Akira Kitabatake

Publications (161)581.55 Total impact

• Article: Minimal dose for effective clinical outcome and predictive factors for responsiveness to carvedilol: Japanese chronic heart failure (J-CHF) study.

  Hiroshi Okamoto, Masatsugu Hori, Masunori Matsuzaki, Hiroyuki Tsutsui, Tsutomu Yamazaki, Ryozo Nagai, Tsutomu Yoshikawa, Yasushi Fujio, Shinpei Nonen, Junichi Azuma, Tohru Izumi, Yasuo Ohashi, Akira Kitabatake
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  ABSTRACT: BACKGROUND: In chronic heart failure (CHF), it remains unclear whether the minimal dose of beta-blockade is related to survival benefits and which parameter predicts morbidity and mortality. We sought to determine the minimal dose related to survival benefits by comparing the efficacy and safety of three doses of carvedilol and the best predictive parameter for effective outcomes in Japanese patients with CHF. METHODS: In this prospective, randomized, stratified trial, 364 patients with mild to moderate CHF were assigned to a daily carvedilol dose of 2.5, 5, or 20mg, plus optimal standard therapy. FINDINGS: During the mean 3-year follow-up, resting heart rate (HR) and BNP were significantly reduced with dose-response relations in the early period but without dose-response relations in the late period. The LVEF and the LVDd were increased and decreased, respectively, without a dose-response relation. No significant difference was seen in the composite primary endpoint of all-cause mortality and hospitalization for cardiovascular diseases and heart failure. Multivariate analysis indicated early decreases in HR and BNP predicted long-term outcomes. However, adverse events increased dose-dependently. Among 237 polymorphisms in 87 heart failure-related genes, the osteopontin G-156 del genotype was associated with an event-free survival rate (Wilcoxon test, P=0.030). CONCLUSIONS: A low carvedilol dose is effective if the HR and/or plasma BNP has been reduced. Carvedilol therapy should be guided by reductions in HR and/or BNP, especially by initial HR reduction, but not only by its dose. OPN might be a surrogate genetic marker for long-term event-free survival.
  International journal of cardiology 12/2012; · 7.08 Impact Factor
• Article: The change in low-density lipoprotein cholesterol concentration is positively related to plasma docosahexaenoic acid but not eicosapentaenoic acid.

  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
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  ABSTRACT: The Japan EPA Lipid Intervention Study (JELIS) reported a 19% reduction of the risk for coronary artery disease after long-term use of pure eicosapentaenoic acid (EPA) in Japanese patients with hypercholesterolemia. The variation in plasma fatty acid composition influenced the risk of coronary events. The aim of this study was to examine in JELIS participants the possible correlation of changes in plasma fatty acids with those of serum lipids. The coefficient for the correlation between the absolute change in plasma fatty acid concentrations and the changes in serum lipids was calculated in 13,901 JELIS participants. Low-density lipoprotein (LDL) cholesterol exhibited a positive correlation with docosahexaenoic acid (DHA; r=0.117 in control group, r=0.155 in EPA group) and linoleic acid (r=0.139 in control group, r=0.177 in EPA group), but the correlation coefficients with EPA (r=0.097 in control group, r=-0.032 in EPA group) were less than 0.1. We distributed the patients into 9 groups according to tertiles of the change in EPA and DHA. The average absolute decrease of LDL cholesterol and L/H ratio in each group was significantly smaller (p<0.001) in the DHA-high tertile, but not in any EPA tertile. The changes in DHA, but not in EPA, showed a positive correlation with the changes in LDL-cholesterol.
  Journal of atherosclerosis and thrombosis 05/2012; 19(7):673-9. · 2.69 Impact Factor
• Article: Doppler echocardiography in diastology: 35 years of Japanese contribution to its advancement and utility

  Satoshi Nakatani, Taisei Mikami, Akira Kitabatake
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  ABSTRACT: Echocardiography is one of the most important and clinically useful techniques in the assessment of diastolic function. Because of the prevalence of this technique, “diastology” and even the concept of diastolic heart failure have become familiar to researchers and physicians. We believe the first description by Kitabatake and his colleagues in 1982 of the use of Doppler technique to assess the transmitral flow velocity pattern in various cardiac diseases was the beginning of this development. Since then, a number of excellent works regarding echocardiographic assessment of diastolic function have emerged from Japan. Here, we review the Japanese contributions to the development of the use of Doppler echocardiography in diastology. KeywordsDoppler–Diastole–Transmitral flow–Diastology
  Journal of Echocardiography 04/2012; 9(1):1-8.
• Article: Measuring medium-sized muscular arteries using a novel broadband 15-MHz linear array probe

  Satoshi Yamada, Taisei Mikami, Keiko Nishihara, Tsuyoshi Mitake, Mikio Izumi, Naohiro Yoshida, Akihiko Hanaoka, Di Wu, Kaoru Komuro, Hisao Onozuka, Satoshi Fujii, Akira Kitabatake
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  ABSTRACT: We recently developed a wideband 15-MHz linear array probe (15 M) with a band width of 8 MHz (9–17 MHz). Both axial and lateral resolution of 15 M, evaluated using a phantom model, were better than those of the current 10-MHz linear probe. To compare interobserver variability in measurement of medium-sized muscular arteries acquired using a 7.5-MHz linear probe (7.5 M), a 10-MHz linear probe (10M) and 15 M, two observers independently acquired images of the brachial and radial arteries, and measured the diameter and intima-media thickness (IMT) of those arteries in 17 male volunteers. Intraobserver variability in determining percent flowmediated dilatation (%FMD) was assessed in the same subjects using 15 M. Coefficients of variation (CV) in arteries measured using 7.5 M, 10 M, and 15 M were 7.0%, 2.5%, and 1.5%, respectively, for the diameter of the brachial artery; 10.3%, 5.8%, and 3.2%, respectively, for the diameter of the radial artery; and 17.0%, 13.8%, and 8.5%, respectively, for IMT of the far wall of the brachial artery. The CV of measurement of %FMD was 4.6%. The new 15-MHz probe thus warrants use in evaluating morphology and function of muscular arteries of medium size.
  Journal of Medical Ultrasonics 04/2012; 30(3):177-185. · 0.33 Impact Factor
• Article: Relationship between coronary artery disease and non-HDL-C, and effect of highly purified EPA on the risk of coronary artery disease in hypercholesterolemic patients treated with statins: sub-analysis of the Japan EPA Lipid Intervention Study (JELIS).

  Jun Sasaki, Mitsuhiro Yokoyama, Masunori Matsuzaki, Yasushi Saito, Hideki Origasa, Yuichi Ishikawa, Shinichi Oikawa, Hiroshige Itakura, Hitoshi Hishida, Toru Kita, Akira Kitabatake, Noriaki Nakaya, Toshiie Sakata, Kazuyuki Shimada, Kunio Shirato, Yuji Matsuzawa
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  ABSTRACT: The present study examined the importance of reducing non-high-density lipoprotein cholesterol (non-HDL-C) for the primary prevention of the occurrence of coronary artery disease (CAD) in the JELIS, and the effects of EPA. The patients were distributed into 4 subgroups using the lipid management goal for LDL-C recommended by the Japan Atherosclerosis Society guideline (2007) and the goal for non-HDL-C defined as 30 mg/dL higher than LDL-C: A) achieved both goals; B) achieved the LDL-C but not non-HDL-C goal; C) achieved the non-HDL-C but not LDL-C goal; and D) did not attain either goal. The incidences of CAD in the 4 subgroups were compared, and the effects of eicosapentaenoic acid (EPA) on the risk of CAD in these subgroups were examined. In the non-EPA group, the incidence of CAD in patients who did not achieve the goals for LDL-C or non-HDL-C was higher than in patients who achieved those goals. Patients in subgroups B, C, and D were at higher risk for CAD than those in subgroup A (B, HR 2.31; C, HR 1.90; D, HR 2.47). EPA reduced the risk of CAD by 38% in subgroups B, C, and D (p= 0.007). We reconfirmed non-HDL-C as a predictor of the risk for CAD and a residual risk marker of CAD after LDL-C-lowering therapy. EPA was useful to reduce the occurrence of CAD in patients who did not achieve the goals for LDL-C and/or non-HDL-C.
  Journal of atherosclerosis and thrombosis 12/2011; 19(2):194-204. · 2.69 Impact Factor
• Article: Relationships between plasma fatty acid composition and coronary artery disease.

  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
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  ABSTRACT: 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. 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. 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. 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.
  Journal of atherosclerosis and thrombosis 11/2010; 18(2):99-107. · 2.69 Impact Factor
• Article: Preventive effects of eicosapentaenoic acid on coronary artery disease in patients with peripheral artery disease.

  Yuichi Ishikawa, Mitsuhiro Yokoyama, Yasushi Saito, Masunori Matsuzaki, Hideki Origasa, Shinichi Oikawa, Jun Sasaki, Hitoshi Hishida, Hiroshige Itakura, Toru Kita, Akira Kitabatake, Noriaki Nakaya, Toshiie Sakata, Kazuyuki Shimada, Kunio Shirato, Yuji Matsuzawa
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  ABSTRACT: The JELIS trial examined the preventive effects of eicosapentaenoic acid (EPA) on coronary artery disease (CAD) in hypercholesterolemia. Previous investigators have reported that patients with peripheral artery disease (PAD) have a poor prognosis due to the potential risk for CAD. We conducted a subanalysis to examine whether the incidence of CAD was high in patients with PAD and whether EPA prevented the occurrence of CAD. Of 18,645 the Japan EPA lipid intervention study (JELIS) patients, 223 had PAD (control group; complicated (n=77), newly diagnosed (n=29), EPA group; complicated (n=96), newly diagnosed (n=21)). We analyzed the incidence of major coronary events (MCE) in the 2 groups. Cox proportional hazard ratio adjusted for baseline risk factor levels was used to test differences between the 2 groups. The incidence of MCE in the control group was significantly higher in patients complicated with PAD and in those newly diagnosed with PAD than in patients without PAD (complicated: hazard ratio 1.97, P=0.039; newly diagnosed: hazard ratio 2.88, P=0.030). As for patients with PAD, the EPA group had a significantly lower MCE hazard ratio than the control group (hazard ratio 0.44, 95% confidence interval 0.19-0.97, P=0.041). Subanalysis of the JELIS trial demonstrated that in patients with PAD the incidence of CAD was higher than in controls, and that EPA markedly reduced the occurrence of CAD in those patients.
  Circulation Journal 07/2010; 74(7):1451-7. · 3.77 Impact Factor
• Article: Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease.

  Masunori Matsuzaki, Mitsuhiro Yokoyama, Yasushi Saito, Hideki Origasa, Yuichi Ishikawa, Shinichi Oikawa, Jun Sasaki, Hitoshi Hishida, Hiroshige Itakura, Toru Kita, Akira Kitabatake, Noriaki Nakaya, Toshiie Sakata, Kazuyuki Shimada, Kunio Shirato, Yuji Matsuzawa
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  ABSTRACT: Results from JELIS (Japan EPA Lipid Intervention Study) demonstrated the efficacy of pure eicosapentaenoic acid (EPA) in preventing coronary artery disease (CAD) in hypercholesterolemic patients under statin treatment. The present study examined in detail whether EPA is effective for the secondary prevention of CAD. Patients with established CAD and a total cholesterol level > or =250 mg/dl were observed with a mean follow-up of 4.6 years. They were randomly assigned to receive either 1,800 mg of EPA + statin (EPA group) or statin alone (control group). The incidence of major coronary events (MCE) were compared in the 2 groups. The incidence of MCE was significantly lower in the EPA group (8.7% vs 10.7%, adjusted hazard ratio =0.77, 95% confidence interval (CI) 0.63-0.96, P=0.017, number needed to treat (NNT) =49). Among 1,050 patients with prior myocardial infarction (MI), the incidence of MCE in the EPA group (15.0%) was significantly lower than that in the control group (20.1%, adjusted hazard ratio =0.73, 95%CI 0.54-0.98, P=0.033, NNT =19). EPA is effective for secondary prevention of CAD, especially in individuals with prior MI, and should be added to conventional treatment.
  Circulation Journal 05/2009; 73(7):1283-90. · 3.77 Impact Factor
• Article: Suppressive effect of EPA on the incidence of coronary events in hypercholesterolemia with impaired glucose metabolism: Sub-analysis of the Japan EPA Lipid Intervention Study (JELIS).

  Shinichi Oikawa, Mitsuhiro Yokoyama, Hideki Origasa, Masunori Matsuzaki, Yuji Matsuzawa, Yasushi Saito, Yuichi Ishikawa, Jun Sasaki, Hitoshi Hishida, Hiroshige Itakura, Toru Kita, Akira Kitabatake, Noriaki Nakaya, Toshiie Sakata, Kazuyuki Shimada, Kunio Shirato
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  ABSTRACT: JELIS was a large-scale clinical trial that investigated the effects of eicosapentaenoic acid (EPA) on coronary artery disease (CAD). In this paper, the data of patients registered in JELIS were analysed to compare the incidence of CAD between patients with impaired glucose metabolism (IGM) and normoglycemic (NG) patients. The effect of EPA on the incidence of CAD in patients with IGM was also assessed. The 18,645 hypercholesterolemic patients registered in JELIS were divided into two groups. One group consisted of patients with IGM (n=4565), which included the patients who had diabetes mellitus and patients who had a fasting plasma glucose of 110mg/dL or higher, either at the time of registration or after 6 months. The other group consisted of NG patients (n=14,080). CAD incidence of the two groups over the average 4.6-year follow-up period was compared, and the effect of EPA was assessed. Compared to NG patients, IGM patients had a significantly higher CAD hazard ratio (1.71 in the non-EPA group and 1.63 in the EPA group). The treatment with EPA resulted in a 22% decrease in the CAD incidence (P=0.048) in IGM patients and an 18% decrease (P=0.062) in NG patients. It was found that the CAD risk in IGM patients is higher than in NG patients, and that highly purified EPA is very effective in decreasing the incidence of CAD among Japanese IGM patients, even though the intake of fish is high.
  Atherosclerosis 05/2009; 206(2):535-9. · 3.79 Impact Factor
• Article: Alterations in endothelium‐dependent hyperpolarization and relaxation in mesenteric arteries from streptozotocin‐induced diabetic rats

  Mitsuhiro Fukao, Yuichi Hattori, Morio Kanno, Ichiro Sakuma, Akira Kitabatake
  British Journal of Pharmacology 02/2009; 121(7):1383 - 1391. · 4.41 Impact Factor
• Source

  Available from: atcs.jp

  Article: Experimental study of the relationship between perfluoro-octyl bromide emulsion and norepinephrine release in reperfusion arrhythmia: isolated guinea pig heart model.

  Mitsuhiro Isaka, Ichiro Sakuma, Norihiko Shiiya, Shoji Fukushima, Kunihiko Nakai, Akira Kitabatake, Keishu Yasuda
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  ABSTRACT: Perfluoro-octyl bromide (PFOB), one of the perfluorochemical oxygen transporters, improved postischemic cardiac dysfunctions. Also norepinephrine (NE) is one of the important inducible factors on reperfusion arrhythmias (ventricular fibrillation [VF]). We used these methods to evaluate the relationship between PFOB emulsion and NE release on reperfusion arrhythmias. The perfusion of isolated guinea pig hearts was employed: each of four groups of 6-7 hearts were used with Krebs-Henseleit solution (KHS) as control, and KHS with 5%, 15%, or 30% PFOB emulsion. The hearts were perfused in a constant pressure Langendorff model, stabilized for 30 min, followed by 30 min preischemia, then 30 min ischemia and 45 min reperfusion at normothermia. PFOB emulsion dose-dependently limited VF and inhibited NE release in reperfusion. Only 30% PFOB emulsion showed the significant improvement of VF (p=0.05). In hemodynamic parameters, only 5% PFOB emulsion showed a significant decrease in reperfusion, but there was no difference in coronary flow rate (CFR). No differences among the four groups were demonstrated in cardiac oxygen metabolic parameters. It was most likely that a high concentration of PFOB emulsion attenuated reperfusion arrhythmia by decreasing NE release.
  Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia. 01/2009; 14(6):363-8.
• Article: Percutaneous coronary intervention plus medical therapy reduces the incidence of acute coronary syndrome more effectively than initial medical therapy only among patients with low-risk coronary artery disease a randomized, comparative, multicenter study.

  Kazuhiko Nishigaki, Tsutomu Yamazaki, Akira Kitabatake, Tetsu Yamaguchi, Katsuo Kanmatsuse, Itsuo Kodama, Noboru Takekoshi, Hitonobu Tomoike, Masatsugu Hori, Masunori Matsuzaki, Akira Takeshita, Takuro Shimbo, Hisayoshi Fujiwara
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  ABSTRACT: This study sought to determine whether initial medical therapy (MT) only or percutaneous coronary intervention plus medical therapy (PCI+MT) is better for patients with low-risk stable coronary artery disease (CAD) indicated for intervention in Japan. Several multicenter studies have suggested that in the above patients, an initial management strategy of PCI+MT does not reduce the long-term risk of cardiovascular events more effectively than initial MT only. We conducted a randomized comparative study (JSAP [Japanese Stable Angina Pectoris] study) in the previously mentioned patients. The patients were randomized to PCI+MT (n = 192) or initial MT only group (n = 192), and the patient characteristics were very similar in the 2 groups. During the 3.3-year follow-up, there was no significant difference in the cumulative death rate between PCI+MT (2.9%) and MT (3.9%). However, the cumulative risk of death plus acute coronary syndrome was significantly smaller in PCI+MT. In stable low-risk CAD, PCI+MT may improve long-term prognosis more effectively than MT.
  11/2008; 1(5):469-79. · 1.07 Impact Factor
• Article: Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS).

  Yasushi Saito, Mitsuhiro Yokoyama, Hideki Origasa, Masunori Matsuzaki, Yuji Matsuzawa, Yuichi Ishikawa, Shinichi Oikawa, Jun Sasaki, Hitoshi Hishida, Hiroshige Itakura, Toru Kita, Akira Kitabatake, Noriaki Nakaya, Toshiie Sakata, Kazuyuki Shimada, Kunio Shirato
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  ABSTRACT: Japan EPA Lipid Intervention Study (JELIS) was a large-scale clinical trial examining the effects of eicosapentaenoic acid (EPA) on coronary artery disease (CAD) in hypercholesterolemic patients. Herein, we focused on risk factors other than low-density lipoprotein cholesterol (LDL-C) to investigate the effects of EPA on CAD among JELIS primary prevention cases. Hypercholesterolemic patients on statin therapy but without evidence of CAD (n=14,981) were randomly assigned to an EPA group (n=7503) or a control group (n=7478). The relationships between incident CAD, the number of CAD risk factors (hypercholesterolemia; obesity; high triglyceride (TG) or low high-density lipoprotein cholesterol (HDL-C); diabetes; and hypertension) and EPA treatment were investigated. For the control and EPA groups combined, a higher number of risk factors was directly associated with an increased incidence of CAD. Incidence was lower for the EPA group than for the control group regardless of the numbers of risk factors. Compared to patients with normal serum TG and HDL-C levels, those with abnormal levels (TG >or=150 mg/dL; HDL-C <40 mg/dL) had significantly higher CAD hazard ratio (HR: 1.71; 95% CI: 1.11-2.64; P=0.014). In this higher risk group, EPA treatment suppressed the risk of CAD by 53% (HR: 0.47; 95% CI: 0.23-0.98; P=0.043). Multiple risk factors besides cholesterol are associated with markedly increased incidence of CAD. High TG with low HDL-C represents a particularly potent risk factor. EPA was effective in reducing the incidence of CAD events for patients with this dyslipidemic pattern, suggesting that EPA may be especially beneficial in patients who with abnormal TG and HDL-C levels.
  Atherosclerosis 10/2008; 200(1):135-40. · 3.79 Impact Factor
• Article: Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients: subanalysis of the JELIS trial.

  Kortaro Tanaka, Yuichi Ishikawa, Mitsuhiro Yokoyama, Hideki Origasa, Masunori Matsuzaki, Yasushi Saito, Yuji Matsuzawa, Jun Sasaki, Shinichi Oikawa, Hitoshi Hishida, Hiroshige Itakura, Toru Kita, Akira Kitabatake, Noriaki Nakaya, Toshiie Sakata, Kazuyuki Shimada, Kunio Shirato
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  ABSTRACT: The JELIS trial examined the preventive effect of eicosapentaenoic acid (EPA) against coronary artery diseases. Hypercholesterolemic patients received statin only (no EPA group: n=9319) or statin with EPA (EPA group: n=9326) for around 5 years. EPA significantly suppressed the incidence of coronary events in previous analysis. Herein, we investigated the effects of EPA on the primary and secondary prevention of stroke. We conducted a subanalysis of JELIS with respect to stroke incidence in the primary and secondary prevention subgroups defined as those without and with a prior history of stroke using Cox proportional hazard ratios, adjusted for baseline risk factor levels. As for primary prevention of stroke, this occurred in 114 (1.3%) of 8862 no EPA group and in 133 (1.5%) of 8841 EPA group. No statistically significant difference in total stroke incidence (Hazard Ratio, 1.08; 95% confidence interval, 0.95 to 1.22) was observed between the no EPA and the EPA groups. In the secondary prevention subgroup, stroke occurred in 48 (10.5%) of 457 no EPA group and in 33 (6.8%) of 485 EPA group, showing a 20% relative reduction in recurrent stroke in the EPA group (Hazard Ratio, 0.80; 95% confidence interval, 0.64 to 0.997). Administration of highly purified EPA appeared to reduce the risk of recurrent stroke in a Japanese population of hypercholesterolemic patients receiving low-dose statin therapy. Further research is needed to determine whether similar benefits are found in other populations with lower levels of fish intake. The trial is registered at ClinicalTrials.gov (number NCT00231738).
  Stroke 08/2008; 39(7):2052-8. · 5.73 Impact Factor
• Article: Prevalence of atrial fibrillation in the general population of Japan: an analysis based on periodic health examination.

  Hiroshi Inoue, Akira Fujiki, Hideki Origasa, Satoshi Ogawa, Ken Okumura, Isao Kubota, Yoshifusa Aizawa, Takeshi Yamashita, Hirotsugu Atarashi, Minoru Horie, Tohru Ohe, Yoshinori Doi, Akihiko Shimizu, Akiko Chishaki, Tetsunori Saikawa, Katsusuke Yano, Akira Kitabatake, Hideo Mitamura, Itsuo Kodama, Shiro Kamakura
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  ABSTRACT: The mortality and morbidity rates of various cardiovascular diseases differ between Western countries and Japan. The age- and gender-specific prevalence rate of atrial fibrillation (AF) in the general population of Japan was determined using the data from periodic health examinations in 2003. Data of 630,138 subjects aged 40 years or more (47% were men and 34% were employees of companies and local governments) were collected from northern to southern Japan. The prevalence of diagnosed AF in each 10-year age group of both men and women was determined. Based on these prevalence rates and the Registry of Residents, the number of people having AF in Japan was estimated. The prevalence rate of AF increased as both male and female subjects aged, and it was 4.4% for men but only 2.2% for women aged 80 years or more (p<0.0001). As a whole, the AF prevalence of men was three times that of women (1.35 versus 0.43%, p<0.0001). There may be approximately 716,000 people (95% confidence interval (CI), 711,000-720,000) with AF in Japan, an overall prevalence of 0.56%. The number of people having AF was projected to be 1.034 (95% CI, 1.029-1.039) million, an overall prevalence of 1.09%, in 2050. The prevalence of AF increased in Japan as the population aged, as in Western countries. The overall prevalence of AF in Japan is approximately two-thirds of that in the USA. The projected increase in the number of people having AF is modest in Japan in 2050.
  International journal of cardiology 08/2008; 137(2):102-7. · 7.08 Impact Factor
• Article: Allograft inflammatory factor-1 augments macrophage phagocytotic activity and accelerates the progression of atherosclerosis in ApoE-/- mice.

  Tetsuya Mishima, Kazuya Iwabuchi, Satoshi Fujii, Shin-Ya Tanaka, Hisako Ogura, Keiko Watano-Miyata, Naoki Ishimori, Yasuhiro Andoh, Yukihito Nakai, Chikako Iwabuchi, Manabu Ato, Akira Kitabatake, Hiroyuki Tsutsui, Kazunori Onoé
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  ABSTRACT: Allograft inflammatory factor (AIF)-1, originally cloned from a rat heart allograft under chronic rejection, is induced in various inflammatory conditions including atherosclerosis. Using mouse AIF-1 transfected macrophages and AIF-1 transgenic (AIF-1 Tg) mice, we analyzed the influence of AIF-1 overexpression on macrophage phagocytosis and the development of atherosclerosis. The AIF-1 transfectants showed significantly increased phagocytosis of latex beads and E. coli BioParticles as well as incorporation of acetylated low-density lipoprotein (LDL) compared to those of vector controls. Concordant results were obtained with elicited peritoneal exudate cells from AIF-1 Tg mice. When AIF-1 Tg mice were crossbred with apolipoprotein E knockout mice (ApoE-/-), these AIF-1 Tg ApoE-/- mice developed significantly increased atherosclerotic lesions compared to ApoE-/- mice. These results suggest that enhanced AIF-1 expression leads to augmented incorporation of degenerated LDL by macrophages and promotes development of atherosclerotic vasculopathy.
  International Journal of Molecular Medicine 03/2008; 21(2):181-7. · 1.98 Impact Factor
• Article: Induction of c-fos mRNA expression by pure pressure overload in cultured cardiac myocytes.

  Hidetsugu Sakai, Kazushi Urasawa, Naotsugu Oyama, Satoshi Kaneta, Takahiko Saito, Akira Kitabatake, Hiroyuki Tsutsui
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  ABSTRACT: Mechanical stress by pressure overload due to hypertension or valvular heart disease such as aortic valve stenosis induces cardiac hypertrophy. It has been well established that the mechanical stretch of cardiac myocytes in vitro induces hypertrophic responses such as the expression of immediate early response genes including c-fos. However, it remains uncertain whether the mechanical forces due to pure atmospheric pressure can induce similar responses in cardiac myocytes. We thus cultured rat neonatal cardiac myocytes in an atmospheric pressure chamber apparatus and determined the effects of pure pressure stress on c-fos gene expression. Pressures greater than 80 mmHg enhanced c-fos mRNA after 30 minutes. These results suggest that pure atmospheric pressure overload can also induce early hypertrophic responses in cardiac myocytes.
  International Heart Journal 06/2007; 48(3):359-67. · 1.16 Impact Factor
• Article: S-nitrosylated and pegylated hemoglobin, a newly developed artificial oxygen carrier, exerts cardioprotection against ischemic hearts.

  Hiroshi Asanuma, Kunihiko Nakai, Shoji Sanada, Tetsuo Minamino, Seiji Takashima, Hisakazu Ogita, Masashi Fujita, Akio Hirata, Masakatsu Wakeno, Hiroyuki Takahama, Jiyoong Kim, Masanori Asakura, Ichiro Sakuma, Akira Kitabatake, Masatsugu Hori, Kazuo Komamura, Masafumi Kitakaze
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  ABSTRACT: Cell-free hemoglobin (Hb) derivatives that have been developed as Hb-based artificial oxygen carrier cause both coronary vasoconstriction and platelet aggregation due to the scavenging actions of nitric oxide (NO). Recently, native Hb is found to undergo S-nitrosylation, which regulates blood flow, whereas artificial oxygen carriers are lacking of S-nitrosylation. Therefore, S-nitrosylated and pegylated hemoglobin (SNO-PEG-Hb) was prepared to overcome the above defects, where pegylation was included to avoid extravasation and to prolong the circulatory half-live. Since SNO-PEG-Hb possesses SNO property, we tested whether SNO-PEG-Hb increases coronary blood flow (CBF) and improves the severity of myocardial ischemia. In 19 open chest dogs, the left anterior descending coronary artery was perfused with blood from the carotid artery via the bypass tube, and then CBF and coronary perfusion pressure (CPP) were measured. After hemodynamic stabilization, CPP was reduced so that CBF decreased to 33% of the baseline and thereafter CPP was maintained constant. Ten minutes after the onset of coronary hypoperfusion, we infused 10% SNO-PEG-Hb into the coronary artery (2.5 ml/min). SNO-PEG-Hb increased CBF (28.1+/-3.3 to 43.3+/-3.9 ml/100 g/min, p<0.05), fractional shortening (4.6+/-1.2 to 16.6+/-2.4%, p<0.01) and lactate extraction ratio (-38.5+/-8.6 to 25.5+/-1.3%, p<0.01). Thus, we conclude that SNO-PEG-Hb increases coronary blood flow and improves the contractile and metabolic dysfunction of the ischemic myocardium. SNO-PEG-Hb, a newly developed artificial oxygen carrier, may mediate a cardioprotection in ischemic heart diseases in addition to blood supplementation.
  Journal of Molecular and Cellular Cardiology 06/2007; 42(5):924-30. · 5.17 Impact Factor
• Article: Expression of amyloid precursor protein mRNA in vascular smooth muscle cells of the human brain

  Reisuke Heavy Takahashi, Hirofumi Sawa, Akio Takada, Akira Kitabatake, Kazuo Nagashima
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  ABSTRACT: Amyloid deposition in the cerebral vessels is the hallmark of cerebral amyloid angiopathy (CAA). In order to establish which type of cell produces amyloid, we performed Northern blot analysis and in situ hybridization studies on human meningeal arteries. Northern blotting showed that amyloid precursor protein (APP) mRNA was expressed not only in the cerebral cortex, but also in the meninges. An antisense RNA probe that hybridizes with APP transcripts was used for in situ hybridization. This analytic modality revealed APP messages in the tunica media of the meningeal arteries and arterioles. The presence of smooth muscle cells in these vessels was verified immunohistochemically on consecutive serial sections. These observations indicate that APP is produced by vascular smooth muscle cells.
  Neuropathology 05/2007; 17(1):11 - 14. · 2.02 Impact Factor
• Article: [J-CHF Study].

  Hiroshi Okamoto, Akira Kitabatake, Hiroyuki Tsutsui
  Nippon rinsho. Japanese journal of clinical medicine 05/2007; 65 Suppl 4:537-42.