Ryusuke Tsunoda

Japanese Red Cross, Edo, Tōkyō, Japan

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Publications (34)204.54 Total impact

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    ABSTRACT: Background:The aim of this study was to examine the effects of different statins on the clinical outcomes of Japanese patients with coronary stent implants.Methods and Results:This study included 5,801 consecutive patients (males, 4,160; age, 69.7±11.1 years, mean±SD) who underwent stent implantation between April 2008 and March 2011. They were treated with a strong statin (n=3,042, 52%, atorvastatin, pitavastatin, or rosuvastatin), a regular statin (n=1,082, 19%, pravastatin, simvastatin, or fluvastatin) or no statin (n=1,677, 29%). The patients with chronic kidney disease (CKD) were divided into mild-to-moderate CKD (30≤eGFR<60, n=1,956) and severe CKD (eGFR <30, n=559). Primary endpoints included cardiovascular death and nonfatal myocardial infarction, including stent thrombosis and ischemic stroke. The clinical outcome for the primary endpoint in mild-to-moderate CKD patients treated with a strong statin (hazard ratio 0.50, 95% confidence interval 0.31-0.81; P=0.005) was significantly lower than in those on no statins, but that in the patients treated with a regular statin was not (P=0.160). The clinical outcome for the primary endpoint in severe CKD patients treated with a strong or regular statin was no different than not being on statin therapy (P=0.446, P=0.194, respectively).Conclusions:In patients with mild-to-moderate CKD, only strong statins were associated with lower risk compared with no statin, but regular statins were not. It is possible that taking a strong statin from the early stage of CKD is useful for suppression of cardiovascular events.
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    ABSTRACT: Although the positive association between achieved low-density lipoprotein cholesterol (LDL-C) level and the risk of coronary artery disease (CAD) has been confirmed by randomized studies with statins, many patients remain at high residual risk of events suggesting the necessity of novel pharmacologic strategies. The combination of ezetimibe/statin produces greater reductions in LDL-C compared to statin monotherapy. The Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound (PRECISE-IVUS) trial was aimed at evaluating the effects of ezetimibe addition to atorvastatin, compared with atorvastatin monotherapy, on coronary plaque regression and change in lipid profile in patients with CAD. The study is a prospective, randomized, controlled, multicenter study. The eligible patients undergoing IVUS-guided percutaneous coronary intervention will be randomly assigned to receive either atorvastatin alone or atorvastatin plus ezetimibe (10mg) daily using a web-based randomization software. The dosage of atorvastatin will be increased by titration within the usual dose range with a treatment goal of lowering LDL-C below 70mg/dL based on consecutive measures of LDL-C at follow-up visits. IVUS will be performed at baseline and 9-12 months follow-up time point at participating cardiovascular centers. The primary endpoint will be the nominal change in percent coronary atheroma volume measured by volumetric IVUS analysis. PRECISE-IVUS will assess whether the efficacy of combination of ezetimibe/atorvastatin is noninferior to atorvastatin monotherapy for coronary plaque reduction, and will translate into increased clinical benefit of dual lipid-lowering strategy in a Japanese population. Copyright © 2015. Published by Elsevier Ltd.
    Journal of Cardiology 01/2015; DOI:10.1016/j.jjcc.2014.12.011 · 2.57 Impact Factor
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    ABSTRACT: Early statin therapy after acute coronary syndrome reduces atherothrombotic vascular events. This study aimed to compare the effects of hydrophilic and hydrophobic statins on myocardial salvage and left ventricular (LV) function in patients with ST-elevated myocardial infarction (STEMI).
    Atherosclerosis 09/2014; 237(1):251-258. DOI:10.1016/j.atherosclerosis.2014.08.053 · 3.97 Impact Factor
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    ABSTRACT: Although nitrates are widely used as a concomitant therapy with calcium channel blockers (CCBs) for vasospastic angina (VSA), their prognostic contribution remains unclear. The present study aimed to examine the prognostic impact of chronic nitrate therapy in patients with VSA.
    European Heart Journal 09/2014; DOI:10.1093/eurheartj/ehu313 · 14.72 Impact Factor
  • International Journal of Cardiology 08/2014; 176(3). DOI:10.1016/j.ijcard.2014.08.027 · 6.18 Impact Factor
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    ABSTRACT: The present study aimed to develop a comprehensive clinical risk score for vasospastic angina (VSA) patients. Previous studies demonstrated various prognostic factors of future adverse events in VSA patients. However, to apply these prognostic factors in clinical practice, the assessment of their accumulation in individual patients is important. The patient database of the multicenter registry study by the Japanese Coronary Spasm Association (JCSA) (n=1,429; median 66 years; median follow-up of 32 months) was utilized for score derivation. Multivariable Cox proportional hazard model selected 7 predictors of major adverse cardiac events (MACE). The integer score was assigned to each predictors proportional to their respective adjusted hazard ratio; history of out-of-hospital cardiac arrest (4 points), smoking, angina at rest alone, organic coronary stenosis, multivessel spasm (2 points each), ST-elevation during angina and β-blocker use (1 point each). According to the total score in individual patients, 3 risk strata were defined; low (score 0-2, n=598), intermediate (score 3-5, n=639) and high (score 6 or more, n=192). The incidence of MACE in the low-, intermediate- and high-risk patients were 2.5%, 7.0% and 13.0%, respectively (P<0.001). Cox model for MACE between the 3 risk strata also showed prognostic utility of the scoring system in various clinical subgroups. The average prediction rate of the scoring system in the internal training and validation sets were 86.6% and 86.5%, respectively. We developed a novel scoring system, the JCSA risk score, which may provide the comprehensive risk assessment and prognostic stratification for VSA patients.
    Journal of the American College of Cardiology 07/2013; 62(13). DOI:10.1016/j.jacc.2013.07.018 · 15.34 Impact Factor
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    ABSTRACT: Background: Accumulating evidence has demonstrated the gender differences in the clinical characteristics and outcomes of patients with ischemic heart disease. However, it remains to be elucidated whether it is also the case for vasospastic angina (VSA). Methods and Results: We enrolled a total of 1,429 VSA patients (male/female, 1090/339; median age 66 years) in our nationwide multicenter registry by the Japanese Coronary Spasm Association. As compared with male patients, female patients were characterized by older age (median 69 vs. 66 years), lower incidence of smoking (20% vs. 72%) and less significant organic stenosis (9% vs. 16%) (all P=0.001). Multivariate analysis demonstrated that the predictors of major adverse cardiac events (MACE) were considerably different by genders; women were more associated with age and electrical abnormalities, whereas men with structural abnormalities. Overall 5-year MACE-free survival was comparable between both genders. However, when the patients were divided into 3 groups by age [young (<50 years), middle-aged (50-64 years) and elderly (≥65 years)], the survival was significantly lower in the young female group (young 82%, middle-aged 92%, elderly 96%, P<0.01), where a significant interaction was noted between age and smoking. In contrast, the survival was comparable among the 3 age groups of male patients. Conclusions: These results indicate that there are gender differences in the characteristics and outcomes of Japanese VSA patients, suggesting the importance of gender-specific management of the disorder.
    Circulation Journal 01/2013; 77(5). DOI:10.1253/circj.CJ-12-1486 · 3.69 Impact Factor
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    ABSTRACT: AimsProvocation tests of coronary artery spasm are useful for the diagnosis of vasospastic angina (VSA). However, these tests are thought to have a potential risk of arrhythmic complications, including ventricular tachycardia (VT), ventricular fibrillation (VF), and brady-arrhythmias. We aimed to elucidate the safety and the clinical implications of the spasm provocation tests in the nationwide multicentre registry study by the Japanese Coronary Spasm Association.Methods and resultsA total of 1244 VSA patients (M/F, 938/306; median 66 years) who underwent the spasm provocation tests were enrolled from 47 institutes. The primary endpoint was defined as major adverse cardiac events (MACEs). The provocation tests were performed with either acetylcholine (ACh, 57%) or ergonovine (40%). During the provocation tests, VT/VF and brady-arrhythmias developed at a rate of 3.2 and 2.7%, respectively. Overall incidence of arrhythmic complications was 6.8%, a comparable incidence of those during spontaneous angina attack (7.0%). Multivariable logistic regression analysis demonstrated that diffuse right coronary artery spasm (P < 0.01) and the use of ACh (P < 0.05) had a significant correlation with provocation-related VT/VF. During the median follow-up of 32 months, 69 patients (5.5%) reached the primary endpoint. The multivariable Cox proportional hazard model revealed that mixed (focal plus diffuse) type multivessel spasm had an important association with MACEs (adjusted hazard ratio, 2.84; 95% confidence interval, 1.34-6.03; P < 0.01), whereas provocation-related arrhythmias did not.Conclusion The spasm provocation tests have an acceptable level of safety and the evaluation of spasm type may provide useful information for the risk prediction of VSA patients.
    European Heart Journal 07/2012; 34(4). DOI:10.1093/eurheartj/ehs199 · 14.72 Impact Factor
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    ABSTRACT: Although the prognosis of patients with stress (takotsubo) cardiomyopathy is relatively favorable, serious complications occur in some patients. It is generally accepted that electrocardiography is an essential tool for the diagnosis of stress cardiomyopathy, with findings highly suggestive of the characteristics of myocardial damage. We tested the hypothesis that the quantitative analysis of electrocardiograhic changes can predict complications in stress cardiomyopathy. The study subjects were 85 patients with stress cardiomyopathy. A total of 34 patients developed ≥1 in-hospital complications (heart failure, intraventricular pressure gradient [>30 mm Hg], cardiogenic shock, ventricular tachycardia/fibrillation, and embolism). Patients with complications were likely to have a higher heart rate (96 ± 25 vs 76 ± 17 beats/min, p <0.001), larger sum of ST-segment elevation in 12 leads (median 10.5 mm; interquartile range 5.0 to 17.5 vs 3.0 mm, interquartile range 0 to 7.0; p <0.001) and extension of ST-segment elevation to limb leads (50% vs 12%, p <0.001) than those without complications. Multivariate logistic regression analysis identified heart rate (odds ratio 1.05, 95% confidence interval 1.02 to 1.07, p = 0.001) and sum of ST-segment elevation in 12 leads (odds ratio 1.24, 95% confidence interval 1.11 to 1.39, p <0.001) as significant and independent predictors of complications. Receiver operating characteristic analysis selected 5.5 mm as the best cutoff value of sum of ST-segment elevation in 12 leads for the prediction of complications, with a sensitivity and specificity of 74% and 73%, respectively, and area under the curve of 0.81 (95% confidence interval 0.72 to 0.90, p <0.001). The results suggest that the extent and magnitude of ST-segment elevation on the electrocardiogram are potentially useful predictors of in-hospital complications in patients with stress cardiomyopathy.
    The American journal of cardiology 03/2012; 109(11):1651-6. DOI:10.1016/j.amjcard.2012.01.393 · 3.43 Impact Factor
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    ABSTRACT: The aim of this study was to examine the effect of proton-pump inhibitor (PPI) on clinical outcomes in Japanese patients who undergo coronary stent implantation. A total of 1,270 patients (males 915, 69 years) were enrolled and dual antiplatelet therapy of aspirin and a thienopyridine derivative was prescribed (clopidogrel 630, ticlopidine 640). Patients were divided into 2 groups treated with or without PPI. PPI was administered in 331 cases (26%), and non-PPI in 939 (74%). There were no significant differences in cardiovascular death (PPI vs. non-PPI: 5 vs. 11 cases), nonfatal myocardial infarction (3 vs. 5), and stroke (3 vs. 16) between PPI and non-PPI groups, but the ratio of gastrointestinal events had a higher tendency in non-PPI group compared with PPI group (1 vs. 17, P=0.08). In subgroup analysis of patients taking clopidogrel, or patients with acute coronary syndrome, there was no significant difference in the ratio of cardiovascular events (7 vs. 16, 6 vs. 17, NS). The non-PPI group had a tendency of an increased risk of gastrointestinal events compared with the PPI group (0 vs. 9, P=0.06; 1 vs. 7, P=0.14). In contrast to the negative drug interaction of PPI reported elsewhere, in the present study the intake of PPI was not associated with an increased risk for adverse clinical outcomes in patients treated with stents.
    Circulation Journal 12/2011; 76(1):71-8. DOI:10.1253/circj.CJ-11-0699 · 3.69 Impact Factor
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    ABSTRACT: Statins have been reported to reduce cardiovascular events in patients with coronary artery disease (CAD). Percutaneous coronary intervention (PCI) is commonly used to relieve ischemic symptoms in patients with CAD. However, there is little information on the effect of statins on cardiovascular events after PCI, even in the era of coronary stent implantation. A total of 1019 patients with acute or chronic CAD and modest total cholesterol levels (180-240 mg/dl) were enrolled and randomly assigned to treatment with or without statins. We evaluated the effect of any available statin on the incidence of cardiovascular events after PCI. The primary endpoint was a composite of cardiovascular death, nonfatal acute myocardial infarction (MI), recurrent angina pectoris requiring emergency rehospitalization (rAP), heart failure, and stroke. Indications for PCI were stable angina in 54%, ST-elevation MI in 41% and non-ST-elevation MI/unstable angina pectoris in 5%. After 2 years of statin treatment, low-density lipoprotein cholesterol (LDL-C) decreased from 133 to 96 mg/dl. Stents were implanted in 84% of all cases. The primary endpoint event rate was 9.5% in the statin group and 14.7% in the non-statin group (p=0.0292). Of all primary endpoint events, only rAP was significantly suppressed by statins (p=0.0027). In rAP patients, coronary angiography revealed that statins suppressed restenosis but not new lesions. For Japanese CAD patients treated with PCI and stent implantation, statin therapy reduced the incidence of recurrent cardiovascular events, particularly rAP. Discretionary statin treatment to achieve LDL-C levels <100 mg/dl effectively reduced restenosis causing rAP.
    Journal of Cardiology 08/2011; 58(3):208-15. DOI:10.1016/j.jjcc.2011.07.002 · 2.57 Impact Factor
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    ABSTRACT: Coronary artery spasm plays an important role in the pathogenesis of ischemic heart disease; however, its role in sudden cardiac death remains to be fully elucidated. We examined the clinical characteristics and outcomes of patients with vasospastic angina (VSA) in our nationwide multicenter registry by the Japanese Coronary Spasm Association. Between September 2007 and December 2008, 1429 patients with VSA (male/female, 1090/339; median, 66 years) were identified. They were characterized by a high prevalence of smoking and included 35 patients who survived out-of-hospital cardiac arrest (OHCA). The OHCA survivors, as compared with the remaining 1394 non-OHCA patients, were characterized by younger age (median, 58 versus 66 years; P<0.001) and higher incidence of left anterior descending coronary artery spasm (72% versus 53%, P<0.05). In the OHCA survivors, 14 patients underwent implantable cardioverter-defibrillator (ICD) implantation while intensively treated with calcium channel blockers. Survival rate free from major adverse cardiac events was significantly lower in the OHCA survivors compared with the non-OHCA patients (72% versus 92% at 5 years, P<0.001), including appropriate ICD shocks for ventricular fibrillation in 2 patients. Multivariable analysis revealed that OHCA events were significantly correlated with major adverse cardiac events (hazard ratio, 3.25; 95% confidence interval, 1.39 to 7.61; P<0.01). These results from the largest vasospastic angina cohort indicate that vasospasm patients who survived OHCA are high-risk population. Further studies are needed to determine whether implantable cardioverter-defibrillator therapy improves patient prognosis.
    Circulation Arrhythmia and Electrophysiology 03/2011; 4(3):295-302. DOI:10.1161/CIRCEP.110.959809 · 5.42 Impact Factor
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    ABSTRACT: Previous studies have suggested that melatonin, a major pineal hormone, possibly modulates the autonomic nervous system in animals. The aim of this study was to examine the effects of melatonin administration on heart rate variability (HRV) in human beings. In 26 healthy men, melatonin (2 mg) or placebo was randomly administered. Power spectral analysis of HRV and blood pressure monitoring were performed in the supine position before and 60 minutes after administration and in the standing position 60 minutes after administration. Plasma catecholamine levels were also assessed. No differences in any baseline parameters were found between the two groups. Compared with placebo, melatonin administration within 60 minutes increased R-R interval, the square root of the mean of the squared differences between adjacent normal R-R intervals, high-frequency power, and low-frequency power of HRV and decreased the low-frequency to high-frequency ratio and blood pressure in the supine position (all P <.01). Plasma norepinephrine and dopamine levels in the supine position 60 minutes after melatonin administration were lower compared with placebo (P <.05 and P <.01, respectively). Standing up resulted in the decrease of HRV and the increase of blood pressure and plasma catecholamine levels in both administration groups, and the differences between the groups found in the supine position disappeared. These findings indicate that melatonin administration increased cardiac vagal tone in the supine position in awake men. Melatonin administration also may exert suppressive effects on sympathetic tone.
    American Heart Journal 05/2001; 141(5):E9. DOI:10.1067/mhj.2001.114368 · 4.56 Impact Factor
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    ABSTRACT: It has been reported that coronary endothelial dysfunction is associated with the pathogenesis of coronary spasm, and that endothelial nitric oxide (NO) mediated vasodilatation was decreased in coronary epicardial arteries in patients with coronary spastic angina (CSA). However, there are few reports about the endothelial function in peripheral resistance vessels of patients with CSA, so the present study investigated the role of NO in forearm resistance vessels in such patients. The responses of forearm blood flow to acetylcholine (ACh; 8-24 microg/min) and sodium nitroprusside (SNP; 0.4-1.2 microg/ml) infusions was examined using plethysmography, and subsequently the responses to ACh after an infusion of N(G)-monomethyl-L-arginine (L-NMMA; 4 micromol/min, for 5 min) in 17 patients with CSA and 17 age- and sex- matched controls. The vasodilator responses to ACh and SNP were comparable between the 2 groups (p=NS). L-NMMA significantly suppressed the vasodilator responses to ACh in controls (p<0.05), but there was no significant difference in the responses to ACh before and after infusion of L-NMMA in patients with CSA (p=NS). These results indicate that endothelial NO-mediated vasodilatation is decreased in the forearm resistance vessels of patients with CSA.
    Japanese Circulation Journal 03/2001; 65(2):81-6. DOI:10.1253/jcj.65.81
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    ABSTRACT: Although echocardiographically determined left ventricular mass and geometry predict cardiovascular morbid events in patients with hypertension, the mechanisms underlying this relation are unclear. There is considerable evidence that endothelium-dependent vasodilation is impaired in patients with hypertension. Thus, endothelial dysfunction may contribute to the mechanism that causes cardiovascular morbid events. This study was designed to examine the relationship between left ventricular geometry and endothelial function in patients with hypertension. The percentage increase in brachial arterial diameter during reactive hyperemia was examined by a high-resolution ultrasound technique in 49 patients with hypertension and 64 normotensive subjects. Patients with hypertension had an impairment of the percentage increase in brachial arterial diameter during reactive hyperemia and an increase in thiobarbituric acid-reactive substances (TBARS) compared to normotensive subjects (percentage increase in diameter 5.6 +/- 3.0 vs. 8.0 +/- 2.5%, p < 0.001; TBARS levels 6.1 +/- 1.3 vs. 5.3 +/- 1.0 nmol/ml, p < 0.001). In patients with hypertension, there was a significant correlation between the left ventricular mass index and the percentage increase in brachial arterial diameter during reactive hyperemia (r = -0.583, p < 0.001), and the percentage increase in brachial arterial diameter during reactive hyperemia varied with the pattern of left ventricular geometry (normal ventricular geometry: 7.7 +/- 2.6%; concentric remodeling: 5.2 +/- 2.3%; eccentric hypertrophy: 4.2 +/- 1.8%; concentric hypertrophy: 2.9 +/- 2.6%). We conclude that (1) flow-mediated endothelium-dependent vasodilation in the brachial artery is impaired in patients with hypertension, (2) a relationship exists between the left ventricular mass index and flow-mediated endothelium-dependent vasodilation in the brachial artery in patients with hypertension and (3) increased oxidative stress may play a role in the endothelial dysfunction in patients with hypertension.
    Cardiology 01/2001; 96(1):7-15. DOI:10.1159/000047380 · 2.04 Impact Factor
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    ABSTRACT: Dehydroepiandrosterone sulfate (DHEAS) is the major secretory steroid of the human adrenal glands. The secretion of DHEAS decreases with aging. The incidence of heart failure also rises in the elderly population. We measured the plasma levels of DHEAS and cortisol in 49 patients with chronic heart failure (CHF) and 32 age-matched controls and assessed its relation to plasma levels of A-type natriuretic peptide and B-type natriuretic peptide, biochemical markers of heart failure. Plasma levels of DHEAS were significantly lower in patients with CHF than in controls, whereas there was no significant difference in plasma levels of cortisol between the two groups. In stepwise regression analysis, the plasma level of DHEAS was significantly and independently correlated with age (beta = -0.451; P < 0.0001) and the plasma level of B-type natriuretic peptide (beta = -0.338; P < 0.001), and the plasma cortisol/DHEAS ratio was significantly and independently correlated with the plasma levels of A-type natriuretic peptide (beta = 0.598; P < 0.0001) and thiobarbituric acid-reactive substances (a marker of oxidative stress; beta = 0.252; P < 0.01) and age (beta = 0.171; P < 0.05). These results indicate that the plasma levels of DHEAS are decreased in patients with CHF in proportion to its severity and that oxidative stress is associated with decreased levels of DHEAS in patients with CHF.
    Journal of Clinical Endocrinology &amp Metabolism 06/2000; 85(5):1834-40. DOI:10.1210/jcem.85.5.6568 · 6.31 Impact Factor
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    ABSTRACT: Remnant lipoproteins are atherogenic, but assays of remnants have not been available in routine clinical laboratories because of the lack of practical and validated methods. A simple and reliable method for such an assay, using an immunochemical approach, has recently been developed. This study prospectively examined whether remnant lipoprotein levels in fasting serum, measured by our method, may have prognostic value in patients with coronary artery disease (CAD). Remnant lipoprotein levels in fasting serum were measured in 135 patients with CAD by an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-1 and anti-apoB-100 monoclonal antibodies. Patients were followed up for </=36 months until occurrence of 1 of the following clinical coronary events: recurrent or refractory angina pectoris requiring coronary revascularization, nonfatal myocardial infarction, or cardiac death. Kaplan-Meier analysis demonstrated a significantly higher probability of developing coronary events in patients with the highest tertile of remnant levels (>5.1 mg cholesterol/dL; 75th percentile of distribution of remnant levels) than in those with the lowest tertile of remnant levels (</=3.3 mg cholesterol/dL; 50th percentile of the distribution). Higher levels of remnants were a significant and independent predictor of developing coronary events in multivariate Cox hazard analysis including the following covariates: extent of coronary artery stenosis, age, sex, smoking, hypertension, diabetes mellitus, hypercholesterolemia, low HDL cholesterol, and hypertriglyceridemia. Higher levels of remnant lipoproteins in fasting serum predict future coronary events in patients with CAD independently of other risk factors. Thus, measurement of fasting remnant levels, assessed by the current immunoseparation method, may be helpful in assessment of CAD risk.
    Circulation 06/1999; 99(22):2858-60. DOI:10.1161/01.CIR.99.22.2858 · 14.95 Impact Factor
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    ABSTRACT: OBJECTIVESThis study sought to examine whether oral intake of alpha-tocopherol, an antioxidant, could improve endothelium-dependent vasorelaxation in patients with high remnant lipoproteins levels.BACKGROUNDRemnant lipoproteins are known to be atherogenic and impair endothelium-dependent arterial relaxation, but the underlying mechanisms remain unclear. Oxidative stress is a common feature of various risk factors for atherosclerosis.METHODSFlow-mediated vasodilation of the brachial artery during reactive hyperemia was examined by high resolution ultrasound technique before and at the end of 4 weeks treatment with oral administration of alpha-tocopherol acetate (300 IU/day) or placebo, which was randomly assigned, in 40 patients with high serum levels of remnants and in 30 patients with low remnants levels in the fasting state (>75th percentile and <25th percentile, respectively, of the distribution of remnants levels in 150 consecutive hospitalized patients).RESULTSBefore treatment, flow-mediated vasodilation was lower in patients with high remnants levels than in those with low levels (4.1 ± 0.3% vs. 6.0 ± 0.5%, p < 0.01). Treatment with alpha-tocopherol but not with placebo significantly increased flow-mediated dilation in patients with high remnants levels (7.5 ± 0.4% after alpha-tocopherol vs. 4.2 ± 0.4% after placebo, p < 0.01). In patients with low remnants levels, alpha-tocopherol was not effective. The beneficial effect with alpha-tocopherol in high remnants patients was associated with decrease in plasma levels of thiobarbituric acid reactive substances, an indicator of lipid peroxidation (6.6 ± 0.3 nmol/ml before alpha-tocopherol vs. 4.6 ± 0.3 after alpha-tocopherol, p < 0.05).CONCLUSIONSAlpha-tocopherol improved impairment of endothelium-dependent vasodilation in patients with high remnants levels. The increase in oxidative stress may at least partly contribute to endothelial vasomotor dysfunction in patients with high remnants levels.
    Journal of the American College of Cardiology 05/1999; 33(6-33):1512-1518. DOI:10.1016/S0735-1097(99)00057-1 · 15.34 Impact Factor
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    ABSTRACT: We examined the effects of oral administration of vitamin E, an antioxidant, on endothelium-dependent vasodilation in patients with coronary spastic angina. We have recently reported that endothelium-dependent vasodilation is impaired in patients with coronary spastic angina (CSA). Furthermore, it is known that oxidative stress may play an important role in the impairment of endothelium-dependent vasodilation in cardiovascular diseases. With the ultrasound technique, flow-dependent vasodilation of the brachial arteries during reactive hyperemia was examined before and after treatment for a month with either oral administration of vitamin E (alpha-tocopherol acetate, 300 mg/day) or placebo, which is randomly assigned, in patients with CSA (n=60). Before treatment, patients with CSA had impaired flow-dependent vasodilation, lower plasma levels of alpha-tocopherol and higher plasma levels of thiobarbituric acid reactive substances (TBARS), as compared with age- and sex-matched control subjects (n=60) (flow-dependent vasodilation: 3.1+/-1.8 vs. 7.1+/-2.5%, p < 0.001; alpha-tocopherol levels: 8.9+/-1.8 vs. 10.8+/-1.8 microg/ml, p < 0.001). In patients with CSA, treatment with vitamin E restored flow-dependent vasodilation (3.1+/-1.7 vs. 8.3+/-2.0%, p < 0.001), and this improvement was associated with the decreases in plasma TBARS levels and anginal attacks. The results indicate that vitamin E treatment improved endothelium-dependent vasodilation and decreased plasma TBARS levels in patients with CSA. Thus, increased oxidative stress may contribute to endothelial dysfunction and anginal attacks in patients with CSA.
    Journal of the American College of Cardiology 12/1998; 32(6):1672-9. DOI:10.1016/S0735-1097(98)00447-1 · 15.34 Impact Factor
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    ABSTRACT: The effects of pilsicainide on vagally induced atrial fibrillation and on electrophysiological parameters were compared with those of propafenone in alpha-chloralose-anesthetized dogs. Conduction velocity, effective refractory period, wavelength, averaged atrial fibrillation cycle length and activation sequence in the right atrial free wall were determined before and after drug administration. Pilsicainide (2 mg/kg/5 min and 3 mg/kg/h)(n=10) or propafenone (2 mg/kg/15 min and 4 mg/kg/h)(n=10) was intravenously infused during stable atrial fibrillation sustaining > 30 min. Pilsicainide terminated atrial fibrillation in nine dogs, while propafenone did so in three (p < 0.01). After the drug, conduction velocity was suppressed more in the pilsicainide than in the propafenone group(p < 0.01). There was no difference in effective refractory period after drug between the two groups. Mean wavelength was prolonged from 46.0 to 70.4 mm in the pilsicainide group and from 45.0 to 110.8 mm in the propafenone (p < 0.01 vs. pilsicainide). Activation mapping during atrial fibrillation showed Type II or III atrial fibrillation as previously defined [Konings, K.T.S., Kirchhof, C.J.H.J., Smeets, J.R.L.M., Wellens, H.J.J., Penn, O.C., Allessie, M.A., 1994. High-density mapping of electrically induced atrial fibrillation in humans. Circulation. Vol. 89, pp. 511-521.] before the drug, and changed to Type I before atrial fibrillation termination. Thus, pilsicainide was more effective to terminate vagally induced atrial fibrillation than was propafenone despite a greater effect of propafenone than of pilsicainide on wavelength. In this canine atrial fibrillation model, the suppression of conduction velocity may play an important role in changing the activation pattern of atrial fibrillation and thus, terminating atrial fibrillation.
    European Journal of Pharmacology 09/1998; 356(1):31-40. DOI:10.1016/S0014-2999(98)00506-8 · 2.68 Impact Factor

Publication Stats

795 Citations
204.54 Total Impact Points


  • 2011–2015
    • Japanese Red Cross
      Edo, Tōkyō, Japan
  • 2011–2014
    • Japan Red Cross Fukuoka Hospital
      Hukuoka, Fukuoka, Japan
  • 1994–2001
    • Kumamoto University
      • Department of Cardiovascular Medicine
      Kumamoto, Kumamoto, Japan