Takuro Kubozono

Kagoshima University, Kagosima, Kagoshima, Japan

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Publications (38)62.29 Total impact

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    ABSTRACT: Circulating cardiac troponin T is a marker of cardiomyocyte injury, and predicts adverse outcomes in patients with chronic heart failure. However, the significance of highly sensitive cardiac troponin T (hs-TnT) in cardiac dysfunction remains uncertain. The purpose of this study is to evaluate the correlation between hs-TnT and echocardiographic parameters or natriuretic peptides in patients with heart failure. We analyzed 283 consecutive out- or in-patients who had B-type natriuretic peptide (BNP) ≥20 pg/mL and were examined by echocardiography (mean age 66.5±13.9 years old; 159 males). Hs-TnT, BNP, N-terminal pro-BNP (NT-proBNP), and creatinine levels were measured simultaneously. LVEDD (left ventricular end-diastolic dimension), LVEF (left ventricular ejection fraction), E', E/E', left ventricular (LV) Tei index, and right ventricular (RV) Tei index were determined with echocardiography. The linear regression analyses demonstrated that loghs-TnT correlated with LVEDD (R=0.242, p<0.0001), LVEF (R=-0.369, p<0.0001), E' (R=-0.447, p<0.0001), E/E' (R=0.364, p<0.0001), LV Tei index (R=0.303, p<0.0001), RV Tei index (R=0.443, p<0.0001), and estimated glomerular filtration rate (eGFR) (R=-0.489, p<0.0001). Using multiple variable regression analysis, loghs-TnT independently correlated with LVEF, E/E', RV Tei index, and eGFR. Furthermore, loghs-TnT significantly correlated with logBNP (R=0.567, p<0.0001) or logNT-proBNP (R=0.647, p<0.0001). Multiple variable regression analysis demonstrated that loghs-TnT independently correlated with logBNP, age, and eGFR, or with logNT-proBNP, age, sex, and eGFR. The hs-TnT correlated with cardiac dysfunction evaluated by echocardiography and natriuretic peptides in patients with heart failure. The elevation of hs-TnT levels in heart failure may represent cardiac dysfunction due to minor and ongoing myocardial injury.
    Journal of Cardiology 03/2012; 59(2):202-8. · 2.30 Impact Factor
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    ABSTRACT: Loop diuretics have two different classes with different duration of activity: short-acting such as furosemide (duration of activity, 6h) and long-acting such as azosemide (duration of activity, 10-12h). We conducted a multicenter, randomized, controlled trial in order to compare the therapeutic effects of azosemide, a long-acting loop diuretic, and furosemide, a short-acting one, on neurohumoral factors and cardiac function in outpatients with chronic heart failure (CHF). We enrolled 98 patients with CHF who were receiving furosemide and an angiotensin-converting enzyme inhibitor, and they were randomly divided into furosemide (n=49) and azosemide (n=49) groups. The furosemide group continued furosemide at the same dosage, and the azosemide group switched from furosemide to azosemide. At baseline and after 3 months, we measured body weight, and levels of brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), norepinephrine, active renin, creatinine, blood urea nitrogen, sodium, potassium, and hematocrit. Chest X-ray and echocardiography were also performed. Body weight and plasma levels of BNP and ANP significantly decreased after 3 months in the azosemide group compared to the furosemide group. There were no significant differences in changes of levels of creatinine, blood urea nitrogen, sodium, potassium, hematocrit, norepinephrine, and active renin after 3 months between the furosemide and azosemide groups. Echocardiography and chest X-ray did not demonstrate significant differences between the two groups. Long-acting azosemide is suggested to be useful for the improvement of neurohumoral factors compared with short-acting furosemide in patients with CHF.
    Journal of Cardiology 02/2012; 59(3):352-8. · 2.30 Impact Factor
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    ABSTRACT: To investigate the prevalence and geographical variation of high arterial stiffness in groups from the Amami islands (Amami) and Kagoshima mainland (mainland), Japan, using the cardio-ankle vascular index (CAVI) as a surrogate marker of arterial stiffness. We recruited 4,523 health checkup examinees from Amami and 440 examinees from the mainland, with an age range of 40-69 years. The frequency of high arterial stiffness (CAVI≥9.0) was geographically compared between the regions, and both mean CAVI values were compared with those of the healthy Japanese population with less risk factors for coronary artery disease. Clinical, lifestyle, and regional factors for increased CAVI values were estimated by the multiple linear regression model. The frequency of high arterial stiffness on Amami was significantly lower than on the mainland. Mean CAVI values on Amami were similar in males and lower in females than in the healthy Japanese population, but those on the mainland were higher for both sexes. Age, systolic blood pressure, triglycerides, fasting blood glucose, and a history of hypertension and diabetes mellitus were positively related to increased CAVI values on Amami. The regional factor of Amami, compared with the mainland, was negatively related to increased CAVI values in both sexes after adjusting for traditional cardiovascular risk factors. CAVI values in Amami residents were significantly lower than in mainland residents, suggesting that environmental or genetic factors might have improved arterial stiffness in the Amami population.
    Journal of atherosclerosis and thrombosis 11/2011; 19(1):69-80. · 2.93 Impact Factor
  • Takuro Kubozono, Masaaki Miyata
    Nippon rinsho. Japanese journal of clinical medicine 11/2011; 69 Suppl 9:468-72.
  • Takuro Kubozono, Masaaki Miyata, Chuwa Tei
    Nihon Naika Gakkai Zasshi 04/2011; 100(4):1067-75.
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    ABSTRACT: Bilirubin has antioxidant properties and may protect against atherosclerosis and coronary heart disease (CHD). Further, in patients with metabolic syndrome, hyperbilirubinemia is associated with attenuation of insulin resistance. The aim of the present study was to determine the relationship between serum bilirubin concentration and coronary endothelial function in overweight patients. The study population consisted of 107 patients without CHD who underwent coronary flow studies. Vascular reactivity was examined by intra-coronary administration of papaverine and nitroglycerin. Coronary endothelial function was evaluated by assessing the change in coronary artery diameter to papaverine [percent change in flow-mediated dilatation (%FMD)] and nitroglycerin (%NTG). Serum total bilirubin, high-sensitivity C-reactive protein (hs-CRP), high density lipoprotein-cholesterol (HDL-C), fasting plasma glucose and immunoreactive insulin levels were also measured, and the homeostasis model assessment insulin resistance (HOMA-IR) index was calculated. Patients were divided into two groups according to body mass index (BMI): an overweight group (BMI ≥ 25; n = 36) and a normal weight group (BMI < 25; n = 71). RESULTs: In the overweight group, univariate analysis revealed that log-transformed total bilirubin was positively correlated with %FMD and HDL-C (r = 0.38, p< 0.05; r = 0.30, p < 0.05, respectively) and was inversely correlated with log-transformed hs-CRP and HOMA-IR (r = -0.45, p < 0.01; r = -0.45, p< 0.05, respectively). Multivariate analysis revealed that log-transformed hs-CRP was the only independent predictor of log-transformed total bilirubin (p< 0.05). These results suggest that a high bilirubin level was associated with favorable coronary endothelial function in overweight patients. Further, the anti-inflammatory effects of bilirubin may mediate this effect.
    Journal of atherosclerosis and thrombosis 02/2011; 18(5):403-12. · 2.93 Impact Factor
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    ABSTRACT: A previous report by our team showed that Waon therapy, using a far infrared-ray dry sauna at 60°C, improves cardiac and vascular function in patients with chronic heart failure (CHF). The purpose of the present study was to clarify the effect of Waon therapy on oxidative stress in CHF patients and investigate its mechanism by animal experiments. Forty patients with CHF were divided into control (n=20) and Waon therapy (n=20) groups. All patients received standard optimal medications for CHF. Waon therapy group was treated with Waon therapy daily for 4 weeks. After 4 weeks of Waon therapy, concentrations of hydroperoxide and brain natriuretic peptide (BNP) decreased significantly (hydroperoxide, 422±116 to 327±88U.CARR, P<0.001; BNP, 402±221 to 225±137pg/ml, P<0.001), and the nitric oxide metabolites increased (71.2±35.4 to 92.0±40.5mmol/L, P<0.05). In contrast, none of these variables changed over the 4-week interval in the control group. Furthermore, animal experiments were performed using TO-2 cardiomyopathic hamsters. On immunohistochemistry, cardiac expression of 4-hydroxy-2-nonenal, a marker of oxidative stress, was decreased in the 4-week Waon therapy compared to untreated hamsters. On Western blotting, cardiac expressions of heat shock protein (HSP) 27, manganese superoxide dismutase and HSP32, which reduce oxidative stress, were significantly upregulated in the 4-week Waon therapy compared to untreated hamsters. Waon therapy decreases oxidative stress in patients and hamsters with heart failure.
    Circulation Journal 02/2011; 75(2):348-56. · 3.58 Impact Factor
  • Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2011; 57(14).
  • Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2011; 57(14).
  • Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2011; 57(14).
  • Journal of Cardiac Failure - J CARD FAIL. 01/2011; 17(9).
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    ABSTRACT: The brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI) are used to evaluate arterial distensibility. The purpose of this study was to elucidate the acute and chronic effects of smoking on arterial stiffness as measured by baPWV and CAVI.  Ten male smokers were studied to evaluate the acute effect of smoking on arterial stiffness. To elucidate the chronic effect of smoking on arterial stiffness, 160 male active smokers were analyzed. CAVI and baPWV were calculated by measuring the pulse volume record, blood pressure (BP), and vascular length from heart to ankle. CAVI and baPWV were measured using a VaSera VS-1000. In the acute study, baPWV and CAVI increased immediately after smoking 1 cigarette. In the chronic study, baPWV and CAVI significantly correlated with mean BP (MBP) and the Brinkman index. In multiple regression analysis, baPWV independently correlated with MBP, and CAVI independently correlated with the Brinkman index, but not with MBP. Receiver-operating characteristics (ROC) curves of baPWV and CAVI to predict Brinkman index ≥500 demonstrated that the area under the ROC curve of CAVI was higher than that of baPWV.  Smoking causes a significant increase in arterial stiffness as measured by baPWV and CAVI. CAVI correlated with the Brinkman index, which suggests that CAVI is a useful index of the degree of arterial stiffness caused by smoking.
    Circulation Journal 12/2010; 75(3):698-702. · 3.58 Impact Factor
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    ABSTRACT: We previously reported that Waon therapy upregulates endothelial nitric oxide synthase protein, and augments ischemia-induced angiogenesis in mice with hindlimb ischemia, and it improves limb ischemia in patients with peripheral arterial disease (PAD). The aim of this study was to investigate the underlying mechanism of Waon therapy for the treatment of patients with PAD, and to determine whether Waon therapy can mobilize blood-derived progenitor cells. 21 consecutive PAD patients received standard medications, and were randomly divided into control (n=10) and Waon therapy groups (n=11). The Waon therapy group received Waon therapy daily for 6 weeks. The control group continued conventional therapy for 6 weeks. Leg pain was scored using a visual analogue scale. The ankle-brachial pressure index (ABPI) and the 6-min walking distance were measured at baseline and 6 weeks after therapy. Frequency of circulating CD34+ progenitor cell numbers was measured by quantitative real-time polymerase chain reaction, and the serum nitrate and nitrite levels were also measured at baseline and 6 weeks after therapy. The leg pain score, ABPI and the 6-min walking distance improved significantly after 6 weeks in the Waon therapy group, but not in the control group. Frequency of circulating CD34+ cells increased after 6 weeks of Waon therapy [2.0 ± 1.2 (×10(-4)) at baseline to 3.9 ± 1.9 (×10(-4)), p=0.015], while it remained unchanged in the control group [1.8 ± 1.8 (×10(-4)) at baseline to 1.2 ± 0.9 (×10(-4))]. Serum nitrate and nitrite levels increased significantly after Waon therapy (29.6 ± 17.6 to 36.0 ± 17.7 μmol/ml, p<0.05), but not in the control group (34.4 ± 9.4 to 38.3 ± 8.8 μmol/ml). Waon therapy mobilized circulating endothelial progenitor cells and improved limb ischemia in patients with PAD. Waon therapy is a highly promising therapy for patients with PAD.
    Journal of Cardiology 11/2010; 56(3):361-6. · 2.30 Impact Factor
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    ABSTRACT: We have reported previously that Waon therapy improves cardiac and vascular function, and prognosis of patients with chronic heart failure (CHF). CHF is characterized by generalized sympathetic activation and parasympathetic withdrawal. The purpose of this study was to evaluate the effect of Waon therapy on autonomic nervous activity in patients with CHF. Fifty-four patients with CHF, who were receiving conventional therapy for CHF, were divided into Waon therapy and control groups. In the Waon therapy group, 27 patients were treated with medication and Waon therapy. In the control group, 27 patients were treated with only conventional CHF therapy. Cardiac function including cardiac output (CO) and left ventricular ejection fraction (LVEF) was evaluated by echocardiography. The heart rate variability, such as the coefficient of variation of RR intervals (CVRR), the low-frequency (LF) component, high-frequency (HF) component, the LF norm [LF/(LF+HF)], and HF norm [HF/(LF+HF)], were measured at admission and 4 weeks after treatment. Echocardiography demonstrated that CO and LVEF significantly increased after 4 weeks in the Waon therapy group, but did not change in the control group. In the Waon therapy group, CVRR, HF, and HF norm significantly increased 4 weeks after Waon therapy. In addition, the LF/HF ratio and LF norm significantly decreased 4 weeks after Waon therapy. In contrast, these parameters remained unchanged in the control group. Moreover, the HF and HF norm were significantly higher, and the LF/HF ratio and LF norm were significantly lower after 4 weeks of Waon therapy group than after 4 weeks of only conventional therapy. Waon therapy improved cardiac function and autonomic nervous activity by increasing parasympathetic and decreasing sympathetic nervous activity in patients with CHF.
    Journal of Cardiology 09/2010; 57(1):100-6. · 2.30 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the role of uric acid (UA) in coronary endothelial function via its effects on renal function, other coronary risk factors and asymmetric dimethylarginine (ADMA) in men and women. The study population consisted of 194 consecutive patients (119 men and 75 women) without coronary artery disease. The relationships between UA and coronary endothelial function, estimated glomerular filtration rate (eGFR), ADMA or other biochemical or anthropometric parameters were investigated. Monovariate analysis of female participants demonstrated that % change in coronary blood flow (CBF) induced by acetylcholine (ACh) was inversely correlated with UA, ADMA and age (r=-0.32, p<0.01; r=-0.31, p<0.05; r=-0.23, p<0.05, respectively), and positively correlated with eGFR (r=0.27, p<0.05). Stepwise regression analysis showed that UA was the only independent predictor of % change in CBF induced by ACh (F value 4.969, p<0.05). Similar analysis of male participants failed to show significant correlations of these variables except for age in monovariate analysis (r=-0.19, p<0.05). Meanwhile, UA was inversely correlated with eGFR in both men and in women (r=-0.25, p<0.01; r=-0.59, p<0.0001, respectively), and ADMA was positively correlated with UA and inversely correlated with eGFR (r=0.36, p<0.05; r=-0.42, p<0.01, respectively) in women but not in men. High concentrations of UA correlate with coronary endothelial microvascular dysfunction in women. Further, serum UA concentration is related to eGFR and ADMA only in women, which may result in impaired endothelial function in resistance coronary arteries in women but not in men.
    Journal of atherosclerosis and thrombosis 03/2010; 17(3):259-69. · 2.93 Impact Factor
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    ABSTRACT: An unhealthy lifestyle can increase the risk of cardiovascular disease. However, the mechanism by which lifestyle influences the development of cardiovascular disease remains unclear. Since coronary endothelial function is a predictor of cardiovascular prognosis, the goal of this study was to characterize the effect of enjoying hobbies on coronary endothelial function and cardiovascular outcomes. A total of 121 consecutive patients (76 men, 45 women) with almost normal coronary arteries underwent Doppler flow study of the left anterior descending coronary artery following sequential administration of papaverine, acetylcholine, and nitroglycerin. On the basis of responses to questionnaires, patients were divided into two groups; the Hobby group (n = 71) who enjoyed hobbies, and the Non-hobby group (n = 50) who had no hobbies. Cardiovascular outcomes were assessed at long-term follow-up using medical records or questionnaire surveys for major adverse cardiovascular events (MACE).The average follow-up period was 916 +/- 515 days. There were no significant differences in demographics when comparing the two groups. The percent change in coronary blood flow and coronary artery diameter induced by acetylcholine was significantly greater in the Hobby group than in the Non-hobby group (49% +/- 77% vs 25% +/- 37%, P < 0.05, 4% +/- 13% vs -3% +/- 20%, P < 0.05, respectively). The MACE rate was significantly lower in the Hobby group than in the Non-hobby group (P < 0.01). Enjoyment of hobbies was the only independent predictor of MACE (odds ratio 8.1 [95% confidence interval 1.60, 41.90], P = 0.01) among the variables tested. In the early stages of arteriosclerosis, enjoying hobbies may improve cardiovascular outcomes via its favorable effects on coronary endothelial function.
    Heart and Vessels 03/2010; 25(2):113-20. · 2.13 Impact Factor
  • Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2010; 55(10).
  • Journal of Cardiac Failure - J CARD FAIL. 01/2010; 16(9).
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    ABSTRACT: The purpose of this study was to evaluate the validity of brachial-ankle pulse wave velocity (baPWV) and the cardio-ankle vascular index (CAVI) as measures of arterial stiffness in hemodialysis (HD) patients. We studied 160 consecutively enrolled HD patients (mean age: 59+/-13 years; 91 male patients). We measured baPWV and CAVI using a VaSera VS-1000, maximum intima-media thickness (max IMT) of the carotid artery by ultrasonography and blood renal and lipid parameters. As a control, baPWV and CAVI were also measured in age- and gender-matched healthy volunteers. Both baPWV and CAVI were significantly higher in HD patients than in controls (baPWV: 1698+/-355 vs. 1454+/-263 cm s(-1), P<0.0001; CAVI: 9.3+/-1.4 vs. 8.9+/-1.2, P<0.01). BaPWV correlated positively with age (r=0.549, P<0.0001), systolic blood pressure (SBP) (r=0.510, P<0.0001), diastolic blood pressure (r=0.203, P<0.0001), pulse pressure (PP) (r=0.499, P<0.0001), Kt V(-1) (r=0.221, P<0.01), Brinkman index (r=0.186, P<0.05) and max IMT (r=0.285, P<0.001). CAVI also correlated positively with age (r=0.562, P<0.0001), SBP (r=0.395, P<0.0001), PP (r=0.490, P<0.0001), Kt V(-1) (r=0.216, P<0.01), Brinkman index (r=0.238, P<0.01) and max IMT (r=0.280, P<0.001). Multiple regression analysis demonstrated baPWV and CAVI correlated independently with age and SBP. Receiver operating characteristics (ROC) curve analysis demonstrated that baPWV and CAVI had similar power to predict increases in max IMT. We also measured baPWV and CAVI immediately before and after HD, and showed CAVI was influenced by changes in water volume. Both baPWV and CAVI are therefore useful indices of arterial stiffness in HD patients.
    Hypertension Research 06/2009; 32(8):716-20. · 2.79 Impact Factor
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    ABSTRACT: We developed a Waon therapy (soothing warm therapy) and have previously reported that repeated Waon therapy improves hemodynamics, peripheral vascular function, arrhythmias, and clinical symptoms in patients with chronic heart failure (CHF). The aim of this study was to investigate the effect of Waon therapy on the prognosis of CHF patients. We studied 129 patients with CHF in NYHA functional class III or IV who were admitted to our hospital between January 1999 and March 2001. In the Waon therapy group, 64 patients were treated with a far infrared-ray dry sauna at 60 degrees C for 15 min and then kept on bed rest with a blanket for 30 min. The patients were treated daily for 5 days during admission, and then at least twice a week after discharge. In the control group, 65 patients, matched for age, gender, and NYHA functional class, were treated with traditional CHF therapy. The follow-up time was scheduled for 5 years. Recent, complete follow-up data on each patient were obtained. The overall survival rate was 84.5% (Kaplan-Meier estimate). Twelve patients died in the control group and 8 patients died in the Waon therapy group at 60 months of follow-up. Cardiac events due to heart failure or cardiac death occurred in 68.7% of the control group but only 31.3% of the Waon therapy group (P<0.01) at 60 months of follow-up. Waon therapy reduced cardiac events in patients with CHF. This therapy is a promising non-pharmacological treatment for CHF.
    Journal of Cardiology 05/2009; 53(2):214-8. · 2.30 Impact Factor