Comparison of efficacy and safety between bisoprolol transdermal patch (TY-0201) and bisoprolol fumarate oral formulation in Japanese patients with grade I or II essential hypertension: randomized, double-blind, placebo-controlled study.

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.

Low salt intake and changes in serum sodium levels in the combination therapy of low-dose hydrochlorothiazide and angiotensin II receptor blocker.

BACKGROUND: The present study was conducted to examine the association of dietary salt intake with changes in serum sodium (srNa) levels when angiotensin II receptor blocker (ARB) treatment is changed to the combination of ARB plus low-dose diuretic (hydrochlorothiazide [HCTZ]). METHODS AND RESULTS: In 88 patients (age 70 ± 12 years), ARB treatment was switched to the combination therapy (same dosage ARB+12.5mg/day HCTZ). The srNa level was measured before and 6 months after administration of the combination. The daily salt intake was estimated by the Kawasaki formula using second morning urine sample. The study subjects were divided into quintile ranges according to daily salt intake. The reduction in srNa levels by switching to the combination treatment was significant in subjects in the lowest quintile Q5 (≤ 8.9 g/day salt intake), but not in those in Q1-4 (28.1-9.3g/day salt intake). Increases in serum creatinine and uric acid levels were significantly larger in the former group than in the latter group. CONCLUSIONS: In elderly Japanese subjects with low salt intake (<8.9 g/day), the addition of a low-dose diuretic (12.5mg HCTZ) to ARB treatment causes significant reduction in srNa levels, which might affect blood osmolarity.

[Calcium antagonists: current and future applications based on new evidence. Calcium channel blockers and EBM].

Calcium channel blockers are antihypertensive drugs which are prescribed widely for reducing high blood pressures. This is due to confirmed and stable efficacy, small side effects, and less influence on metabolism. Nowadays, many clinical trials, studies have proven that calcium channel blockers strongly reduce high blood pressure, prevent cardiovascular disease and stroke, and regress left ventricular hypertrophy. Some studies suggest that they are as beneficial as ACE inhibitors, angiotensin II receptor blockers, and diuretics.

[Difference in blood pressure measured in the office and out of office].

For a long time, diagnosis and treatment of hypertension were conducted based on the blood pressure measured in the office. However, recent clinical evidence clearly indicated the blood pressure measured out-of-office predict future development of cardiovascular events compared with BP measured in the office.

[Antihypertensive effects of nifedipine and changing for modified-release formula].

Nifedipine was initially developed as an anti-anginal drug, and it was Professor Murakami who first reported its usefulness in the management of hypertension. However, rapid decrease in blood pressure with immediate-release formulations of nifedipine led to simultaneous increases in heart rate, presumably because of reflex sympathetic activation, and a meta-analysis in the mid-1990s suggested an increased incidence of serious adverse events (AEs) with short-acting Ca2+ channel antagonists. Although subsequent reviews of the literature found little scientific basis for increased serious AEs with short-acting Ca2+ channel antagonists, this controversy led to the accelerated development of long-acting preparations. Recent clinical research has found improved outcomes in hypertensive patients receiving long-acting Ca2+ channel antagonist preparations and reconfirmed the role of nifedipine as a first-line agent.

Workplace hypertension is associated with obesity and family history of hypertension.

Job strain, which is a risk for hypertension and increased left ventricular mass, is thought to cause masked hypertension during work even if blood pressure (BP) is normal at health examinations. To study the prevalence of and factors related to workplace hypertension, 265 public officials (mean age, 41.4+/-10.7 years) measured their own BP at their workplace using semiautomated BP measurement devices. Factors related to workplace hypertension were assessed with multiple regression analysis. Workplace hypertension, defined as a BP no less than 140/90 mmHg, was observed in 23% of subjects (n=61). Compared with subjects without workplace hypertension (n=204), subjects with workplace hypertension were older (48.5+/-10.0 vs. 39.3+/-10.0 years), more likely to be men (69% vs. 46%), and had a higher body mass index (BMI) (23.4+/-2.7 vs. 21.6+/-3.2 kg/m(2)), higher cholesterol levels (214+/-33 vs. 194+/-36 mg/dl), and a higher Brinkman index (134+/-228 vs. 59+/-148). Subjects with workplace hypertension had higher BPs at checkup than did those without it (125+/-11/79+/-9 vs. 110+/-11/68+/-9 mmHg). The increases in BPs at the workplace were independently and significantly correlated with BMI, and a family history of hypertension. BP no less than 130/ 85 mmHg at health checkup was a good detector of workplace hypertension (sensitivity, 49%; specificity, 91%), suggesting that subjects with high-normal BPs at health checkup might have workplace hypertension. In conclusion, workplace hypertension was found to be associated with age, BMI, a family history of hypertension, and high-normal BPs at health checkup.

Increase in pulse pressure relates to diabetes mellitus and low HDL cholesterol, but not to hyperlipidemia in hypertensive patients aged 50 years or older.

Higher pulse pressure is associated with higher cardiovascular risk. We investigated the relationship between pulse pressure and known metabolic risk factors in hypertensive patients who had not experienced stroke or myocardial infarction. In a multicenter cross-sectional survey made in 1995, we registered 939 hypertensive patients aged > or = 50 years. Of these, 734 had never experienced stroke or myocardial infarction. We divided these 734 patients into two groups based on the value of their pulse pressures: 396 patients with a pulse pressure > or = 60 mmHg, and 338 patients with a pulse pressure<60 mmHg. The average pulse pressure value was 72 +/- 12 mmHg in the former group, and 49 +/- 8 mmHg in the latter group. The former group exhibited advanced age, a higher women-to-men ratio, lower high-density lipoprotein (HDL) cholesterol, and higher systolic and lower diastolic blood pressure. Diabetes mellitus (DM) and left ventricular hypertrophy were more frequently noticed in the former group than in the latter group. The prevalence of hyperlipidemia, however, was similar in the two groups. The association of pulse pressure with DM and low HDL cholesterol was statistically significant by multiple logistic analysis adjusted for age, sex, and other known cardiovascular risk factors. In conclusion, pulse pressure increases with advancing age. DM made a substantially larger contribution to the increase in pulse pressure than hyperlipidemia.

Effects of the long-acting calcium channel blocker barnidipine hydrochloride on 24-h ambulatory blood pressure.

The effect of the long acting calcium channel blocker, barnidipine hydrochloride (barnidipine) on 24-h ambulatory blood pressure (ABP) was evaluated in J-MUBA (Japanese Multicentre Study on Barnidipine with Ambulatory Blood Pressure Monitoring). Following an observation period of two weeks, antihypertensive treatment with barnidipine was continued for at least six months. At the end of each period, ABP were measured. The patients were divided into high- and low-range groups based on ABP measurement. Throughout the 24 h, barnidipine exerted an excellent antihypertensive effect in the high-range group, but not in the low-range group. Barnidipine had comparable effects in the daytime and nighttime in inverted dippers and non-dippers, but it was more effective on daytime ABP than on nighttime ABP in dippers and in extreme dippers. Morning blood pressure before and after waking was evaluated before and after barnidipine administration in 233 patients. Barnidipine inhibited increases in blood pressure before and after waking, especially in surge-type patients whose blood pressure increased rapidly after waking. A positive correlation among 24-h ABP, daytime and night time ABP, morning blood pressure, and clinic blood pressure during the observation period and the antihypertensive effect of barnidipine was observed, with barnidipine exhibiting stronger antihypertensive effects in patients with persistently high blood pressure. It was concluded that the antihypertensive effects of barnidipine are maintained for 24 h but it has no excessive hypotensive effects on lower blood pressure and is thus a safe antihypertensive agent.

Blood pressure measurement in research.

OBJECTIVE: The aim of this paper is to summarize the issues raised during a consensus conference on the role of different blood pressure (BP) monitoring techniques in research, including pathophysiological studies, clinical outcome trials and clinical pharmacology trials. METHODS: This review includes the contribution of the participants in a task force at the Eighth Consensus Conference on Ambulatory BP Monitoring (October 28-31, 2001, Sendai, Japan) and the results of a discussion open to all conference participants. Individual contributions have been summarized together with the points raised during the subsequent discussion, and the main statements are also presented in a table format. POINTS OF CONSENSUS: (1) BP monitoring in pathophysiological studies. The essential role played by continuous BP monitoring in this field had been acknowledged, and further development of non-invasive beat-by-beat monitoring techniques has been advocated. (2) BP monitoring in clinical trials. In clinical trials automated ambulatory BP monitoring (ABPM) and self BP measurements (SBPM) at home share similar advantages, with specific features that make these approaches not alternative solutions but rather approaches able to complement each other. A few examples of application of ABPM and SBPM in clinical trials include the Treatment of Hypertension according to Home or Office Blood Pressure (THOP) trial and the Trial of Preventing Hypertension (TROPHY). (3) Use of ABPM in clinical pharmacology studies. Use of ABPM is now an established routine, aimed at describing the 24-h effect of new antihypertensive drugs. An example of these applications that was discussed in the conference is the use of ABPM in the evaluation of a new long-acting calcium channel blocker (Barnidipine) (J-MUBA study). (4) Specific models for the analysis of BP fluctuations. The features characterizing the chronobiological approach to description of 24-h BP profiles and its limitations (mainly consisting of the high risk of data over-modelling) are discussed. Also the possible occurrence of a circaseptan (approximately with a 7-day period) rhythm in BP has been addressed, although repeated performance of 24-h ABPM over a week obviously faces a number of practical problems. (5) Progress in technology: BP monitoring and telemedicine. The possibility to implement an interactive telemonitoring system of home SBPM values and the perspectives for a clinical application of this technology in the Hypertension Objective treatment based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) trial is discussed.

Expressing health experience through embodied language.

PURPOSE: To describe embodied language for Japanese elders who suffered a stroke or cardiac disease within the previous year. Embodied language is the overlap of feeling and temporal word use with blood pressure during descriptions of health experience. DESIGN: Exploratory. METHODS: Blood pressure and word use were recorded simultaneously when 17 cardiac and 20 stroke participants described their health experiences for 4 minutes. Blood pressure was measured using a tonometric monitor and word use was measured using linguistic analysis software. Descriptive and nonparametric statistics were used. FINDINGS: Participants with strokes retained higher blood pressure after talking than did cardiac participants. The two groups showed contrasting relationships between word use and blood pressure, particularly for temporal words. CONCLUSIONS: This collaborative research between Japanese and American colleagues was a step toward deciphering shared values, which are important to understanding health for people who have lived through life-changing illness events.

A eficácia e segurança da terapia anti-hipertensiva a longo prazo com nifedipina / The efficacy and safety of long-term anti-hypertensive therapy with nifedipine

O efeito anti-hipertensivo e a segurança da terapia a longo prazo com nifedipina foi avaliada em 132 pacientes hipertensos, incluindo 100 pacientes idosos que receberam apenas nifedipina ou nifedipina juntamente com outros agentes anti-hipertensivos durante um período médio de 28,6 meses. Foi observado um pronto efeito anti-hipertensivo um mês após o início da terapia com nifedipina. O efeito anti-hipertensivo persistiu durante todo o período de acompanhamento e estava relacionado ao nível pressórico sangüíneo médio do pré-tratamento. Näo foi observada tolerância tardia à droga. Tonturas, rubor facial e outras sensaçöes desagradáveis foram observadas em 7,5% dos pacientes e edema de tornozelo em 9,8%. A terapêutica näo influenciou significativamente os níveis de creatinina sérica. Hipotensäo e outros efeitos colaterais foram a causa de interrupçäo da terapêutica em 10,6% e 4,5% dos pacientes, respectivamente. Concluiu-se que a terapia anti-hipertensiva a longo prazo com nifedipina é eficaz e segura, näo apenas em pacientes adultos mas também em pacientes idosos de alto risco