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Tomohiro Sakamoto,
Hisao Ogawa,
Koichi Nakao,
Shunichi Koide,
Nobuyasu Yamamoto,
Hideki Shimomura,
Toshiyuki Matsumura,
Shuichi Oshima,
Koichi Kikuta,
Hideki Oka,
Kazuo Kimura, Kunihiko Matsui
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ABSTRACT: Aim: Few multicenter studies have assessed the effects of angiotensin receptor blockers on cardiovascular events after drug-eluting stent implantation in patients with ischemic heart disease.Methods: An open-label multicenter randomized prospective study is in progress to evaluate the effects of candesartan on cardiovascular events in patients with ischemic heart disease after implantation of sirolimus- and/or paclitaxel-eluting stents.Results: A total of 1,145 patients were enrolled at 39 institutes in the Candesartan for prevention of Cardiovascular events after CYPHER or TAXUS Coronary stenting (4C trial). Patients were randomized into a group treated with candesartan (n=602) and a group treated with standard medical therapy without candesartan (n=543). The primary endpoint of the 4C trial is a composite of all-cause death, successful resuscitation after cardiopulmonary arrest and cardiovascular events including non-fatal myocardial infarction, unstable angina requiring emergent hospitalization, congestive heart failure requiring emergent hospitalization and cerebrovascular attacks. All patients will be followed-up for 36 months.Conclusions: The 4C trial will be the first multicenter study to elucidate the effects of candesartan after drug-eluting stent implantation and may provide new information to optimize medical therapy after percutaneous coronary interventions.
Journal of atherosclerosis and thrombosis 02/2013; · 2.69 Impact Factor
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Daisuke Sueta,
Keiichiro Kataoka,
Nobutaka Koibuchi,
Kensuke Toyama,
Ken Uekawa,
Tetsuji Katayama,
Ma Mingjie,
Takashi Nakagawa,
Hidefumi Waki,
Masanobu Maeda,
Osamu Yasuda, Kunihiko Matsui,
Hisao Ogawa,
Shokei Kim-Mitsuyama
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ABSTRACT: This study was performed to determine the characteristics and mechanism of hypertension in SHR/NDmcr-cp(+/+) rats (SHRcp), a new model of metabolic syndrome, with a focus on the autonomic nervous system, aldosterone, and angiotensin II.
We measured arterial blood pressure (BP) in SHRcp by radiotelemetry combined with spectral analysis using a fast Fourier transformation algorithm and examined the effect of azilsartan, an AT1 receptor blocker. Compared with control Wistar-Kyoto rats (WKY) and SHR, SHRcp exhibited a nondipper-type hypertension and displayed increased urinary norepinephrine excretion and increased urinary and plasma aldosterone levels. Compared with WKY and SHR, SHRcp were characterized by an increase in the low-frequency power (LF) of systolic BP and a decrease in spontaneous baroreflex gain (sBRG), indicating autonomic dysfunction. Thus, SHRcp are regarded as a useful model of human hypertension with metabolic syndrome. Oral administration of azilsartan once daily persistently lowered BP during the light period (inactive phase) and the dark period (active phase) in SHRcp more than in WKY and SHR. Thus, angiotensin II seems to be involved in the mechanism of disrupted diurnal BP rhythm in SHRcp. Azilsartan significantly reduced urinary norepinephrine and aldosterone excretion and significantly increased urinary sodium excretion in SHRcp. Furthermore, azilsartan significantly reduced LF of systolic BP and significantly increased sBRG in SHRcp.
These results strongly suggest that impairment of autonomic function and increased aldosterone in SHRcp mediate the effect of angiotensin II on circadian blood pressure rhythms.
Journal of the American Heart Association. 01/2013; 2(3):e000035.
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ABSTRACT: The OSCAR study was a multicenter, prospective randomized open-label blinded end-point study of 1164 Japanese elderly hypertensive patients comparing the efficacy of angiotensin II receptor blocker (ARB) uptitration to an ARB plus calcium channel blocker (CCB) combination. In this prospective study, we performed prespecified subgroup analysis according to baseline estimated glomerular filtration rate (eGFR) with chronic kidney disease (CKD) defined as an eGFR <60 ml/min per 1.73 m(2). Blood pressure was lower in the combined therapy than in the high-dose ARB cohort in both groups with and without CKD. In patients with CKD, significantly more primary events (a composite of cardiovascular events and noncardiovascular death) occurred in the high-dose ARB group than in the combination group (30 vs. 16, respectively, hazard ratio 2.25). Significantly more cerebrovascular and more heart failure events occurred in the high-dose ARB group than in the combination group. In patients without CKD, however, the incidence of primary events was similar between the two treatments. The treatment-by-subgroup interaction was significant. Allocation to the high-dose ARB was a significant independent prognostic factor for primary events in patients with CKD. Thus, the ARB plus CCB combination conferred greater benefit in prevention of cardiovascular events in patients with CKD compared with high-dose ARB alone. Our findings provide new insight into the antihypertensive strategy for elderly hypertensive patients with CKD.Kidney International advance online publication, 10 October 2012; doi:10.1038/ki.2012.326.
Kidney International 10/2012; · 6.61 Impact Factor
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Keisuke Ohba,
Seigo Sugiyama,
Hitoshi Sumida,
Toshimitsu Nozaki,
Junichi Matsubara,
Yasushi Matsuzawa,
Masaaki Konishi,
Eiichi Akiyama,
Hirofumi Kurokawa,
Hirofumi Maeda, [......],
Kenichi Tsujita,
Eiichiro Yamamoto,
Megumi Yamamuro,
Sunao Kojima,
Koichi Kaikita,
Shinji Tayama,
Seiji Hokimoto, Kunihiko Matsui,
Tomohiro Sakamoto,
Hisao Ogawa
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ABSTRACT: Angina without significant stenosis, or nonobstructive coronary artery disease, attracts clinical attention. Microvascular coronary artery spasm (microvascular CAS) can cause nonobstructive coronary artery disease. We investigated the clinical features of microvascular CAS and the therapeutic efficacy of calcium channel blockers.
Three hundred seventy consecutive, stable patients with suspected angina presenting nonobstructive coronary arteries (<50% diameter) in coronary angiography were investigated with the intracoronary acetylcholine provocation test, with simultaneous measurements of transcardiac lactate production and of changes in the quantitative coronary blood flow. We diagnosed microvascular CAS according to lactate production and a decrease in coronary blood flow without epicardial vasospasm during the acetylcholine provocation test. We prospectively followed up the patients with calcium channel blockers for microvascular coronary artery disease. We identified 50 patients with microvascular CAS who demonstrated significant impairment of the endothelium-dependent vascular response, which was assessed by coronary blood flow during the acetylcholine provocation test. Administration of isosorbide dinitrate normalized the abnormal coronary flow pattern in the patients with microvascular CAS. Multivariate logistic regression analysis indicated that female sex, a lower body mass index, minor-borderline ischemic electrocardiogram findings at rest, limited-baseline diastolic-to-systolic velocity ratio, and attenuated adenosine triphosphate-induced coronary flow reserve were independently correlated with the presence of microvascular CAS. Receiver-operating characteristics curve analysis revealed that the aforementioned 5-variable model showed good correlation with the presence of microvascular CAS (area under the curve: 0.820). No patients with microvascular CAS treated with calcium channel blockers developed cardiovascular events over 47.8±27.5 months.
Microvascular CAS causes distinctive clinical features and endothelial dysfunction that are important to recognize as nonobstructive coronary artery disease so that optimal care with calcium channel blockers can be provided.
URL: www.umin.ac.jp/ctr. Unique identifier: UMIN000003839.
Journal of the American Heart Association. 10/2012; 1(5):e002485.
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Eiichi Akiyama,
Seigo Sugiyama,
Yasushi Matsuzawa,
Masaaki Konishi,
Hiroyuki Suzuki,
Toshimitsu Nozaki,
Keisuke Ohba,
Junichi Matsubara,
Hirofumi Maeda,
Yoko Horibata,
Kenji Sakamoto,
Koichi Sugamura,
Megumi Yamamuro,
Hitoshi Sumida,
Koichi Kaikita,
Satomi Iwashita, Kunihiko Matsui,
Kazuo Kimura,
Satoshi Umemura,
Hisao Ogawa
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ABSTRACT: The purpose of this study was to investigate whether peripheral endothelial dysfunction could predict the occurrence of cardiovascular events in patients with heart failure (HF) with normal left ventricular ejection fraction (HFNEF).
Endothelial dysfunction plays an important role in HF, but the relation between peripheral endothelial dysfunction and prognosis in HFNEF remains unknown.
We conducted a prospective cohort study of 321 patients with HFNEF. We evaluated cardiac function by echocardiography measuring the ratio of early transmitral flow velocity to tissue Doppler early diastolic mitral annular velocity (E/e'), noninvasively assessed peripheral endothelial function by reactive hyperemia-peripheral arterial tonometry (RH-PAT) as the RH-PAT index (RHI), and followed cardiovascular events.
A total of 59 patients had a cardiovascular event. Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in the low RHI group than in the high RHI group (mean follow-up: 20 months; log-rank test: p < 0.001). Multivariate Cox hazard analysis identified RHI (per 0.1) (hazard ratio [HR]: 0.80; 95% confidence interval [CI]: 0.67 to 0.94; p = 0.007), E/e' (Ln[E/e'] [per 0.1]) (HR: 1.15; 95% CI: 1.04 to 1.26; p = 0.006), and B-type natriuretic peptide (BNP) (Ln[BNP] [per picogram/milliliter]) (HR: 1.81; 95% CI: 1.44 to 2.28; p < 0.001) as independent predictors of cardiovascular events. The C-statistics for cardiovascular events substantially increased when the RHI was added to the HFNEF prognostic 5 factors (PF5)-age, diabetes, New York Heart Association classification, HF hospitalization history, and left ventricular ejection fraction-which were identified in the I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction Study) (PF5 alone: 0.671; PF5 + RHI: 0.712). The net reclassification index was significant after addition of the RHI (19.0%, p = 0.01).
Peripheral endothelial dysfunction independently correlated with future cardiovascular events, adding incremental clinical significance for risk stratification in patients with HFNEF. (Endothelial Dysfunction Assessed by Reactive Hyperemia Peripheral Arterial Tonometry and Heart Failure with Preserved Left Ventricular Ejection Fraction; UMIN000002640).
Journal of the American College of Cardiology 09/2012; 60(18):1778-86. · 14.16 Impact Factor
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ABSTRACT: It is unknown whether high-dose angiotensin II receptor blocker therapy or angiotensin II receptor blocker + calcium channel blocker combination therapy is better in elderly hypertensive patients with high cardiovascular risk. The objective of the study was to compare the efficacy of these treatments in elderly, high-risk Japanese hypertensive patients.
The OlmeSartan and Calcium Antagonists Randomized (OSCAR) study was a multicenter, prospective, randomized, open-label, blinded-end point study of 1164 hypertensive patients aged 65 to 84 years with type 2 diabetes or cardiovascular disease. Patients with uncontrolled hypertension during treatment with olmesartan 20 mg/d were randomly assigned to receive 40 mg/d olmesartan (high-dose angiotensin II receptor blocker) or a calcium channel blocker + 20 mg/d olmesartan (angiotensin II receptor blocker + calcium channel blocker). The primary end point was a composite of cardiovascular events and noncardiovascular death.
During a 3-year follow-up, blood pressure was significantly lower in the angiotensin II receptor blocker + calcium channel blocker group than in the high-dose angiotensin II receptor blocker group. Mean blood pressure at 36 months was 135.0/74.3 mm Hg in the high-dose angiotensin II receptor blocker group and 132.6/72.6 mm Hg in the angiotensin II receptor blocker + calcium channel blocker group. More primary end points occurred in the high-dose angiotensin II receptor blocker group than in the angiotensin II receptor blocker + calcium channel blocker group (58 vs 48 events, hazard ratio [HR], 1.31, 95% confidence interval, 0.89-1.92; P=.17). In patients with cardiovascular disease at baseline, more primary events occurred in the high-dose angiotensin II receptor blocker group (HR, 1.63, P=.03); in contrast, fewer events were observed in the subgroup without cardiovascular disease (HR, 0.52, P=.14). This treatment-by-subgroup interaction was significant (P=.02).
The angiotensin II receptor blocker and calcium channel blocker combination lowered blood pressure more than the high-dose angiotensin II receptor blocker and reduced the incidence of primary end points more than the high-dose angiotensin II receptor blocker in patients with cardiovascular disease. The addition of a second antihypertensive agent is more effective at lowering blood pressure than simply doubling the dose of an existing agent.
The American journal of medicine 04/2012; 125(10):981-90. · 4.47 Impact Factor
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Junichi Matsubara,
Seigo Sugiyama,
Koichi Sugamura,
Taishi Nakamura,
Yukio Fujiwara,
Eiichi Akiyama,
Hirofumi Kurokawa,
Toshimitsu Nozaki,
Keisuke Ohba,
Masaaki Konishi,
Hirofumi Maeda,
Yasuhiro Izumiya,
Koichi Kaikita,
Hitoshi Sumida,
Hideaki Jinnouchi, Kunihiko Matsui,
Shokei Kim-Mitsuyama,
Motohiro Takeya,
Hisao Ogawa
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ABSTRACT: The aim of this study was to investigate the antiatherogenic effects of the dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin (DFS).
The new class of anti-type 2 diabetes drugs, dipeptidyl peptidase-4 inhibitors, improves glucose metabolism by increasing levels of active glucagon-like peptide (GLP)-1.
Endothelial function was examined by acetylcholine-induced endothelium-dependent vasorelaxation using aortic rings and atherosclerotic lesion development in the entire aorta in apolipoprotein E-deficient mice fed a high-fat diet with or without DFS, and the antiatherogenic effects of DFS were investigated in cultured human macrophages and endothelial cells. Plasma levels of active GLP-1 were measured in patients with or without coronary artery disease.
DFS significantly improved endothelial dysfunction (89.9 ± 3.9% vs. 79.2 ± 4.3% relaxation at 10(-4) mol/l acetylcholine, p < 0.05) associated with increased endothelial nitric oxide synthase phosphorylation and reduced atherosclerotic lesion area (17.7% [15.6% to 25.8%] vs. 24.6% [19.3% to 34.6%], p < 0.01) compared with vehicle treatment. In cultured human macrophages, DFS significantly increased GLP-1-induced cytosolic levels of cyclic adenosine monophosphate compared with GLP-1 alone, resulted in inhibiting phosphorylation of c-jun N-terminal kinase and extracellular signal-regulated kinase 1/2 and nuclear factor-kappa B p65 nuclear translocation through the cyclic adenosine monophosphate/protein kinase A pathway, and suppressed proinflammatory cytokines (i.e., interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha) and monocyte chemoattractant protein-1 production in response to lipopolysaccharide. DFS-enhanced GLP-1 activity sustained endothelial nitric oxide synthase phosphorylation and decreased endothelial senescence and apoptosis compared with GLP-1 alone. In the human study, fasting levels of active GLP-1 were significantly lower in patients with coronary artery disease than those without (3.10 pmol/l [2.40 to 3.62 pmol/l] vs. 4.00 pmol/l [3.10 to 5.90 pmol/l], p < 0.001).
A DPP-4 inhibitor, DFS, exhibited antiatherogenic effects through augmenting GLP-1 activity in macrophages and endothelium.
Journal of the American College of Cardiology 01/2012; 59(3):265-76. · 14.16 Impact Factor
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ABSTRACT: Coenzyme Q10 levels are low in patients with coronary artery disease (CAD), and increasing or preserving coenzyme Q10 could be a beneficial strategy. Exercise and statins improve high-density lipoprotein cholesterol (HDL-C) levels. However, statins inhibit coenzyme Q10 biosynthesis, and the combination of statins with coenzyme Q10 supplementation increases HDL-C compared to statins alone. We compared the effects of two statins (rosuvastatin and atorvastatin) combined with exercise on coenzyme Q10 and HDL-C levels in CAD patients.
After randomizing 28 CAD patients to rosuvastatin (n=14) and atorvastatin (n=14) groups, patients performed weekly in-hospital aerobic exercise and daily home exercise for 20 weeks. We measured serum lipids, ubiquinol, and exercise capacity.
Both statins equally improved exercise capacity and lowered low-density lipoprotein cholesterol and triglyceride levels. Rosuvastatin significantly increased HDL-C (rosuvastatin, +12 ± 9 mg/dL [+30%], atorvastatin, +5 ± 5 mg/dL [+13%], p=0.014) and apolipoprotein A1 (ApoA1) (rosuvastatin, +28.3 ± 20.7 mg/dL, atorvastatin, +13.4 ± 12.0 mg/dL, p=0.030) compared to atorvastatin. Atorvastatin significantly decreased serum ubiquinol (731 ± 238 to 547 ± 219 nmol/L, p=0.001), but rosuvastatin (680±233 to 668 ± 299 nmol/L, p=0.834) did not. There was a significant positive correlation between changes in ubiquinol and ApoA1 (r=0.518, p=0.005). Multivariate regression analysis showed that changes in ubiquinol correlated significantly with changes in ApoA1 after adjusting for age, sex, body mass index, and smoking (β=0.502, p=0.008).
Compared to atorvastatin, rosuvastatin combined with exercise significantly preserved ubiquinol levels associated with an increase in HDL-C. Rosuvastatin with regular exercise could be beneficial for CAD patients.
Atherosclerosis 03/2011; 217(1):158-64. · 3.79 Impact Factor
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ABSTRACT: The epidemiology of adverse drug events (ADEs) and medication errors has received little evaluation outside the U.S. and Europe, and extrapolating from these data might not be valid, especially regarding selecting and prioritizing solutions.
To assess the incidence and preventability of ADEs and medication errors in Japan.
The Japan Adverse Drug Events (JADE) study was a prospective cohort study.
A cohort of 3,459 adults admitted to a stratified random sample of seven medical and eight surgical wards and three intensive care units in three tertiary care hospitals over 6 months.
We measured ADE and medication error rates from daily reviews of charts, laboratories, incident reports, and prescription queries by on-site reviewers; presence of a signal was considered an incident. Two independent physicians reviewed incidents to determine whether they were ADEs or medication errors and to assess severity and preventability.
We identified 1,010 ADEs and 514 medication errors (incidence: 17.0 and 8.7 per 1,000 patient-days, respectively) during the study period. Among ADEs, 1.6%, 4.9% and 33% were fatal, life-threatening and serious, respectively. Among ADEs, 14% were preventable. The rate per admission was 29 per 100 admissions, higher than in U.S. studies because associated with of the long length of hospital stay in Japan (mean, 17 days).
The epidemiology and nature of ADEs and medication errors in Japan were similar to other countries, although more frequent per admission. Solutions that worked in these countries might thus improve medication safety in Japan, as could shortening hospital length of stay.
Journal of General Internal Medicine 02/2011; 26(2):148-53. · 2.83 Impact Factor
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Mio Sakuma,
Takeshi Morimoto, Kunihiko Matsui,
Susumu Seki,
Nobuo Kuramoto,
Jinichi Toshiro,
Junji Murakami,
Tsuguya Fukui,
Mayuko Saito,
Atsushi Hiraide,
David W Bates
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ABSTRACT: The elderly receive many medications which may have adverse effects. Little evidence is available about the epidemiology of potentially inappropriate medications being prescribed to the elderly in Japan as defined by the Beers criteria, or whether or not these medications result in harm when used in this population.
We conducted a prospective cohort study of patients aged ≥65 years who were admitted to three acute care hospitals in Japan. Trained research nurses followed up patients from randomly selected wards and collected data about their medications and all potential adverse drug events (ADEs). Two independent reviewers evaluated all the data. The use of potentially inappropriate medications and their effects on patients were identified using the updated Beers criteria.
A total of 2155 elderly patients were eligible; 56.1% received at least one drug listed in the Beers criteria (BL drug). The rates of BL drug prescriptions were 103.8 per 100 admissions and 53.7 per 1000 patient-days, and the incidence rate of ADEs related to BL drugs was 1.7 per 100 BL drug prescriptions. Among patients aged ≥65 years, relatively younger patients (p = 0.0002) and those with less complications (p = 0.04) were likely to be prescribed BL drugs.
Although BL drugs were frequently prescribed to elderly Japanese inpatients, the incidence of related ADEs appeared infrequent. These data suggest that re-evaluation of the appropriateness of the Beers criteria is needed before they are used in Japan and other nations to assess quality or for decision support.
Pharmacoepidemiology and Drug Safety 01/2011; 20(4):386-92. · 2.53 Impact Factor
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Toshimitsu Nozaki,
Seigo Sugiyama,
Koichi Sugamura,
Keisuke Ohba,
Yasushi Matsuzawa,
Masaaki Konishi,
Junichi Matsubara,
Eiichi Akiyama,
Hitoshi Sumida, Kunihiko Matsui,
Hideaki Jinnouchi,
Hisao Ogawa
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ABSTRACT: Heart failure (HF) is associated with endothelial dysfunction. Endothelium-derived microparticles (EMPs) are a novel quantitative plasma marker of endothelial dysfunction. We investigated whether plasma levels of EMPs can predict future cardiovascular events in patients with HF.
We enrolled 169 consecutive HF patients (70 ischaemic, 99 non-ischaemic HF) with New York Heart Association (NYHA) class I or more. Plasma CD144-positive EMP levels were measured by flow cytometry in the HF patients and in 31 healthy subjects. We followed the HF patients for mean 30 months. Endpoints were: a composite of cardiovascular events (myocardial infarction, stroke, re-hospitalization for HF, and cardiovascular death) and all-cause mortality. Endothelium-derived microparticle levels increased significantly with NYHA functional class [EMP median (range): healthy, 0.325 (0.164-0.354) ×10⁶/mL; NYHA I, 0.484 (0.426-0.575); II, 0.646 (0.439-0.795); and III/IV, 0.786 (0.569-1.026), P < 0.001]. A total of 33 cardiovascular events and 22 all-cause deaths were registered. Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in the high-EMP group, but there was only a borderline difference for all-cause mortality (above median; log rank test P = 0.01, P = 0.053, respectively). Multivariate Cox regression analysis adjusted for clinical factors, identified high-EMP levels as an independent predictor of future cardiovascular events, but not for all-cause mortality in HF patients [hazard ratio (95% confidence interval): 2.423 (1.034-5.681), P = 0.04 for cardiovascular events; and 2.095 (0.825-5.323), P = 0.12 for all-cause mortality].
Endothelial dysfunction assessed by plasma levels of EMPs can independently predict future cardiovascular events in patients with HF. Endothelium-derived microparticles are a potentially useful biomarker of endothelial dysfunction in HF risk stratification.
European Journal of Heart Failure 11/2010; 12(11):1223-8. · 4.90 Impact Factor
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Yasushi Matsuzawa,
Seigo Sugiyama,
Koichi Sugamura,
Toshimitsu Nozaki,
Keisuke Ohba,
Masaaki Konishi,
Junichi Matsubara,
Hitoshi Sumida,
Koichi Kaikita,
Sunao Kojima,
Yasuhiro Nagayoshi,
Megumi Yamamuro,
Yasuhiro Izumiya,
Satomi Iwashita, Kunihiko Matsui,
Hideaki Jinnouchi,
Kazuo Kimura,
Satoshi Umemura,
Hisao Ogawa
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ABSTRACT: We investigated the utility of digital reactive hyperemia peripheral arterial tonometry (RH-PAT) in predicting ischemic heart disease (IHD), including obstructive coronary artery disease (CAD) and nonobstructive coronary artery disease (NOCAD), in women.
IHD is the leading cause of mortality, and its pathogenesis is diverse in women. Fingertip RH-PAT is a new device that provides noninvasive, automatic, and quantitative evaluation of endothelial dysfunction.
RH-PAT was measured using Endo-PAT2000 (Itamar Medical, Caesarea, Israel) before cardiac catheterization in 140 stable women scheduled for hospitalization to examine chest pain. NOCAD was diagnosed by angiography with measurement of coronary blood flow and cardiac lactate production during intracoronary acetylcholine provocation test and cardiac scintigraphy with stress tests.
Sixty-eight women (49%) had obstructive CAD and 42 women (30%) had NOCAD. RH-PAT indexes were significantly attenuated in both obstructive CAD and NOCAD as compared with non-IHD (n = 30) (obstructive CAD: median 1.57, interquartile range [IQR] 1.42 to 1.76; NOCAD: median 1.58, IQR 1.41 to 1.78; non-IHD: median 2.15, IQR 1.85 to 2.48, p < 0.001). By multivariate logistic regression analysis, only RH-PAT index was significantly associated with IHD, including obstructive CAD and NOCAD (odds ratio 0.51; 95% confidence interval: 0.38 to 0.68; p < 0.001). In receiver-operating characteristic analysis, RH-PAT index was a significant predictor of IHD (area under the curve 0.86; p < 0.001). Furthermore, only RH-PAT was useful for the prediction of NOCAD after excluding obstructive CAD (area under the curve 0.85; p < 0.001; RH-PAT index of <1.82 had 81% sensitivity and 80% specificity).
RH-PAT indexes were significantly attenuated in women with IHD. Digital RH-PAT can predict patients with IHD, especially NOCAD before angiography. RH-PAT is potentially useful for identifying high-risk women for IHD. (Endothelial Dysfunction and Coronary Artery Spasm; NCT00619294).
Journal of the American College of Cardiology 04/2010; 55(16):1688-96. · 14.16 Impact Factor
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Takuro Shimbo,
Tsuguya Fukui,
Chikashi Ishioka,
Kohji Okamoto,
Takahiro Okamoto,
Shingo Kameoka,
Atsushi Sato,
Masakazu Toi, Kunihiko Matsui,
Toshihiko Mayumi,
Shigetoyo Saji,
Masaru Miyazaki,
Yuichi Takatsuka,
Koichi Hirata
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ABSTRACT: The Japan Society of Clinical Oncology started implementing clinical practice guidelines for cancer in 2001. It created a Guideline Committee and has published cancer-related information in collaboration with individual subspecialty cancer societies. The society then established an Evaluation Committee to assess the quality of guidelines.
The quality of development and general characteristics of guidelines were reviewed using the AGREE instrument. The six standardized domain scores and 23-item crude scores were described, and items with a low median score or a wide inter-quartile range were explored. Kappa statistics for inter-rater reproducibility were also described.
Domains in which the median score was >50 points in 18 guidelines developed between March 2005 and May 2009 included "scope and purpose," "rigor of development," and "clarity and presentation." Domains with a median score < 50 points were "stakeholder involvement," "applicability," and "editorial independence." Scores in all domains except "stakeholder involvement" were higher during the second half of the period than during the first half of the period, although P values were 0.10-0.93. Crude scores remained low for items 5, 7, 19, 20, 22, and 23, and the inter-quartile ranges of items 2, 6, 10, and 22 were wide. Kappa statistics ranged from -0.02 to 0.64, and they were especially low for items 3, 5, 7, 18, and 23.
Guideline quality has tended to improve during the 10 years since the society started this activity. However, issues remain to be improved through continuous revisions.
International Journal of Clinical Oncology 03/2010; 15(3):227-33. · 1.41 Impact Factor
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ABSTRACT: Randomized trials have established statins as an agent for prevention of coronary heart disease (CHD). The purpose of this study was to assess the hypothesis that standard-dose statin therapy has a beneficial effect in normocholesterolemic diabetic patients with CHD.
A prospective, randomized, open, blinded-endpoint trial was conducted from 2002 to 2004 at 55 hospitals in Japan to evaluate the effect of statins on subsequent cardiovascular events. A total number of 1,016 CHD patients (301 patients with type 2 diabetes mellitus [DM] and 715 non-DM patients) with serum total cholesterol levels of 180-240 mg/dl were randomly divided into non-statin and statin treatments. Clinical parameters were comparable between DM and non-DM groups. Serum low-density lipoprotein (LDL)-cholesterol levels were equally decreased after statin treatment in the 2 groups. Statin treatment improved prognosis in both the DM and non-DM groups; however, the number needed to treat (NNT) and relative risk reduction (RRR) were remarkable especially in the DM group (NNT=8, RRR=67%) compared with the non-DM group (NNT=30, RRR=24%).
Standard-dose statin therapy provides incremental clinical benefits in DM patients with normal cholesterol levels compared with non-DM patients. The data suggest that DM patients may enjoy the pleiotropic effects of statins, independent of the LDL-cholesterol lowering effects of these agents.
Circulation Journal 02/2010; 74(4):779-85. · 3.77 Impact Factor
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Masaaki Konishi,
Seigo Sugiyama,
Koichi Sugamura,
Toshimitsu Nozaki,
Keisuke Ohba,
Junichi Matsubara,
Yasushi Matsuzawa,
Hitoshi Sumida,
Yasuhiro Nagayoshi,
Takeshi Nakaura,
Kazuo Awai,
Yasuyuki Yamashita,
Hideaki Jinnouchi, Kunihiko Matsui,
Kazuo Kimura,
Satoshi Umemura,
Hisao Ogawa
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ABSTRACT: The purpose of this study was to examine the association of pericardial fat with the presence of coronary plaques.
Waist circumference, reflecting abdominal obesity, is a risk factor of metabolic syndrome and coronary artery disease (CAD). Adipose tissue secretes many factors implicated in atherogenesis, however, the role of pericardial fat (ectopic visceral fat around coronary arteries) in the pathogenesis of CAD is not clear.
We measured total pericardial fat volume (PFV) and determined presence and characteristics of coronary plaques using 64-slice computed tomography in 171 consecutive patients suspected of CAD (101 men; mean age, 66+/-11 years, +/-SD).
PFV correlated with age (p<0.05), body mass index (p<0.05), waist circumference (p<0.01), and high-density lipoprotein cholesterol (p<0.01) by multivariate regression analysis. PFV was significantly larger in patients with coronary plaques, even nonstenotic or noncalcified ones, than those without plaques (any plaques, n=123; 201+/-71cm(3), nonstenotic plaques, n=51; 192+/-63, noncalcified plaques, n=32; 196+/-56 vs. no plaque, n=48; 144+/-45, p<0.001, respectively). Multivariate backward logistic regression analysis demonstrated that PFV, but not waist circumference, significantly associated with the presence of any coronary plaques (odds ratio [OR]; 2.876, 95% confidence interval [95% CI]; 1.614-5.125, p<0.001), nonstenotic plaques confirmed by coronary angiography (OR; 3.423, 95% CI; 1.764-6.642, p<0.001), and noncalcified plaques (OR; 3.316, 95% CI; 1.435-7.661, p<0.01).
PFV correlated significantly with the presence of nonstenotic and noncalcified coronary plaques assessed by multislice computed tomography. Pericardial fat is more highly associated with early development of CAD than simple anthropometric measures of abdominal obesity.
Atherosclerosis 10/2009; 209(2):573-8. · 3.79 Impact Factor
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ABSTRACT: The aim of this study was to examine the effects of gastric medicines on gastroduodenal injury during antiplatelet therapy after coronary intervention.
A total of 501 patients were enrolled and as dual antiplatelet therapy, aspirin and thienopyridine were administered. Patients were divided into four groups: histamine H2-receptor antagonists (H2RA); proton pump inhibitors (PPI); other gastromucosal protective agents (GMP); or nothing (None), and follow-up lasted 8-20 months.
H2RA were prescribed in 212 cases (42%), PPI in 150 (30%), GMP in 56 (11%), and None in 83 (17%). Significant findings by endoscopy were recognized in 18 cases and upper gastrointestinal bleeding requiring hospitalization occurred in 7 patients (1.4%; H2RA in 4, GMP in 2, and None in 1). There were no gastrointestinal injuries in the PPI group. To minimize the effect of selection bias on gastroduodenal lesions, the propensity score analysis for clinical characteristics was used. The results of propensity score matching showed that administration of PPI reduced the incidence of gastrointestinal lesions compared with that of the non-PPI group.
Administration of PPI reduced the incidence of gastrointestinal lesions compared with that of the non-PPI group.
Journal of Cardiology 09/2009; 54(1):71-5. · 1.28 Impact Factor
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ABSTRACT: We investigated whether a multiple biomarkers strategy that includes plasma levels of endothelium-derived microparticles (EMP), reflecting endothelial dysfunction, can improve prediction of future cardiovascular events in patients at high risk for coronary heart disease (CHD).
Detailed risk stratification using multiple biomarkers can provide clinical benefits in high-risk patients. Endothelial dysfunction has been described as a predictor of cardiovascular complications.
We measured 3 biomarkers in 488 consecutive patients with various CHD risks: B-type natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), and EMP. We followed 387 stable patients at high risk for CHD and examined future cardiovascular events.
During a mean follow-up of 36 months, 55 patients developed cardiovascular events. Multivariate Cox proportional hazards analysis adjusted for established risk factors identified age, BNP, hsCRP, and EMP as significant and independent predictors of future cardiovascular events (age: hazard ratio [HR]: 1.042, 95% confidence interval [CI]: 1.007 to 1.080, p = 0.02; BNP: HR: 1.242, 95% CI: 1.004 to 1.536, p = 0.046; hsCRP: HR: 1.468, 95% CI: 1.150 to 1.875, p = 0.002; EMP: HR: 1.345, 95% CI: 1.094 to 1.652, p = 0.005). The C statistics for cardiovascular events increased when each biomarker or combinations of biomarkers were added to the Framingham risk model (C statistics: Framingham risk model alone 0.636, Framingham risk + BNP 0.695, Framingham risk + hsCRP 0.696, Framingham risk + EMP 0.682, and Framingham risk + BNP + hsCRP + EMP 0.763).
The assessment of endothelial dysfunction by plasma levels of EMP can independently predict future cardiovascular events in patients at high risk for CHD. A multiple biomarkers strategy that includes endothelial dysfunction assessed by EMP can identify patients vulnerable to cardiovascular disease. (University Hospital Medical Information Network number: UMIN000000876).
Journal of the American College of Cardiology 09/2009; 54(7):601-8. · 14.16 Impact Factor
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ABSTRACT: Higher doses of angiotensin II receptor blockers (ARBs) are expected to exert more protective effects against cardiovascular diseases. However, the significance of treatment of hypertension with high-dose ARB remains to be defined. The OlmeSartan and Calcium Antagonists Randomized (OSCAR) Study was designed to determine whether high-dose ARB monotherapy is superior to the combination therapy of ARB plus calcium channel blocker (CCB) in the prevention of cardiovascular morbidity/mortality in Japanese elderly high-risk hypertensive patients. The OSCAR study is a multicenter, active-controlled, two-arm parallel group comparison, using the prospective randomized open-blinded end-point method. In the 'Step 1' period, elderly hypertensive patients with diabetes or cardiovascular disease received monotherapy with ARB olmesartan medoxomil at a dose of 20 mg day(-1). If the target blood pressure control (less than 140/90 mm Hg) was not achieved by ARB monotherapy, the patients were randomized to receive either (1) the increased dose of olmesartan at 40 mg day(-1) (high-dose ARB monotherapy) or (2) the addition of a CCB (amlodipine or azelnidipine) to 20 mg day(-1) olmesartan (ARB plus CCB combination) in the 'Step 2' period. The follow-up duration will be 3 years. The primary end points will be the composite of fatal and non-fatal cardiovascular events, and death from any cause. Recruitment for the OSCAR study (around 1200 patients) was completed by the end of May 2007. The OSCAR study is the first large clinical trial comparing the efficacy of high-dose ARB monotherapy with that of an ARB plus CCB combination therapy in elderly high-risk hypertensive patients.
Hypertension Research 06/2009; 32(7):575-80. · 2.58 Impact Factor
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Circulation Journal 06/2008; 72(5):865. · 3.77 Impact Factor
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ABSTRACT: Basic clinical skills training in the Japanese medical education system has traditionally incorporated on-the-job training with patients. Recently, the complementary use of simulation techniques as part of this training has gained popularity. It is not known, however, whether the participants view this new type of education program favorably; nor is the impact of this program known. In this study we developed a new simulation-based training program in phlebotomy for new medical residents and assessed their satisfaction with the program
The education program comprised two main components: simulator exercise sessions and the actual drawing of blood from other trainees. At the end of the session, we surveyed participant sentiment regarding the program.
There were 43 participants in total. In general, they were highly satisfied with the education program, with all survey questions receiving scores of 3 or more on a scale of 1-5 (mean range: 4.3 - 4.8), with 5 indicating the highest level of satisfaction. Additionally, their participation as a 'patient' for their co-trainees was undertaken willingly and was deemed to be a valuable experience.
We developed and tested an education program using a simulator for blood collection. We demonstrated a high satisfaction level among the participants for this unique educational program and expect that it will improve medical training, patient safety, and quality of care. The development and dissemination of similar educational programs involving simulation for other basic clinical skills will be undertaken in the future.
BMC Medical Education 02/2008; 8:7. · 1.15 Impact Factor
