Important Note: The following information is provided for your education. It should not be relied upon for personal diagnosis or treatment. If you believe that a particular therapy applies to you or someone you care about, be sure to consult a doctor before trying it.
   

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Previous Hypertension Research: 2002-2006   
The Hypertension File also contains summaries of past research that has shown promise and may still be standard practice among many physicians. To download earlier research findings on Hypertension, click HERE.
 

Latest Research on Hypertension
     
Dtsch Med Wochenschr. 2008 Sep;133(37):1853-6. Epub 2008 Sep 3.
[The kidneys and hypertension]
[Article in German]
Hausberg M, Mann J, Kühn K.
Schwerpunkt Nephrologie/Rheumatologie und allgemeine Innere Medizin, Städtisches Klinikum Karlsruhe.

In patients with severe hypertension a search for a renal cause, particularly for a renal artery stenosis, needs to be undertaken with 24-hour blood pressure measurement, urinary examination, determination of renal function and duplex sonography of the kidneys.--Sympathetic hyperactivity, which is associated with an increased cardiovascular risk, may already be found in an early stage of renal diseases. There is evidence that administration of an ACE inhibitor or an angiotensin receptor antagonist (ARB) may induce a decrease of sympathetic hyperactivity as well as a reduced rate of adverse cardiovascular events in patients in renal failure.--In patients with renal disease and high proteinuria antihypertensive therapy with ACE-inhibitors or ARB delays the progression of chronic renal failure. Combined therapy of ACE-inhibitors plus ARB may reduce proteinuria more than that would be the case with either of these drugs alone. However, there is no evidence that combination of these two drugs improves renal function more than monotherapy.--Renal artery stenosis of > 70% should be treated by dilatation, if there is evidence of fibromuscular dysplasia. Dilatation and/or stent implantation in an atherosclerotic renal artery stenosis of > 70% should be performed if indicated by the patient's clinical state. i.e. severe hypertension has proved to be resistant to triple drug antihypertensive therapy or pulmonary edema has occurred frequently. Preservation of renal function by angioplasty of an atherosclerotic renal artery stenosis remains a challenge. However, exact criteria for such intervention need to be established. But so far there have not been adequate data from controlled prospective trials.

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Ugeskr Laeger. 2008 Sep 1;170(36):2782-4.
[Hypertension--does it matter how blood pressure is lowered?]
[Article in Danish]
Mehlsen J.
Frederiksberg Hospital, Klinisk Fysiologisk/nuklearmedicinsk Afdeling, Frederiksberg. j_mehlsen@mac.com

ASCOT compared the effect of atenolol combined with a thiazide versus amlodipine with perindopril in hypertensive patients. It also studied the effect of atorvastatin in those with normal cholesterol. ASCOT concluded that reductions in cardiovascular events with atorvastatin were significant, and that amlodipine-based treatment prevented more cardiovascular events. The latter seemed to be due to better control of central blood pressure. Both statin and amlodipine-based treatments were cost-effective. According to the ASCOT study, it does matter how blood pressure is lowered.

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JAMA. 2008 Aug 27;300(8):924-32.
Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial.
Feig DI, Soletsky B, Johnson RJ.
Department of Pediatrics, Renal Section, Baylor College of Medicine, Houston, TX 77030, USA. dfeig@bcm.tmc.edu

CONTEXT: Hyperuricemia is a predictor for the development of hypertension and is commonly present in new-onset essential hypertension. Experimentally increasing uric acid levels using a uricase inhibitor causes systemic hypertension in animal models. OBJECTIVE: To determine whether lowering uric acid lowers blood pressure (BP) in hyperuricemic adolescents with newly diagnosed hypertension. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, placebo-controlled, crossover trial (September 2004-March 2007) involving 30 adolescents (aged 11-17 years) who had newly diagnosed, never-treated stage 1 essential hypertension and serum uric acid levels > or = 6 mg/dL. Participants were treated at the Pediatric Hypertension Clinic at Texas Children's Hospital in Houston. Patients were excluded if they had stage 2 hypertension or known renal, cardiovascular, gastrointestinal tract, hepatic, or endocrine disease. INTERVENTION: Allopurinol, 200 mg twice daily for 4 weeks, and placebo, twice daily for 4 weeks, with a 2-week washout period between treatments. The order of the treatments was randomized. MAIN OUTCOME MEASURES: Change in casual and ambulatory blood pressure. RESULTS: For casual BP, the mean change in systolic BP for allopurinol was -6.9 mm Hg (95% confidence interval [CI], -4.5 to -9.3 mm Hg) vs -2.0 mm Hg (95% CI, 0.3 to -4.3 mm Hg; P = .009) for placebo, and the mean change in diastolic BP for allopurinol was -5.1 mm Hg (95% CI, -2.5 to -7.8 mm Hg) vs -2.4 (95% CI, 0.2 to -4.1; P = .05) for placebo. Mean change in mean 24-hour ambulatory systolic BP for allopurinol was -6.3 mm Hg (95% CI, -3.8 to -8.9 mm Hg) vs 0.8 mm Hg (95% CI, 3.4 to -2.9 mm Hg; P = .001) for placebo and mean 24-hour ambulatory diastolic BP for allopurinol was -4.6 mm Hg (-2.4 to -6.8 mm Hg) vs -0.3 mm Hg (95% CI, 2.3 to -2.1 mm Hg; P = .004) for placebo. Twenty of the 30 participants achieved normal BP by casual and ambulatory criteria while taking allopurinol vs 1 participant while taking placebo (P < .001). CONCLUSIONS: In this short-term, crossover study of adolescents with newly diagnosed hypertension, treatment with allopurinol resulted in reduction of BP. The results represent a new potential therapeutic approach, although not a fully developed therapeutic strategy due to potential adverse effects. These preliminary findings require confirmation in larger clinical trials. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00288184.

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Am J Med. 2008 Aug;121(8 Suppl):S8-15.
Management of hypertension in patients with cardiac disease: use of renin-angiotensin blocking agents.
Prisant LM.
Hypertension and Pharmacology Unit, Medical College of Georgia, Augusta, Georgia 30912, USA. mprisant@mcg.edu

Inhibition of renin-angiotensin system (RAS) activity using angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ARBs) is beneficial in patient populations with left ventricular dysfunction or systolic heart failure (HF) and other forms of heart disease. In high-risk patients with coronary heart disease (CHD), treatment with these agents reduces the mortality rate and improves secondary outcomes. Individuals with stable CHD who are at lower risk benefit less from treatment. RAS inhibition also provides some clinical benefit to patients with diastolic HF and preserved left ventricular function. Left ventricular hypertrophy (LVH) is a strong predictor of cardiovascular events and all-cause mortality in patients with hypertension. Treatment with an ARB reduces the risk for adverse cardiovascular outcomes in patients with hypertension and LVH. The benefits correlate with regression of LVH, and the effect is independent of the degree of blood pressure lowering. Finally, studies indicate that a history of hypertension in patients who have not had a myocardial infarction (MI) increases the risk for HF after MI; the risk is decreased in patients with hypertension who receive treatment with a RAS inhibitor.

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Am J Med. 2008 Aug;121(8 Suppl):S16-22.
Management of hypertension in patients with chronic kidney disease and diabetes mellitus.
Palmer BF.
Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75225-8856, USA. biff.palmer@utsouthwestern.edu

Treatment of patients at high risk for developing cardiovascular disease aims at controlling blood pressure, optimizing blood glucose levels, and providing renoprotection. Chronic kidney disease (CKD) and diabetes mellitus are prevalent causes of cardiovascular disease owing to associations with major cardiovascular risk factors, such as hypertension, and they are substantial health burdens. Even mild-to-moderate CKD and prehypertension increase cardiovascular risk. First-line agents for reducing cardiovascular risk are inhibitors of the renin-angiotensin system: angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). In clinical trials, treatment of high-risk patients with ACE inhibitors and ARBs delays or prevents the onset of diabetes and prevents progression of renal disease and cardiovascular events, including cardiovascular mortality. Current evidence indicates that the clinical efficacy of these end points includes effects that may be beyond blood pressure reduction.

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Hypertension. 2008 Aug;52(2):408-14. Epub 2008 Jul 7. Erratum in: Hypertension. 2008 Sep;52(3):e29.
Relationship of dietary linoleic acid to blood pressure. The International Study of Macro-Micronutrients and Blood Pressure Study [corrected]
Miura K, Stamler J, Nakagawa H, Elliott P, Ueshima H, Chan Q, Brown IJ, Tzoulaki I, Saitoh S, Dyer AR, Daviglus ML, Kesteloot H, Okayama A, Curb JD, Rodriguez BL, Elmer PJ, Steffen LM, Robertson C, Zhao L; International Study of Macro-Micronutrients and Blood Pressure Research Group.
Department of Health Science, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Shiga 520-2192, Japan. miura@belle.shiga-med.ac.jp

Findings from observational and interventional studies on the relationship of dietary linoleic acid, the main dietary polyunsaturated fatty acid, with blood pressure have been inconsistent. The International Study of Macro-Micronutrients and Blood Pressure is an international cross-sectional epidemiological study of 4680 men and women ages 40 to 59 years from 17 population samples in China, Japan, United Kingdom, and United States. We report associations of linoleic acid intake of individuals with their blood pressure. Nutrient intake data were based on 4 in-depth multipass 24-hour dietary recalls per person and 2 timed 24-hour urine collections per person. Systolic and diastolic blood pressures were measured 8 times at 4 visits. With several models to control for possible confounders (dietary or other), linear regression analyses showed a nonsignificant inverse relationship of linoleic acid intake (percent kilocalories) to systolic and diastolic blood pressure for all of the participants. When analyzed for 2238 "nonintervened" individuals (not on a special diet, not consuming nutritional supplements, no diagnosed cardiovascular disease or diabetes, and not taking medication for high blood pressure, cardiovascular disease, or diabetes), the relationship was stronger. With adjustment for 14 variables, estimated systolic/diastolic blood pressure differences with 2-SD higher linoleic acid intake (3.77% kcal) were -1.42/-0.91 mm Hg (P<0.05 for both) for nonintervened participants. For total polyunsaturated fatty acid intake, blood pressure differences were -1.42/-0.98 mm Hg (P<0.05 for both) with 2 SD higher intake (4.04% kcal). Dietary linoleic acid intake may contribute to prevention and control of adverse blood pressure levels in general populations.

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Hypertension. 2008 Aug;52(2):336-41. Epub 2008 Jun 23. Comment in: Hypertension. 2008 Aug;52(2):220-1.
Sympathoadrenal stress reactivity is a predictor of future blood pressure: an 18-year follow-up study.
Flaa A, Eide IK, Kjeldsen SE, Rostrup M.
Department of Acute Medicine, Ullevaal University Hospital, N-0407 Oslo, Norway. arnljot.flaa@medisin.uio.no

In the present study we hypothesized that arterial catecholamine concentrations during rest and 2 laboratory stress tests were independent predictors of blood pressure at an 18-year follow-up. At entry, blood pressure, heart rate, and arterial plasma epinephrine and norepinephrine concentrations were measured in 99 healthy men (age: 19.3+/-0.4 years, mean+/-SD) at rest, during a mental arithmetic test, and during a cold pressor test. After 18.0+/-0.9 years of follow-up, resting blood pressure was measured. The norepinephrine and epinephrine concentrations during the mental arithmetic explained 12.7% of the variation of future systolic blood pressure after adjusting for initial resting blood pressure, family history, body mass index, and systolic blood pressure during the stress test in a multiple regression analysis (adjusted R(2)=0.651; P<0.001). To conclude, the present study shows that sympathetic nervous activity during mental arithmetic predicts future blood pressure, indicating a possible causal factor in the development of essential hypertension independent of the initial blood pressure.

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J Nutr. 2008 Aug;138(8):1407-10.
Role of vitamin A in determining nephron mass and possible relationship to hypertension.
Bhat PV, Manolescu DC.
Laboratory of Nutrition and Cancer, Centre Hospitalier de l'Université de Montréal, CHUM-Hotel Dieu, Université de Montreal, H2W 1T8 Montreal, Canada. pangala.v.bhat@umontreal.ca

Vitamin A (retinol) and its analogs (retinoids) are important regulators of cell proliferation, differentiation, immune function, and apoptosis. The kidneys are target organs for vitamin A action. Retinoic acid (RA), a vitamin A metabolite, is involved in embryonic kidney patterning through the control of receptor tyrosine kinase expression, which modulates ureteric bud branching morphogenesis. Vitamin A status of the mother profoundly affects kidney organogenesis of the newborn. In rodents, mild vitamin A deficiency results in a 20% reduction of nephron number. In adult humans, nephron number varies between 0.3 and 1.3 million per kidney, which is accepted as normal. However, recent studies indicate that humans at the low end of nephron number are predisposed to primary hypertension. Because RA regulates nephron mass, its optimal availability during nephrogenesis is critical. RA levels in the embryo are affected by several factors, such as maternal vitamin A nutrition and disturbances in retinol metabolism. Maternal vitamin A deficiency during pregnancy is widespread in developing countries and segments of these populations may be exposed to low vitamin A during fetal life when nephron number is determined. Infants are likely to be born with suboptimal nephrons and may develop primary hypertension later in life. Although maternal vitamin A deficiency is not common in developed countries, congenital nephron number nevertheless varies widely, indicating low fetal RA levels due to common variants of the enzymes that convert retinol to RA. These infants might require heightened surveillance for hypertension later in life.

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Ann Fam Med. 2008 Jul-Aug;6(4):295-301.
Integration of depression and hypertension treatment: a pilot, randomized controlled trial.
Bogner HR, de Vries HF.
Department of Family Medicine and Community Health, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. hillary.bogner@uphs.upenn.edu

PURPOSE: We wanted to examine whether integrating depression treatment into care for hypertension improved adherence to antidepressant and antihypertensive medications, depression outcomes, and blood pressure control among older primary care patients. METHODS: Older adults prescribed pharmacotherapy for depression and hypertension from physicians at a large primary care practice in West Philadelphia were randomly assigned to an integrated care intervention or usual care. Outcomes were assessed at baseline, 2, 4, and 6 weeks using the Center for Epidemiologic Studies Depression Scale (CES-D) to assess depression, an electronic monitor to measure blood pressure, and the Medication Event Monitoring System to assess adherence. RESULTS: In all, 64 participants aged 50 to 80 years participated. Participants in the integrated care intervention had fewer depressive symptoms (CES-D mean scores, intervention 9.9 vs usual care 19.3; P <.01), lower systolic blood pressure (intervention 127.3 mm Hg vs usual care 141.3 mm Hg; P <.01), and lower diastolic blood pressure (intervention 75.8 mm Hg vs usual care 85.0 mm Hg; P <.01) compared with participants in the usual care group at 6 weeks. Compared with the usual care group, the proportion of participants in the intervention group who had 80% or greater adherence to an antidepressant medication (intervention 71.9% vs usual care 31.3%; P <.01) and to an antihypertensive medication (intervention 78.1% vs usual care 31.3%; P <.001) was greater at 6 weeks. CONCLUSION: A pilot, randomized controlled trial integrating depression and hypertension treatment was successful in improving patient outcomes. Integrated interventions may be more feasible and effective in real-world practices, where there are competing demands for limited resources.

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Harefuah. 2008 Jun;147(6):536-42, 573.
[Oral inhibitors of renin and their potential use as therapeutic agents in treating hypertension]
[Article in Hebrew]
Abassi Z, Armaly Z, Nakhoul F, Hoffman A.
Department of Physiology and Biophysics, Faculty of Medicine, Technion, Israel. abassi@tx.technion.ac.il

Hypertension is the most common risk factor for cardiovascular disease, constituting the most common cause of death in industrialized countries. Therefore, the task of blood pressure reduction has significant importance in reducing vascular damage, myocardial infarctions, kidney damage and incidence of cerebrovascular accidents. The renin-angiotensin-aldosterone system (RAAS) plays a central role in control and function of the cardiovascular and renal systems, and is deeply involved in the pathophysiology of diseases of vasculature, heart, kidneys and others. Therefore, blockade of RAAS by angiotensin converting enzyme (ACE) inhibitors and blockers of angiotensin II type AT1 receptors (ARBs) is widely utilized by clinicians. Indeed, it has long been known that ACE inhibitors and ARBs protect different targets of angiotensin II, due to impedance of the negative effects of the hormone and the inhibition of aldosterone production, which contributes both directly and indirectly to the damages, independent of angiotensin II. Despite this, the morbidity and mortality resulting from the progression of cardiovascular diseases in patients treated with ACE inhibitors or ARBs remain high. As such, over the years, much effort has been dedicated to the development of direct inhibitors of renin. The earliest renin inhibitors, developed 30 years ago were not effective due to their protein nature, which prevents their oral administration and limited their clinical use. In the last decade, several non-protein renin inhibitors which could be given orally were developed, of which Aliskiren is the most well known representative. Due to the fact that neutralization of the RAAS by ACE inhibitors and ARBs has been reviewed at length many times, this review will focus on the renewed subject of renin inhibition. The earliest research, both in humans as well as in animal models, show that Aliskiren has therapeutic potential in treatment of patients with hypertension, cardiovascular disease and renal disease. However, the efficacy of Aliskiren in treating systolic and diastolic hypertension in patients was not better than that obtained using ACE inhibitors or ARBs. Even so, there is no need to lower levels of optimism for potential therapy using direct inhibitors of renin. Current research is still in its early stages and there is a need to remember that it took many years to prove the clinical usefulness of ACE inhibitors, which are now central to treatment of cardiovascular and renal diseases, including hypertension.

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J Renin Angiotensin Aldosterone Syst. 2008 Jun;9(2):66-74.
Cardioprotective effects of telmisartan in uncomplicated and complicated hypertension.
Grassi G, Quarti-Trevano F, Mancia G.
Department of Internal Medicine and Cardiovascular Prevention, S Gerardo Hospital, University of Milano-Bicocca, Monza, Milan, Italy. guido.grassi@unimib.it

The development of angiotensin II receptor blockers (ARB) as a new class of drugs for the management of hypertension has elicited the attention of many clinicians worldwide with the aim of improving blood pressure (BP) control as well as cardiovascular protection. Among ARB telmisartan has been shown to be characterised by an antihypertensive efficacy fully covering the 24-hour period, thereby allowing to antagonise the adverse effects of early morning BP rise on cardiovascular risk. Other specific effects of the drug are represented by its favourable metabolic profile (particularly on insulin sensitivity) and neutral effects on sympathetic cardiovascular function. These properties are coupled with cardioprotective effects, documented by the evidence that the drug: 1) is effective in favouring the regression of cardiac and vascular organ damage, 2) reduces arterial stiffness and improves vascular distensibility and 3) reverses the endothelial dysfunction typical of the hypertensive state particularly when complicated by renal failure, diabetes, obesity or metabolic syndrome. Several of these properties can account for the results of the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), documenting the beneficial effects on the drug on cardiovascular morbidity and mortality.

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Prescrire Int. 2008 Jun;17(95):115-8.
Arterial hypertension: second-line treatment. Try other single-agent treatments.
[No authors listed]

(1) Reliable evidence supports the use of thiazide diuretics (chlortalidone or hydrochlorothiazide) as first-line treatment for uncomplicated arterial hypertension. (2) When patients fail to reach blood pressure targets with well-conducted treatment with thiazide diuretics, or this treatment is poorly tolerated, what are the best second-line options? To answer this question, we reviewed the available evidence, based on our standard in-house methodology. (3) We found no published trials specifically designed to evaluate second-line antihypertensive treatments in cardiovascular prevention. There were no available trials of dual- versus single-agent therapy after failure of a thiazide diuretic. (4) When the blood pressure target is not reached, inadequate drug efficacy is only one of several possible causes. Various other factors affecting blood pressure should also be investigated. (5) Dual-agent therapy carries an increased risk of adverse effects and drug interactions compared to monotherapy. (6) There is no consensus among clinical practice guidelines on second-line antihypertensive therapy. However, to minimise the risk of adverse effects, it is clearly better to select single-agent therapy with a drug that has been shown to prevent cardiovascular events in first-line treatment of otherwise healthy hypertensive patients. Possible options include: angiotensin-converting-enzyme inhibitors, angiotensin II antagonists, calcium channel blockers or betablockers. In patients over the age of 60, betablockers seem less effective that the other drugs in preventing strokes. (7) There is too little evidence to choose a specific third-line combination rather than another. However, any adverse effects that the patient experienced during prior treatments should be taken into account.

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Clin Cardiol. 2008 Apr 10;31(4):153-158 [Epub ahead of print]
A Comparison of the Aldosterone-blocking Agents Eplerenone and Spironolactone.
Struthers A, Krum H, Williams GH.
Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, UK;

Improved understanding of the adverse pharmacological properties of aldosterone has prompted investigation of the clinical benefits of blocking aldosterone at the receptor level. This article reviews the pharmacology, clinical efficacy, and tolerability of the two available blocking agents, spironolactone and eplerenone. A Medline search identified clinical studies assessing spironolactone and eplerenone. Priority was given to large, well-controlled, clinical trials and comparative studies. Pharmacological differences between spironolactone and eplerenone include lower affinity of eplerenone for progesterone, androgen, and glucocorticoid receptors; more consistently demonstrated nongenomic properties for eplerenone; and the presence of long-acting metabolites for spironolactone. Both agents effectively treat hypertension and heart failure but comparisons are complicated by the deficiency of head-to-head trials and differences between patient populations. There are differences in the tolerability profiles; spironolactone is associated with dose-dependent sexual side effects. Both agents produce dose-dependent increases in potassium concentrations, although the effect with spironolactone appears to be greater when both agents are administered at recommended doses. Choice of a specific agent should be based on individual patient issues, such as the nature of heart failure and patient concerns about adverse events. Copyright (c) 2008 Wiley Periodicals, Inc.

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Expert Rev Cardiovasc Ther. 2008 Apr;6(4):471-9.
Beta-blockers in the management of hypertension: focus on nebivolol.
Wojciechowski D, Papademetriou V.
Department of Veterans Affairs Medical Center, Georgetown University Medical Center, Washington, DC 20422, USA. davidwojciechowski@yahoo.com

Hypertension is a major cardiovascular risk factor but most patients remain asymptomatic for many years. Successful therapy not only needs to be effective, it also needs to be well tolerated. beta-blockers are well established as effective antihypertensive agents. However, one major drawback to the currently available beta-blockers, particularly the noncardioselective beta-blockers, is their side-effect profile, including sexual dysfunction, fatigue, depression and metabolic abnormalities such as impaired glucose tolerance and lipid abnormalities. Nebivolol (Bystolic), a novel, highly cardioselective, third-generation beta-blocker that recently received approval by the US FDA for the treatment of hypertension in the USA, is effective in treating blood pressure and has a favorable side-effect profile. Studies conducted in Europe, where nebivolol has been available for some time for the treatment of hypertension, have shown that nebivolol achieves blood pressure reductions comparable to other beta-blockers but with fewer side effects. Additionally, nebivolol has demonstrated similar efficacy in blood pressure reduction when compared with calcium channel blockers and inhibitors of the renin-angiotensin system. When combined with hydrochlorothiazide there was an additive antihypertensive effect. Lastly, nebivolol exhibits a vasodilatory property that is related to its effect on nitric oxide, an intrinsic vasodilator produced in the vascular endothelium. Nebivolol enhances nitric oxide bioavailability. Studies have also demonstrated nebivolol's ability to function as an antioxidant and decrease markers of oxidative stress. These effects are believed to ultimately produce a modulation of the endothelial dysfunction typically seen in hypertension.

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Clin Ther. 2008 Mar;30(3):482-498.
The effects of amlodipine and enalapril on renal function in adults with hypertension and nondiabetic nephropathies: A 3-year, randomized, multicenter, double-blind, placebo-controlled study.
Esnault VL, Brown EA, Apetrei E, Bagon J, Calvo C, Dechatel R, Holdaas H, Krcmery S, Kobalava Z; for the Amlodipine Versus Enalapril in Renal failure (AVER) Study Group.
Pasteur Hospital, Université de Nice-Sofia Antipolis, Nice, France.

Background: Placebo-controlled trials have found that angiotensin-converting enzyme inhibitors (ACEIs) decrease proteinuria and slow the progression of nondiabetic nephropathies. However, head-to-head comparisons of ACEIs and calcium channel blockers (CCBs) have shown conflicting results. Indeed, a recent metaanalysis concluded that there is still uncertainty about the greater renoprotection seen with ACEIs or angiotensin II receptor blockers in nondiabetic patients with renal disease, particularly when using true glomerular filtration rate (GFR) as the primary outcome. Objective: The objective of this 3-year, randomized, multicenter, double-blind, placebo-controlled study was to compare true GFR decline (measured by yearly 51Cr-EDTA blood clearance) in nondiabetic, nonnephrotic adult hypertensive patients with estimated creatinine clearance of 20 to 60 mL/min . 1.73 m(2), when randomized to a CCB (amlodipine, 5-10 mg/d) or an ACEI (enalapril, 5-20 mg/d). Methods: Patients (a
ged 18-80 years) entered a 4-week placebo run-in washout period and previous antihypertensive drugs were tapered off over 2 weeks. Add-on treatments were atenolol (50-100 mg/d), loop diuretics (furosemide, 20-500 mg/d or torsemide, 5-200 mg/d), alpha-blockers (prazosin, 2.5-5 mg/d or doxazosin, 1-16 mg/d), and centrally acting drugs (rilmenidine, 1-2 mg/d or methyldopa, 250-500 mg/d). The primary end point was true GFR measured by yearly (51)Cr-EDTA blood clearance. Secondary end points included a clinical composite of renal events and tolerability collected by a full clinical and laboratory evaluation at each study visit. Post hoc analyses for the change in GFR, proteinuria, and time to clinical events were also planned on baseline proteinuria subgroups (<1 and >/=1 g/d) before unblinding the database. Results: Three hundred eighteen patients entered the run-in period and 263 patients (156 men/107 women; mean age, 58 years) were randomized to receive either amlodipine (5 mg/d, n = 132) or enalapril (5 mg/d, n = 131). Blood pressure declined from 165/102 mm Hg to 138/84 mm Hg and 138/85 mm Hg with amlodipine and enalapril, respectively (no between-group significance). Only 20.8% of the patients randomized to ACEI treatment received diuretics at the last observation. No statistically significant difference was found between amlodipine and enalapril in GFR decline (-4.92 and -3.98 mL/min . 1.73 m(2), respectively, at last observation) and composite secondary end point after a median follow-up of 2.9 years, including in the subgroup of patients with proteinuria >1 g/d at baseline. Protein excretion rate decreased significantly from baseline in patients taking enalapril plus diuretics (median -270 mg/d; P < 0.001) but not in patients taking amlodipine plus diuretics (-25 mg/d at last observation). Conclusion: In this cohort of nondiabetic, nonnephrotic hypertensive patients, no statistically significant difference in true GFR decline was found over 3 years between amlodipine-treated patients and enalapril-treated patients with main add-on treatment with ss-blockers, including in the subgroup of patients with proteinuria >1 g/d.

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J Renin Angiotensin Aldosterone Syst. 2008 Mar;9(1):49-56.
Effect of angiotensin receptor blockade on central haemodynamics in essential hypertension: results of a randomised trial.
Schneider MP, Delles C, Klingbeil AU, Ludwig M, Kolloch RE, Krekler M, Stumpe KO, Schmieder RE.
Department of Medicine IV/Nephrology, University of Erlangen-Nürnberg, Germany.

OBJECTIVE: Angiotensin-converting enzyme (ACE) inhibitors have been shown to lower central augmentation index (cAI), an index of arterial wave reflection, more than beta-blockers. We tested whether this is also true for long-term treatment with an angiotensin receptor blocker (ARB). METHODS: One-hundred and fifty-six subjects with essential hypertension were randomised to treatment with either irbesartan or atenolol. cAI and central blood pressure (BP) were determined by pulse wave analysis from the radial and the carotid artery after six and after 18 months treatment. RESULTS: Peripheral and central systolic and diastolic BP were reduced to a similar extent in the two groups. cAI was reduced with irbesartan, but increased with atenolol (derived from the carotid artery: -6+/-10 vs. -4+/-12% after six months, p<0.001; -4+/-12 vs. +1+/-11% after 18 months; p=0.011). Furthermore, central to peripheral pulse pressure (PP) amplification was unaffected by treatment with irbesartan, but decreased with atenolol. CONCLUSIONS: Although treatment with irbesartan and atenolol similarly decreased peripheral and central BP, only treatment with irbesartan had beneficial effects on arterial wave reflection and preserved PP amplification. These haemodynamic effects may at least partly explain the reported differential effects of ARB versus beta-blocker treatment on cardiovascular mortality in patients with essential hypertension.

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J Renin Angiotensin Aldosterone Syst. 2008 Mar;9(1):1-9.
Concomitant calcium entry blockade and inhibition of the renin-angiotensin system: a rational and effective means for treating hypertension.
Gojanovic B, Feihl F, Liaudet L, Waeber B.
Division of Clinical Pathophysiology, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland.

Pharmacological treatment of hypertension is effective in preventing cardiovascular and renal complications. Calcium antagonists (CAs) and blockers of the renin-angiotensin system [angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists (ARBs)] are widely used today to initiate antihypertensive treatment but, when given as monotherapy, do not suffice in most patients to normalise blood pressure (BP). Combining a CA and either an ACE-inhibitor or an ARB considerably increases the antihypertensive efficacy, but not at the expense of a deterioration of tolerability. Several fixed-dose combinations are available (CA + ACE-inhibitors: amlodipine + benazepril, felodipine + ramipril, verapamil + trandolapril; CA + ARB: amlodipine + valsartan). They are expected not only to improve BP control, but also to facilitate long-term adherence with antihypertensive therapy, thereby providing maximal protection against the cardiovascular and renal damage caused by high BP.

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Prev Cardiol. 2008 Spring;11(2):82-9.
The effect of tai chi exercise on blood pressure: a systematic review.
Yeh GY, Wang C, Wayne PM, Phillips RS.
From the Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center; the Division of Rheumatology, Tufts-New England Medical Center; Boston, MA.

A systematic review of the literature on the effect of tai chi exercise on blood pressure (BP) was performed. The authors searched Medline, CAB, Alt HealthWatch, BIOSIS previews, Science Citation Index, and EMBASE systems (inception through January 2007); researched Chinese Medical, China Hospital Knowledge, China National Knowledge Infrastructure, and China Traditional Chinese Medicine databases (inception to June 2005); and performed hand searches at the medical libraries of Beijing and Nanjing Universities. Clinical studies of tai chi examining BP as an outcome published in English or Chinese were included. Studies reporting only acute exercise effects were excluded. Data were extracted in a standardized manner and 2 independent investigators assessed methodologic quality. Twenty-six studies examining patients with and without cardiovascular conditions met inclusion criteria: 9 randomized controlled trials, 13 nonrandomized studies, and 4 observational studies. Study heterogeneity precluded formal meta-analyses. Twenty-two studies (85%) reported reductions in BP with tai chi (3-32 mm Hg systolic and 2-18 mm Hg diastolic BP reductions). Five randomized controlled trials were of adequate quality (Jadad score >/=3). No adverse effects were reported. Tai chi exercise may reduce BP and serve as a practical, nonpharmacologic adjunct to conventional hypertension management. Prev Cardiol. 2008;11:82-89.

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Am J Hypertens. 2008 Jan 10 [Epub ahead of print]
Pulse Pressure Lowering Effect of Dual Blockade With Candesartan and Lisinopril vs. High-dose ACE Inhibition in Hypertensive Type 2 Diabetic Subjects: A CALM II Study Post-hoc Analysis.
Knudsen ST, Andersen NH, Poulsen SH, Eiskjær H, Hansen KW, Helleberg K, Poulsen PL, Mogensen CE.
1Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital, Aarhus, Denmark.

Background: Elevated pulse pressure (PP) is strongly associated with micro- and macrovascular complications in type 2 diabetic patients. We examined the effect of 12 months of dual blockade with candesartan and lisinopril vs. high-dose lisinopril monotherapy on ambulatory PP in hypertensive type 2 diabetic patients from the CALM (Candesartan and Lisinopril Microalbuminuria Trial) II study. Methods: The CALM II study was a 12-month prospective, randomized, parallel-group, double-masked study that included 75 type 1 and type 2 diabetic subjects with hypertension. Participants were randomized for treatment with either high-dose lisinopril (40 mg once daily (o.d.)) or for dual blockade treatment with candesartan (16 mg o.d.) and lisinopril (20 mg o.d.). In this article, we present data from the post-hoc subgroup of 51 type 2 diabetic subjects who completed the full 12-month study period with successful ambulatory blood pressure (BP) measurements at both baseline and follow-up visits.
Results: Baseline 24-h BP values were similar in the two groups (24-h systolic BP (SBP) 130 +/- 12 vs. 127 +/- 9, 24-h diastolic BP (DBP) 77 +/- 8 vs. 74 +/- 7, and 24-h PP 53 +/- 8 vs. 53 +/- 7 mm Hg, for the lisinopril and dual blockade groups, respectively, P > 0.2 for all). Compared with lisinopril monotherapy, dual blockade treatment caused a highly significant reduction in 24-h PP levels (-5 +/- 5 mm Hg, P = 0.003), albeit the difference in the BP lowering effect between the treatment groups did not differ significantly for 24-h systolic (P = 0.21) or diastolic (P = 0.49) BP. Dual blockade treatment significantly lowered 24-h SBP (-5 +/- 11 mm Hg, P = 0.03), but not 24-h DBP (-2 +/- 7 mm Hg, P = 0.29), whereas in the lisinopril group, the opposite effect was observed (24-h SBP -1 +/- 9 mm Hg, P = 0.45, 24-h SBP -3 +/- 7 mm Hg, P = 0.03.
Conclusions: Twelve months of dual blockade with candesartan and lisinopril significantly reduced PP when compared with high-dose monothera
py with lisinopril. Larger studies are needed to confirm this observation, and to evaluate whether this effect translates into a greater degree of end-organ protection from dual blockade treatment than from conventional angiotensin-converting enzyme (ACE) inhibition.American Journal of Hypertension (2008) doi:10.1038/ajh.2007.2.

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Am J Hypertens. 2008 Jan 10 [Epub ahead of print]
Hypertension Control at Physicians' Offices in the United States.
Fang J, Alderman MH, Keenan NL, Ayala C, Croft JB.
1Division for Heart Disease and Stroke Prevention, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Background: Uncontrolled hypertension is a common and important risk factor for heart disease and stroke. Nevertheless, the control rate among patients taking prescribed medication and/or therapeutic lifestyle modification has remained about the same for the past several decades. Methods: We analyzed 2003 and 2004 National Ambulatory Medical Care Survey (NAMCS) data to determine hypertension control in the physician offices in the United States. All visits for hypertension with measured blood pressure levels were included in the analyses. Survey weights were applied to obtain national estimates. Characteristics associated with hypertension control status were identified. Results: About 176 million hypertension-related office visits occurred (9.7% of total office visits) during 2003 and 2004. Of these, 17, 44, and 62% of visits had blood pressure <130/80 mm Hg, 140/90 mm Hg, and 145/95 mm Hg, respectively. The likelihood of hypertension control (<140/90 mm Hg) was associated with a diagnosis of coronary heart disease (odds ratio (OR) 1.54, 95% confidence interval (CI) = 1.01-2.35), visits with increased serum cholesterol (OR = 1.34, 95% CI = 1.09-1.65), visits with patients' primary care physician vs. those with non-primary care physicians (OR = 1.49, 95% CI = 1.05-2.10), and visits with internists (OR = 1.32, 95% CI = 1.05-1.67) or cardiologists (OR = 1.70, 95% CI = 1.17-2.471) vs. those with family physicians. Age, gender, race/ethnicity, health insurance status, and prescription of types of antihypertensive medicine were not associated with hypertension control in office visits. Conclusions: The hypertension control rate of 44% in US office visits leaves substantial room for improvement. A strong emphasis on improving hypertension management is needed to reduce hypertension-related morbidity and mortality.American Journal of Hypertension (2008) doi:10.1038/ajh.2007.35American Journal of Hypertension (2008)

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Drugs Aging. 2008;25(1):1-8.
Optimal drug treatment of systolic hypertension in the elderly.
Pannarale G.
Department of Cardiovascular, Respiratory and Morphological Sciences, Sapienza University, Rome, Italy.

Approximately two-thirds of the elderly population has hypertension, mainly of the isolated systolic hypertension (ISH) type. However, while large-scale, randomized controlled intervention trials have demonstrated that treatment of ISH reduces rates of total mortality, cardiovascular mortality and stroke in older hypertensives, control of ISH in the elderly remains poor. The aim of this review of drug treatment of ISH in the elderly is to provide a succinct, practical and clinically orientated guide that summarizes international recommendations and practices with special emphasis on newer approaches. Knowledge of pathophysiological changes in older subjects (decreased elastic artery compliance, reduced plasma renin activity, increased salt sensitivity) and evidence from epidemiological surveys and randomized controlled trials give clear clues that thiazide(-like) diuretics and long-acting dihydropyridine calcium channel antagonists are the drugs of choice in the treatment of ISH. Thus, based on this evidence, American, European and international guidelines for hypertension management still offer the best available recommendations for optimal treatment of ISH in the elderly. Newer combination treatments, especially the fixed combination of a dihydropyridine calcium channel antagonist and an ACE inhibitor, have valuable benefits in terms of efficacy and tolerability. Use of nitrates added to other antihypertensive medications can provide the practising physician with a further unconventional therapeutic strategy.

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J Clin Hypertens (Greenwich). 2008 Jan;10(1):51-7.
Treatment with metoprolol succinate, a selective Beta adrenergic blocker, lowers blood pressure without altering insulin sensitivity in diabetic patients.
Falkner B, Kushner H.
From the Department of Medicine, Division of Nephrology, Thomas Jefferson University, Philadelphia, PA;

Insulin resistance is a risk factor for cardiovascular disease. Therapies to lower blood pressure should not decrease insulin sensitivity, especially among high-risk patients such as diabetics. This study examined the effect of the beta1-selective adrenergic receptor-blocking agent extended-release metoprolol succinate (ER metoprolol) on insulin sensitivity in type 2 diabetic patients with suboptimal blood pressure control. Diabetic patients with average blood pressure levels >130/85 mm Hg despite antihypertensive therapy had insulin sensitivity quantified by insulin clamp. ER metoprolol was then added to their ongoing therapy. Following 12 weeks of ER metoprolol plus other therapy, the insulin clamp study was repeated. There were no significant changes in measures of insulin sensitivity, plasma lipids, or hemoglobin A1c with use of ER metoprolol. When beta-blocker therapy is considered, it appears that this agent can be used to treat hypertension without adverse effects on insulin sensitivity in patients with type 2 diabetes, at least over the period of time treated. (J Clin Hypertens (Greenwich). 2008;10:51-57).

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Am J Geriatr Cardiol. 2008 Jan;17(1):27-36.
Efficacy and Safety of Fixed Combinations of Irbesartan/Hydrochlorothiazide in Older vs Younger Patients With Hypertension Uncontrolled With Monotherapy.
Cushman WC, Neutel JM, Saunders E, Bakris GL, Ferdinand KC, Ofili EO, Sowers JR, Madder R, Weber MA.
From the University of Tennessee College of Medicine and Veterans Affairs Medical Center, Memphis, TN; Orange County Research Center, Tustin, CA; the University of Maryland School of Medicine, Baltimore, MD; the Department of Medicine, University of Chicago, Chicago, IL; the Association of Black Cardiologists, Atlanta, GA; Morehouse School of Medicine, Atlanta, GA; the University of Arizona, Tucson, AZ; Tri-State Medical Group, Inc, Beaver, PA;

Subgroup analysis of the Irbesartan/Hydrochlorothiazide Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial evaluated the efficacy and safety of irbesartan/hydrochlorothiazide (HCTZ) fixed combinations in patients aged 65 years or older with uncontrolled systolic blood pressure (SBP) after >/=4 weeks of antihypertensive monotherapy. The INCLUSIVE trial was a prospective, open-label, single-arm trial carried out in 119 sites. Of 844 patients completing placebo treatment, 212 were aged 65 years or older. Participants received treatment with placebo (4-5 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and then irbesartan/HCTZ 300/25 mg (8 weeks). From baseline to week 18 (n=184, intent-to-treat population), mean change in SBP was -23.0+/-13.3 mm Hg (P<.001) and diastolic BP (DBP) was -10.9+/-7.7 mm Hg (P<.001). Mean SBP/DBP at study end was 134.0+/-14.7/75.1+/-8.4 mm Hg, and SBP, DBP, and SBP/DBP goal was achieved in 73%, 96%, and 72% of patients, respectively. Irbesartan/HCTZ combination therapy allowed SBP goal attainment in 73% of patients aged 65 years or older whose hypertension was previously uncontrolled with antihypertensive monotherapy. (Am J Geriatr Cardiol. 2008;17:27-36).

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Patient Educ Couns. 2007 Dec 28 [Epub ahead of print]
Take Control of Your Blood pressure (TCYB) study: A multifactorial tailored behavioral and educational intervention for achieving blood pressure control.
Bosworth HB, Olsen MK, Neary A, Orr M, Grubber J, Svetkey L, Adams M, Oddone EZ.
Center for Health Services Research in Primary Care, Durham VAMC, United States; Department of Medicine, Division of General Internal Medicine, Duke University, United States; Department of Psychiatry and Behavioral Sciences, Duke University, United States; Center for Aging and Human Development, Duke University, United States.

OBJECTIVE: Evaluating a randomized controlled trial involving a tailored behavioral intervention conducted to improve blood pressure control. METHODS: Adults with hypertension from two outpatient primary care clinics were randomly allocated to receive a nurse-administered behavioral intervention or usual care. In this ongoing study, patients receive the tailored behavioral intervention bi-monthly for 2 years via telephone; the goal of the intervention is to promote medication adherence and improve hypertension-related health behaviors. Patient factors targeted in the tailored behavioral intervention include perceived risk of hypertension and knowledge, memory, medical and social support, patients' relationship with their health care provider, adverse effects of medication therapy, weight management, exercise, diet, stress, smoking, and alcohol use. RESULTS: The sample randomized to the behavioral intervention consisted of 319 adults with hypertension (average age=60.5 years; 47% African-American). A comparable sample of adults was assigned to usual care (n=317). We had a 96% retention rate for the overall sample for the first 6 months of the study (93% at 12 months). The average phone call has lasted 18min (range 2-51min). From baseline to 6 months, self-reported medication adherence increased by 9% in the behavioral group vs. 1% in the non-behavioral group. CONCLUSION: The intervention is easily implemented and is designed to enhance adherence with prescribed hypertension regimen. The study includes both general and patient-tailored information based upon need assessment. The study design ensures internal validity as well as the ability to generalize study findings to the clinic settings. PRACTICE IMPLICATIONS: Despite knowledge of the risks and acceptable evidence, a large number of hypertensive adults still do not have their blood pressure under effective control. This study will be an important step in evaluating a tailored multibehavioral intervention focusing on improving blood pressure control.

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Adv Ther. 2007 Nov-Dec;24(6):1260-70.
Medium-term effects of bisoprolol administration on renal hemodynamics and function in mild to moderate essential hypertension.
Paterna S, Parrinello G, Pasquale PD, Torres D, Rocca GL, Antona R, Vernuccio L, Fornaciari E, Tarantino A, Piccione E, Fasullo S, Licata G.
Department of Emergency Care.

Arterial hypertension is a significant cause of end-stage renal failure; effective treatment of hypertensive patients reduces the rate of progression of this disorder. ss-Blockers, particularly nonselective agents, are associated with deterioration of renal function in patients with chronic renal failure. Previous studies on the interaction of the ss(1)-selective adrenergic antagonist bisoprolol with kidney function have been performed only acutely and over the short term. This study was designed to evaluate the antihypertensive efficacy and effects on renal hemodynamics and function of bisoprolol during medium-term (6 mo) treatment of patients with mild to moderate essential hypertension. After a 2-wk run-in period on placebo, 87 consecutive hypertensive patients (46 men, 41 women) according to ESH-ESC (European Society of Hypertension/European Society of Cardiology) guidelines, aged from 27 to 64 y (mean age, 50+/-11 y), without renal or cardiovascular disease, were enrolled and assigned to treatment with bisoprolol 5 mg once daily for 6 mo. At recruitment and at 6 mo after treatment, renal function was assessed and renal hemodynamics evaluated in all patients through radioisotope studies. The mediumterm effects of bisoprolol included a significant reduction in blood pressure and heart rate (P<.001) without significant adverse drug reactions. Moreover, bisoprolol produced no alteration in renal function or hemodynamics, or in cardiac output. Data presented here indicate that bisoprolol 5 mg given once daily to treat patients with mild to moderate essential hypertension is effective and safe for treatment and for preservation of renal performance when given on a medium-term basis.

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Curr Hypertens Rep. 2007 Nov;9(5):368-72.
Weight reduction for treatment of obesity-associated hypertension: nuances and challenges.
Mark AL.
Cardiovascular Division, Department of Internal Medicine, Center on Functional Genomics of Hypertension, Carver College of Medicine, 3111 MERF, University of Iowa, Iowa City, IA 52242-1101 USA. allyn-mark@uiowa.edu

Weight reduction is generally recommended as the first line of treatment for the increasing problem of obesity-associated hypertension. At first glance, this recommendation seems compelling, but evidence suggests that weight loss for obesity-associated hypertension is neither simple nor consistently effective as antihypertensive therapy. First, dietary and behavioral therapy is accompanied by an extremely high rate of weight regain after loss. Mounting evidence shows that this recidivism reflects neurobiologic and not simply psychologic adaptations to dietary restriction. Second, chronic blood pressure-lowering effects of weight loss produced by diet, weight-reducing drugs, or bariatric surgery may not be as pronounced as commonly thought. Third, there is evidence that dietary restriction, independent of weight loss, reduces sympathetic nervous system activity and might thereby contribute to reducing blood pressure. This phenomenon deserves more consideration in designing and interpreting studies of blood pressure changes during diet-induced weight loss. This article reviews these issues and highlights the nuances and challenges in the effectiveness of weight loss for treatment of obesity-induced hypertension.

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Am J Geriatr Cardiol. 2007 Sep-Oct;16(5):280-6.
Persistence of treatment and blood pressure control in elderly hypertensive patients treated with different classes of antihypertensive drugs.
Borghi C, Veronesi M, Dormi A, Prandin MG, Cosentino E, Strocchi E.
From the Department of Internal Medicine and Applied Biotechnology "D. Campanacci," University of Bologna, Bologna, Italy.

Unsatisfactory blood pressure (BP) control in the treated hypertensive patient is largely related to poor compliance with antihypertensive drug regimens. The aim of the present study was to prospectively evaluate the rate of persistence on treatment and the extent of BP control in 301 elderly, uncomplicated grade I or II hypertensive patients randomly allocated to monotherapy with angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), beta-blockers, angiotensin II receptors (ARBs), or diuretics according to an open-label single-blind study design. After 24 months, the percentage of patients continuing their initial therapy was higher in those treated with ARBs (68.5%) and ACE inhibitors (64.5%) and lower in patients taking diuretics (34.4%; P<.01). The logistic regression model using ARBs as reference term showed that patients treated with ACE inhibitors (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.79-0.99) or CCBs (OR, 0.76; 95% CI, 0.54-0.85) were more likely to continue their initial antihypertensive therapy when compared with those treated with beta-blockers (OR, 0.67; 95% CI, 0.57-0.79) or diuretics (OR, 0.56; 95% CI, 0.38-0.84). The average systolic and diastolic BP decrease was greater in patients treated with ARBs (-11.2+/-4/-5.8+/-2 mm Hg), ACE inhibitors (-10.5+/-4/-5.1+/-2 mm Hg), and CCBs (-8.5+/-3/-4.6+/-2 mm Hg) and lesser in those treated with diuretics (-2.3+/-4/-2.1+/-3 mm Hg, P<.05) and beta-blockers (-4.0+/-2/-2.3+/-2 mm Hg; P<.05). The study confirms the importance of persistence with treatment for the effective management of hypertension in clinical practice. (AJGC. 2007;16:280-286).

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Am J Health Syst Pharm. 2007 Sep 15;64(18):1922-6.
Treatment of pulmonary arterial hypertension in pregnancy.
Huang S, Desantis ER.
Scientific Connexion, Yardley, PA.

PURPOSE: The treatment of pulmonary arterial hypertension (PAH) in pregnancy is reviewed. SUMMARY: PAH is a disease characterized by narrowing of the pulmonary arteries and increased vascular resistance. Women with PAH should avoid becoming pregnant, as the physiological, cardiovascular, and pulmonary changes that occur during pregnancy can exacerbate the condition. However, several viable treatment options are available to improve the outcomes in this patient population, including inhaled nitric oxide, calcium-channel blockers, targeted pulmonary vasodilators, and sildenafil. Epoprostenol, a naturally occurring prostaglandin and vasodilator, is a pregnancy category B drug. Reproductive studies in rats and rabbits have found no impaired fertility or fetal harm at 2.5-4.8 times the recommended human dosage of epoprostenol. Most of the published case reports describe initiating epoprostenol 2-4 ng/kg/min i.v. several weeks before or near the time of delivery. Iloprost is a pregnancy category C drug but has demonstrated benefit in pregnant patients with PAH, with no congenital abnormalities and no postpartum maternal or infant mortality reported. Sildenafil causes vasodilation of the pulmonary vascular bed and vasodilation in the systemic circulation. Two case reports have described the successful treatment with sildenafil, a pregnancy category B drug, of pregnant patients with PAH. Patients with idiopathic PAH or chronic thromboembolic PAH should receive full-dose subcutaneous low-molecular-weight heparin therapy instead of warfarin for bleeding prophylaxis during pregnancy. CONCLUSION: Targeted pulmonary vasodilators are viable treatment options for pregnant patients with PAH. Early recognition and management of worsening symptoms are essential to improve outcomes for both the mother and infant.

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J Clin Hypertens (Greenwich). 2007 Sep;9(9):667-76.
A Randomized, Double-Blind, Placebo-Controlled Parallel-Group Study to Assess the Efficacy and Safety of Nebivolol, a Novel beta-Blocker, in Patients With Mild to Moderate Hypertension.
Weiss RJ, Weber MA, Carr AA, Sullivan WA.
From Androscoggin Cardiology Associates, Auburn, ME; State University of New York, Downstate College of Medicine, Brooklyn, NY; Southern Clinical Research and Management, Augusta, GA;

This double-blind, multicenter, randomized placebo-controlled study evaluated the antihypertensive efficacy and safety of nebivolol, a selective beta1-adrenoreceptor blocker with vasodilating effects, in patients with mild to moderate hypertension (sitting diastolic blood pressure [SiDBP] >/=95 mm Hg and </=109 mm Hg). A total of 909 patients were randomized to receive placebo or nebivolol 1.25, 2.5, 5, 10, 20, or 40 mg once daily for up to 84 days. The primary end point was the change in trough SiDBP from baseline to study end. Nebivolol significantly reduced trough SiDBP (8.0-11.2 mm Hg compared with 2.9 mm Hg with placebo; P<.001) and trough sitting systolic blood pressure (a 4.4-9.5-mm Hg decrease compared with a 2.2-mm Hg decrease with placebo; P</=.002). The overall adverse event experience was similar in the nebivolol (46.1%) and placebo (40.7%) groups (P=.273). Once-daily nebivolol is an effective antihypertensive in mild to moderate hypertensive patients.

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J Am Diet Assoc. 2007 Sep;107(9):1541-51.
The PREMIER Intervention Helps Participants Follow the Dietary Approaches to Stop Hypertension Dietary Pattern and the Current Dietary Reference Intakes Recommendations.
Lin PH, Appel LJ, Funk K, Craddick S, Chen C, Elmer P, McBurnie MA, Champagne C.

OBJECTIVE: To examine the influence of the PREMIER study lifestyle interventions on dietary intakes and adherence to the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and the Dietary Reference Intakes (DRI). DESIGN: An 18-month multicenter, randomized controlled trial comparing two multicomponent lifestyle intervention programs to an advice only control group. SUBJECTS/SETTING: A total of 810 participants were recruited from local communities and randomized into the study. Individuals were eligible if they were aged 25 years or older, had body mass index between 18.5 and 45.0, not taking antihypertensive medication, and had prehypertension or stage 1 hypertension (systolic blood pressure 120 to 159 mm Hg and diastolic blood pressure 80 to 95 mm Hg). INTERVENTION: The two active intervention programs were a behavioral lifestyle intervention that implements established recommendations, and an established intervention plus the DASH dietary pattern. Both interventions consisted of intensive group and individual counseling sessions. The control group received a brief advice session after randomization and again after 6 months of data collection. Dietary intakes were collected by two random 24-hour recalls at baseline, 6 months, and 18 months. MAIN OUTCOME MEASURES: The primary outcome of the PREMIER study was change in systolic blood pressure at 6 months. The main outcomes examined here include dietary variables collected by 24-hour recall at each time point. STATISTICAL ANALYSES: Nutrient intakes were calculated and compared among the time points and the three intervention groups using mixed models with repeated measures at 6 and 18 months. Proportion of participants who met or achieved the original DASH nutrient intake levels and the DRIs were calculated and compared among the three intervention groups. P<0.01 was considered statistically significant. RESULTS: Participants in both the established intervention and established intervention plus DASH dietary pattern groups substantially reduced energy, total fat, saturated fat, and sodium intake and these reductions persisted throughout the study. Established intervention plus DASH dietary pattern group participants increased intakes of fruits, vegetables, dairy, and many vitamins and minerals; these increases were significantly greater than that of the control and established intervention groups. A majority of established intervention plus DASH dietary pattern group participants achieved at least two thirds of the DRI recommendations for most nutrients at 6 months, despite their reduction in total energy intake. Some but relatively small recidivism occurred at 18 months. CONCLUSIONS: Both the established intervention and established intervention plus DASH dietary pattern group intervention were effective in helping participants follow established recommendations to control blood pressure. The advice-only control group also made some behavior changes, mainly decreasing energy and sodium intake. Only the established intervention plus DASH dietary pattern group significantly increased intakes of DASH-specific food groups, including fruits, vegetables, and dairy products, and nutrients, including protein, fiber, calcium, potassium, and magnesium. Most of the increases did not reach the levels consumed in the original DASH feeding studies. Whereas the established intervention plus DASH dietary pattern group intervention provides a useful platform to achieve the DASH dietary pattern and current DRI recommendations, intervention enhancements, including a greater emphasis on nutrient-dense foods, would likely improve this intervention.

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Curr Med Res Opin. 2007 Aug 21; [Epub ahead of print]
Systematic review of trials of the effect of continued use of oral non-selective NSAIDs on blood pressure and hypertension.
Morrison A, Ramey DR, van Adelsberg J, Watson DJ.

OBJECTIVE: To investigate the effects of continued use of non-selective NSAIDs (nsNSAIDs) on blood pressure and hypertension.Research design and methods: This was a systematic review of randomized clinical trials of oral nsNSAIDs used for at least a 4-week duration. Searches were conducted of PubMed and the Cochrane Database of Systematic Reviews, using key terms for nsNSAIDs and blood pressure or hypertension, to identify articles published in the English language peer-reviewed literature through March 2007.MAIN OUTCOME MEASURES: Change from baseline to end of study in systolic blood pressure (SBP) and diastolic blood pressure (DBP), and the incidence of hypertension. Pooled statistics were computed using fixed and random-effects analyses.RESULTS: Thirty-two articles were included. The mean change (95% confidence interval [CI]) in blood pressure (in mmHg) from baseline to end of study for five trials of ibuprofen was 3.54 (2.70, 4.39) for SBP and 1.16 (0.68, 1.64) for DBP (p
< 0.001 for both changes). Results of four trials of indomethacin were similar to those for ibuprofen: 2.90 (0.28, 6.08) for SBP (p = 0.07) and 1.58 (0.29, 2.87) for DBP (p = 0.02). Mean changes from baseline for two trials of diclofenac were 0.46 (1.48, 0.56) for SBP (p = 0.38) and 0.56 (1.19, 0.07) for DBP (p = 0.08) and were similar to those for placebo. Changes from baseline in SBP were positive but not statistically significant for naproxen, sulindac, and nabumetone. Compared with placebo, the risk ratio (95% CI) of hypertension was 2.85 (1.44, 5.65; p= 0.003) in two ibuprofen trials. CONCLUSIONS: Continued use of ibuprofen increases blood pressure and raises the incidence of hypertension. There appears to be heterogeneity in such effects with continued use of other nsNSAIDs but, due to limitations in the data, results for naproxen, sulindac, and nabumetone are inconclusive.

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J Ethnopharmacol. 2007 Jul 31; [Epub ahead of print]
Herbal medicines as diuretics: A review of the scientific evidence.
Wright CI, Van-Buren L, Kroner CI, Koning MM.
Nutrition, Nutrition and Health Enhancement, Unilever Food and Health Research Institute, Olivier van Noortlaan 120, P.O. Box 114, 3130 AC, Vlaardingen, The Netherlands.

There is increasing interest in the health and wellness benefits of herbs and botanicals. This is with good reason as they might offer a natural safeguard against the development of certain conditions and be a putative treatment for some diseases. One such area may be the lowering of blood pressure in those where it is elevated (i.e., hypertension). One class of clinical medicines used to lower blood pressure are known as diuretics and work by increasing the excretion of urine from the body as well as the amount of sodium in urine. There are a growing number of studies purporting diuretic effects with traditional medicines. The aim of this article was to review these studies and identify which extracts promote diuresis (which we assessed on terms of urine excreted and urinary sodium excretion) and also to identify the research needs in this area. We identified a number of species and genuses reporting diuretic effects. Of these, the most promising, at the present time, are the species Foeniculum vulgare, Fraxinus excelsior, Hibiscus sabdariffa, Petroselinum sativum and Spergularia purpurea, and species from the genuses Cucumis (Cucumis melo and Cucumis trigonus), Equisetum (Equisetum bogotense, Equisetum fluviatile, Equisetum giganteum, Equisetum hiemale var. affine and Equisetum myriochaetum), Lepidium (Lepidium latifolium and Lepidium sativum), Phyllanthus (Phyllanthus amarus, Phyllanthus corcovadensis and Phyllanthus sellowianus) and Sambucus (Sambucus mexicana and Sambucus nigra). However, there the number of studies is limited and we recommend that further studies be conducted to confirm reported effects. Such evidence is needed to provide scientific credence to the folklore use of traditional medicines and even be helpful in the development of future medicines, treatments and treatment guidelines.

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Prog Cardiovasc Nurs. 2007 Summer;22(3):159-65.
Taking the Pressure off Type 2 Diabetes Mellitus: Implementing Hypertension Guidelines.
Grubbs RS, Sica DA.
From the Division of Nephrology, Virginia Commonwealth University Health System, Richmond, VA.

Successful treatment of hypertension in patients with type 2 diabetes mellitus increases life expectancy and reduces the risk of many of the complications associated with diabetes, such as heart disease, stroke, and retinopathy. Controlling blood pressure also protects against advancing renal disease, with several recent studies having clearly shown the advantage of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in slowing the progression of renal disease. Here, the authors review current guidelines for the management of hypertension in patients with type 2 diabetes mellitus and explore ways in which nurse practitioners can improve care for these patients. (Prog Cardiovasc Nurs. 2007;22:159-165).

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J Clin Nurs. 2007 Jul;16(7B):144-51.
Outcomes following a programme for lifestyle changes with people with hypertension.
Drevenhorn E, Kjellgren KI, Bengtson A.
Faculty of Health and Caring Sciences, Institute of Nursing, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden. eva.drevenhorn@comhem.se

AIM: The purpose of the study was to explore the effects of using a structured nursing intervention programme in hypertension care. BACKGROUND: Counselling on lifestyle changes to address hypertension helps patients reduce risk factors such as smoking, high alcohol consumption, overweight, dyslipidemia, negative stress and physical inactivity. DESIGN: The study was performed as a pre-test-post-test study. METHODS: All 177 patients diagnosed with hypertension visiting a health centre in Southern Sweden were invited to be counselled by a public health nurse about hypertension, cardiovascular risk factors and non-pharmacological treatment with 15 months follow up. RESULTS: One hundred patients participated in the study. Systolic blood pressure decreased overall (p < 0.01), three patients with high alcohol consumption were identified, two smokers stopped smoking, two new diabetics were discovered, physical activity increased (p = 0.035) and one-third of the patients changed their medication. CONCLUSION: The level of exercise increased and a reduction in systolic blood pressure and in women's weight were the most obvious results of this intervention study. The study elucidates the challenge of executing health behaviour changes. RELEVANCE TO CLINICAL PRACTICE: Counselling following a hypertension programme gives hypertensive patients a chance to execute lifestyle changes and have their medication adjusted to achieve goals for blood pressure control. Further prospective studies in this area, with well-defined intervention approaches and several years of follow up, are necessary.

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J Soc Integr Oncol. 2007 Summer;5(3):92-105.
Flax and Flaxseed Oil (Linum usitatissimum): A Review by the Natural Standard Research Collaboration.
Basch E, Bent S, Collins J, Dacey C, Hammerness P, Harrison M, Smith M, Szapary P, Ulbricht C, Vora M, Weissner W.

The objective of this study was to evaluate the scientific evidence on flaxseed, including expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing. Electronic searches were conducted in 9 databases, 20 additional journals (not indexed in common databases), and bibliographies from 50 selected secondary references. No restrictions were placed on the language or quality of the publications. All literature collected pertained to efficacy in humans, dosing, precautions, adverse effects, use in pregnancy/lactation, interactions, alteration of laboratory assays, and mechanisms of action. Standardized inclusion/exclusion criteria are used for selection. Grades were assigned using an evidence-based grading rationale. A review of the literature on flaxseed yielded 13 categories for which flaxseed had been studied in humans, including constipation/laxative, attention-deficit hyperactivity disorder, hyperlipidemia, atherosclerosis/coronary artery disease, breast cancer, cyclic mastalgia (breast pain), menopausal symptoms, hyperglycemia/diabetes, hypertension, lupus nephritis, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and prostate cancer. Most of the available evidence investigates the efficacy of alpha-linoleic acid found in flaxseed compared with fish oil, and almost all of the available studies are poor quality. Although flaxseed and flaxseed oil have several promising future uses, the available literature does not support recommendation for any condition at this time.

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Rev Med Liege. 2007 May-Jun;62(5-6):254-7.
[Evidence for avoiding the use of beta-blockers as first line therapy in hypertension]
[Article in French]
Krzesinski JM, Saint-Remy A.
Service de Néphrologie, CHU Sart Tilman, Liège, Belgique.

Arterial hypertension is a significant risk factor for cardiovascular disease, proportional to the blood pressure level. Treating hypertension reduces the risk. Until recently, beta-blockers were considered as a first line class for hypertension management. The British Hypertension Society has recently pronounced that using beta-blockers as first line antihypertensive therapy is no good choice since these agents are less protective than other antihypertensive classes against cardiovascular disorders and diabetes mellitus, especially when used in association with diuretics.

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Curr Drug Targets. 2007 Apr;8(4):561-70.
Lipid management and peripheral arterial disease.
Daskalopoulou SS, Daskalopoulos ME, Mikhailidis DP, Liapis CD.
Department of Medicine, Division of Clinical Epidemiology, McGill University, Montreal, Quebec, Canada.

Peripheral arterial disease (PAD) is a common disorder usually associated with silent or symptomatic arterial disease elsewhere in the circulation and a "cluster" of cardiovascular risk factors (e.g. smoking, dyslipidemia, hypertension, and insulin resistance/diabetes mellitus). The medical management of PAD should focus on both the relief of symptoms and prevention of secondary cardiovascular complications. This approach must include smoking cessation, optimal cholesterol levels, blood pressure and glycemic control as well as prescribing antiplatelet therapy. This review focuses on the evidence supporting the use of lipid-lowering drugs in PAD. Several trials indicate that getting low density lipoprotein-cholesterol levels to target (<2.6 mmol/l; 100 mg/dl), or even lower, is associated with improvement of symptoms and a reduction in vascular events in patients with PAD.

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Curr Med Res Opin. 2007 Apr;23(4):783-91.
Clinical practice and recent recommendations in hypertension management—reporting a gap in a global survey of 1259 primary care physicians in 17 countries.
Bramlage P, Thoenes M, Kirch W, Lenfant C.
Institute for Clinical Pharmacology, Medical Faculty, Dresden, Germany. bramlage@mailbox.tu-dresden.de <bramlage@mailbox.tu-dresden.de>

OBJECTIVE: High blood pressure (BP) is a leading risk factor for cardiovascular morbidity and mortality. Effective antihypertensive pharmacotherapy is available but recognition and proper management of hypertension and BP goal achievement is still poor. Therefore, it was hypothesized that physicians' attitude towards high BP, as well as patients' perception and knowledge, may influence actual management of hypertension. RESEARCH DESIGN AND METHODS: Telephone interviews were carried out with a random sample of 1259 primary care physicians in 17 countries worldwide from 12 December 2005 to 13 January 2006 using a central computer assisted telephone interview methodology (CATI). RESULTS: (1) Physicians believed that 62 +/- 21% of their patients had their BP controlled. (2) They were mostly in line with guideline recommended BP goals and 96% were aware of the elevated cardiovascular risk of hypertension, but 41% aimed to reduce BP to acceptable levels only. (3) Physicians indicated that in 41% of patients monotherapy controls BP and 71% would escalate to combination therapy after monotherapy failure. (4) 54% regard hypertension management as difficult. (5) Physicians estimated that between 60 and 70% of patients know their BP goal but thought that there was still room for improvement of hypertension management on the patient side. CONCLUSION: Although many effective treatment options for arterial hypertension exist, BP goal achievement worldwide is suboptimal, leaving patients at an unnecessary cardiovascular risk. An increase in patients' awareness and compliance together with an increased adherence of physicians to current guidelines should help in reducing the long term cardiovascular consequences of hypertension.

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Internist (Berl). 2007 Apr 4; [Epub ahead of print]
[Treatment of arterial hypertension.][Article in German]
Zidek W.
Med. Klinik IV, Campus Benjamin Franklin, Charite - Universitatsmedizin Berlin, Hindenburgdamm 30, 12203, Berlin, Deutschland, Walter.Zidek@charite.de.

Arterial hypertension is the most common internal disease. Treatment is highly effective in lowering cardiovascular morbidity and mortality and is indicated based on total cardiovascular risk as assessed by all relevant risk factors. Target blood pressure is <140/90 mmHg, or with concomitant diabetes mellitus or renal insufficiency <130/80 mmHg. Lifestyle modifications are helpful, either alone or as an adjuvant to drug treatment, depending on the severity of the disease. First-line drugs are diuretics, calcium antagonists, ACE inhibitors, AT1 blockers and beta blockers. In most cases, combination therapy is appropriate. Possible treatment strategies include stepped care, initial low-dose combination therapy and sequential monotherapy.

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Am J Hypertens. 2007 Apr;20(4):392-7.
Supplementation with vitamins C and e improves arterial stiffness and endothelial function in essential hypertensive patients.
Plantinga Y, Ghiadoni L, Magagna A, Giannarelli C, Franzoni F, Taddei S, Salvetti A.
Department of Internal Medicine, University of Pisa, Pisa, Italy.

BACKGROUND: Essential hypertension is characterized by endothelial dysfunction, arterial stiffness, and increased oxidative stress. We evaluated the effect of short-term combined treatment with the antioxidants vitamins C and E on endothelial function, arterial stiffness, and oxidative stress in untreated essential hypertensive patients. METHODS: A randomized, double-blind, placebo-controlled, crossover study design was used to assign 30 male essential hypertensive patients to either vitamin C (1 g) and vitamin E (400 IU) or placebo for 8 weeks. Endothelium-dependent response was assessed as flow-mediated dilation (FMD) of the brachial artery. Arterial stiffness was assessed as central pulse wave velocity (PWV) and augmentation index (AIx). Plasma markers of oxidative stress and antioxidant status were measured. RESULTS: After vitamin supplementation, FMD was significantly improved. Central PWV was significantly reduced, while AIx tended to decrease. Plasma vitamin levels and antioxidant capacity increased significantly. Levels of oxidative stress decreased. Changes in central PWV were related to changes in levels of oxidative stress. CONCLUSIONS: Combined treatment with vitamins C and E has beneficial effects on endothelium-dependent vasodilation and arterial stiffness in untreated, essential hypertensive patients. This effect is associated with changes in plasma markers of oxidative stress.

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Catheter Cardiovasc Interv. 2007 Apr 1;69(5):690-6.
Intensive treatment of hypertension decreases the risk of hyperperfusion and intracerebral hemorrhage following carotid artery stenting.
Abou-Chebl A, Reginelli J, Bajzer CT, Yadav JS.
Interventional Neurology, Section of Stroke and Neurological Critical Care, The Cleveland Clinic Foundation, Cleveland, Ohio.

Objectives: To assess the efficacy of a comprehensive blood pressure (BP) management protocol in reducing intracerebral hemorrhage (ICH) following carotid artery stenting (CAS). Background: Following CAS hyperperfusion syndrome (HPS) can lead to significant morbidity and mortality. Hypertension plays an essential role in its development. Methods:We instituted a comprehensive BP protocol following the last case of ICH complicating a CAS procedure. All patients received comprehensive monitoring of BP and treatment to a BP < 140/90 mm Hg; those with a treated stenosis >/=90%, contralateral stenosis >/=80%, and hypertension (i.e., risk factors for HPS) were treated to a BP < 120/80 mm Hg. Patients who developed HPS received parenteral beta-blockers or nitrates titrated to resolution of symptoms and discharged when asymptomatic and normotensive. Patients and families were instructed to measure BP twice daily for 2 weeks and to call if hypertension or headache developed. Results: A total of 836 patients had CAS, 266 prior to the comprehensive BP management program and 570 subsequently. The incidence of HPS/ICH was 5/266 (1.9%) patients prior to comprehensive BP management and 3/570 (0.5%) patients afterwards, P = 0.12. The incidence of ICH was 3/266 (1.1%) and 0/570, respectively, P = 0.032. In high-risk patients both HPS and ICH were significantly reduced from 29.4 to 4.2% (P = 0.006) and 17.6-0% (P = 0.006), respectively. There were no complications attributable to the comprehensive program and lengths of hospitalization were similar (2.6 vs. 2.1 days, P = 0.18). Conclusions: Comprehensive management of arterial hypertension can lower the incidence of ICH and HPS in high-risk patients following CAS, without additional complications or prolonged hospitalizations. (c) 2007 Wiley-Liss, Inc.

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Curr Opin Lipidol. 2007 Feb;18(1):20-4.
Nutritional effects on blood pressure.
Myers VH, Champagne CM.
Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.

PURPOSE OF REVIEW: There has not been a thorough recent evaluation of the nutritional effects on blood pressure. Apart from outstanding clinical trials like Dietary Approaches to Stop Hypertension, there have been controversial papers on a number of factors influencing blood pressure. This paper is a systematic review of the current literature as it relates to hypertension. RECENT FINDINGS: Results from many meta-analyses and well controlled clinical trials on the effects of a variety of nutritional factors are presented in this review. Evidence suggests that dietary sodium intake needs reduction. There is a seemingly inverse relationship between protein intake and blood pressure, but data are inconclusive. High monounsaturated fat and fish oil appear to be beneficial. Several studies on dietary fiber indicate that the strongest evidence for blood pressure lowering effects is in hypertensive as opposed to normotensive participants. Vegetarians seem to have lower levels of hypertension and cardiovascular disease risk. Low carbohydrate diets show short-term beneficial effects but are not sustained. High levels of potassium, magnesium, calcium and soy seem to have some benefit, but results remain inconclusive. Weight reduction positively impacts blood pressure. SUMMARY: More compelling research defining specific factors is needed to inform the public as to steps needed to reduce blood pressure and improve cardiovascular risk.

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Menopause. 2007 Jan 11; [Epub ahead of print]
Randomized, placebo-controlled trial of the effects of drospirenone-estradiol on blood pressure and potassium balance in hypertensive postmenopausal women receiving hydrochlorothiazide.
Preston RA, Norris PM, Alonso AB, Ni P, Hanes V, Karara AH.
>From the 1Division of Clinical Pharmacology and Pharmacokinetics Clinical Research Center, Department of Medicine, and 2Division of Gynecology, Department of Obstetrics and Gynecology, Miller School of Medicine, University of Miami, Miami, FL; and 3Berlex Pharmaceuticals, Inc., Montville NJ.

OBJECTIVE:: Drospirenone (DRSP), a spironolactone analog with aldosterone antagonist activity, is a novel progestogen developed for use as hormone therapy in postmenopausal women in combination with 17beta-estradiol (E2). DRSP/E2 lowers blood pressure when used alone in hypertensive postmenopausal women or when administered concomitantly with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. DRSP/E2 has not been studied in combination with the widely prescribed hydrochlorothiazide (HCTZ). We investigated the effects of 3 mg DRSP/1 mg E2 versus placebo on blood pressure and potassium balance when added to existing therapy with 25 mg HCTZ in postmenopausal women with established stage I hypertension. DESIGN:: This was a single-center, double-blind, randomized, placebo-controlled, two-treatment, two 4-week treatment period crossover study in 36 postmenopausal women with stage I hypertension maintained on 25 mg HCTZ. The endpoint was a change from baseline in systolic and diastolic blood pressures by 24-hour ambulatory blood pressure monitoring. Safety monitoring included serum potassium (mEq/L) and adverse events. RESULTS:: Mean systolic and diastolic blood pressures by 24-hour ambulatory blood pressure monitoring were reduced significantly, by -7.2 and -4.5 mm Hg, respectively, with DRSP/E2 as compared with placebo. The decrease in potassium with HCTZ was 0.2 mEq/L less with DRSP/E2 than placebo, suggesting a potassium-sparing effect. The most frequently observed adverse events with DRSP/E2 were vaginal bleeding and breast tenderness, which were attributable to the hormone therapy. CONCLUSIONS:: DRSP/E2 substantially lowers systolic and diastolic blood pressure when added to existing antihypertensive therapy with HCTZ in hypertensive postmenopausal women. In addition, DRSP/E2 has a potassium-sparing effect that counteracts HCTZ-induced potassium loss.

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Dtsch Med Wochenschr. 2007 Jan 12;132(3):81-6.
[Effect of candesartan cilexetil with hydrochlorothiazide on blood pressure and ST-segment depression in patients with arterial hypertension.]
[Article in German]
Uen S, Un I, Fimmers R, Vetter H, Mengden T.
Abteilung fur Hypertonie und Angiologie, Medizinische Universitats Poliklinik der Universitat Bonn.

OBJECTIVE: To examine the effect of candesartan cilexetil with hydrochlorothiazide (6 mg and 12.5 mg, respectively) on blood pressure and ST-segment depression during daily life of patients with treated but not controlled arterial hypertension (blood pressure taken at doctor's practice (3)140/90 mmHg, despite being on at least two antihypertensive drugs) PATIENTS AND METHODS: 51 patients (45 men, 17 women) with treated but reportedly uncontrolled hypertension were placed on self-measurement of blood pressure for 4 weeks of a run-in period and 8 weeks as a follow-up period. Combined 24-hour automatic blood pressure measurement (ABPM) and electrocardiography were done at the end of the run-in and the follow-up periods. Ten patients proved to be normotensive according to the self-measurement and ABPM after the run-in period (group A), while 41 were still uncontrolled according to both methods (group B). In group B the least efficacious component of the antihypertensive medication was replaced by candesartan with hydrochlorothiazide (C + HCT) and any changes in blood pressure and ST-segment depression analysed after 8 weeks of follow-up in both groups. RESULTS: In group A no significant blood pressure change was observed between run-in- and follow-up periods. But in group B (n=41) the self-measured systolic blood pressure had significantly decreased (155/84 mmHg compared with [vs] 147/81 mmHg; p<0.0073) as had the systolic 24-h ABPM (148/81 mmHg vs 137/753 mmHg; p<0.0015) after C + HCT had replaced the previous noneffective medication. After the run-in period 15 patients of group B had ST-segment depression (1 mm of horizontal or descending depression for at least 1 minute). In 16 other patients of group B and in all patients of group A no ST depressions were recorded. At the end of the follow-up period significant reduction of mean ischemic burden per patient (106 vs 72 minutes), of total ischemic events (228 vs 153) and of mean duration of ST depression (372 vs 210 seconds) had occurred. CONCLUSIONS: Replacing candesartan + hydrochlorothiazide for previously ineffective antihypertensive drugs in patients with uncontrolled arterial hypertension significantly reduced both blood pressure and ST-segment depression during daily life.

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J Cardiovasc Pharmacol Ther. 2006 Dec;11(4):256-61.
Effect of barnidipine on blood pressure and serum metabolic parameters in patients with essential hypertension: a pilot study.
Spirou A, Rizos E, Liberopoulos EN, Kolaitis N, Achimastos A, Tselepis AD, Elisaf M.
Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.

The effect of barnidipine, a calcium channel blocker, on metabolic parameters is not well known. The authors conducted the present pilot study to evaluate the possible effects of barnidipine on parameters involved in atherogenesis, oxidative stress, and clotting activity. This open-label intervention study included 40 adult patients with essential hypertension who received barnidipine 10 mg once daily. Barnidipine significantly reduced systolic and diastolic blood pressure as well as isoprostane levels, which represent a reliable marker of oxidative stress. In contrast, barnidipine had a neutral effect on lipid profile and apolipoprotein levels, did not influence glucose homeostasis, had no effect on renal function, and did not cause any changes in electrolyte levels. Moreover, barnidipine did not affect either the clotting/fibrinolytic status (evaluated by measurement of fibrinogen, total plasminogen activator inhibitor, tissue plasminogen activator, and a2 antiplasmin) or the enzymatic activity of the inflammatory/anti-inflammatory mediators lipoprotein-associated phospholipase A2 and paraoxonase 1, respectively. Barnidipine should be mainly considered as an antihypertensive
agent with neutral effects on most of the studied metabolic parameters in hypertensive patients. Any antioxidant effect of barnidipine needs further investigation.

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J Am Coll Nutr. 2006 Dec;25(6):533-40.
Randomised, controlled, cross-over trial of soy protein with isoflavones on blood pressure and arterial function in hypertensive subjects.
Teede HJ, Giannopoulos D, Dalais FS, Hodgson J, McGrath BP.
Jean Hailes Research Group, Monash Institute of Health Services Research, Level 1 Block E, Monash Medical Centre, 246 Clayton Road, Clayton 3168, Melbourne, AUSTRALIA. helena.teede@med.monash.edu.au.

OBJECTIVE: To examine the effects of dietary soy/isoflavones on 24 hr blood pressure profiles and arterial function [systemic arterial compliance (SAC), pulse wave velocity (PWV) and brachial arterial flow mediated vasodilation (FMD)] compared to non legume-based plant protein without isoflavones, in hypertensive subjects. DESIGN: In a 6 month double-blind, placebo controlled, cross-over trial, 41 hypertensive subjects (26 men, 15 postmenopausal women), 30-75 years, received soy cereal (40 g soy protein, 118 mg isoflavones) and gluten placebo cereal, each for 3 months. RESULTS: Thirty-eight subjects completed protocol with results expressed as mean or mean change (+/-SEM) with each intervention. Soy increased urinary isoflavones (daidzein: 8-fold; genistein: 8-fold; equol: 9-fold; ODMA: 18-fold) with no change during gluten placebo. There was no difference in the change in individual 24 hr ambulatory BP parameters (SBP: 2 +/- 2 vs -1 +/- 1 mmHg, p = 0.21; DBP: 1 +/- 1 vs -1 +/- 1 mmHg, p = 0.06) central BP (cSBP: -4 +/- 2 vs 0 +/- 2 mmHg, p = 0.2) or the change in arterial function (FMD: 0.3 +/- 0.5 vs -0.2 +/- 0.5%, p = NS; SAC: 0.02 +/- 0.02 vs -0.02 +/- 0.02 U/mmHg, p = NS; PWV central: -0.2 +/- 0.2 vs 0.0 +/- 0.2 m/sec, p = NS; PWV peripheral: 0.01 +/- 0.3 vs -0.4 +/- 0.4 m/sec, p = NS) noted between interventions. Analysis of the area under curve of 24 hr BP outputs demonstrated that soy protein compared to gluten protein resulted in higher 24 hr systolic BP by 2.3 mmHg (p = 0.003), a higher daytime systolic BP by 3.4 mmHg (p = 0.0002) and a higher daytime diastolic BP by 1.4 mmHg (p = 0.008). Overall 24 hr diastolic BP, night systolic BP and night diastolic BP were not significantly different between groups. Furthermore, soy protein compared to gluten protein resulted in higher 24 hr heart rates by 3.5 bpm (p < 0.0001). CONCLUSIONS: In hypertensive subjects, compared to gluten placebo, soy dietary supplementation containing isoflavones had no effect on arterial function, on average 24 hr ambulatory blood pressure parameters or central blood pressure in men and women with hypertension. Area under the curve of 24 hr profiles demonstrated that daytime BP was higher after soy compared to gluten.

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Med Klin (Munich). 2006 Nov 15;101(11):880-5.
[Sleep apnea - treatment improves hypertension.]
[Article in German]
Grotz W, Buchner N, Wessendorf T, Teschler H, Grote L, Becker HF, Rump LC.
Klinik fur Innere Medizin II, Alfried Krupp Krankenhaus Essen, Essen, Deutschland.

Obstructive sleep apnea and arterial hypertension are frequent diseases, but they are also often overlooked. There is a causal relationship of sleep apnea and hypertension. Undiagnosed sleep apnea is probably the most important reason for "essential" hypertension. It is important to identify these patients. All hypertensive patients should be asked for snoring, breathing arrest and daytime sleepiness, neck circumference should be measured, and an ambulant sleep apnea monitoring should be performed, if necessary. Especially patients with refractory hypertension or non-dippers should be screened for sleep apnea and patients with sleep apnea should be examined for arterial hypertension.Continuous positive airway pressure (CPAP) can effectively lower blood pressure in the hypertensive sleep apnea patient. This is especially true for the obstructive sleep apnea patient with refractory hypertension. CPAP therapy is probably the best therapy for sleep apnea-induced nocturnal blood pressure rises.
  
Previous Hypertension Research: 2002-2006   
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