Differential effectiveness of ARB plus CCB therapy and high-dose ARB therapy in high-risk elderly hypertensive patients: subanalysis of the OSCAR study.

The OSCAR study was a multicenter prospective randomized study that examined the relative benefit of combined ARB (olmesartan 20 mg per day) plus calcium channel blocker (CCB) therapy vs. high-dose ARB monotherapy (olmesartan 40 mg per day) for prevention of cardiovascular events in elderly Japanese hypertensive patients. The present subanalysis of patients enrolled in the OSCAR study (n = 1078) was performed to assess whether baseline eGFR coupled with cardiovascular disease (CVD) could predict the relative benefit of these two treatments.

Sex differences in response to angiotensin II receptor blocker-based therapy in elderly, high-risk, hypertensive Japanese patients: a subanalysis of the OSCAR study.

The OlmeSartan Calcium Antagonists Randomized (OSCAR) study is a multicenter, prospective, randomized, open-label, blinded, end point study of elderly hypertensive Japanese patients that compared the efficacy of a high-dose angiotensin II receptor blocker (ARB) treatment to an ARB plus calcium channel blocker (CCB) combination. In this pre-specified subgroup analysis, we compared the response to such therapy according to sex. A total of 1164 patients (515 (44%) men and 649 (56%) women) were included, and each gender was split into two nearly equal treatment groups.

An angiotensin II receptor blocker-calcium channel blocker combination prevents cardiovascular events in elderly high-risk hypertensive patients with chronic kidney disease better than high-dose angiotensin II receptor blockade alone.

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).

Angiotensin II receptor blocker-based therapy in Japanese elderly, high-risk, hypertensive patients.

Background: 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.

Methods: 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.

Salt-induced hemodynamic regulation mediated by nitric oxide.

Excess daily salt intake impairs vasodilatation and enhances vasoconstriction, resulting in reduction of regional blood flow and elevation of blood pressure in healthy individuals and hypertensive patients with either salt sensitivity or not tested for salt sensitivity or not evaluated for salt sensitivity. The mechanism may involve decreased production of nitric oxide via endothelial nitric oxide synthase (eNOS), impaired bioavailability of nitric oxide, and elevated plasma levels of asymmetric dimethylarginine (ADMA). Experimental animals, irrespective of salt sensitivity, although less extensive in those with salt-resistance, fed a high-salt diet have deteriorated endothelial functions; the mechanisms involved include an impairment of eNOS activation, a decrease in eNOS expression, and an increase in oxidative stress and ADMA.

Comparative pharmacodynamics of olmesartan and azelnidipine in patients with hypertension: a population pharmacokinetic/pharmacodynamic analysis.

The objectives of this study were to identify the factors influencing antihypertensive response to the angiotensin receptor blocker, olmesartan medoxomil, or the calcium channel blocker, azelnidipine, and to discuss the possibility of utilizing them as predictors for drug selection prior to therapy. A two-way crossover study of olmesartan medoxomil and azelnidipine was conducted in 29 patients with mild to moderate essential hypertension. The 24-hour ambulatory blood pressure measurements (ABPM) and plasma drug concentrations were obtained on the first and at the end of each treatment period, and were analyzed using population pharmacokinetic/pharmacodynamic (PK/PD) modeling approach.

Rationale, design and patient baseline characteristics of OlmeSartan and calcium antagonists randomized (OSCAR) study: a study comparing the incidence of cardiovascular events between high-dose angiotensin II receptor blocker (ARB) monotherapy and combination therapy of ARB with calcium channel blocker in Japanese elderly high-risk hypertensive patients (ClinicalTrials. gov no. NCT00134160).

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.

Antihypertensive efficacy of olmesartan medoxomil and candesartan cilexetil in achieving 24-hour blood pressure reductions and ambulatory blood pressure goals.

Background: For patients with hypertension, effective 24-hour blood pressure (BP) control is vital to ensure protection against the early morning surge in BP and the associated increased risk of cardiovascular events. The aim of this analysis was to assess the 24-hour antihypertensive efficacy of olmesartan medoxomil (20mg once daily) compared with candesartan cilexetil (8mg once daily), with particular emphasis on BP control during the early morning period.

Methods: This is an additional analysis of a previously reported randomised, double-blind study in which 635 patients with mainly mild to moderate hypertension were randomised to 8 weeks of treatment with either olmesartan medoxomil 20 mg/day or candesartan cilexetil 8 mg/day.

Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial.

Background: Evidence-based treatment for hypercholesterolaemia in Japan has been hindered by the lack of direct evidence in this population. Our aim was to assess whether evidence for treatment with statins derived from western populations can be extrapolated to the Japanese population.

Methods: In this prospective, randomised, open-labelled, blinded study, patients with hypercholesterolaemia (total cholesterol 5.

Relation of serum total cholesterol and other factors to risk of cerebral infarction in Japanese men with hypercholesterolemia.

Background: Risk factors for cerebral infarction have not been well clarified, except for hypertension (HT), and few studies have examined the risk factors in the elderly.

Methods And Results: Clinical and behavioral risk factors for cerebral infarction were examined in 4,349 Japanese men aged 45-74 years with a serum total cholesterol (TC) concentration of 220 mg/dl or greater who participated in the Kyushu Lipid Intervention Study. A total of 81 men developed definite cerebral infarction in a 5-year follow-up period.

Nifedipine retard was as effective as angiotensin converting enzyme inhibitors in preventing cardiac events in high-risk hypertensive patients with diabetes and coronary artery disease: the Japan Multicenter Investigation for Cardiovascular Diseases-B (JMIC-B) subgroup analysis.

We stratified findings from the Japan Multicenter Investigation for Cardiovascular Diseases-B according to whether or not the patients had diabetes and compared the incidence of cardiac events occurring over a 3-year period between treatment with nifedipine retard and angiotensin converting enzyme (ACE) inhibitor. The primary endpoint was the overall incidence of cardiac events (cardiac death or sudden death, myocardial infarction, hospitalization for angina pectoris or heart failure, serious arrhythmia, and coronary interventions), and the secondary endpoints were a composite of other events (cerebrovascular accidents, worsening of renal dysfunction, non-cardiovascular events, and total mortality). The results showed no significant difference in the incidence of the primary endpoint between the nifedipine group (n=199) and the ACE inhibitor group (n=173) in diabetic patients: 15.

Role of prehypertension in the development of coronary atherosclerosis in Japan.

Background: Hypertension is an important risk factor of coronary heart disease. A new guidelines for hypertension prevention and management in The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure in the United States recommended lifestyle modification or medical treatment for subjects with prehypertension. However, whether prehypertension increases the risk of coronary atherosclerosis in the Japanese population is still unknown.

Relation of serum total cholesterol and other risk factors to risk of coronary events in middle-aged and elderly Japanese men with hypercholesterolemia: the Kyushu Lipid Intervention Study.

Background: The role of serum total cholesterol (TC) in the development of coronary heart disease (CHD) may differ in different age groups.

Methods And Results: The relation of serum TC and other risk factors to CHD events was examined in middle-aged (<65 years) and elderly (> or =65 years) men separately in the Kyushu Lipid Intervention Study (KLIS). Subjects were 4,349 men aged 45-74 years with serum TC of 220 mg/dl or greater who had no history of myocardial infarction, coronary angioplasty, or stroke.

Comparison of nifedipine retard with angiotensin converting enzyme inhibitors in Japanese hypertensive patients with coronary artery disease: the Japan Multicenter Investigation for Cardiovascular Diseases-B (JMIC-B) randomized trial.

The Japan Multicenter Investigation for Cardiovascular Diseases-B was performed to investigate whether nifedipine retard treatment was associated with a significantly higher incidence of cardiac events than angiotensin converting enzyme inhibitor treatment in Japanese patients. The study used a prospective, randomized, open, blinded endpoint (PROBE) design. Patients were enrolled at 354 Japanese hospitals specializing in cardiovascular disease.

Human chymase expression in a mice induces mild hypertension with left ventricular hypertrophy.

A number of in vitro studies have suggested potential pathophysiological roles of human (h-) chymase. However, the lack of an appropriate animal model has left the in vivo roles of chymase unclear. To approach this problem, a transgenic mouse (TGM) model carrying the h-chymase gene was established.

Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation.

Unlabelled: The purpose of the present study was to evaluate the effect of angiotensin II type 1 receptor (AT1R) antagonist on chronic structural remodeling in atrial fibrillation (AF).

Background: We previously reported that an AT1R antagonist, candesartan, prevents acute electrical remodeling in a rapid pacing model. However, the effect of candesartan on chronic structural remodeling in AF is unclear.

Reduction in serum total cholesterol and risks of coronary events and cerebral infarction in Japanese men: the Kyushu Lipid Intervention Study.

Lowering serum total cholesterol is shown to decrease the risk of coronary heart disease (CHD) in Western countries,but evidence is limited regarding cerebral infarction (CI). The present study used the Kyushu Lipid Intervention Study to examine the risks of CHD events and CI in relation to reduction in serum total cholesterol. Subjects were 4,615 men aged 45-74 years with serum total cholesterol of 220 mg/dl (5.

Reperfusion-induced arrhythmias are suppressed by inhibition of the angiotensin II type 1 receptor.

We examined antiarrhythmic effects of drugs, including renin-angiotensin system (RAS) inhibitors, on reperfusion arrhythmias in rats in vivo. Anesthetized rats were subjected to 5 min of coronary occlusion and 30 min of reperfusion. Arrhythmia scores, calculated as the product of the type of arrhythmia (1 for ventricular tachycardia, 2 for ventricular fibrillation) and its duration (in seconds), were adopted to evaluate the severity of arrhythmias.

Chymase inhibitor improves survival in hamsters with myocardial infarction.

The purpose of the present study was to assess the effects of chronic treatment with an orally active chymase inhibitor, 4-[1-(naphthylmethyl)benzimidazol-2-ylthio]butanoic acid (TEI-E548), in a hamster myocardial infarction model. In the first experiment, after confirming the biochemical inhibitory action of TEI-E548 on human and hamster chymases (Ki = 6.2 and 30.