Pulse Wave Velocities Derived From Cuff Ambulatory Pulse Wave Analysis.

Pulse wave velocity (PWV), a measure of arterial stiffness, is an independent risk factor for cardiovascular morbidity and mortality. We investigated the relationship of ambulatory brachial cuff-based oscillometric PWV (oPWV) to 2 known correlates: age and brachial systolic blood pressure (SBP). In 234 participants in the Masked Hypertension Study, we analyzed 7284 validated hourly ambulatory SBP and oPWV readings using the Mobil-O-Graph monitor, which uses a proprietary pulse wave analysis algorithm to determine oPWV.

Sodium and Fluid Excretion With Torsemide in Healthy Subjects is Limited by the Short Duration of Diuretic Action.

Background: Loop diuretics are highly natriuretic but their short duration of action permits postdiuretic sodium retention, which limits salt loss unless dietary salt is severely restricted. We tested the hypothesis that a more prolonged duration of action would enhance salt loss.

Methods And Results: Ten healthy participants were crossed over between 20 mg of oral immediate-release or extended-release (ER) torsemide while consuming a fixed diet with 300 mmol·d of Na.

Clinical Use of Pulse Wave Analysis: Proceedings From a Symposium Sponsored by North American Artery.

The use of pulse wave analysis may guide the provider in making choices about blood pressure treatment in prehypertensive or hypertensive patients. However, there is little clinical guidance on how to interpret and use pulse wave analysis data in the management of these patients. A panel of clinical researchers and clinicians who study and clinically use pulse wave analysis was assembled to discuss strategies for using pulse wave analysis in the clinical encounter.

Efficacy and safety of the selective 11β-HSD-1 inhibitors MK-0736 and MK-0916 in overweight and obese patients with hypertension.

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) may be involved in several abnormalities associated with the metabolic syndrome. This study evaluated the antihypertensive efficacy and safety of two 11β-HSD1 inhibitors, MK-0736 and MK-0916, in overweight-to-obese hypertensive patients. Patients aged 18-75 years with sitting diastolic blood pressure (SiDBP) 90-104 mm Hg, systolic BP <160 mm Hg (after washout of prior antihypertensive medications), and BMI ≥27 to <41 kg/m(2) were randomized to receive 2 or 7 mg/d MK-0736, 6 mg/d MK-0916, or placebo for 12 weeks (n = 51-54/group).

Training the translational scientist.

A Clinical and Translational Science Awards Industry Forum titled "Promoting Efficient and Effective Collaborations Among Academia, Government, and Industry" was held in February 2010. A session at this forum was organized to address the training and skills needed to develop a biomedical scientific workforce that interfaces academia, government agencies, and industry to support the process of translating science into applicable means to improve health. By examining the requisite competencies and training resources for scientists in each of these sectors, opportunities for collaboration and adoption of new educational strategies were identified that could help to address barriers to translational research education and career development.

Single-dose effects of isosorbide mononitrate alone or in combination with losartan on central blood pressure.

Antihypertensive drugs can have different effects on central and brachial blood pressures, which may affect outcomes. Nitric oxide donors have acute effects on central blood pressure but have not been assessed with renin-angiotensin system blockade. Thirteen patients with prehypertensive/Stage 1 hypertension were randomized to five single-dose treatments separated by ≤4 days using a double-blind, crossover study design: angiotensin receptor blocker (ARB) losartan 100 mg, isosorbide mononitrate (ISMN) 60 mg, losartan 100 mg + ISMN 15 mg, losartan 100 mg + ISMN 60 mg, and placebo.

Central blood pressure measurements-an opportunity for efficacy and safety in drug development?

Over a century of experience with brachial blood pressure has produced a substantial amount of information on the role of blood pressure as a factor in heart disease, stroke and kidney failure. Successful interventions lowering blood pressure and reducing damage to vital organs testify further to the importance of this vital sign. In recent years attempts to probe deeper into the value of knowledge of blood pressure levels closer to the heart (central blood pressures) suggest that noninvasive measurement of central aortic blood pressure may improve further efforts directed at both understanding drug benefit and uncovering potential drug safety issues.

Effects of the renin inhibitor MK-8141 (ACT-077825) in patients with hypertension.

The renin inhibitor MK-8141 (ACT-077825) demonstrates substantial immunoreactive active renin (ir-AR) increase (sevenfold) without a persistent plasma renin activity (PRA) decrease. The present study assessed the antihypertensive efficacy of MK-8141 in hypertensive patients. In this double-blind, placebo- and active comparator-controlled study, 195 patients with hypertension (trough sitting diastolic blood pressure ≥92 to <105 mm Hg, trough sitting systolic blood pressure <170 mm Hg, and 24-hour mean diastolic blood pressure [DBP] ≥80 mm Hg) were randomized to one of four treatments (stratified by race, black versus others): MK-8141 250 mg, MK-8141 500 mg, enalapril 20 mg, or placebo.

Antihypertensive drug development: current challenges and future opportunities.

The growing rate of obesity and diabetes, and an aging population has led to increased demand for new antihypertensive compounds. This review highlights the challenges and opportunities associated with each phase of drug discovery and development of novel antihypertensive agents. Discovery and development starts with identification of a protein hypothesized to be linked to hypertension.

Next-generation biomarkers for detecting kidney toxicity.

There is a paucity of biomarkers that reliably detect nephrotoxicity. The Predictive Safety Testing Consortium (PSTC) faced several challenges in identifying novel safety biomarkers in the renal setting.

Fifty years of thiazide diuretic therapy for hypertension.

Background: The use of thiazide diuretics has decreased over the past 30 years despite data from many well-controlled clinical trials demonstrating that the use of these agents as monotherapy or in combination with other antihypertensive agents will reduce blood pressure and decrease cardiovascular as well as cerebrovascular events.

Methods: We reviewed clinical and experimental data on thiazide diuretics since their introduction in the late 1950s.

Results: The results of thiazide-based therapy in young and old are consistently positive despite concerns about some metabolic changes, eg, insulin resistance or hypokalemia, that may occur.

A multicenter, randomized, double-blind, parallel-group trial of the antihypertensive efficacy and tolerability of a combination of once-daily losartan 100 mg/hydrochlorothiazide 12.5 mg compared with losartan 100-mg monotherapy in the treatment of mild to severe essential hypertension.

Background: Because patients with hypertension may require >1 antihypertensive agent to control blood pressure (BP), physicians often prescribe a fixed combination of antihypertensive medications.

Objective: This study evaluated the effect of adding low-dose hydrochlorothiazide 12.5 mg (HCTZ12.