponectinemia is frequently observed in patients with metabolic syndrome complicated with macroangiopathy and predicts poor clinical outcome. Spectral analysis of intravascular ultrasonography radiofrequency (IVUS-Virtual Histology [VH]) allows quantitative analysis of plaque composition. The purpose of this study was to verify the effects of low-density lipoprotein (LDL) cholesterol level on plaque morphology, and test the hypothesis that adiponectin influences coronary plaque volume and composition. Methods: Preintervention IVUS-VH using a continuous pullback was performed in 92 coronary vessels in 92 patients with coronary artery disease. The morphological distribution of plaque was evaluated prospectively in a 60-mm segment of coronary vessels containing the culprit lesion. Results: Serum LDL cholesterol levels correlated positively with necrotic core volume (r = 0.217, P = 0.037) and percent necrotic core tissue (r = 0.308, P = 0.003), while plasma adiponectin levels correlated negatively with plaque volume (r = - 0.297, P = 0.004) and necrotic core volume (r = - 0.306, P = 0.003). Multiple regression analyses showed close association between necrotic core volume and statin-use (β = - 21.68, P = 0.004) and adiponectin levels (β = - 31.25, P = 0.038), and that percent necrotic core tissue was influenced by statin-use (β = - 4.595, P = 0.026) and LDL cholesterol levels (β = 0.092, P = 0.031). Conclusions: Adiponectin is closely linked to coronary plaque volume. Hypercholesterolemia and hypoadiponectinemia correlate with necrotic core lesions and may contribute to increased risk of coronary plaque vulnerability. Statins can affectively prevent necrotic core plaque formation associated with hypercholesterolemia and hypoadiponectinemia. © 2009 Elsevier Ireland Ltd. All rights reserved.
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Yamamoto K., Hokimoto S., Chitose T., Morita K., Ono T., Kaikita K., Tsujita K., Abe T., Deguchi M., Miyagawa H., Saruwatari J., Sumida H., Sugiyama S., Nakagawa K., Ogawa H.
Journal of Cardiology 57 ( 2 ) 194 - 201 2011年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Cardiology
Background and purpose: CYP2C19*2 loss-of-function allele in Caucasians may be associated with wide interindividual variability in platelet response to clopidogrel, and the incidence of gene mutation varies with racial differences, especially between Asians and Caucasians. The aim was to examine the impact of CYP2C19 genotype on the residual platelet reactivity in Japanese patients with coronary heart disease (CHD) during antiplatelet therapy. Methods and results: We measured the CYP2C19 genotype and platelet aggregation in 201 patients with stable CHD. Moreover, we examined the relation of CYP2C19 polymorphism to cardiovascular events in 98 patients treated with stent implantation. The distribution of CYP2C19 genotype was 37%, 33%, 11%, 11%, 7%, and 1% in CYP2C19*1/*1, *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3, respectively. Residual platelet reactivity was lower in patients during dual antiplatelet therapy (DAT) than in those with aspirin (3975±1569 aggregation units. minute (AU min) vs 5850±938 AU min, p<0.05). In the DAT group, the platelet reactivity decreased significantly in the wild-type homozygotes (CYP2C19*1/*1), subsequently in the *2, or *3 heterozygotes (*1/*2, *1/*3), and was not well inhibited in the *2, and/or *3 homozygotes (*2/*2, *2/*3, *3/*3; 3194±1570 AU min, 4148±1400 AU min, and 5088±1080 AU min, respectively). However, when the duration of DAT was used to divide subjects into 2 groups, <7 days, and >7 days, patients carrying the variant allele showed significantly decreased platelet reactivities at >7 days compared with those at <7 days. Moreover, the incidence of cardiovascular events was higher in patients carrying at least one variant allele than in wild-type homozygotes. Conclusions: CYP2C19 polymorphism may be associated with high residual platelet reactivity and the occurrence of cardiovascular events. © 2011 Japanese College of Cardiology.
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Matsubara J., Sugiyama S., Nozaki T., Sugamura K., Konishi M., Ohba K., Matsuzawa Y., Akiyama E., Yamamoto E., Sakamoto K., Nagayoshi Y., Kaikita K., Sumida H., Kim-Mitsuyama S., Ogawa H.
Journal of the American College of Cardiology 57 ( 7 ) 861 - 869 2011年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of the American College of Cardiology
Objectives: This study investigated the clinical significance of plasma pentraxin 3 (PTX3) levels in patients with heart failure with normal ejection fraction (HFNEF) and whether PTX3 is produced from coronary circulation. Background: Pentraxin 3 is a novel inflammatory marker and a member of pentraxin superfamily including C-reactive protein (CRP). The relationship between inflammatory markers and HFNEF remains unclear. Methods: We measured peripheral blood levels of PTX3, high-sensitivity CRP, tumor necrosis factor-alpha, and interleukin-6 in 323 patients comprising 82 HFNEF, 70 heart failure (HF) with reduced EF, and 171 non-HF patients. Levels of PTX3 were also measured at the aortic root and the coronary sinus in 75 patients. Results: The levels of PTX3, tumor necrosis factor-alpha, and interleukin-6, but not high-sensitivity CRP, were significantly higher in HFNEF patients than in non-HF patients. Multivariate logistic regression analysis identified only high levels of PTX3 as the independent inflammatory marker correlated with the presence of HFNEF in patients with normal left ventricular (LV) EF (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.11 to 1.98, p < 0.01) and with the presence of left ventricular diastolic dysfunction (LVDD) in non-HF patients (OR: 1.23, 95% CI: 1.02 to 1.50, p < 0.05). Levels of PTX3 at the coronary sinus were significantly higher than at the aortic root in HFNEF patients (p < 0.05) and in non-HF patients with LVDD (p < 0.01), but not different in non-HF patients without LVDD (p = 0.33). Conclusions: Pentraxin 3 is significantly elevated in HFNEF patients and produced in the coronary circulation in patients with LVDD. Pentraxin 3, but not high-sensitivity CRP, is an independent inflammatory marker correlated with the presence of LVDD and HFNEF. (The Clinical Significance of Plasma Pentraxin 3 levels for Patients with Diastolic Heart Failure; UMIN000002170) © 2011 American College of Cardiology Foundation.
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Long-term use of oral nicorandil stabilizes coronary plaque in patients with stable angina pectoris 査読あり
Izumiya Y., Kojima S., Kojima S., Araki S., Usuku H., Matsubara J., Sakamoto K., Tsujita K., Nagayoshi Y., Kaikita K., Sugiyama S., Ogawa H.
Atherosclerosis 214 ( 2 ) 415 - 421 2011年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Atherosclerosis
Objective: The Impact of Nicorandil in Angina (IONA) trial demonstrated that the use of nicorandil, an anti-anginal drug, reduced future cardiovascular events in patients with stable angina. We hypothesized that nicorandil has beneficial effects on coronary arterial plaque characteristics and atherosclerogenesis. Methods and Results: Preintervention intravascular ultrasound-virtual histology was performed prospectively in 65 consecutive patients with stable angina pectoris. There were no differences in coronary risk factors between the nicorandil (n = 16) and non-nicorandil (n = 49) groups. However, the nicorandil group demonstrated a larger %fibrous tissue (68 ± 10 vs. 62 ± 11%, P = 0.049) and a smaller %necrotic core tissue (11 ± 7 vs. 16 ± 10%, P = 0.049) compared with the non-nicorandil group. Multiple regression analysis showed that %necrotic core tissue (P = 0.045) was negatively and %fibrous tissue (P = 0.026) was positively associated with the use of nicorandil independent of statin use. We also analyzed the effect of nicorandil on atherosclerotic lesion formation in a mouse model of atherosclerosis. Lipid profiles were unaffected, but the area of atherosclerotic lesion and plaque necrosis were significantly reduced following 8-week nicorandil treatment in ApoE-deficient mice fed an atherogenic diet. Nicorandil significantly reduced the expression levels of endoplasmic reticulum stress markers, C/EBP homologous protein (CHOP) and glucose regulated protein/BiP (GRP78) in atherosclerotic lesions. Nicorandil significantly attenuated tunicamycin-induced CHOP upregulation in cultured THP-1 macrophages. Conclusions: Nicorandil exerts its anti-atherogenic effect by mechanisms different from those of statins. Long-term nicorandil treatment is a potentially suitable second-line prevention therapy for patients with coronary artery disease. © 2010 Elsevier Ireland Ltd.
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Double-blind, placebo-controlled phase II studies of the protease-activated receptor 1 antagonist E5555 (atopaxar) in Japanese patients with acute coronary syndrome or high-risk coronary artery disease 査読あり
Goto S＊, Ogawa H, Takeuchi M, Flather MD, Bhatt DL; J-LANCELOT (Japanese-Lesson from Antagonizing the Cellular Effect of Thrombin) Investigators (including Kaikita K)
European Heart Journal 31 2601 - 2613 2010年8月
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Waveform of ophthalmic artery doppler flow predicts the severity of systemic atherosclerosis 査読あり
Maruyoshi H., Kojima S., Kojima S., Nagayoshi Y., Horibata Y., Kaikita K., Sugiyama S., Ogawa H.
Circulation Journal 74 ( 6 ) 1251 - 1256 2010年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Circulation Journal
Background: Doppler imaging of ophthalmic artery (OA), the first major branch of the internal carotid artery, provides anatomical advantages due to the vertical angle to the body surface and absence of ultrasonic obstacles. It was hypothesized that the Doppler waveform indices of OA correlate with severity of systemic atherosclerosis. Methods and Results: The study subjects were 180 patients who underwent cardiac catheterization and OA Doppler imaging (90 patients with coronary artery disease (CAD) and 90 control patients). The ratio of stroke volume to pulse pressure, an index of arterial compliance, was closely associated with the ratio of systolic to diastolic mean velocity (Sm/Dm) in OA. The level of Sm/Dm increased in proportion with the increase in number of stenosed coronary arteries (0-vessel disease 2.1±0.3, 1-vessel disease 2.3±0.3, multi-vessel disease 2.6±0.5, P<0.0001). The Sm/Dm level in OA correlated positively with age, pulse pressure, pulse wave velocity, resistive index and pulsatility index in OA. The best Sm/Dm cut-off to predict CAD was 2.3, and patients with Sm/Dm >2.3 had 8.0-fold risk for CAD. Conclusions: The waveform indices of OA are clinically useful for evaluating the severity of CAD and may help explain the missing link between OA circulation and systemic arterial compliance.
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循環器疾患
三浦光年, 海北幸一, 小川久雄
臨牀と研究 87 ( 6 ) 766 - 770 2010年6月
掲載種別：研究論文（学術雑誌）
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Digital Assessment of Endothelial Function and Ischemic Heart Disease in Women 査読あり
Matsuzawa Y., Sugiyama S., Sugamura K., Nozaki T., Ohba K., Konishi M., Matsubara J., Sumida H., Kaikita K., Kojima S., Nagayoshi Y., Yamamuro M., Izumiya Y., Iwashita S., Matsui K., Jinnouchi H., Kimura K., Umemura S., Ogawa H.
Journal of the American College of Cardiology 55 ( 16 ) 1688 - 1696 2010年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of the American College of Cardiology
Objectives: We investigated the utility of digital reactive hyperemia peripheral arterial tonometry (RH-PAT) in predicting ischemic heart disease (IHD), including obstructive coronary artery disease (CAD) and nonobstructive coronary artery disease (NOCAD), in women. Background: IHD is the leading cause of mortality, and its pathogenesis is diverse in women. Fingertip RH-PAT is a new device that provides noninvasive, automatic, and quantitative evaluation of endothelial dysfunction. Methods: RH-PAT was measured using Endo-PAT2000 (Itamar Medical, Caesarea, Israel) before cardiac catheterization in 140 stable women scheduled for hospitalization to examine chest pain. NOCAD was diagnosed by angiography with measurement of coronary blood flow and cardiac lactate production during intracoronary acetylcholine provocation test and cardiac scintigraphy with stress tests. Results: Sixty-eight women (49%) had obstructive CAD and 42 women (30%) had NOCAD. RH-PAT indexes were significantly attenuated in both obstructive CAD and NOCAD as compared with non-IHD (n = 30) (obstructive CAD: median 1.57, interquartile range [IQR] 1.42 to 1.76; NOCAD: median 1.58, IQR 1.41 to 1.78; non-IHD: median 2.15, IQR 1.85 to 2.48, p < 0.001). By multivariate logistic regression analysis, only RH-PAT index was significantly associated with IHD, including obstructive CAD and NOCAD (odds ratio 0.51; 95% confidence interval: 0.38 to 0.68; p < 0.001). In receiver-operating characteristic analysis, RH-PAT index was a significant predictor of IHD (area under the curve 0.86; p < 0.001). Furthermore, only RH-PAT was useful for the prediction of NOCAD after excluding obstructive CAD (area under the curve 0.85; p < 0.001; RH-PAT index of <1.82 had 81% sensitivity and 80% specificity). Conclusions: RH-PAT indexes were significantly attenuated in women with IHD. Digital RH-PAT can predict patients with IHD, especially NOCAD before angiography. RH-PAT is potentially useful for identifying high-risk women for IHD. (Endothelial Dysfunction and Coronary Artery Spasm; NCT00619294). © 2010 American College of Cardiology Foundation.
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Miura M., Kaikita K., Matsukawa M., Soejima K., Fuchigami S., Miyazaki Y., Ono T., Uemura T., Tsujita K., Hokimoto S., Sumida H., Sugiyama S., Matsui K., Yamabe H., Ogawa H.
Thrombosis and Haemostasis 103 ( 3 ) 623 - 629 2010年3月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Thrombosis and Haemostasis
High plasma level of von Willebrand factor (VWF) is a marker of future cardiovascular events in patients at high risk of coronary artery disease (CAD). The purpose of this study was to examine the changes and the prognostic value of plasma VWF-cleaving protease (ADAMTS13) levels in patients with CAD. Plasma VWF and ADAMTS13 levels were measured in 225 patients with CAD (152 men and 73 women, age, 70.3 ± 8.9 years, mean ± SD) and 100 patients without CAD who were age-and gender-matched to the CAD patients (60 men and 40 women, age, 68.6 ± 8.9 years). The CAD patients had higher VWF and lower ADAMTS13 antigen levels compared to patients without CAD. During 22.3 ± 10.4 months follow-up period, 20 major adverse cardiac and cerebrovascular events (MACCE) occurred in 222 patients with CAD who could be followed up. Kaplan-Meier analysis demonstrated that CAD patients with high plasma VWF antigen levels were significantly more likely to develop MACCE. Furthermore, eight cardiac and cerebrovascular thrombotic events [acute coronary syndrome (n=4) and cerebral infarction (n=4)] occurred in CAD patients with both high plasma VWF and low ADAMTS13 antigen levels. Multivariate Cox hazards regression analysis identified high plasma VWF and low ADAMTS13 antigen levels as significant and independent predictors of future MACCE and thrombotic events during the follow-up period in CAD patients. Our findings suggest that low plasma ADAMTS13 as well as high VWF level is a useful predictor of cardiac and cerebrovascular events in CAD patients. © Schattauer 2010.
DOI： 10.1160/TH09-08-0568
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Arima Y., Kojima S., Kusuhara K., Nagayoshi Y., Kawano H., Kaikita K., Sugiyama S., Kinoshita Y., Ogawa H.
Journal of Cardiology Cases 1 ( 1 ) e45 - e48 2010年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Cardiology Cases
A 76-year-old woman with a diagnosis of dilated-phase hypertrophic cardiomyopathy was admitted to our hospital for exacerbation of congestive heart failure. After admission, she developed cardiac arrest and the electrocardiogram showed pulseless electrical activity. Cardiopulmonary resuscitation was started immediately; however, return of spontaneous circulation was achieved 56 min after cardiopulmonary arrest. Therapeutic hypothermia was considered as an adjunct therapy, together with intensive treatment. The target temperature of 33.0 °C was achieved 10 h after cardiopulmonary arrest. Core temperature was maintained between 33.0 and 35.0 °C for 72 h with no cardiac arrhythmia detected during this period. Re-warming was initiated at a rate of 1 °C/day. On day 6, the core temperature returned to 37 °C and recovery of consciousness was achieved on day 9. No impairment of neurological function was noted. She had no heart failure-related symptoms and B-type natriuretic peptide level decreased from 4174 pg/mL on admission to 450 pg/mL at discharge. Therapeutic hypothermia may be a promising post-resuscitation therapy for comatose survivors of in-hospital cardiac arrest with non-ventricular fibrillation leading to improvement in neurological outcome. © 2009 Japanese College of Cardiology.
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Clinical factors affecting serum potassium concentration in cardio-renal decompensation syndrome 査読あり
Ueno H., Yoshimura M., Nakayama M., Yamamuro M., Nishijima T., Kusuhara K., Nagayoshi Y., Kojima S., Kaikita K., Sumida H., Sugiyama S., Ogawa H.
International Journal of Cardiology 138 ( 2 ) 174 - 181 2010年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Cardiology
Background: Renin-angiotensin-aldosterone system (RAAS) inhibitors are currently indispensable for the treatment of heart failure. It is well known that hyperkalemia is likely to occur in renal failure; however, it has not yet been clarified how the serum potassium concentration changes as heart failure progresses. Currently, the cardio-renal decompensation syndrome holds that the serum potassium concentration is altered similarly by both heart failure and renal failure; however, there are no definitive reports on this. In order to use RAAS inhibitors more safely and effectively in heart failure, it is necessary to understand the factors affecting serum potassium concentration in the clinical setting. Methods and results: We examined the clinical factors affecting serum potassium concentration in 1035 consecutive patients with cardiovascular disease who were hospitalized in our institution. Multiple regression analysis showed that the independent factors associated with an elevated serum potassium concentration were renal insufficiency evaluated by estimated glomerular filtration rate (eGFR) (P < 0.0001), diabetes mellitus evaluated by HbA (P = 0.0005) and the use of RAAS inhibitors (P = 0.0010). The independent factors associated with a decreased serum potassium concentration were mean blood pressure (P < 0.0001), heart failure evaluated by log BNP (P = 0.0164) and the use of diuretics (P = 0.0232). Conclusions: The serum potassium concentration decreases with the severity of heart failure if renal function is preserved. From the perspective of potassium homeostasis, we could use the RAAS inhibitors more aggressively in patients with heart failure who do not have renal failure. © 2008 Elsevier Ireland Ltd. All rights reserved. 1c
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Cannabinoid 1 receptor blockade reduces atherosclerosis with enhances reverse cholesterol transport 査読あり
Sugamura K., Sugiyama S., Fujiwara Y., Matsubara J., Akiyama E., Maeda H., Ohba K., Matsuzawa Y., Konishi M., Nozaki T., Horibata Y., Kaikita K., Sumida H., Takeya M., Ogawa H.
Journal of Atherosclerosis and Thrombosis 17 ( 2 ) 141 - 147 2010年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Atherosclerosis and Thrombosis
Aim: A recent clinical study using coronary intravascular ultrasound showed that rimonabant, a cannabinoid 1 (CB1) receptor antagonist, significantly reduced total atheroma volume, suggesting that CB1 receptor blockade could be beneficial in anti-atherogenic therapy. The reverse cholesterol transport (RCT) system plays important roles in atherogenesis. We investigated whether CB1 receptor blockade could modulate atherogenesis in mice. Methods and Results: Oral administration of rimonabant (8 mg/kg/day) to apolipoprotein E-deficient mice for 3 months significantly reduced the relative area of atherosclerotic lesions in the aorta (vehicle; 12.6 ± 4.0% vs. rimonabant; 9.7 ± 2.3, n = 12 each, p < 0.05) with an increase in serum adiponectin levels (15.6 ± 2.3 μg/mL vs. 12.2 ± 2.1, n = 12 each, p < 0.001), without affecting body weight or serum cholesterol levels. Rimonabant tended to increase serum high-density lipoprotein cholesterol (HDL-C) (p = 0.05). The relative area of atherosclerotic lesions in the aorta correlated inversely with serum HDL-C levels (r = -0.45, n = 24, p < 0.05). Rimonabant upregulated the mRNA expression levels of various components of the RCT system on THP-1 cell-derived macrophages (scavenger receptor B1: 1.15 ± 0.12 fold, n = 6; p < 0.05, ATP-binding cassette [ABC] transporter G1: 1.23 ± 0.11 fold, n = 6; p < 0.01), but not ABCA1 (1.13 ± 0.20 fold, n = 6; p = 0.13). Conclusion: CB1 receptor blockade reduced atherosclerosis in apoE-deficient mice through an increase in serum adiponectin levels and activation of the RCT system. CB1 receptor blockade may be therapeutically beneficial for atherogenesis by increasing the serum adiponectin level and enhancing of the RCT system.
DOI： 10.5551/jat.2865
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Standard-dose statin therapy provides incremental clinical benefits in normocholesterolemic diabetic patients 査読あり
Kojima S＊, Sakamoto T, Ogawa H, Kitagawa A, Matsui K, Shimomura H, Kimura K, Ogata Y, Sakaino N; multicenter study for aggressive lipid-lowering strategy by HMG-CoA reductase inhibitors investigators (including Kaikita K)
Circulation Journal 74 ( 4 ) 779 - 785 2010年
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Nakamura Y., Yamada Y., Shimomura H., Nagayoshi Y., Tsujita K., Yamashita T., Fukuda M., Ohba K., Nako H., Ogura Y., Chitose T., Yamaguchi M., Nagata T., Soejima H., Kaikita K., Sugiyama S., Ogawa H.
Journal of Cardiology 54 ( 3 ) 416 - 424 2009年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Cardiology
Background: Monocyte chemoattractant protein-1 (MCP-1) plays an important role in the pathogenesis of acute coronary syndrome. We have recently demonstrated that the administration of edaravone before reperfusion attenuated reperfusion injury in patients with acute myocardial infarction (AMI). Methods: Plasma MCP-1 levels were measured in 45 consecutive patients with AMI (edaravone group, n = 25; control group, n = 20). In the edaravone group, 30 mg edaravone was intravenously infused just before reperfusion. Plasma samples were obtained before and at 24 h, 3, 5, 7, and 14 days after reperfusion. Cardiovascular events were defined as cardiac death, subacute thrombosis, or fatal arrhythmia. Heart failure requiring rehospitalization was evaluated at 12 months after reperfusion. Results: Plasma MCP-1 levels were not different between the two groups before reperfusion. Compared with the placebo group, the edaravone group had statistically lower maximum creatine kinase-MB levels (218 ± 31 IU/l versus 145 ± 21 IU/l, p < 0.05) and plasma MCP-1 levels on day 3 after reperfusion (873 ± 118 pg/ml versus 516 ± 66 pg/ml, p < 0.05). Heart failure requiring rehospitalization occurred in four patients in the control group, but did not occur in the edaravone group (p < 0.05). At 12 months after reperfusion, left ventricular ejection fraction was statistically higher in the edaravone group than in the control group (62 ± 2% versus 54 ± 3%, p < 0.05). Conclusion: Edaravone suppressed plasma MCP-1, improved left ventricular ejection fraction, and reduced rehospitalization due to heart failure. Suppression of plasma MCP-1 level by edaravone might induce better prognosis for AMI patients. © 2009 Japanese College of Cardiology.
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Nagayoshi Y., Kawano H., Hokamaki J., Uemura T., Soejima H., Kaikita K., Sugiyama S., Yamabe H., Shioji I., Sasaki S., Kuroda Y., Ogawa H.
Free Radical Research 43 ( 12 ) 1159 - 1166 2009年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Free Radical Research
Various oxidative stress markers have been measured to evaluate the status of heart failure (HF). However, the relationships between these markers and the aetiology of HF have not been fully investigated. This study compared 8-hydroxy-2′-deoxyguanosine (8-OHdG) and biopyrrins levels in patients with ischemic and non-ischemic HF. Study subjects were divided into a coronary artery disease (CAD) group (n70), a non-CAD group (n61) and a control group (n33). In the CAD group, 8-OHdG and biopyrrins levels increased with the severity of the New York Heart Association (NYHA) functional class and log BNP levels correlated with 8-OHdG and biopyrrins levels. However, non-CAD patients with NYHA class III/IV had significantly lower 8-OHdG levels than CAD patients with NYHA class III/IV and the levels did not correlate with log BNP levels. In the CAD group, 8-OHdG levels reflected the severity of atherosclerosis. These results indicate that the properties of oxidative stress markers should be carefully taken into consideration for the assessment of HF status.