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Tochigi, Japan

Katsuda S.-I.,Fukushima Medical University | Miyashita H.,Jichi Medical University | Shimada K.,Shin oyama City Hospital | Miyawaki Y.,Omron Healthcare Co | And 3 more authors.
Hypertension Research | Year: 2014

We investigated whether the subservient relationship of peripheral to central hemodynamic parameters, such as the augmentation index (AI) and the second systolic (SBP 2) and pulse pressures, were preserved with the progression of atherosclerosis in the Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbit, an animal model for hypercholesterolemia and atherosclerosis. Male KHC rabbits, aged 12 and 24 months, were anesthetized with pentobarbital sodium. Two catheter-tip transducers were introduced to the central (ascending aorta) and peripheral (distal region of the right brachial artery) arteries through the left common carotid and the right radial arteries, respectively. Pressure waves were simultaneously recorded under regular atrial pacing to investigate changes in response to the intravenous infusion of angiotensin II (Ang II) (30-40 ng kg-1 min-1) and sodium nitroprusside (NTP) (20-30 μg kg-1 min-1). Central systolic blood pressure (cSBP) and diastolic blood pressure (DBP), peripheral systolic blood pressure (pSBP) and DBP, and peripheral second systolic blood pressure (pSBP 2) showed no significant difference between the 12-and 24-month-old groups before the administration of vasoactive drugs. There was no significant difference in central AI (cAI) between the two age groups before the drug infusion, even though atherosclerosis progressed with aging. Peripheral AI (pAI) changed in parallel with cAI in response to vasopressor and depressor actions due to the infusion of Ang II and NTP, respectively. We conclude that the subservience of pSBP 2 to cSBP and pAI to cAI, in addition to the regression relationship of these parameters between peripheral and central arteries, were well preserved, irrespective of the progression of atherosclerosis. © 2014 The Japanese Society of Hypertension.

Matsuoka H.,Utsunomiya Chuoh Hospital | Kuwajima I.,Tokyo Metropolitan Geriatric Hospital | Shimada K.,Shin oyama City Hospital | Mitamura H.,Tachikawa Hospital | Saruta T.,Keio University
Journal of Clinical Hypertension | Year: 2013

TY-0201 (TY) is a new drug absorbed by the transdermal delivery system developed for the treatment of hypertension, which contains the free base of bisoprolol fumarate that is widely used. An 8-week randomized, double-blind, placebo-controlled study was conducted in hypertensive patients to evaluate the superiority of TY 8 mg to placebo and the noninferiority of TY 8 mg to bisoprolol fumarate oral formulation (BO) 5 mg. Changes in diastolic blood pressure (BP) (primary endpoint) from baseline in the TY 8 mg group, the BO 5 mg group, and the placebo group were -12.2 mm Hg, -11.8 mm Hg, and -3.7 mm Hg, respectively, with TY 8 mg demonstrating superiority to placebo and noninferiority to BO 5 mg. Changes from baseline for systolic BP and pulse rate produced significant reductions compared with placebo. TY is expected to serve as a new treatment approach for hypertensive patients. © 2013 Wiley Periodicals, Inc.

Ikeda Y.,Waseda University | Shimada K.,Shin oyama City Hospital | Teramoto T.,Teikyo University | Uchiyama S.,International University of Health and Welfare | And 7 more authors.
JAMA - Journal of the American Medical Association | Year: 2014

Importance: Prevention of atherosclerotic cardiovascular diseases is an important public health priority in Japan due to an aging population.Objective: To determine whether daily, low-dose aspirin reduces the incidence of cardiovascular events in older Japanese patients with multiple atherosclerotic risk factors.Design, Setting, and Participants: The Japanese Primary Prevention Project (JPPP)was a multicenter, open-label, randomized, parallel-group trial. Patients (N = 14 464) were aged 60 to 85 years, presenting with hypertension, dyslipidemia, or diabetes mellitus recruited by primary care physicians at 1007 clinics in Japan between March 2005 and June 2007, and were followed up for up to 6.5 years, with last follow-up in May 2012. A multidisciplinary expert panel (blinded to treatment assignments) adjudicated study outcomes.Interventions: Patients were randomized 1:1 to enteric-coated aspirin 100mg/d or no aspirin in addition to ongoing medications.Main Outcomes and Measures: Composite primary outcomewas death from cardiovascular causes (myocardial infarction, stroke, and other cardiovascular causes), nonfatal stroke (ischemic or hemorrhagic, including undefined cerebrovascular events), and nonfatalmyocardial infarction. Secondary outcomes included individual end points.Results The studywas terminated early by the data monitoring committee after a median follow-up of 5.02 years (interquartile range, 4.55-5.33) based on likely futility. In both the aspirin and no aspirin groups, 56 fatal events occurred. Patients with an occurrence of nonfatal stroke totaled 114 in the aspirin group and 108 in the no aspirin group; of nonfatalmyocardial infarction, 20in the aspirin group and 38 in the no aspirin group; of undefined cerebrovascular events, 3 in the aspirin group and 5 in the no aspirin group. The 5-year cumulative primary outcome event rate was not significantly different between the groups (2.77%[95%CI, 2.40%-3.20%]for aspirin vs 2.96%[95%CI, 2.58%-3.40%]for no aspirin; hazard ratio [HR], 0.94 [95%CI, 0.77-1.15]; P = .54). Aspirin significantly reduced incidence of nonfatalmyocardial infarction (0.30 [95%CI, 0.19- 0.47] for aspirin vs0.58 [95%CI, 0.42-0.81] for no aspirin;HR, 0.53 [95%CI, 0.31-0.91]; P = .02) and transient ischemic attack (0.26 [95%CI, 0.16-0.42] for aspirin vs0.49 [95%CI, 0.35-0.69] for no aspirin;HR, 0.57 [95%CI, 0.32-0.99]; P = .04), and significantly increased the risk of extracranial hemorrhage requiring transfusion or hospitalization (0.86 [95%CI, 0.67-1.11] for aspirin vs0.51 [95%CI, 0.37-0.72] for no aspirin;HR, 1.85 [95%CI, 1.22-2.81]; P = .004).Conclusions and Relevance: Once-daily, low-dose aspirin did not significantly reduce the risk of the composite outcome of cardiovascular death, nonfatal stroke, and nonfatalmyocardial infarction among Japanese patients 60 years or older with atherosclerotic risk factors.

Kario K.,Jichi Medical University | Saito I.,Keio University | Kushiro T.,Nihon University | Teramukai S.,Kanazawa University | And 4 more authors.
Journal of Human Hypertension | Year: 2013

Morning home blood pressure (BP) levels are more closely associated with cardiovascular risk than clinic BP levels. However, control of morning home BP has been worse than that of clinic BP in clinical practice. We examined the effects of olmesartan-based treatment using data (n=21 341) from the first 16 weeks of the Home BP measurement with Olmesartan Naive patients to Establish Standard Target blood pressure (HONEST) study, a prospective observational study for olmesartan-naive patients with essential hypertension. After 16-week olmesartan-based treatment, the clinic and morning home systolic BP (SBP) lowered from 151.6±16.4 and 153.6±19.0 mm Hg to 135.0±13.7 and 135.5±13.7 mm Hg, respectively (P<0.0001). The achievement percentage of target morning home SBP (<135 mm Hg) in all patients, those with diabetes mellitus (DM), and those with chronic kidney disease (CKD) increased from 13.5, 16.4 and 17.2% to 50.8, 47.9 and 48.8%, respectively, and the proportion of patients with well-controlled hypertension (clinic SBP<140 mm Hg and morning home SBP<135 mm Hg) increased from 7.9, 9.2 and 10.2% to 38.9, 34.5 and 36.3%, respectively. After 16-week olmesartan-based treatment, the proportion of patients with masked and white coat hypertension changed from 11.8 to 24.2% and 5.6 to 11.9%. In conclusion, both clinic and morning home BP in all, DM and CKD patients improved with 16-week olmesartan-based treatment in the 'real world', and the results showed a sustained 24-hour BP-lowering effect of olmesartan. Decrease in clinic and home BP resulted in an increased rate of masked and white coat hypertension, and further management is needed in those patients. © 2013 Macmillan Publishers Limited. All rights reserved.

Kario K.,Jichi Medical University | Saito I.,Keio University | Kushiro T.,Life Planning Center Foundation | Teramukai S.,Kyoto Prefectural University of Medicine | And 4 more authors.
Hypertension | Year: 2014

This study aimed to investigate the relationship between on-treatment morning home blood pressure (HBP) and incidence of cardiovascular events using data from the Home Blood Pressure Measurement With Olmesartan Naive Patients to Establish Standard Target Blood Pressure (HONEST) study, a prospective observational study of 21 591 outpatients with essential hypertension (mean age, 64.9 years; women, 50.6%) enrolled between 2009 and 2010 at clinics and hospitals in Japan. They received olmesartan-based treatment throughout. The primary end point was major cardiovascular events. After a mean follow-up period of 2.02 years, cardiovascular events occurred in 280 patients (incidence, 6.46/1000 patient-years). The risk for the primary end point was significantly higher in patients with ontreatment morning HBP ≥145 to <155 mm Hg (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.12-2.99) and ≥155 mm Hg (HR, 5.03; 95% CI, 3.05-8.31) than <125 mm Hg and with on-treatment clinic blood pressure ≥150 to <160 mm Hg (HR, 1.69; 95% CI, 1.10-2.60) and ≥160 mm Hg (HR, 4.38; 95% CI, 2.84-6.75) than <130 mm Hg. Morning HBP associated with minimum risk was 124 mm Hg by spline regression analysis. Cardiovascular risk was increased in patients with morning HBP ≥145 mm Hg and clinic blood pressure <130 mm Hg (HR, 2.47; 95% CI, 1.20-5.08) compared with morning HBP <125 mm Hg and clinic blood pressure <130 mm Hg. In conclusion, it is essential to control morning HBP to <145 mm Hg, even in patients with controlled clinic blood pressure. Clinical Trial Registration-URL: http://www.umin.ac.jp/ctr/index.htm. UMIN Clinical Trials Registry, trial No. UMIN000002567. (Hypertension. 2014;64:989-996.) • Online Data Supplement. © 2014 American Heart Association, Inc.

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