Ken Umetani

University of Yamanashi, Kōhu, Yamanashi, Japan

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Publications (61)159.75 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Adiponectin, the most abundant protein secreted from adipose tissue, possesses anti-atherogenic properties. This study tested whether adiponectin plasma levels predict in-stent restenosis (ISR) after successful percutaneous coronary intervention (PCI) with bare-metal stents. The study included 148 consecutive patients who had elective PCI with bare-metal stents in de novo lesions of native coronary arteries for symptomatic coronary artery disease. Adiponectin levels were measured by ELISA 3 days or less before PCI. Angiographic ISR (defined as >50% diameter stenosis) was found in 49 (33%) patients during 6 months of the follow-up. Adiponectin levels were lower in patients with ISR than those without ISR (3.5+/-0.3 vs. 6.9+/-0.4 microg/ml, respectively, p<0.01). Adiponectin levels were inversely correlated with late luminal loss of the stented lesions (r=-0.40, p<0.01). Using multivariate logistic regression analysis, low adiponectin levels (<4.5 microg/ml, arbitrarily determined from a receiver operating characteristic curve) served as a predictor of ISR that was independent of angiographic and procedural variables, and clinical factors known to be associated with ISR (odds ratio, 7.9; 95% CI, 3.0-21; p<0.01). Furthermore, low adiponectin levels also independently predicted target lesion revascularization (n=35) during follow-up (odds ratio, 3.7; 95% CI, 1.4-9.7; p<0.01). Low adiponectin levels have a predictive value for late ISR after PCI with bare-metal stents in native coronary arteries.
    International journal of cardiology 12/2008; 131(1):78-82. DOI:10.1016/j.ijcard.2007.09.004 · 6.18 Impact Factor
  • Ken Umetani, Sadayoshi Komori
    Nippon rinsho. Japanese journal of clinical medicine 09/2007; Suppl 4:271-5.
  • Atherosclerosis 09/2007; 193(2):449-51. DOI:10.1016/j.atherosclerosis.2006.08.028 · 3.97 Impact Factor
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    ABSTRACT: Angiogenic growth factors, produced in the myocardium and coronary vascular bed, increase myocardial blood flow. This study examined whether plasma levels of vascular endothelial growth factor (VEGF) in coronary circulation may be related to coronary blood flow responses. Blood flow responses in the left anterior descending coronary artery to an intracoronary infusion of acetylcholine (ACh) were measured by an intracoronary flow wire technique in 46 consecutive control subjects with normal coronary angiograms and left ventriculograms. Circulating VEGF levels were measured by ELISA in plasma obtained from the aortic root (AO) and anterior interventricular vein (AIV). The transcardiac gradient of VEGF, calculated by the difference in VEGF concentrations between the AIV and AO, showed a positive correlation with the coronary blood flow increase in response to ACh independently of traditional coronary risk factors. In patients with cardiac syndrome X (n=17), defined as a positive exercise stress test with a normal coronary angiograms and left ventriculogram, the transcardiac VEGF gradient was significantly lower than in the risk factors-matched control subjects (n=21). The transcardiac gradient of plasma VEGF was independently and positively correlated with the coronary blood flow increase in response to ACh. A reduced transcardiac VEGF gradient was present in cardiac syndrome X, a condition with a blunted coronary blood flow response.
    International journal of cardiology 08/2007; 119(2):156-62. DOI:10.1016/j.ijcard.2006.07.112 · 6.18 Impact Factor
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    ABSTRACT: Because metabolic syndrome is associated with cardiovascular diseases, its association with the risk of paroxysmal atrial fibrillation (PAF) and/or atrial flutter (PAFL) was examined in the present study. A prospective analysis was performed in 592 consecutive hospitalized patients without obvious structural heart diseases. Sinus rhythm was confirmed by electrocardiography in all patients. PAF/PAFL occurred in 32 (5%) and metabolic syndrome was present in 127 (21%) of the patients enrolled. PAF/PAFL occurred in 12 (9%) of the patients with metabolic syndrome, but only 20 (4%) of patients without metabolic syndrome (p=0.02). Multivariate logistic regression analysis showed that metabolic syndrome was a significant risk factor for PAF/PAFL that was independent of left atrial diameter (> 44 mm) or age (> 70 years) (odds ratio (OR) 2.8, 95% confidence interval (CI) 1.3-6.2, p<0.01). Among the 5 components of the metabolic syndrome, body mass index > or = 25 kg/m2 was the most strongly associated with PAF/PAFL (OR; 3.0, 95% CI 1.2-7.4, p=0.02). Metabolic syndrome is highly associated with PAF/PAFL in patients without structural heart diseases and obesity may be an underlying mechanism for the higher prevalence.
    Circulation Journal 03/2007; 71(2):252-5. DOI:10.1253/circj.71.252 · 3.69 Impact Factor
  • Annals of the New York Academy of Sciences 12/2006; 783(1):330 - 332. DOI:10.1111/j.1749-6632.1996.tb26735.x · 4.38 Impact Factor
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    ABSTRACT: This study examined whether atorvastatin increases plasma levels of soluble Fms-like tyrosine kinase 1 (sFlt-1) and reciprocally decreases vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) levels in patients with acute myocardial infarction (AMI). Statins exert cardioprotective actions partly through anti-inflammatory actions. By capturing VEGF and PlGF in plasma, sFlt-1 acts as a natural inhibitor of VEGF and PlGF, which have proinflammatory properties. Left ventriculography and enzyme-linked immunosorbent assay of plasma levels of sFlt-1, VEGF, and PlGF were repeated after AMI in 50 consecutive patients with a first AMI. Patients were randomized to treatment with atorvastatin (10 mg/day; n=25) or placebo (n=25) within 3 days after AMI, and therapy was continued for 6 months. The sFlt-1 levels were low in the acute phase, followed by an increase at 2 weeks after AMI, whereas free VEGF and PlGF levels were high in the acute phase, followed by a decrease at 2 weeks. Atorvastatin increased sFlt-1 levels and reciprocally decreased VEGF and PlGF levels at 6 months compared with placebo. The increase in sFlt-1 levels and the decrease in VEGF and PlGF levels were correlated with improvement of left ventricular ejection fraction during the follow-up period. There was a reciprocal relationship between changes in sFlt-1 levels and changes in VEGF and PlGF levels after AMI; and atorvastatin increased sFlt-1 levels while decreasing VEGF and PlGF levels. These changes were associated with late improvement of post-MI ventricular function, and may represent an additional benefit of statin therapy.
    Journal of the American College of Cardiology 08/2006; 48(1):43-50. DOI:10.1016/j.jacc.2006.03.035 · 15.34 Impact Factor
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    ABSTRACT: Adiponectin, an adipocyte-derived protein, has cardioprotective actions. We elucidated the role of the adiponectin receptors AdipoR1 and AdipoR2 in the effects of adiponectin on endothelin-1 (ET-1)-induced hypertrophy in cultured cardiomyocytes, and we examined the expression of adiponectin receptors in normal and infarcted mouse hearts. Recombinant full-length adiponectin suppressed the ET-1-induced increase in cell surface area and [(3)H]leucine incorporation into cultured cardiomyocytes compared with cells treated with ET-1 alone. Transfection of small interfering RNA (siRNA) specific for AdipoR1 or AdipoR2 reversed the suppressive effects of adiponectin on ET-1-induced cellular hypertrophy in cultured cardiomyocytes. Adiponectin induced phosphorylation of AMP-activated protein kinase (AMPK) and inhibited ET-1-induced ERK1/2 phosphorylation, which were also reversible by transfection of siRNA for AdipoR1 or AdipoR2 in cultured cardiomyocytes. Transfection of siRNA for alpha(2)-catalytic subunits of AMPK reduced the inhibitory effects of adiponectin on ET-1-induced cellular hypertrophy and ERK1/2 phosphorylation. Effects of globular adiponectin were similar to those of full-length adiponectin, and siRNA for AdipoR1 reversed the actions of globular adiponectin. Compared with normal left ventricle, expression levels of AdipoR1 mRNA and protein were decreased in the remote, as well as the infarcted, area after myocardial infarction in mouse hearts. In conclusion, AdipoR1 and AdipoR2 mediate the suppressive effects of full-length and globular adiponectin on ET-1-induced hypertrophy in cultured cardiomyocytes, and AMPK is involved in signal transduction through these receptors. AdipoR1 and AdipoR2 might play a role in the pathogenesis of ET-1-related cardiomyocyte hypertrophy after myocardial infarction.
    AJP Heart and Circulatory Physiology 07/2006; 290(6):H2409-16. DOI:10.1152/ajpheart.00987.2005 · 4.01 Impact Factor
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    ABSTRACT: This study aimed to determine whether elevated levels of remnant lipoprotein, an atherogenic triglyceride-rich lipoprotein, might be associated with coronary artery disease (CAD) and endothelial vasomotor dysfunction in metabolic syndrome. The fasting serum levels of remnant lipoproteins (remnant-like lipoprotein particles cholesterol; RLP-C) were measured by an immunoseparation method in 210 patients with metabolic syndrome meeting ATP III criteria. Flow-mediated endothelium-dependent dilatation (FMD) in the brachial artery during reactive hyperemia was examined by high-resolution ultrasound technique. This study found that elevated RLP-C levels were a significant and independent risk factor for impaired FMD and angiographically proven coronary artery disease (CAD). Treatment with bezafibrate (n = 20) or atorvastatin (n = 20) for 4 weeks significantly reduced RLP-C levels, with a concomitant improvement in FMD. The % reduction in RLP-C levels from baseline after the treatment was independently correlated with the magnitude of improvement in FMD after adjustment for the % changes in levels of triglyceride, hsCRP, and IL-6, and HOMA index. Thus, elevated levels of RLP-C are a risk factor for CAD and endothelial vasomotor dysfunction, a predictor of coronary events, in metabolic syndrome. Measurement of RLP-C is useful for assessment of CAD risk and therapeutic effects in metabolic syndrome.
    Atherosclerosis 09/2005; 181(2):321-7. DOI:10.1016/j.atherosclerosis.2005.01.012 · 3.97 Impact Factor
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    ABSTRACT: This study examined whether endothelial dysfunction in the brachial artery might be associated with late in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). Simple and noninvasive identification of late ISR might help to select patients who require further angiographic evaluation. Endothelium-dependent flow-mediated dilation (FMD) of the brachial artery was measured before (initial FMD) and at six months (follow-up FMD) after PCI in 141 consecutive patients who had elective and successful PCI with bare metal stents in de novo lesions of native coronary arteries for symptomatic coronary artery disease. Follow-up angiography was performed at six months after PCI in all patients. With multivariate logistic regression analysis, the impairment (< or = 4.8% dilation from baseline diameter) of FMD at follow-up showed the strongest association with late ISR (defined as > 50% diameter stenosis, n = 46) independently of other clinical and angiographic variables known to be associated with ISR (odds ratio 7.4, 95% confidence interval 2.8 to 19.2, p < 0.001), whereas the initial FMD did not have the association. The sensitivity of impaired FMD at follow-up (69%) in detecting ISR was higher than chest pain during the follow-up period (45%), with comparable specificity. The impaired FMD in combination with the chest pain increased the sensitivity to 90%. The impairment of FMD in the brachial artery at the time of follow-up was independently and closely associated with late ISR in native coronary arteries. The noninvasive assessment of FMD at the time of follow-up might be useful for identification of late ISR.
    Journal of the American College of Cardiology 08/2005; 46(4):648-55. DOI:10.1016/j.jacc.2005.04.055 · 15.34 Impact Factor
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    ABSTRACT: This study was aimed to determine the relationship between pulse pressure (PP) and coronary vasomotor dysfunction, a predictor of coronary events. Pulse pressure is a strong risk factor for coronary artery disease (CAD). However, the mechanisms by which an increase in PP affects the pathogenesis of CAD are unclear. Ambulatory blood pressure (BP) monitoring for 24 h was performed in 103 consecutive patients with normal coronary angiograms (51 hypertensive and 52 normotensive; age 42 to 70 years). The relationship between changes in coronary arterial diameter and blood flow during an intracoronary infusion of acetylcholine (ACh) (5, 10, 50 microg/min), and BP parameters, and other traditional risk factors was evaluated using univariate and multivariate linear regression analyses. With multivariate analyses, the 24-h PP showed an inverse correlation with the epicardial coronary dilator response to ACh independently of other covariates including age, smoking, and 24-h systolic BP in normotensive as well as hypertensive patients. Furthermore, multivariate analysis showed that the 24-h PP was inversely and independently correlated with the increase in coronary blood flow in response to ACh. The dilator response of epicardial coronary arteries to nitrate was not significantly correlated with 24-h PP. Increased 24-h PP is independently associated with endothelial vasomotor dysfunction in conduit and resistance coronary arteries irrespective of the presence of hypertension. Increased ambulatory PP may have an intimate relation to coronary endothelial vasomotor dysfunction.
    Journal of the American College of Cardiology 06/2005; 45(9):1461-6. DOI:10.1016/j.jacc.2005.01.038 · 15.34 Impact Factor
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    ABSTRACT: Secretion of A-type (atrial) and B-type (brain) natriuretic peptides (ANP and BNP) increases in relation to left ventricular (LV) dysfunction in patients with myocardial infarction (MI). However, it is unknown what determines the concentrations of ANP and BNP in asymptomatic MI patients with preserved LV function, so the aim of the present study was to examine if they are associated with MI size. Plasma concentrations of ANP and BNP in the peripheral blood were measured in 88 asymptomatic (New York Heart Association class I) patients with previous MI. The infarct size was quantitatively calculated from rest thallium-201 myocardial single photon emission computed tomography. In multivariate linear regression analysis that included MI size, hemodynamic parameters, and age as covariables, only BNP concentrations had a significant association with MI size (p=0.0001). In contrast, ANP concentrations were not significantly correlated with MI size in either the univariate or multivariate analysis. BNP but not ANP concentrations increased in proportion to the scintigraphic MI size despite the lack of heart failure in asymptomatic patients with previous MI. Thus, the increase in plasma BNP concentrations reflects the MI size, an important determinant of prognosis, in asymptomatic patients with MI.
    Circulation Journal 11/2004; 68(10):923-7. · 3.69 Impact Factor
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    ABSTRACT: Increased pulse pressure (PP) is recognized as a risk factor for cardiovascular disease, especially in elderly patients. However, blood pressure (BP) is known to have a circadian variation. Therefore, this study asked whether or not PP has a circadian variation and, if so, whether a circadian variation of PP has clinical importance. Ambulatory BP monitoring (every 30 min for 48 h) was performed in 255 patients with untreated essential hypertension (24 to 82 years old; mean: 52+/-12 years). Left ventricular mass index (LVMI) was estimated from M-mode echocardiography. PP was decreased during nighttime (10+/-11% reduction from daytime PP). Multivariate linear regression analysis showed that, among four variables-the degree of nighttime PP reduction, daytime PP, 48-h systolic BP, and nondipper hypertension-the degree of nighttime PP reduction had the strongest (inverse) correlation with LVMI in a subgroup of elderly patients (> or =60 years old, n =67) (standardized regression coefficient=-0.32, p =0.02), whereas this association was not significant in the whole patient population unclassified by age. Furthermore, a blunted reduction of nighttime PP in combination with nondipper hypertension was an incremental risk for increase in LVMI in the elderly patients. In conclusion, PP is reduced during nighttime, but the degree of reduction varies among patients. The blunted reduction of nighttime PP is a risk for left ventricular hypertrophy, an established predictor of hypertension-induced cardiovascular events, and it may thus play a role in cardiovascular complications, especially in elderly patients with nondipper hypertension.
    Hypertension Research 09/2004; 27(8):573-9. DOI:10.1291/hypres.27.573 · 2.94 Impact Factor
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    ABSTRACT: A 78-year-old woman with arteriosclerosis obliterans was admitted with complaints of progressive ischemic change and resting pain of the left leg. She had severe ischemic limb in stage IV of the Fontaine classification. Angiography showed total occlusion of the three main arteries with poor collateral flow at the left crus. Autologous transplantation of bone-marrow mononuclear cell to her left leg was performed to achieve therapeutic angiogenesis. One month later, follow-up angiography showed excellent angiogenesis of collateral vessels at the left crus. Her pain was relieved and leg amputation was not necessary. Recently, the TACT study in Japan showed the efficacy of angiogenesis by autologous bone-marrow transplantation for peripheral artery disease. This case illustrates the efficacy of this therapy.
    Journal of Cardiology 05/2004; 43(4):179-83. · 2.57 Impact Factor
  • Circulation Journal 01/2004; 68(10):923-927. DOI:10.1253/circj.68.923 · 3.69 Impact Factor
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    ABSTRACT: Two patients with amiodarone-induced pulmonary toxicity (APT) showed abnormally increased serum SP-D concentrations, although their KL-6 level was within the normal range. In a 59-year-old man with ischemic heart disease, APT progressed rapidly and required steroid pulse therapy. During the clinical course, SP-D was as high as 375 ng/ml, although the KL-6 level was only 289 U/ml. In a 58-year-old man treated for dilated cardiomyopathy, SP-D increased to 289 ng/ml, while KL-6 remained at less than 500 U/ml. These cases indicate that SP-D is a useful and early diagnostic marker for APT even when KL-6 is not elevated.
    Internal Medicine 10/2002; 41(9):709-12. · 0.97 Impact Factor
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    ABSTRACT: Two patients with amiodarone-induced pulmonary toxicity (APT) showed abnormally increased serum SP-D concentrations, although their KL-6 level was within the normal range. In a 59-year-old man with ischemic heart disease, APT progressed rapidly and required steroid pulse therapy. During the clinical course, SP-D was as high as 375 ng/ml, although the KL-6 level was only 289 U/ml. In a 58-year-old man treated for dilated cardiomyopathy, SP-D increased to 289 ng/ml, while KL-6 remained at less than 500 U/ml. These cases indicate that SP-D is a useful and early diagnostic marker for APT even when KL-6 is not elevated.
    Internal Medicine 09/2002; 41(9):709-712. DOI:10.2169/internalmedicine.41.709 · 0.97 Impact Factor
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    ABSTRACT: Heat resistance appears to cycle in concert with energy metabolism in continuous culture of the yeast Saccharomyces cerevisiae. To study the mechanism of this oscillation, the authors first examined if heat shock proteins (Hsps) are involved. Neither the protein levels of major Hsps nor the expression of the beta-galactosidase gene as a reporter under the control of the promoter carrying heat-shock element oscillated during the metabolic oscillation. The level of trehalose in yeast cycled with the same periodicity, as did energy metabolism. This oscillation was not found in a GTS1-deleted mutant that also did not show cyclic changes in heat resistance. These results suggest that heat resistance oscillation is induced by fluctuations in trehalose level and not by an oscillatory expression of Hsps. The increase in trehalose began at the start of the respiro-fermentative phase and the decrease began after the elevation of the cyclic adenosine monophosphate (cAMP) level. The authors hypothesize that the synthesis of trehalose parallels the activation of the glycolytic pathway and that trehalose is degraded by trehalase activated by cAMP coupled with the metabolic oscillation in the continuous culture of yeast.
    Chronobiology International 04/2002; 19(2):361-75. DOI:10.1081/CBI-120002916 · 2.88 Impact Factor
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    ABSTRACT: Atrial standstill is electrophysiologically characterized by the loss of spontaneous excitation in atrial muscle and the inability to cause action potential firing upon electrical stimulation. Clinical diagnosis of transient standstill of the right atrium was made in a patient with acute occlusion of the right coronary artery and acute renal failure. Percutaneous coronary intervention, performed 5 days after the onset, restored the coronary blood flow and resulted in full recovery of electrical activity and regular sinus rhythm.
    Pacing and Clinical Electrophysiology 03/2002; 25(2):217-9. DOI:10.1046/j.1460-9592.2002.00217.x · 1.25 Impact Factor
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    ABSTRACT: Hot bathing has been associated with sudden death and so the present study investigated its effects on autonomic activity and hemodynamics in the elderly patient and the healthy young by analyzing heart rate variability (HRV). Subjects were 9 elderly men (mean age, 75 years) and 9 young men (mean age, 27 years), who were immersed up to shoulder level while in a sitting position for 10min with the bath temperature at 40 degrees C. Blood pressure (BP) and heart rate (HR) were monitored. BP in the young decreased during bathing (p<0.01), whereas in the elderly BP had a maximum value just at the start of immersion (p<0.05) with a slight decline at 4 min after the start of immersion. Although HR in the young increased (p<0.01), in the elderly there was an abrupt increase in HR just at the start of immersion (p<0.05), followed by a decrease in HR. With regard to HRV, the high-frequency (HF) component in the young men was suppressed during immersion (p<0.01), but was unaffected in the elderly. The LF (low frequency)/HF ratio in the elderly decreased at 4 min (p<0.05). In conclusion, hypotensive syncope may cause sudden death by drowning during hot bathing, and is a consequence of the decrease in sympathetic tone that develops approximately 4min after immersion.
    Japanese Circulation Journal 08/2001; 65(7):587-92.