Tokyo, Japan
Tokyo, Japan

Time filter

Source Type

Background: The Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS) trial has found that early aggressive statin therapy in patients with acute coronary syndrome (ACS) significantly reduces the plaque volume (PV) of non-culprit coronary lesions. The purpose of the present study was to evaluate clinical factors that have an impact on plaque regression using statin therapy. Methods and Results: Serial intravascular ultrasound observations over 8-12 months were performed in 252 ACS patients receiving pitavastatin or atorvastatin. Linear regression analysis identified the presence of diabetes mellitus (DM) and PV at baseline as inhibiting factors, and serum remnant-like particle-cholesterol level at baseline as a significant factor significantly affecting the degree of plaque regression. Significant correlation between % change of PV and low-density lipoprotein cholesterol (LDL-C) level was found in patients with DM (n=73, P<0.05, r=0.4), whereas there was no significant correlation between the 2 parameters in patients without DM (n=178). Conclusions: The regression of coronary plaque induced by statin therapy after ACS was weaker in diabetic patients than their counterparts. Moreover, vigorous reduction of the LDL-C levels might induce a greater degree of plaque regression in ACS patients with DM.


Kawashiri M.-A.,Kanazawa University | Yamagishi M.,Kanazawa University | Sakamoto T.,Saiseikai Kumamoto Hospital | Takayama T.,Nihon University | And 6 more authors.
Cardiovascular Therapeutics | Year: 2013

Background: Previous studies have demonstrated that intensive lipid lowering using rosuvastatin results in regression of coronary plaques. However, few data exist regarding lipid profiles over time, drug tolerability, and the effects of prior use of lipid lowering agents in patients on rosuvastatin treatment. Therefore, we studied these matters in a subanalysis of the Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects (COSMOS). Methods: Rosuvastatin was titrated for 76 weeks to attain LDL-C < 80 mg/dL in 213 Japanese dyslipidemic patients with CAD. Clinic visits were scheduled for every 4 weeks during the 76-week study period. Changes over time in lipid parameters, changes in those according to prior lipid-lowering therapy, and changes in those according to baseline lipid levels were evaluated in this subanalysis. Results: Overall, 126 patients completed the study. The mean rosuvastatin dose at the last observation carried forward was 16.9 mg (range, 2.5-20 mg). Rosuvastatin significantly increased HDL-C, lowered LDL-C, and improved the LDL-C/HDL-C ratio (all, P < 0.0001). Increases in serum HDL-C levels were significantly greater in patients with HDL-C < 40 mg/dL than in those with HDL-C ≥ 40 mg/dL at baseline (P = 0.0005). The estimated glomerular filtration rate increased significantly by 2.84 ± 9.01 mL/min/1.73 m2 (P < 0.0001). Of 166 adverse events in 74 patients, 113 events in 54 patients were laboratory values beyond the normal range. Conclusion: Rosuvastatin significantly improved lipid profiles, with an acceptable safety profile, contributing to plaque regression in Japanese patients with CAD. © 2013 John Wiley & Sons Ltd.


Daida H.,Juntendo University | Takayama T.,Nihon University | Hiro T.,Nihon University | Yamagishi M.,Kanazawa University | And 4 more authors.
Cardiovascular Diabetology | Year: 2012

Background: The incidence of cardiac events is higher in patients with diabetes than in people without diabetes. The Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects (COSMOS) demonstrated significant plaque regression in Japanese patients with chronic coronary disease after 76 weeks of rosuvastatin (2.5 mg once daily, up-titrated to a maximum of 20 mg/day to achieve LDL cholesterol <80 mg/dl).Methods: In this subanalysis of COSMOS, we examined the association between HbA1c and plaque regression in 40 patients with HbA1c ≥6.5% (high group) and 86 patients with HbA1c <6.5% (low group).Results: In multivariate analyses, HbA1c and plaque volume at baseline were major determinants of plaque regression. LDL cholesterol decreased by 37% and 39% in the high and low groups, respectively, while HDL cholesterol increased by 16% and 22%, respectively. The reduction in plaque volume was significantly (p = 0.04) greater in the low group (from 71.0 ± 39.9 to 64.7 ± 34.7 mm3) than in the high group (from 74.3 ± 34.2 to 71.4 ± 32.3 mm3). Vessel volume increased in the high group but not in the low group (change from baseline: +4.2% vs -0.8%, p = 0.02). Change in plaque volume was significantly correlated with baseline HbA1c.Conclusions: Despite similar improvements in lipid levels, plaque regression was less pronounced in patients with high HbA1c levels compared with those with low levels. Tight glucose control during statin therapy may enhance plaque regression in patients with stable coronary disease.Trial registration: ClinicalTrials.gov, Identifier NCT00329160. © 2012 Daida et al.; licensee BioMed Central Ltd.


Higuchi T.,Keiai Hospital | Abe M.,Nihon University | Yamazaki T.,Keiai Hospital | Okawa E.,Keiai Hospital | And 6 more authors.
American Journal of Kidney Diseases | Year: 2016

Background Levocarnitine deficiency in hemodialysis patients is common. Although the effect of levocarnitine therapy on uremic anemia has been studied in small trials, its effects on cardiac function remain unclear. Study Design Multicenter, prospective, open-label, parallel, randomized, controlled trial. Setting & Participants Patients undergoing maintenance hemodialysis with carnitine deficiency (free carnitine plasma concentration < 40 μmol/L) enrolled in 3 hemodialysis centers. Intervention Random assignment to treatment for 12 months with oral levocarnitine therapy at a dose of 20 mg/kg/d or control group (no levocarnitine therapy). Outcomes & Measurements Cardiac function was assessed by echocardiography. The primary end point was change in ejection fraction from baseline at the end of the study. Secondary end points included changes in left ventricular mass index and clinical parameters from baseline at the end of the study. Results 222 patients were randomly assigned, of whom 148 patients (levocarnitine group, n = 75; control group, n = 73) were analyzed. Ejection fraction increased from baseline to the end of the study in the levocarnitine group by 5.43% (95% CI, 4.53%-6.32%), but not in the control group (change, -0.14%; between-group difference, 5.57% [95% CI, 4.48%-6.66%]; P < 0.001). Left ventricular mass index decreased from baseline to the end of the study in the levocarnitine group (change of -8.89 [95% CI, -11.7 to -6.09] g/m2), but not in the control group (change of 1.62 g/m2; between-group difference, 10.50 [95% CI, 7.51 to 13.60] g/m2; P < 0.001). Levocarnitine therapy reduced N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and improved the erythropoietin responsiveness index, whereas no such effects were observed in the control group. Limitations Not a double-blinded study. Conclusions Levocarnitine therapy is useful for hemodialysis patients with carnitine deficiency; these patients may benefit from such therapy, with amelioration of cardiac function and reduction of left ventricular mass index. © 2016 National Kidney Foundation, Inc.


Ito M.,Nihon University | Abe M.,Nihon University | Okada K.,Nihon University | Sasaki H.,Nihon University | And 5 more authors.
Endocrine Journal | Year: 2011

The potent and selective dipeptidyl peptidase-4 inhibitor vildagliptin improves glycemic control in patients with type 2 diabetes through incretin hormone-mediated increases in both α- and β-cell responsiveness to glucose. We conducted a prospective, open-label, parallel group, controlled study of 51 patients with type 2 diabetic patients undergoing hemodialysis (HD) during the 24-week study period. Patients were assigned to two groups: the vildagliptin group (n = 30) and the control group (n = 21). Vildagliptin was administered at 50 mg/day for the first 8 weeks. Then doses were titrated by dose-doubling to a maximum of 100 mg/day if hemoglobin A1c (HbA1c) or glycated albumin (GA) target levels had not been reached. No vildagliptin was administered to the controls. The average final dose of vildagliptin was 80 ± 5 mg daily. After 24 weeks, vildagliptin had decreased average HbA1c levels from 6.7% baseline to 6.1%, average GA levels from 24.5% baseline to 20.5% and average postprandial plasma glucose levels from 186 mg/dL baseline to 140 mg/dL (all p < 0.0001). In the control group, we observed no such changes. Vildagliptin efficacy did not differ according to age or body mass index, but the GA reduction was significantly greater in the anti-diabetic agents-naïve group. Furthermore, in patients with higher baseline GA levels, a higher vildagliptin dosage was required to produce a noticeable effect. No serious adverse effects such as hypoglycemia or liver impairment were observed in any patient. Vildagliptin was effective as a treatment for diabetic patients undergoing HD. © The Japan Endocrine Society.


PubMed | Meirikai Chuo General Hospital, Keiai Hospital and Nihon University
Type: Journal Article | Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation | Year: 2016

Levocarnitine deficiency in hemodialysis patients is common. Although the effect of levocarnitine therapy on uremic anemia has been studied in small trials, its effects on cardiac function remain unclear.Multicenter, prospective, open-label, parallel, randomized, controlled trial.Patients undergoing maintenance hemodialysis with carnitine deficiency (free carnitine plasma concentration< 40mol/L) enrolled in 3 hemodialysis centers.Random assignment to treatment for 12 months with oral levocarnitine therapy at a dose of 20mg/kg/d or control group (no levocarnitine therapy).Cardiac function was assessed by echocardiography. The primary end point was change in ejection fraction from baseline at the end of the study. Secondary end points included changes in left ventricular mass index and clinical parameters from baseline at the end of the study.222 patients were randomly assigned, of whom 148 patients (levocarnitine group, n=75; control group, n=73) were analyzed. Ejection fraction increased from baseline to the end of the study in the levocarnitine group by 5.43% (95% CI, 4.53%-6.32%), but not in the control group (change,-0.14%; between-group difference, 5.57% [95% CI, 4.48%-6.66%]; P<0.001). Left ventricular mass index decreased from baseline to the end of the study in the levocarnitine group (change of-8.89 [95% CI,-11.7 to-6.09] g/m(2)), but not in the control group (change of 1.62g/m(2); between-group difference, 10.50 [95% CI, 7.51 to 13.60] g/m(2); P<0.001). Levocarnitine therapy reduced N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and improved the erythropoietin responsiveness index, whereas no such effects were observed in the control group.Not a double-blinded study.Levocarnitine therapy is useful for hemodialysis patients with carnitine deficiency; these patients may benefit from such therapy, with amelioration of cardiac function and reduction of left ventricular mass index.


PubMed | Keiai Clinic, Keiai Hospital and Nihon University
Type: Journal Article | Journal: Sleep medicine | Year: 2015

Restless legs syndrome (RLS) is a common comorbidity in patients undergoing hemodialysis, but clinical factors predictive of RLS risk and severity have not been identified. The aims of this multicenter cross-sectional study were to document RLS prevalence and severity in patients undergoing hemodialysis and to identify associated risk factors.One-hundred and fifty-nine stable patients on maintenance hemodialysis were enrolled (113 men, 46 women; mean age: 6811 years; mean duration of dialysis: 5460 months). Diagnosis of RLS was based on the criteria proposed by the International Restless Legs Syndrome Study Group (IRLSSG), and RLS severity was assessed using the IRLSSG Severity Scale. Potential factors associated with RLS and IRLSSG Severity Scale score were assessed by univariate and multivariate regression analyses.RLS affected 22% of the study population. The RLS subgroup had a significantly longer duration of hemodialysis and higher cardiothoracic ratio compared to the non-RLS subgroup. The RLS subgroup also had significantly higher serum levels of high-sensitivity C-reactive protein, interleukin-6, ferritin, N-terminal pro-B-type natriuretic peptide, and 8-hydroxy-2-deoxyguanosine (8-OHdG), and a significantly lower transferrin saturation level compared to the non-RLS subgroup, suggesting a chronic inflammatory state and associated oxidative stress in comorbid patients. Serum 8-OHdG level was an independent risk factor for high IRLSSG Severity Scale score.This study confirms the high prevalence of RLS among hemodialysis patients and identifies the oxidative stress marker serum 8-OHdG as a significant independent predictor of RLS severity. Further studies are needed to identify detailed risk factors and the pathophysiological role of oxidative stress in RLS.


Kitano D.,Nihon University | Chiku M.,Keiai Hospital | Li Y.,Nihon University | Okumura Y.,Nihon University | And 6 more authors.
Cardiovascular Diabetology | Year: 2013

Background: Hyperglycemia, a risk factor for development of cardiovascular disease, causes endothelial dysfunction. Alpha-glucosidase inhibitors (α-GIs) improve postprandial hyperglycemia (PPHG) and may have favorable effects on associated cardiovascular disease. Effects of α-GIs in patients with acute coronary syndrome (ACS) and PPHG remain unclear; thus, we assessed the effect of α-GI miglitol on endothelial function in such patients by digital reactive hyperemia peripheral arterial tonometry (RH-PAT).Methods: Fifty-four patients with ACS who underwent primary percutaneous coronary intervention were enrolled in the study: 36 with new-onset PPHG and 18 with normal glucose tolerance. Eighteen PPHG patients were given 50 mg of miglitol with each meal for 1 week. Endothelial function was assessed on the basis of the RH-PAT index (RHI) before and after the 1-week miglitol treatment. The other 18 PPHG patients and the 18 NGT patients were not given any anti-diabetic agent for 1 week, and endothelial function was assessed.Results: Postprandial RHI decreased significantly in patients with PPHG. Miglitol improved PPHG significantly; postprandial RHI also improved (p = 0.007). Significant inverse correlation was found between the postprandial change in RHI and postprandial fasting-to-60-minutes surge in glucose (r = -0.382, p = 0.009). Moreover, the improvement in endothelial function correlated with the reduced postprandial glucose surge achieved with miglitol (r = -0.462, p = 0.001).Conclusions: Postprandial changes in glucose are related to endothelial dysfunction in ACS. Miglitol-based improvement in PPHG appears to improve endothelial function. The effect of miglitol on glucose-dependent endothelial function might improve outcomes of ACS. © 2013 Kitano et al.; licensee BioMed Central Ltd.


Fujii Y.,Nihon University | Abe M.,Nihon University | Higuchi T.,Keiai Hospital | Mizuno M.,Keiai Hospital | And 6 more authors.
Expert Opinion on Pharmacotherapy | Year: 2013

Objectives: The potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin improves glycemic control in patients with type 2 diabetes through incretin hormone-mediated increases in both α- and β-cell responsiveness to glucose. In this study, the efficacy and safety of alogliptin in type 2 diabetic patients undergoing hemodialysis (HD) were evaluated. Methods: A prospective, open-label study of 30 patients (male/female: 24/6; mean age: 69.7 ± 1.7 years) with type 2 diabetes who were undergoing HD without insulin injection therapy was conducted. Patients were administered 6.25 mg/day alogliptin and efficacy and safety were determined by monitoring clinical and laboratory parameters during the 48-week study period. Results: After 48 weeks, alogliptin had decreased postprandial plasma glucose levels from 212 ± 8 mg/dL baseline to 156 ± 7 mg/dL, hemoglobin A1c levels from 7.1 ± 0.2% baseline to 6.3 ± 0.2% and glycated albumin (GA) levels from 25.6 ± 0.6% baseline to 20.7 ± 0.4% (all p < 0.0001). Alogliptin efficacy did not differ according to median age or body mass index, but the GA reduction was significantly greater in the antidiabetic agents-naïve group. The magnitude of GA reduction was baseline GA-dependent, being greater at higher baseline GA levels. No serious adverse effects, such as hypoglycemia or liver impairment, were observed in any patient. Conclusion: Alogliptin as monotherapy or in combination with other oral antidiabetic agents improved glycemic control and was generally well tolerated in patients with HD over a 48-week period. © 2013 Informa UK, Ltd.


PubMed | Keiai Hospital and Nihon University
Type: | Journal: Clinical drug investigation | Year: 2016

Pregabalin is a gamma aminobutyric acid derivative administered for neuropathic pain. It binds to 2 subunits of voltage-dependent calcium channels, and inhibits calcium inflow of synapses and the release of excitatory neurotransmitters. This study investigated the efficacy and safety of pregabalin in patients with peripheral neuropathic pain undergoing maintenance hemodialysis.This study was a prospective, open-label, single-arm, multi-center trial. Patients were treated with an initial dose of pregabalin at 25mg; this was then increased up to a maximum of 150mg depending on the patient during a 12-week study period. Visual Analog Scale, Eight-Item Short Form Health Survey (SF-8), and laboratory data were collected at baseline and the end of the study.A total of 45 patients with peripheral neuropathic pain were included, of whom 35 patients were analyzed. The final mean dose of pregabalin was 50.7mg daily. Mean Visual Analog Scale scores significantly decreased from 52.4mm at baseline to 34.1mm at the end of the study (p<0.0001). Scores for all eight categories of the SF-8 significantly increased compared with baseline (p<0.05). Both physical and mental component summary scores of the SF-8 also significantly increased (p<0.05). Ten patients were withdrawn from the study because of drowsiness, dizziness, and invalidity; however, no serious adverse drug reactions were recorded.If adverse effects are carefully monitored and the administered dosage prudently determined, pregabalin can be an effective treatment for peripheral neuropathic pain in patients undergoing hemodialysis.UMIN000023117.

Loading Keiai Hospital collaborators
Loading Keiai Hospital collaborators