Hypertension Research: 2002-2006
     
Curr Hypertens Rep. 2006 Oct;8(5):425-32.
New drugs for hypertension: what do they offer?
Gradman AH, Vivas Y.
Chief, Division of Cardiovascular Diseases,The Western Pennsylvania Hospital, 4800 Friendship Avenue,Suite 3411 N, Pittsburgh, PA 15224, USA.

A new drug might make a positive contribution to existing therapies for hypertension by: 1) reducing blood pressure (BP) via a novel pharmacologic mechanism; 2) possessing pharmacologic or pharmacokinetic properties that make it superior to other members of its class; or 3) facilitating BP control in refractory patients. In this paper, we review four experimental agents that promise to advance therapeutics by one of these mechanisms. Aliskiren is the first in a new class of potent, orally effective renin inhibitors. Aliskiren produces dose-dependent BP reduction with few side effects and constitutes a novel pharmacologic approach to renin-angiotensin-aldosterone inhibition. Nebivolol is a third-generation, cardioselective beta-blocker that produces vasodilation and improves endothelial function via the l-arginine/nitric oxide pathway. Clevidipine is an ultra-short-acting, vascular-selective, dihydropyridine calcium antagonist that is being developed for intravenous use in acute hospitalized patients. Darusentan is an endothelin(A) selective endothelin receptor antagonist that is effective in achieving BP control in a significant percentage of patients who remain uncontrolled despite treatment with three or more antihypertensive drugs.

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Curr Hypertens Rep. 2006 Oct;8(5):420-4.
Electrical Stimulation of theCarotid Sinus for the Treatmentof Resistant Hypertension.
Filippone JD, Sloand JA, Illig KA, Bisognano JD.
Program in Heart Failure and Transplantation, Universityof Rochester, Cardiology Division, 601 Elmwood Avenue,Box 679T, Rochester, New York 14642-8679, USA.

Hypertension is a major cause of morbidity and mortality worldwide. Despite a myriad of oral agents, many patients fail to reach their target blood pressure. Electrical stimulation of the carotid sinus, an old therapeutic concept, lowers blood pressure by initiating the baroreflex and reducing sympathetic tone. Recent evidence suggests that the baroreflex is more important in the setting of chronic hypertension than originally believed. The carotid stimulator may be a safe and effective therapeutic option for patients with resistant hypertension.

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Curr Hypertens Rep. 2006 Oct;8(5):377-83.
Treatment of isolated systolic hypertension.
Stokes GS.
P.O. Box 666, Mona Vale, NSW 2103, Australia.

Isolated systolic hypertension (ISH) is the dominant form of hypertension in the elderly. It is associated with increased arterial pulse pressure, to which an early-returning and magnified pulse-wave reflection makes an important contribution. Treatment of ISH with diuretics, calcium channel blockers (CCBs), and angiotensin II inhibitors is effective in reducing systolic blood pressure, preventing cardiovascular morbid events, and lowering mortality; these agents may have to be used in combination to achieve the systolic blood pressure goal of < 140 mm Hg. Treatment with beta-blockers appears to be less effective. The relative efficacy of various classes of antihypertensive drugs for lowering pulse pressure and systolic blood pressure is determined in part by their differing abilities to reduce pulse-wave reflection. In patients with ISH that is refractory to dual or triple therapy, measurement of the reflected wave by applanation tonometry may be useful in determining which additional antihypertensive agent to use.

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Curr Hypertens Rep. 2006 Oct;8(5):409-12.
Lessons from the African-American Study of Kidney Disease andHypertension: An Update.
Toto RD.
Mary M. Conroy Professorship in Kidney Disease,The University of Texas Southwestern Medical Center Dallas,5323 Harry Hines Boulevard, Dallas, Texas 75390-8856, USA.

Hypertension is the second leading attributable cause of end-stage renal disease in the United States today. The African-American Study of Kidney Disease and Hypertension was a randomized, double-blind, controlled trial designed to determine whether strict blood pressure (BP) control, angiotensin-converting enzyme inhibitor (ACEI)-based, or calcium channel blocker (CCB)-based regimens were superior to less strict BP control and beta-blocker (BB)-based regimens, respectively. The study enrolled 1093 African Americans with hypertensive nephrosclerosis and followed them for 4 years with repeated direct measurement of glomerular filtration rate (GFR) and monitoring of end points, including rapid decline in GFR, end-stage kidney disease, and death. From this landmark study, we learned that strict BP control is achievable in this study population, but it did not slow progression of kidney disease, and we learned that an ACEI-based therapy was superior to either a BB- or CCB-based regimen. In addition, we learned that proteinuria is the most important predictor of progression of kidney disease; ACEI and CCB have differential effects on proteinuria; and a CCB-based regimen combined with strict BP control may be the next best choice to an ACEI-based regimen in this population.

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Curr Hypertens Rep. 2006 Oct;8(5):368-76.
Estrogen and hypertension.
Ashraf MS, Vongpatanasin W.
Divisions of Hypertension and Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center,5323 Harry Hines Boulevard, J4 134, Dallas, TX 75390-8586, USA.

Menopause is accompanied by a dramatic rise in the prevalence of hypertension in women, suggesting a protective role of endogenous estradiol on blood pressure (BP). Both animal experimental and human clinical investigations suggest that estrogen engages several mechanisms that protect against hypertension, such as activation of the vasodilator pathway mediated by nitric oxide and prostacyclin and inhibition of the vasoconstrictor pathway mediated by the sympathetic nervous system and angiotensin. However, emerging evidence from recent clinical trials indicates a small increase, rather than decrease, in systolic BP with oral estrogen administration in postmenopausal women, without anydetectable effect on diastolic BP. Mechanisms underlyingthis selective rise in systolic BP in postmenopausal women and oral contraceptive-induced hypertension in premenopausal women remain unknown, but the rise may be related to supraphysiologic concentration of estrogen in the liver. To date, transdermal delivery of estrogen, which avoids the first-pass hepatic metabolism of estradiol, appears to have a small BP-lowering effect in postmenopausal women and may be a safer alternative in hypertensive women.

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Curr Med Res Opin. 2006 Sep;22(9):1849-58.
Efficacy and tolerability of the perindopril/indapamide combination therapy for hypertension: the PRIMUS study.
Holzgreve H, Risler T, Trenkwalder P.
Kardiologische Praxis, Munich, Germany.

BACKGROUND: Tight blood pressure (BP) control is required to reduce cardiovascular morbidity and mortality.OBJECTIVE: To evaluate the efficacy and tolerability of the first line combination perindopril/indapamide in hypertension in daily practice.Design and methods: In this prospective, open-label, observational trial, 1892 general practitioners in Germany recruited patients with hypertension (n = 8023; mean age 59.6 years, 48.1% males, body mass index 27.6 kg/m(2), systolic BP >/= 140 mmHg and/or diastolic BP >/= 90 mmHg) between October 2002 and December 2004. Patients received perindopril 2 mg/indapamide 0.625 mg for 12 weeks. BP measured in the general practice setting, safety, and tolerability were evaluated after 4 and 12 weeks.RESULTS: At baseline, most patients had moderate to severe hypertension (78%); initial BP was 164.6/95.8 mmHg. At inclusion, 38% of the patients were newly diagnosed hypertensives (mean BP 166.1/97.2 mmHg) and 58% of patients had uncontrolled BP despite preexisting antihypertensive treatment (163.5/94.9 mmHg). Previous treatment consisted of beta-blockers (49.5%), ACE inhibitors (36.4%), calcium-antagonists (29.3%), diuretics (28.8%), AT-I receptor antagonists (7.1%), and other treatments (8.1%). In the entire study cohort, treatment with perindopril/indapamide significantly decreased systolic BP (27.9 mmHg), diastolic BP (13.7 mmHg), and pulse pressure (14.2 mmHg), compared with baseline (p < 0.0001); 96% of patients responded to treatment and in 50% of patients BP was normalized (< 140/90 mmHg). Treatment dose was doubled in 9.5% of patients. Similar results were found in various subgroup analyses (newly diagnosed patients, the elderly, and patients with isolated systolic hypertension, additional cardiovascular risk factors, associated diseases, or target organ damage). The most frequent adverse events (< 1% of patients) were dry cough and nausea.CONCLUSIONS: The open-label, observational study PRIMUS, extends the existing evidence that the first line combination treatment of hypertension with perindopril/indapamide is effective, safe, and well tolerated in a representative cross-section of patients with newly diagnosed or pretreated but uncontrolled hypertension in daily practice.

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J Hum Hypertens. 2006 Sep 7; [Epub ahead of print]
Treatment of allergic rhinitis can improve blood pressure control.
Magen E, Yosefy C, Viskoper RJ, Mishal J.
1Internal Medicine 'B' Department, WHO Collaborative Center for Prevention of CVD, Barzilai Medical Center Campus, Ben-Gurion University of the Negev, Ashkelon, Israel.

Owing to high prevalence of arterial hypertension (AH) and allergic rhinitis (AR), these diseases frequently coexist. The study aimed to assess whether improvement of AR by conventional treatment can improve blood pressure (BP) control in this population. Sixty-eight subjects of both sexes aged 35-60 years with AR and AH were randomized into two groups to receive in addition to their antihypertensive medications: treatment group (n=34) Fluticasone nasal 50 mug/spray b.i.d. and Fenoxifenadine 180 mg tablets q.d., and control group (n=34) 0.9% NaCl nasal drops b.i.d. Office BP and AR severity (using the Relative Quality of Life Questionnaire (RQLQ)) and high-sensitive C-reactive protein (hs-CRP) were measured at study entry and after 8 weeks in both groups, without changing of antihypertensive medications. In Treatment group an improvement in RQLQ, significant reduction of systolic BP (SBP) (DSBP 7.4+/-4.3 mm Hg, P=0.006) and reduction of hs-CRP level (DCRP 2.05+/-1.08; P=0.028) were observed, whereas diastolic BP (DBP) remained unchanged (DDBP 0.9+/-1.7 mm Hg, P=0.7). There was a significant correlation between DRQLQ and DSBP (r=0.86; P=0.019) and between DCRP and DSBP (r=0.56; P=0.027). No statistically significant changes of RQLQ, BP and CRP were observed in the control group. In patients with coincidence of AH and AR, medications meant to improve AR attenuate low-grade systemic inflammation and can lower SBP, but not DBP.Journal of Human Hypertension advance online publication, 7 September 2006; doi:10.1038/sj.jhh.1002088.

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Proc Am Thorac Soc. 2006 Sep;3(7):594-600.
Medical therapies for chronic thromboembolic pulmonary hypertension: an evolving treatment paradigm.
Bresser P, Pepke-Zaba J, Jais X, Humbert M, Hoeper MM.
Department of Pulmonology, Academic Medical Center (AMC), P.O. Box 22660, Amsterdam 1100 DD, The Netherlands. p.bresser@amc.uva.nl.

Pulmonary endarterectomy (PEA) is recommended as the treatment of choice for eligible patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, only a proportion of patients fulfill the criteria for surgical intervention. In addition, operated patients with CTEPH may experience a gradual hemodynamic and symptomatic decline related to a secondary hypertensive arteriopathy in the small precapillary pulmonary vessels. It has also been questioned what can be done to reduce risks from PEA surgery to improve outcome in "high risk" patients with CTEPH with substantial impairment of pulmonary hemodynamics before surgery. Such patients may benefit from preoperative reduction of pulmonary vascular resistance by means of medical therapy. Conventional medical treatments, such as anticoagulation, diuretics, digitalis, and chronic oxygen therapy, show low efficacy in the treatment of CTEPH as they do not affect underlying disease processes. Over the last decade, several novel therapies have been developed for pulmonary arterial hypertension (PAH), including prostacyclin analogs (epoprostenol, beraprost, iloprost), endothelin receptor antagonists (bosentan, sitaxsentan, ambrisentan), and phosphodiesterase-5 inhibitors (sildenafil). Evidence of efficacy in PAH, coupled with studies showing histopathologic similarities between CTEPH and PAH, provides a rationale to extend the use of some of these medications to the treatment of CTEPH. However, direct evidence from clinical trials in CTEPH is limited to date. This article reviews evidence supporting, and issues surrounding, the possible use of novel PAH medications in CTEPH.

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Int J Clin Pharmacol Ther. 2006 Aug;44(8):344-57.
Nebivolol: a review of its clinical and pharmacological characteristics.
Gielen W, Cleophas TJ, Agrawal R.
European College of Pharmaceutical Medicine, Lyon, France.

Nebivolol is a cardioselective lipophilic beta-blocker devoid of intrinsic sympathomimetic and membrane-stabilizing actions. The pharmacological profile differs from that of conventional cardioselective beta3-blockers in that it displays nitric oxide- (NO) mediated vasodilator activity. The net hemodynamic effect of nebivolol is the result of a balance between the depressant effects of beta3-blockade and an action that tends to maintain cardiac output, presumably connected with its afterload reducing vasodilator effect. Recent studies suggest that nebivolol may also restore endothelial dysfunction. Long-term follow-up studies indicate that the compound is efficacious and safe both in patients with mild hypertension and those with stable angina. An interesting effect of chronic nebivolol therapy in elderly patients with mild hypertension is the reversal of a depressor effect into a pressor effect on standing. This action indicates that nebivolol has advantages over other antihypertensive drugs and that it may protect elderly hypertensive patients from orthostatic complaints. The observation that nebivolol improves exercise capacity in non-claudicant hypertensives is also of clinical interest. Nebivolol resembles serotonin reuptake inhibitors in that it is metabolized by CYP450 2D6 and, therefore, concomitant treatment with serotonin uptake inhibitors may lead to overdosing. Nebivolol compared to placebo does not significantly reduce the mortality risk in elderly subjects. The effects of biological age and comorbidities may be responsible for this finding. In conclusion, clinical studies suggest that nebivolol is effective and safe in patients with hypertension, angina pectoris and heart failure. The beneficial effects on endothelial function, autonomic control and exercise capacity are of considerable clinical interest.

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J Hum Hypertens. 2006 May 4; [Epub ahead of print]
Aggressive antihypertensive strategies based on hydrochlorothiazide, candesartan or lisinopril decrease left ventricular mass and improve arterial compliance in patients with type II diabetes mellitus and hypertension.
Spoelstra-de Man AM, van Ittersum FJ, Schram MT, Kamp O, van Dijk RA, Ijzerman RG, Twisk JW, Brouwer CB, Stehouwer CD.
[1] 1Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands [2] 2Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.

We investigated the effects of aggressive antihypertensive therapy based on hydrochlorothiazide, candesartan or lisinopril on left ventricular mass (LVM) index and arterial stiffness in hypertensive type II diabetic individuals. Seventy hypertensive type II diabetic individuals were treated with three antihypertensive strategies in a randomized, double-blind, double-dummy design. Blood pressure was titrated to levels below 130/85 mm Hg or a decrease in systolic pressure of 10% with a diastolic pressure below 85 mm Hg. After titration, patients were treated for 12 months. Mean blood pressures were 157/93, 151/94 and 149/93 mm Hg at baseline in the hydrochlorothiazide (n=24), candesartan (n=24) and lisinopril (n=22) groups, and 135/80, 135/82 and 131/80 mm Hg after titration. About 70% reached target blood pressures, with the median use of three antihypertensive drugs. Left ventricular mass index and all estimates of arterial stiffness showed significant improvement after 12 months: that is, LVM index (-11 g/m(2); -8%); carotid distensibility coefficient (DC; +2.8 x 10(-3) kPa(-1); +27%), compliance coefficient (CC; +0.13 mm(2)/kPa; +21%) and elastic modulus (-0.19 kPa; -16%); femoral DC (+1.6 x 10(-3) kPa(-1); +50%) and CC (+0.08 mm(2)/kPa; +26%); brachial DC (+2.1 x 10(-3) kPa(-1); +39%) and CC (+0.03 mm(2)/kPa; +27%) and total systemic arterial compliance (+0.29 ml/mm Hg; +16%). No differences in outcome variables between treatment groups were observed. Aggressive antihypertensive treatment, although difficult to achieve, resulted in substantial reductions of LVM index and arterial stiffness in relatively uncomplicated hypertensive type II diabetic individuals. Strategies based on renin-angiotensin system inhibitors were not clearly superior to conventional (i.e. diuretic-based) strategies.Journal of Human Hypertension advance online publication, 4 May 2006; doi:10.1038/sj.jhh.1002025.

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J Hum Hypertens. 2006 May 4; [Epub ahead of print]
Blood pressure response to calcium supplementation: a meta-analysis of randomized controlled trials.
van Mierlo LA, Arends LR, Streppel MT, Zeegers MP, Kok FJ, Grobbee DE, Geleijnse JM.
1Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.

Calcium plays a role in blood pressure (BP) regulation, but the importance of supplemental calcium intake for the prevention of hypertension is still debated. We conducted a meta-analysis of randomized controlled trials to determine the effect of calcium supplementation on BP. A systematic search for randomized trials of calcium supplementation and BP in non-pregnant subjects was performed in Medline from 1966 to June 2003. Seventy-one trials were identified, 40 of which met the criteria for meta-analysis (total of 2492 subjects). Two persons independently extracted data from original publications on changes in calcium intake and BP. In addition, data were collected on subjects' characteristics, that is, age, gender, initial BP and initial calcium intake. A random effects model was used to obtain the effect of calcium supplementation on BP, overall and in predefined population subgroups. Calcium supplementation (mean daily dose: 1200 mg) reduced systolic BP by -1.86 mm Hg (95% confidence interval: -2.91 to -0.81) and diastolic BP by -0.99 mm Hg (-1.61 to -0.37). In people with a relatively low calcium intake (</=800 mg per day) somewhat larger BP estimates were obtained, that is, -2.63 (-4.03 to -1.24) for systolic BP and -1.30 (-2.13 to -0.47) for diastolic BP. Our study suggests that an adequate intake of calcium should be recommended for the prevention of hypertension. More research on BP in people with calcium-deficient diets is warranted.Journal of Human Hypertension advance online publication, 4 May 2006; doi:10.1038/sj.jhh.1002038.

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Circulation. 2006 May 1; [Epub ahead of print]
Role of Diuretics in the Prevention of Heart Failure. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.
Davis BR, Piller LB, Cutler JA, Furberg C, Dunn K, Franklin S, Goff D, Leenen F, Mohiuddin S, Papademetriou V, Proschan M, Ellsworth A, Golden J, Colon P, Crow R.
University of Texas School of Public Health, Houston; National, Heart, Lung, and Blood Institute, Bethesda, Md; Wake Forest University School of Medicine, Winston-Salem, NC; University of California at Irvine, Irvine; University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Creighton Cardiac Center, Omaha, Neb; Veterans Affairs Medical Center, Washington, DC; University of Washington, Seattle; Penderbrook Medical Center, Fairfax, Va; Centro Cardiovascular de Caguas, Caguas, Puerto Rico; and University of Minnesota, Minneapolis.

BACKGROUND: Hypertension is a major cause of heart failure (HF) and is antecedent in 91% of cases. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) stipulated assessment of the relative effect of chlorthalidone, lisinopril, and amlodipine in preventing HF. METHODS AND RESULTS: ALLHAT was a double-blind, randomized, clinical trial in 33 357 high-risk hypertensive patients aged >/=55 years. Hospitalized/fatal HF outcomes were examined with proportional-hazards models. Relative risks (95% confidence intervals; P values) of amlodipine or lisinopril versus chlorthalidone were 1.35 (1.21 to 1.50; <0.001) and 1.11 (0.99 to 1.24; 0.09). The proportional hazards assumption of constant relative risk over time was not valid. A more appropriate model showed relative risks of amlodipine or lisinopril versus chlorthalidone during year 1 were 2.22 (1.69 to 2.91; <0.001) and 2.08 (1.58 to 2.74; <0.001), and after year 1, 1.22 (1.08 to 1.38; P=0.001) and 0.96 (0.85 to 1.10; 0.58). There was no significant interaction between prior medication use and treatment. Baseline blood pressures were equivalent (146/84 mm Hg) and at year 1 were 137/79, 139/79, and 140/80 mm Hg in those given chlorthalidone, amlodipine, and lisinopril. At 1 year, use of added open-label atenolol, diuretics, angiotensin-converting enzyme inhibitors, and calcium channel blockers in the treatment groups was similar. CONCLUSIONS: HF risk decreased with chlorthalidone versus amlodipine or lisinopril use during year 1. Subsequently, risk for those individuals taking chlorthalidone versus amlodipine remained decreased but less so, whereas it was equivalent to those given lisinopril. Prior medication use, follow-up blood pressures, and concomitant medications are unlikely to explain most of the HF differences. Diuretics are superior to calcium channel blockers and, at least in the short term, angiotensin-converting enzyme inhibitors in preventing HF in hypertensive individuals.

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Rev Med Suisse. 2006 Apr 5;2(60):942-6.
[When can the treatment of isolated systolic hypertension be avoided?]
[Article in French]
Vischer UM, Benetos A.
Hopital de geriatrie 3, ch. Du Pont Bochet 1226 Thonex. ulrich.vischer@hcuge.ch

The treatment of isolated systolic hypertension (ISH) in the elderly reduces the cardiovascular (CV) risk, in particular in patients with diabetes or previous CV events. However, in the very old (> 80-85 years) the treatment of ISH may increase global mortality, although it still decreases the risk of stroke. The benefits of treatment on the risk of dementia remain uncertain. To verify the indication for therapy, the diagnosis of ISH should be confirmed by ambulatory blood pressure monitoring. Since the absolute benefit of treatment is related to its duration, a limited life expectancy may restrict the real impact of treatment. The advantages and limitations of anti-hypertensive therapy in the elderly should be discussed individually, respecting the patient's autonomy.

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Crit Care Med. 2006 Apr 25; [Epub ahead of print]
Treatment of acute hypertension in patients with intracerebral hemorrhage using American Heart Association guidelines*
Qureshi AI, Harris-Lane P, Kirmani JF, Ahmed S, Jacob M, Zada Y, Divani AA.
>From the Clinical Trials Division, Zeenat Qureshi Stroke Research Center, Department of Neurology and Neurosciences, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ.

OBJECTIVE:: To determine the feasibility and safety of treatment of acute hypertension in patients with intracerebral hemorrhage within 24 hrs of symptom onset. Elevated blood pressure, observed in up to 56% of patients with intracerebral hemorrhage, may predispose to hematoma expansion; on the other hand, reduction of blood pressure may reduce hematoma expansion and subsequent death and disability. DESIGN:: Single-center prospective registry supplemented by retrospective chart review. SETTINGS:: University-affiliated medical center with dedicated stroke service. PATIENTS:: All patients admitted to the stroke service with spontaneous intracerebral hemorrhage and acute hypertension within 24 hrs of symptom onset. INTERVENTION:: Patients were treated with intravenous nicardipine within 24 hrs of symptom onset to reduce and maintain mean arterial pressure of <130 mm Hg. The mean arterial pressure goal was consistent with the American Heart Association guidelines. MEASUREMENTS AND MAIN RESULTS:: The primary outcome was the tolerability of the treatment as assessed by achieving and maintaining the mean arterial pressure goals for 24 hrs after initiation of intravenous nicardipine infusion. Other end points ascertained were: neurologic deterioration defined by a decline in Glasgow Coma Scale from pretreatment assessment by >/=2 points or increase in National Institutes of Health Stroke Scale score by >/=2 points and hemorrhage growth defined as an increase in the volume of intraparenchymal hemorrhage of >33% as measured by image analysis on the 24-hr computed tomographic scan compared with the baseline computed tomographic scan. Rates of favorable outcome and death were ascertained at 1 month. Of the total 46 patients admitted with intracerebral hemorrhage in our service, 29 patients were treated. Mean age of the treated patients was 58 +/- 13 yrs; ten were women. Initial National Institutes of Health Stroke Scale ranged from 1 to 38. The primary outcome of tolerability was achieved in 25 of the 29 patients (86%). Neurologic deterioration was observed in 4 of 29 patients. Hematoma enlargement was observed in five patients. Favorable outcome (defined as modified Rankin scale of </=2) and death at 1-month mortality was observed in 11 (38%) and 9 (31%) of the 29 patients, respectively. CONCLUSIONS:: We observed a high rate of tolerability among patients with intracerebral hemorrhage who were treated with intravenous nicardipine using mean arterial pressure goals de- fined by American Heart Association guidelines within 24 hrs of symptom onset.

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J Clin Hypertens (Greenwich). 2006 Jan;8(1 Suppl 1):31-9.
Building on the Specialist's Antihypertensive Treatment Recommendation: It's Just the Beginning.
Saunders E.
University of Maryland School of Medicine, Baltimore, MD 21201 esaunder@medicine.umaryland.edu.

Patients with established cardiovascular disease are a top priority for preventive medicine. Evidence from clinical trials supports the merits of aggressive risk reduction therapies in survivors of an acute event. Improving their cardiovascular risk factor profile prolongs survival, reduces the incidence of recurrent atherosclerotic events, and improves quality of life. Blood pressure (BP) control is an essential component of cardiovascular disease secondary prevention programs; however, many patients are not receiving adequate antihypertensive therapy to meet their BP goal. By building on the specialist's discharge antihypertensive prescription, primary care physicians are ideally positioned to assume responsibility for ensuring BP goals are achieved and maintained over the long term in patients who have survived an acute event. Current hypertension management guidelines define appropriate BP goals and incorporate clear advice on how these goals can be met. BP should be lowered slowly and carefully through lifestyle modifications and pharmacologic therapy. Antihypertensive treatment should be given according to guidelines for primary prevention, although specific antihypertensive classes are indicated for initial use in post-myocardial infarction and post-stroke patients. In many cases, BP goal attainment will require the use of combination therapy with two or more drugs from different classes. With the availability of effective and safe antihypertensive drug therapies, including fixed-dose combinations, a BP goal of <140/90 mm Hg should be achievable in most patients.

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J Clin Hypertens (Greenwich). 2006 Jan;8(1 Suppl 1):21-30.
Hypertension-related morbidity and mortality in african americans-why we need to do better.
Ferdinand KC, Saunders E.
Heartbeats Life Center, Xavier University College of Pharmacy, New Orleans, LA kcferdmd@aol.com.

Almost one third of adults in the United States have hypertension. Prevalence data among different racial or ethnic groups indicate that a disproportionate number of African Americans have hypertension compared with non-Hispanic whites and Mexican Americans. Earlier onset of high blood pressure and greater severity of hypertension contribute to a greater burden of hypertensive target organ damage in African Americans and may be a factor in the shorter life expectancy of this population compared with white Americans. There is a clear need for improved management of hypertension in African Americans via therapeutic lifestyle interventions and pharmacotherapy. While there is some evidence that particular antihypertensive agent classes provide blood pressure-lowering advantages over others, there is no support for withholding agents of any one class. When given as monotherapy, diuretics and calcium channel blockers may be relatively more effective in lowering blood pressure in African Americans than beta blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers. However, when combined with a diuretic, African Americans respond as well to these agents as other racial groups. Combination therapy using antihypertensive agents with differing modes of action provides additive antihypertensive efficacy and is well tolerated. Recent guidelines recommend combination therapy as the standard of care for patients with significant blood pressure elevation, especially those with diabetes mellitus and renal disease. These comorbidities are more common in African Americans and indicate the potential need for initial therapy with more than one agent or a combination of agents in one pill.

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J Clin Hypertens (Greenwich). 2006 Jan;8(1 Suppl 1):12-20.
Hypertension-a treatable component of the cardiometabolic syndrome: challenges for the primary care physician.
Manrique CM, Lastra G, Palmer J, Stump CS, Sowers JR.
University of Missouri-Columbia and Harry S. Truman VA Medical Center, Columbia, MO 65212 sowersj@health.missouri.edu.

Patients with the cardiometabolic syndrome (CMS) have an adverse cardiovascular risk factor profile, placing them at increased risk of stroke, coronary artery disease, chronic kidney disease, and type 2 diabetes mellitus. Although no specific treatments for CMS are available per se, prompt recognition and treatment of the individual components of the condition can prevent or delay the development of comorbidities. Primary care physicians are ideally positioned to identify patients with CMS and implement early intervention strategies. Hypertension contributes to many complications of CMS, and rigorous blood pressure control will help to delay or prevent end-organ vascular damage. Achieving blood pressure control to current guideline standards should be eagerly sought in the majority of patients through a combination of lifestyle modifications and appropriate pharmacologic therapy. Antihypertensive drug choice should be personalized, taking into account the CMS determinants present and any compelling indications for specific agents. As an initial approach, a thiazide diuretic is suitable for most cases of uncomplicated hypertension, although many patients will require additional antihypertensives from other classes to achieve their blood pressure goal. It is predicted that, due to the increase in unhealthy lifestyles, the prevalence of CMS will rise in the coming years. Therefore, by meeting the challenge of attaining and maintaining blood pressure control in patients with CMS, primary care physicians have the unique opportunity to markedly improve the health of the nation.

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J Clin Hypertens (Greenwich). 2006 Jan;8(1 Suppl 1):4-11.
Dispelling the myth of "aggressive" antihypertensive therapy.
Ofili EO.
Morehouse School of Medicine, Atlanta, GA 30310 eofili@msm.edu.

Data from well designed randomized trials have proven the effectiveness of an intensive approach to hypertension management in reducing morbidity and mortality. Based on these data, guidelines recommend a blood pressure goal of <140/90 mm Hg in the general population, with lower goals for high-risk patients. Clinical trials also show that most patients will require at least two antihypertensive agents to reach goal. Despite this evidence base, only about one third of individuals with hypertension receive sufficient therapy to attain a blood pressure of <140/90 mm Hg. Physicians may be reluctant to use multiple antihypertensive agents to achieve this goal because they may consider it to be "aggressive" and not always in the best interests of the patient, especially in those deemed at low risk. Such perceptions may be founded on several myths: 1) the approach demands a complex, time-consuming titration-to-response strategy, during which the patient may be lost to follow-up; 2) it increases the pill burden, which will decrease patient compliance; 3) it increases treatment-related side effects; and 4) it is not cost-effective. The availability of fixed-dose combinations containing two antihypertensive agents should help to dispel these myths. Careful selection of efficacious, well tolerated, once-daily, fixed-dose combinations allows goal blood pressure to be achieved quickly in a broad range of patients and encourages patient concordance with therapy. Such formulations are also cost-effective. Thus, reducing blood pressure using multiple drugs as fixed-dose combinations is a strategy that recognizes the multiple pathophysiologic changes that lead to hypertension.

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Tex Heart Inst J. 2005;32(4):467-71.
Management of systemic and pulmonary hypertension.
Levy JH.
Department of Anesthesiology, Emory University School of Medicine, and Cardiothoracic Anesthesiology, Emory Healthcare, Atlanta, Georgia, USA.

The major therapeutic approach to systemic and pulmonary hypertension and vasospasm in cardiac surgery patients involves the use of parenteral agents that reverse systemic vasoconstriction and produce vasodilation. Potential pharmacologic approaches include 1) alpha1-adrenergic receptor blockers, ganglionic blockers, and calcium channel blockers; 2) central alpha2-adrenergic receptor agonists, dopamine1-adrenergic receptor agonists, potassium channel modulators, and vascular cyclic nucleotide stimulators; 3) phosphodiesterase enzyme inhibitors, and 4) angiotensin-converting enzyme inhibitors. Of the currently available intravenous vasoactive therapies, the mainstay agents are the nitrovasodilators and the dihydropyridine-type calcium channel blockers. The nitrovasodilators, a diverse group of drugs that achieve vascular relaxation by stimulating cyclic nucleotides and thereby releasing nitric oxide, include nitroglycerin and sodium nitroprusside. Although these drugs are useful, rapid development of tolerance is a drawback to nitroglycerin, while nitroprusside can cause coronary steal and increase intracranial pressure. Intravenous dihydropyridine-type calcium channel blockers inhibit mechanical responses of cardiac muscle and vascular smooth muscle by blocking inward calcium currents. Nicardipine is an arterial specific vasodilator. Treatment for vasospasm is usually empiric; pharmacologic options include nitroglycerin, but dihydropyridine calcium channel blockers and phosphodiesterase inhibitors should also be considered.

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Z Kardiol. 2005 Dec;94(Supplement 4):iv19-iv23.
[Risk adapted therapy in vascular diseases: Antihypertensive treatment in peripheral arterial disease.]
[Article in German]
Sternitzky R.
Praxisklinik Herz und Gefasse Kardiologie-Angiologie-Radiologie-Nuklearmedizin, Forststr. 3, 01099, Dresden, r.sternitzky@praxisklinik-dresden.de.

Arterial hypertension must also be consistently treated in patients with PAD. Current guidelines and recommendations have to be considered, although in some patients the walk performance may be affected temporary by blood pressure dropping. In PAD, ideal antihypertensives are ACE inhibitors, AT1 receptor antagonists, calcium channel blockers and also alpha receptor blockers in combination. Beta receptor blockers-indicated in coronary heart disease-do not influence pain-free walking distance (PFWD) in patients with PAD. Diuretics should only be given in low dosage and in combination with other antihypertensive drugs in order to avoid a decrease of blood flow ability with clinical events.

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Prev Cardiol. 2006 Winter;9(1):35-41.
Optimal vascular protection: a case for combination antihypertensive therapy.
Vogel RA.
University of Maryland School of Medicine, Baltimore, MD 21201 rvogel@heart.umaryland.edu.

Endothelial dysfunction is an important factor in the pathogenesis of atherosclerosis, hypertension, and heart failure. The endothelium mediates vascular tone, structure, and function by the release and regulation of multiple vasoactive substances that promote or inhibit vasodilation, vasoconstriction, cell growth, and other mechanisms. The effect of antihypertensive drugs on endothelial function may be an important indicator of their ability to reduce risks for cardiovascular morbidity and mortality. Endothelium-dependent vasodilation induced by various antihypertensive drugs is accurately measured with high-resolution ultrasound of flow-mediated dilation of the brachial artery. Calcium channel blockers and angiotensin-converting enzyme inhibitors have been shown to reverse endothelial dysfunction. The benefits of angiotensin-converting enzyme inhibitors and calcium channel blockers on the endothelium are believed to derive from their effects on nitric oxide production and antioxidant effects, possibly independent of blood pressure reduction. Due to their complementary mechanisms of action, it has been hypothesized that the combination of an angiotensin-converting enzyme inhibitor and a calcium channel blocker will provide superior cardiovascular protection, in part by producing an additive effect of increased nitric oxide availability, when compared with either agent alone.

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Diabetes Metab. 2005 Dec;31 Spec No 2:82-91.
Management of hypertension in elderly diabetic patients.
Blickle J.
Service de Medecine Interne, Diabete et Maladies Metaboliques, Hopitaux Universitaires de Strasbourg, Strasbourg, France.

Hypertension is a major vascular risk factor in the elderly diabetic. The benefit of proper management is well recognized, even if treatment has no influence on overall mortality or might even tend to increase it in very elderly subjects. Globally, the efficacy of the major classes of antihypertensive drugs, diuretics, beta-blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, or angiotensin II receptor antagonists appears to be equivalent so that the therapeutic choice depends on the type of hypertension, systolic or systolic-diastolic, and the rapidity of the desired effect, co-morbid conditions, particularly coronary or renal disease, or drug tolerance. Blood pressure goals are similar to those in middle-aged persons, except in very old, frail or sick subjects.

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Pharmacol Rep. 2005;57 Suppl:97-107.
Polyphenols as potential therapeutical agents against cardiovascular diseases.
Curin Y, Andriantsitohaina R.
Laboratoire de Pharmacochimie de la Communication Moleculaire, UMR 7081 CNRS, Faculte de Pharmacie, 74 route du Rhin, 67401 Illkirch, France. ramaroson.andriantsitohaina@univ-angers.fr.

Increasing evidence suggests that polyphenols from fruits, vegetables and beverages such as wine and tea may exert protective effects on the cardiovascular system. Indeed, research in the field of polyphenols points out their antioxidant and free radical scavenging properties, leading to lower low-density lipoprotein (LDL) oxidation and platelet aggregation. These compounds are also able to modulate the generation of nitric oxide (NO) from vascular endothelium and to interfere with the mechanisms leading to inflammation and endothelial apoptosis, contributing to the prevention of the endothelial dysfunction, known to play a central role in the pathogenesis of cardiovascular diseases. This article reviews the potential targets of polyphenols involved in the complex pathophysiological events occurring in cardiovascular diseases, such as hypertension, atherosclerosis and stroke.

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Can J Neurol Sci. 2005 Nov;32(4):403-8.
Hypertension and stroke: 2005 Canadian Hypertension Educational Program recommendations.
Boulanger JM, Hill MD; CHEP (Canadian Hypertension Educational Program).
Canadian Hypertension Educational Program, Foothills Hospital, Calgary, Alberta, Canada.

BACKGROUND: Hypertension is the most important modifiable cause of stroke. The Canadian Hypertension Educational Program, representing Canada's experts in the field of hypertension, publishes annual evidence-based recommendations on the diagnosis and treatment of hypertension. METHODS: We present the 2005 Canadian Hypertension Educational Program guidelines regarding the management of hypertension in patients with stroke. RESULTS: The diagnosis of hypertension should be expedited and can be made as early as the second visit in patients with stroke. Unless contraindicated, a combination of angiotensin-converting-enzyme (ACE) inhibitors and diuretics is the preferred therapy in these patients. A target blood pressure below 140/90 mmHg for non-diabetic patients, below 130 mmHg/80 mmHg for diabetic patients and below 125 mmHg/75 mmHg for those with renal disease and proteinuria (> 1 gram per day) should be reached. Lifestyle interventions may be as effective as medication and should be used in conjunction with medical management. Waist circumference should be less than 102 cm for men and 88 cm for women. There remains uncertainty about the management of high blood pressure in the context of acute stroke. CONCLUSIONS: A combination of ACE-inhibitors and diuretics is recommended in hypertensive stroke patients. Blood pressure should be maintained below 140/90 mmHg.

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J Hypertens. 2005 Nov;23(11):2083-92.
Adding hydrochlorothiazide to olmesartan dose dependently improves 24-h blood pressure and response rates in mild-to-moderate hypertension.
Sellin L, Stegbauer J, Laeis P, Rump LC.
aKlinikum der Ruhr-Universitat Bochum, Marienhospital Herne, Bochum bSankyo Pharma, Munich, Germany.

OBJECTIVE: To test whether adding hydrochlorothiazide (HCTZ) (12.5 or 25 mg) to olmesartan 20 mg improves 24-h blood pressure in patients whose conventional diastolic blood pressure is inadequately controlled by olmesartan monotherapy. PATIENTS: Male and female patients >/= 18 years with mean sitting diastolic blood pressure (DBP) of 100-115 mmHg, mean sitting systolic blood pressure (SBP) greater than 150 mmHg, mean 24-h DBP of at least 84 mmHg, and at least 30% of DBP daytime readings > 90 mmHg. INTERVENTIONS: Four weeks of single-blind treatment with olmesartan 20 mg once daily, followed in non-responders by 8 weeks of randomized double-blind treatment with placebo or HCTZ (12.5 or 25 mg) once-daily, added to olmesartan. RESULTS: HCTZ 25 mg added to olmesartan 20 mg decreased mean daytime DBP significantly more (P = 0.0012) than placebo added to olmesartan 20 mg. Compared to olmesartan monotherapy, mean 24-h DBP and SBP were significantly reduced by combination therapy with olmesartan/HCTZ 20/12.5 mg (-1.9 mmHg, P = 0.0167 and -3.9 mmHg, P = 0.0018, respectively) and 20/25 mg (-3.7 and -7.4 mmHg respectively, P < 0.0001 for both). Mean 24-h DBP and SBP and mean night-time SBP reductions were significantly greater for HCTZ 25 mg than for HCTZ 12.5 mg. Response rates (mean daytime DBP assessed by ambulatory blood pressure measurement </= 85 mmHg) approximately doubled following the addition of HCTZ (12.5 mg = 57.6% and 25 mg = 69.5%). CONCLUSION: Combination of olmesartan 20 mg with HCTZ provides significantly better 24-h blood pressure reduction than olmesartan monotherapy in patients with mild-to-moderate hypertension. Moreover, increasing the dose of HCTZ from 12.5 to 25 mg is a reasonable step to reach better daytime and night-time blood pressure control.

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J Hypertens. 2005 Nov;23(11):1947-51.
How many alcoholic drinks might benefit an older person with hypertension?
Bulpitt CJ.
Faculty of Medicine, Imperial College London, UK.

Lowering alcohol intake reduces blood pressure and hence cardiovascular risk. However, abstainers have an increase in cardiovascular risk and the advice to reduce intake to low levels may not be sound. This review examines the effects of lowering alcohol consumption in terms of blood pressure and coronary heart disease (CHD). The relationship between both CHD and stroke and alcohol consumption, and the benefits and disadvantages of alcohol consumption in the general population, are discussed. Where available, the results of large meta-analyses are reported. It is concluded that the hypertensive patient over the age of 60 who drinks over 16 drinks per week should be advised to reduce his or her alcohol intake but a daily drink may be advisable and the patient should not stop drinking entirely. It is not suggested that the non-drinker should start drinking, but most hypertensives are over the age of 60 when community studies suggest that drinking alcohol does more good than harm.

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Am J Hypertens. 2005 Oct;18(10):1360-3.
Antihypertensive effect of sweetie fruit in patients with stage I hypertension.
Reshef N, Hayari Y, Goren C, Boaz M, Madar Z, Knobler H.
Metabolic Unit, Kaplan Medical Center, Rehovot, Israel.

BACKGROUND: Interventional studies have shown that increased intake of fruit and vegetables reduces blood pressure (BP). However, the contribution of specific dietary components has not been evaluated. The aim of the present study was to determine, in patients with stage I hypertension, the antihypertensive effect of juice of the so-called sweetie fruit (a hybrid between grapefruit and pummelo) with and without high flavonoid content. METHODS: A double-blind, cross-over study was conducted in 12 patients. Each patient received alternately high-flavonoid (HF) sweetie juice and low-flavonoid (LF) sweetie juice, each for a 5-week period. The LF sweetie juice had 25% of naringin and 30% of narirutin content compared with the original HF sweetie juice. RESULTS: The HF sweetie juice was more effective than LF sweetie juice in reducing diastolic blood pressure (P = .04). Systolic blood pressure declined in both groups; however there was no significant difference between subjects given HF sweetie versus those given LF sweetie juice. CONCLUSIONS: In this study HF sweetie juice was shown to have a significant beneficial effect in reducing diastolic blood pressure, compared with the effect observed with LF sweetie juice, in patients with stage I hypertension. These data suggest that the active ingredients associated with the antihypertensive effect of sweetie juice are the flavonoids naringin and narirutin.

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Am J Hypertens. 2005 Oct;18(10):1313-9.
Felodipine-metoprolol combination tablet: maintained health-related quality of life in the presence of substantial blood pressure reduction.
Dahlof B, Degl' Innocenti A, Elmfeldt D, Puig JG, Gundersen T, Hosie J, Januszewicz W, Lindstrom CJ, Magometschnigg D, Tanser P, Toutouzas P, Waeber B, Wiklund I.
Clinical Experimental Research Laboratory, Department of Medicine, Sahlgrenska University Hospital/Ostra, Goteborg, Sweden.

BACKGROUND: Most treated hypertensive patients do not achieve adequate blood pressure (BP) control. Initiating therapy with two drugs has been suggested when BP is >20/10 mm Hg above goal. To ensure patients' compliance, such treatment needs to be well tolerated and must not compromise health-related quality of life (HRQL). The primary objective of this study was to compare the effects on HRQL of initiating treatment with felodipine + metoprolol (F+M) fixed combination tablets, or enalapril (E), or placebo (P). METHODS: A total of 947 patients of both sexes with primary hypertension (diastolic BP 95 to 110 mm Hg), aged 20 to 70 years, participated in this randomized, double-blind, parallel group, 12-week, multicenter trial. Treatment was initiated with F+M 5 + 50 mg, or E 10 mg, or P. Doses were doubled after 4 or 8 weeks if diastolic BP was >90 mm Hg. The HRQL was measured at baseline and at the last visit using two validated questionnaires: the Psychological General Well-being Index (PGWB) and the Subjective Symptom Assessment Profile (SSA-P). Office BP was measured at trough, that is, 24 h after the previous dose. RESULTS: The HRQL was high at baseline and generally well maintained during the study. For example, the mean (SD) PGWB total score was 104 (16) at baseline and 105 (16) at 12 weeks in all three treatment groups. The BP reductions after F+M (18/14 mm Hg) and E (12/9 mm Hg) were significantly greater than after P (7/7 mm Hg), and the reduction after F+M was significantly greater than after E. CONCLUSIONS: The HRQL is maintained in the presence of substantial BP reduction during antihypertensive treatment with F+M fixed combination tablets.

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Am J Hypertens. 2005 Oct;18(10):1300-1305.
Increased Sodium Intake Correlates With Greater Use of Antihypertensive Agents by Subjects With Chronic Kidney Disease.
Boudville N, Ward S, Benaroia M, House AA.
Department of Medicine, University of Western Ontario, London, Ontario, Canada; Division of Nephrology, London Health Sciences Centre, London, Ontario, Canada; School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.

BACKGROUND: Hypertension is a common disease in patients with chronic kidney disease (CKD) and predisposes to heart disease, stroke, and progression of renal failure. In the general population, sodium restriction has been shown to improve blood pressure (BP) control, but this is not widely recommended in CKD patients. The aim of this study was to assess the sodium balance in a CKD clinic and its effect on BP management. METHODS: We retrospectively reviewed charts from June 1998 through to June 2003 and included all patients with an estimated glomerular filtration rate (GFR) of <30 mL/min who completed a 24-h urine collection for sodium. Patients were divided into tertiles based upon their 24-h sodium excretion and analyzed by ANOVA. RESULTS: We included 141 CKD patients who had a mean (+/- SE) sodium excretion of 145.7 +/- 4.7 mmol/day. There were a significantly greater number of antihypertensive agents used with increasing sodium excretion (2.00 +/- 0.16, 2.61 +/- 0.20, and 2.77 +/- 0.19 medications, respectively for each tertile; P = .01). This difference was even more prominent when only those patients with a GFR </=15 mL/min (n = 77) were examined (1.69 +/- 0.19, 2.52 +/- 0.27, and 3.08 +/- 0.26 medications, respectively; P = .001). Control of BP was equivalent in all groups. Multivariable analysis revealed sodium excretion (P = .00005) and age (P = .007) to be significantly associated with use of antihypertensive medication. CONCLUSIONS: We have demonstrated that increased sodium intake is associated with an increased number of antihypertensive medications to achieve comparable BP control in a population with CKD.

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Semin Nephrol. 2005 Jul;25(4):261-71.
Renovascular hypertension: current concepts.
Garovic V, Textor SC.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN.

Hypertension produced by renal artery occlusive disease is an important secondary form of hypertension. Clinicians commonly encounter forms of renal arterial disease of varying severity, many of which are of little hemodynamic significance when first detected. Experimental studies emphasize that transient activation of the renin-angiotensin-aldosterone system is necessary for initiation of renovascular hypertension. At some point, angiotensin II activates additional mechanisms responsible for sustained increased blood pressure including sodium retention, endothelial dysfunction, and vasoconstriction related to production of reactive oxygen species. Widespread application of agents that block the renin-angiotensin system, including angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, render many patients with unilateral renal arterial disease manageable primarily by medical means for many years. In the setting of high a priori likelihood of renovascular disease, recognizing the potential for disease progression during medical therapy and individually evaluating the risks and benefits of renal revascularization are important tasks. Recent prospective studies show limited, but real, benefit regarding blood pressure control for patients with atherosclerotic disease. Whether earlier renal revascularization offers benefits regarding improved morbidity and mortality from cardiovascular end point reduction is an important question to be addressed in multicenter, prospective, randomized trials. Our paradigm stresses the fact that patients with renovascular hypertension require intensive blood pressure control and cardiovascular risk factor intervention, both before and after revascularization. Hence, management of such patients requires close attention and periodic review regarding restenosis and progression of vascular disease.

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Semin Nephrol. 2005 Jul;25(4):252-60.
Hypertension in kidney transplantation.
Castillo-Lugo JA, Vergne-Marini P.
Dallas Nephrology Associates, Dallas TX; and the Transplantation and Renal Disease Unit, Methodist Medical Center, Dallas, TX.

Arterial hypertension in renal transplant patients plays a major role in the progression to chronic allograft failure, and in morbidity and mortality associated with cardiovascular disease. Its cause is diverse, with contributions not only from donor and/or recipient factors, but it also is influenced strongly by the type of immunosuppressive regimen. Despite increased awareness of the adverse effects of hypertension in both graft and patient survival, long-term studies have shown that arterial hypertension in the transplant population has not been controlled adequately. Ambulatory blood pressure measurements provide the advantage of a better assessment of the diurnal blood pressure variation, a predictor of target organ damage and cardiovascular morbidity and mortality events. Although the available data do not support the recommendation of any class of antihypertensive medication as preferred agents for blood pressure management in the transplant population, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers have shown beneficial effects beyond their antihypertensive effects. Clinical data in transplant recipients are emerging that suggest that applying interventions proven to be effective in reducing cardiovascular morbidity and mortality in the general population may be effective for the transplant population.

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Semin Nephrol. 2005 Jul;25(4):236-45.
Hypertension and the kidney.
Wiederkehr M, Toto R, Fenves AZ, Ram CV.
Baylor University Medical Center; Dallas Nephrology Associates; Dallas Texas.

Hypertension is an important and widely prevalent risk factor for the development of chronic kidney disease (CKD), which unfortunately may progress to end-stage renal disease. CKD is a progressive condition that causes significant morbidity and mortality. Diabetes is the leading cause of end-stage renal disease in the Western world. Both hypertension and diabetes are the causative factors for the occurrence of CKD and its consequences. Aggressive control of hypertension and diabetes is indicated to reduce the risk for kidney disease in the community. Certainly, effective control of hypertension is a proven modality to prevent renal disease. The concept of decreasing the systemic blood pressure as well as the intraglomerular pressure has led to the application of rational therapeutic options in patients with renal insufficiency. Although treatment of hypertension alone is critical, drugs that block the renin-angiotensin system have been shown to have special renal (and cardiovascular) benefits. Early detection and treatment of microalbuminuria is an integral part of disease management. This article reviews the pathophysiologic and therapeutic implications of the link between hypertension and the kidney.

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Semin Nephrol. 2005 Jul;25(4):227-35.
Therapeutic controversies in hypertension.
Messerli FH, Grossman E.
St. Lukes-Roosevelt Hospital Center, New York, NY; Internal Medicine D and Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Israel.

Although numerous prospective randomized trials since the Veterans Administration studies clearly have attested to the efficacy and safety of antihypertensive therapy, there remain some controversial issues with all classes of antihypertensive drugs. Thiazide diuretics increase the risk for new-onset diabetes and their long-term safety has been questioned. Alpha-blockers do not reduce morbidity and mortality in uncomplicated hypertension but are well known to cause a variety of poorly tolerated side effects. The safety of calcium antagonists has been questioned for many years, although recent large prospective randomized trials such as Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, International Verapamil-Trandolapril Study, Intervention as a Goal in Hypertension, Valsartan Antihypertensive Long-Term Use Evaluation and the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) have attested to their safety and efficacy. Angiotensin-converting enzyme inhibitors, in general, are well tolerated but have potentially fatal adverse effects in a few patients. Angiotensin-receptor blockers are exceedingly well tolerated, but may be less-efficacious antihypertensive agents than other drug classes. Most antihypertensive drug classes have an effect on new-onset diabetes that should be taken into account in patients at risk. No head-to-head comparison of combination therapy looking at efficacy and safety has been available. The long-term safety of antihypertensive therapy is documented poorly because most trials only last 4 to 6 years. Despite these drawbacks and concerns, the benefits of antihypertensive therapy clearly outweigh its potential risk.

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Semin Nephrol. 2005 Jul;25(4):198-209.
Hypertension treatment guidelines: practical implications.
Choi KL, Bakris GL.
Rush Hypertension Center, Department of Preventive Medicine, Rush University Medical Center, Chicago, IL.

The focus of blood pressure (BP) lowering is to prevent or reduce the risk for cardiovascular and renal events. This rationale forms the basis for the recent guideline statements issued by the Seventh Joint National Committee, the American Diabetes Association, the European Society of Hypertension, and the Kidney Disease Outcomes Quality Initiative. The goal BP in the majority of hypertensive patients should be less than 140/90 mm Hg, with a lower goal of less than 130/80 mm Hg in patients with diabetes or kidney disease. Meta-analyses of clinical trials with renal end points make it clear that the presence of 1 gram or more of proteinuria mandates a BP approaching 115 mm Hg to slow the progression of advanced nephropathy adequately. Compelling indications also exist for the use of certain antihypertensive agents in the setting of kidney dysfunction, diabetes, heart failure, and coronary artery disease. Initiation with 2 antihypertensive agents should be considered strongly for patients with a BP of more than 20 mm Hg greater than the systolic BP goal. This means that those with a goal BP of less than 130 mm Hg should be started on 2 antihypertensive medications with complementary actions when the systolic BP is 150 mm Hg or greater. In patients with kidney disease, reaching the BP goal requires multiple agents that should include an appropriate diuretic and an agent that blocks the renin-angiotensin-aldosterone system to slow the progression of kidney disease.

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Blood Press. 2005 Jul 1;14 Suppl 1:39-44.
A calcium-channel blocker, benidipine, improves forearm reactive hyperemia in patients with essential hypertension.
Makino H, Aoki M, Hashiya N, Yamasaki K, Shimizu H, Miwa K, Ogihara T, Morishita R.
Department of Geriatric Medicine, Osaka University Medical School, Osaka, Japan.

The pathophysiological role of endothelial cells is important in the mechanism of progression of atherosclerosis and improvement of endothelial function may be important for cardiovascular morbidity. Calcium antagonists are reported to have protective effects on the endothelium in vitro and in vivo. In this clinical study, we investigated the effect of calcium antagonist, benidipine, on endothelial function in the patients with essential hypertension, which causes endothelial dysfunction. Twenty-five patients with hypertension without other risk factors for atherosclerosis were treated with monotherapy (8 mg benidipine, n = 25) for 8 weeks. Blood pressure was reduced significantly. Endothelial function was evaluated using forearm blood flow by strain-gauge plethysmography after 8 weeks of treatment. Changes in vasodilator response to reactive hyperemia were significantly improved (p<0.01), while the response to nitroglycerin was not changed, suggesting the improvement of endothelial function. Moreover, we focused on hepatocyte growth factor (HGF), which is a novel angiogenic growth factor with an anti-apoptotic action on endothelial cells, and evaluated involvement of HGF in improvement of endothelial function. Serum HGF concentration in subjects treated with benidipine was significantly elevated at 8 weeks (p<0.05). Overall, these results demonstrated that benidipine improved endothelial dysfunction in patients with hypertension. Interestingly, an increase in serum HGF concentration by benidipine might contribute to the improvement of endothelial dysfunction.

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Blood Press. 2005 Jul 1;14 Suppl 1:23-31.
Effect of irbesartan monotherapy compared with ACE inhibitors and calcium-channel blockers on patient compliance in essential hypertension patients: A multicenter, open-labeled, three-armed study.
Koylan N, Acarturk E, Canberk A, Caglar N, Caglar S, Erdine S, Guneri S, Ilerigelen B, Kabakci G, Onder R, Sagkan O, Buyukozturk K.
Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey.

Objectives. This multicenter, three-armed, open-labeled study investigated patient compliance of patients receiving irbesartan, angiotensin-converting enzyme (ACE) inhibitors or calcium-channel blockers (CCB) for essential hypertension for a 6-month period. Patients were either newly diagnosed or switched from existing antihypertensive medication due to lack of efficacy or side-effects. Methods. Patients were started monotherapy with irbesartan (n = 377), ACE inhibitors (n = 298) or CCB (n = 308) and were reevaluated on 1st, 3rd, and 6th months of the treatment. The primary endpoint was patient compliance, assessed by proportion of patients who had taken their study medication every day. Efficacy was recorded as mean reductions in blood pressure and the proportion of patients whose blood pressure normalized. Tolerability was assessed by reported adverse events. Results. Significantly more patients receiving irbesartan had complied with study medication after 3 and 6 months of treatment than ACE inhibitors or CCB. Significantly fewer patients receiving irbesartan needed to change their antihypertensive medication. All three study treatments exhibited similar efficacy profiles, but irbesartan had significantly less adverse events. Conclusions. This study demonstrated that patient compliance to irbesartan was significantly superior to other study treatments. Irbesartan is therefore a suitable first-line therapy for essential hypertension in everyday clinical practice.

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Blood Press. 2005 Jul 1;14 Suppl 1:14-22.
Effects of nifedipine GITS 20 mg or enalapril 20 mg on blood pressure and inflammatory markers in patients with
mild-moderate hypertension.
Rosei EA, Morelli P, Rizzoni D.
Chair of Internal Medicine, Department of Medical and Surgical Sciences, University of Brescia, Brescia, Italy.

Objective. Calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors and other drug classes either alone or in combination have been recommended for the treatment of hypertension. Nifedipine gastrointestinal therapeutic system (GITS) 20 mg is a new low-dose formulation with an improved tolerability. The aim of the present study was to compare the effects of nifedipine GITS 20 mg and enalapril 20 mg on blood pressure and circulating adhesion molecules in hypertensive patients. Methods. This randomized, double-blind, multicentre trial compared the blood pressure lowering effects of a 12-week treatment of nifedipine GITS 20 mg vs enalapril 20 mg in 264 patients with mild-to-moderate hypertension. Results. Nifedipine GITS 20 mg induced a reduction of clinic blood pressure, which was similar to that observed with enalapril 20 mg. Nifedipine GITS and enalapril lowered mean sitting diastolic blood pressure by 11.8 and 12.4 mmHg, respectively, while systolic blood pressure was reduced by 15.3 and 16.3 mmHg, respectively. Ambulatory blood pressure monitoring-derived blood pressure data showed similar results in both groups without any statistically significant differences between treatments. Both enalapril and nifedipine tended to reduce ICAM-1 and E-selectin, while only nifedipine reduced von Willebrand factor. Both treatments were well tolerated. Conclusions. Our findings demonstrate a similar antihypertensive effectiveness of a low dose (20 mg) of nifedipine GITS in comparison with a standard dose of enalapril (20 mg). Given its clinical efficacy and good tolerability, low-dose nifedipine GITS may be considered a valuable treatment option for hypertensive patients.

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Blood Press. 2005 Jul 1;14 Suppl 1:6-13.
Fixed combination of manidipine and delapril in the treatment of mild to moderate essential hypertension: Evaluation by 24-hour ambulatory blood pressure monitoring.
Mugellini A, Vaccarella A, Celentano A, Scanferla F, Zoppi A, Fogari R.
Dipartimento di Medicina Interna e Terapia Medica, Clinica Medica II, Universit di Pavia, IRCCS Policlinico San Matteo.

This present study assessed the antihypertensive efficacy of the fixed combination of manidipine and delapril by ambulatory blood pressure monitoring in patients with hypertension inadequately controlled by monotherapy with either component. After a 2-week placebo period, 55 mild to moderate hypertensive patients were randomized to manidipine 20 mg o.d. or delapril 30 mg b.i.d. for 4 weeks. After this period, 30 patients, aged 30-76 years (18 males and 12 females) whose diastolic blood pressure was not adequately controlled (>/=90 mmHg) by monotherapy were treated with the fixed combination of manidipine 10 mg plus delapril 30 mg o.d. for 8 weeks. A 24-h ambulatory blood pressure monitoring recording was performed at the end of the placebo washout, of the monotherapy and of the combination therapy. Blood pressure control over the 24 h was quantified by the trough-to-peak ratio and the smoothness index. As compared to placebo, the fixed combination of manidipine and delapril produced a statistically significant (p<0.01) decrease in sitting clinic (18+/-9/14+/-5 mmHg) and 24-h blood pressure (12+/-7/10+/-5 mmHg) without affecting heart rate. This reduction was greater than that observed with single components. At the end of the 8-week combination treatment period, the rate of normalilized patients was 73%. Treatment with the fixed combination was associated with a positively high smoothness index (1.2+/-0.7/13.8+/-0.8) and with a relatively good trough-to-peak ratio (0.46/0.60). The combination of manidipine and delapril produced significant and smooth reductions in blood pressure values, which persisted over the 24-h dosing interval. These results support the use of fixed manidipine-delapril combination in the treatment of mild to moderate hypertensive patients inadequately controlled by monotherapy.

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J Hum Hypertens. 2005 Jul 21; [Epub ahead of print]
Effects of low-dose aspirin on blood pressure and endothelial function of treated hypertensive hypercholesterolaemic subjects.
Magen E, Viskoper JR, Mishal J, Priluk R, London D, Yosefy C.
1WHO Collaborative Center for Prevention of CVD, Barzilai Medical Center, Ben Gurion University of Negev, Ashkelon, Israel.

The main objective of this study was to assess whether aspirin 100 mg QD can improve blood pressure (BP) control and endothelial function in subjects with arterial hypertension (AH) and hypercholesterolaemia. In total, 21 patients of both sexes (52.1+/-11.5 years) with treated AH and hypercholesterolaemia on antihypertensive and statin therapy were included in the treatment group. In the control group, 20 matched patients of both sexes (51.3+/-12.7 years), but without statin therapy, were recruited. Treatment group subjects received aspirin (100 mg QD) for a duration of 12 weeks at randomization (Treatment phase-1), followed by single blind matching placebo for 12 weeks (Placebo phase) and then again received aspirin (100 mg QD) for an additional 12 weeks (Treatment phase-2). The control group participated in Treatment phase-1, but did not continue Placebo phase and Treatment phase-2. At randomization and at the end of each study phase, mean 24-h systolic BP (SBP) and diastolic BP (DBP) were assessed by 24-h ambulatory blood pressure monitoring (ABPM) and endothelium-dependent (flow mediated, FMD) and -independent (nitroglycerin induced, NTG) vasodilatations of brachial artery were measured using high-resolution ultrasound. In Treatment phase-1, reduction of SBP and DBP (DeltaSBP 5.7+/-2.6 mmHg, P=0.008; DeltaDBP 3.8+/-1.7 mmHg, P=0.014) and improvement of FMD (4.1+/-0.6%, P=0.019), in Placebo phase an elevation of SBP and DBP (DeltaSBP -6.2+/-2.9 mmHg, P=0.002; DeltaDBP -4.2+/-1.9 mmHg, P=0.031) and worsening of FMD (-3.8+/-0.9%, P=0.027), and in Treatment phase-2 reduction of SBP and DBP (DeltaSBP 4.9+/-2.3 mmHg, P=0.005; DeltaDBP 4.1+/-1.3 mmHg, P=0.024) and improvement of FMD (4.5+/-1.3%, P=0.009) were observed in the treatment Group but not in the control group. Addition of low-dose aspirin to antihypertensive medications and statins in hypertensive and hypercholesterolaemic subjects can reduce both SBP and DBP by improvement of endothelial function.Journal of Human Hypertension advance online publication, 21 July 2005; doi:10.1038/sj.jhh.1001910.

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MMW Fortschr Med. 2005 Jun 23;147(25):38-40.
[Which cardiac patients may be allowed to travel by air?]
[Article in German]
Flesch M.
Klinik III fur Innere Medizin der Universitat zu Koln. markus.flesch@uni-koeln.de

During airline flights, cardiological patients in particular are put at stress by the decrease in pressure in the passenger cabin and the associated decrease in oxygen partial pressure in the blood. Possible risks are, in particular, rhythm disorders, myocardial ischemic states or an excessive increase in pulmonary artery pressure. Flight travel may be permitted at the earliest two weeks after a myocardial infarction or coronary event. It should be forbidden in patients with decompensated cardiac failure, instable angina pectoris, severe pulmonary arterial or arterial hypertension, uncontrolled arrhythmias and surgery on the heart within a period of 2 weeks prior to the intended flight.

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Curr Pharm Des. 2005;11(17):2235-42.
Antihypertensive therapy: role of aldosterone antagonists.
Grandi AM.
Professor of Internal Medicine, Department of Clinical Medicine, University of Insubria, Varese, Italy. amgrandi@libero.it

The interest for the therapeutic potential of aldosterone antagonists in essential hypertension comes from the recently discovered nonclassical pathways of aldosterone actions, above all the presence of extra-adrenal aldosterone production and the discovery of aldosterone's proinflammatory and profibrotic actions. The review begins with the discussion of experimental studies on animals, demonstrating the role of aldosterone in cardiovascular remodeling and the effects of aldosterone blockade on hypertensive target organ damage. Then recent clinical studies are presented, that confirm in humans the deleterious role of aldosterone, in particular in the development of myocardial hypertrophy, cardiovascular fibrosis and arterial stiffness. After a brief description of the new selective aldosterone antagonist, eplerenone, compared to the well-known non-selective aldosterone antagonist, spironolactone, the results of studies on essential hypertensive patients are discussed, evaluating the efficacy of aldosterone antagonists in lowering blood pressure, but, more important, in protecting against target organ damage.

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Int J Cardiol. 2005 May 11;101(1):97-104.
Doxazosin GITS versus standard doxazosin in mild to moderate hypertension.
Calvo C, Gil-Extremera B, Gomez-Fernandez P, Masramon X, Pueyo C, Armada B.
Unidad de Hipertension y Riesgo Vascular, Hospital Clinico Univeritario, Travesia de la Choupana s/n, 15706 Santiago de Compostela, Spain.

BACKGROUND: The selective alpha(1)-adrenoceptor antagonist doxazosin in both standard formulation and gastrointestinal therapeutic system (GITS) controlled-release formulation is effective for hypertension without having a negative impact on serum lipids. This study was designed to compare the relative efficacy of these two formulations of doxazosin on clinic and ambulatory blood pressure and serum lipids in patients with mild to moderate hypertension. METHODS: Hypertensive patients aged 18-70 years (n=335) were evaluated in a multi-center prospective randomized study. Following a 2-week placebo run-in phase, patients were randomized to receive doxazosin 2 or 4 mg, with dose titration, or doxazosin GITS 4 mg, no dose titration, for 9 weeks. RESULTS: Both doxazosin formulations reduced clinic diastolic and systolic blood pressure from baseline (P<0.0001). Doxazosin GITS and doxazosin 4 mg had similar blood pressure-lowering effects. Doxazosin GITS reduced sitting diastolic and systolic blood pressure compared with doxazosin 2 mg (P<0.01 for both). A greater proportion of the doxazosin GITS group reached goal blood pressure (</=140/90 mm Hg) after 9 weeks compared with the doxazosin 2-mg group. All doses of doxazosin reduced 24-h and daytime (7:00 am to 10:00 pm) ambulatory blood pressure from baseline (all P<0.01). Doxazosin GITS significantly reduced nighttime (10:00 pm to 7:00 am) ambulatory blood pressure from baseline. A neutral effect on serum lipids was observed with doxazosin. CONCLUSIONS: Doxazosin GITS and doxazosin were effective in reducing clinic and ambulatory blood pressure. The GITS formulation reduced the need for dose titration. Both doxazosin formulations were well tolerated.

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Am J Ophthalmol. 2005 May;139(5):855-9.
The use of acetazolamide in idiopathic intracranial hypertension during pregnancy.
Lee AG, Pless M, Falardeau J, Capozzoli T, Wall M, Kardon RH.
Departments of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, Iowa; Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa; Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa.

PURPOSE: To describe the pregnancy outcomes after the use of acetazolamide in pregnant patients with idiopathic intracranial hypertension (IIH). DESIGN: Observational case series. METHODS: setting: Two tertiary care academic neuro-ophthalmology units. patient population: Patients with IIH treated with acetazolamide. observation procedure: Documentation of pregnancy outcome. main outcome measures: Normal pregnancy, fetal loss, or congenital malformation. RESULTS: Twelve patients were treated with acetazolamide for IIH during pregnancy, and there were no adverse pregnancy outcomes. A critical review of the English language literature on the subject failed to demonstrate any convincing evidence for any adverse effect on pregnancy for acetazolamide. CONCLUSIONS: Acetazolamide at high doses may produce birth defects in animals, but there is little clinical or experimental evidence to support any adverse effect of the drug on pregnancy outcomes in humans. If the clinical situation warrants the use of acetazolamide in IIH, then the drug probably can be offered after appropriate informed consent.

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Prev Cardiol. 2005 Spring;8(2):87-92.
Effect of Fixed-Dose ACE-Inhibitor/Calcium Channel Blocker Combination Therapy vs. ACE-Inhibitor Monotherapy on Arterial Compliance in Hypertensive Patients With Type 2 Diabetes.
Winer N, Folker A, Murphy JA, Hung E, Bard M, Perkelvald A, Sowers JR, Bakris GL.
SUNY Downstate Medical Center, Brooklyn, NY nathaniel.winer@downstate.edu.

Assessment of vascular compliance may be a useful measurement of the clinical effects of antihypertensive treatment. Both angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers are known to improve vascular elasticity. A study was performed to test the hypothesis that combined therapy with an ACE inhibitor and a calcium channel blocker would have additive benefits on vascular compliance at similar levels of blood pressure (BP), as compared with monotherapy with an ACE inhibitor. This 12-week, double-blind study was a substudy of a larger clinical hypertension study conducted in patients with hypertension and type 2 diabetes. Subjects (N=20) were randomized to either a fixed-dose combination of amlodipine besylate/benazepril HCl or to enalapril monotherapy. BP, heart rate, large- and small-vessel compliance, systemic vascular resistance, and urinary microalbumin excretion were assessed at baseline and after treatment. Both treatments were similarly effective in lowering BP, reducing systemic vascular resistance, and decreasing urinary microalbumin excretion. Improvement in large-vessel compliance was significantly greater among subjects who received ACE-inhibitor/calcium channel blocker combination therapy (52%) as compared with those who received ACE-inhibitor monotherapy (32%; p<0.05). No significant change in small-vessel compliance was observed with either treatment. Greater improvement in large-vessel compliance with combination therapy was independent of BP lowering.

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J Clin Hypertens (Greenwich). 2005 Apr;7(4 Suppl 1):27-31.
Comparison of blood pressure control with amlodipine and controlled-release isradipine: an open-label, drug substitution study.
Ganz M, Mokabberi R, Sica DA.
Clinical Research Center of Cleveland, CCH-Eastern Region, Cleveland, OH mganz@cchseast.org.

An open-label drug substitution study showed that controlled-release isradipine (Dynacirc-CR) can be safely substituted for amlodipine on a mg-for-mg basis in patients with mild-to-moderate hypertension. When controlled-release isradipine was substituted for amlodipine, blood pressure was more effectively controlled, and edema rates were reduced. When subjects resumed amlodipine therapy, the previous gain in blood pressure reduction and lessening of edema vanished. The basis for this more favorable pattern of efficacy and side-effects with controlled-release isradipine, although mechanistically unresolved, may relate to a lesser degree of sympathetic nervous system activation.

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J Clin Hypertens (Greenwich). 2005 Apr;7(4 Suppl 1):15-20.
Management of hypertensive chronic kidney disease: role of calcium channel blockers.
Toto RD.
University of Texas Southwestern Medical Center, Dallas, TX robert.toto@utsouthwestern.edu.

Both the prevalence and incidence of end-stage renal disease have been increasing in the United States over the past two decades. Diabetes and hypertension are the attributable causes for more than three fourths of all new cases of end-stage renal disease. The overwhelming majority of diabetics with nephropathy are hypertensive, and lowering blood pressure is indicated in all patients with chronic kidney disease because of the increased risk for cardiovascular morbidity and mortality. Multiple studies indicate that reaching goal systolic blood pressure in patients with chronic kidney disease generally requires three to four antihypertensive agents. A number of medication combinations can effectively reduce blood pressure in the chronic kidney disease patient. In this regard, adding a calcium channel blocker to an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker helps in reaching goal blood pressure while preserving renal function in both diabetics and nondiabetics with proteinuria.

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J Clin Hypertens (Greenwich). 2005 Apr;7(4 Suppl 1):9-14.
Therapeutic considerations in the african-american patient with hypertension: considerations with calcium channel blocker therapy.
Flack JM, Sica DA.
Wayne State University, University Health Center, Detroit, MI jflack@intmed.wayne.edu.

African Americans have a higher prevalence, earlier onset, and more rapid progression of hypertensive end-organ disease, as well as excessive hypertensive mortality compared with other racial/ethnic groups. Most differences in hypertension and pressure-related complications between African Americans and whites appear to be quantitative and not qualitative. Improving the diagnosis, treatment, and control of hypertension in this highly vulnerable population is a major health care goal for the new millennium. In this regard the dietary pattern to be promoted for reduction of hypertension risk in African Americans is one of increased consumption of dairy products, fruit, and vegetables as well as a continued emphasis on decreased Na+ intake. When pharmacologic therapy is considered, multi-drug approaches are generally required, with diuretics, angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers), and calcium channel blocker therapy as oft-selected components of most such treatment regimens.

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Int J Clin Pract. 2005 Feb;59(2):214-24.
Redefining efficacy of antihypertensive therapies beyond blood pressure reduction--the role of angiotensin II antagonists.
Conlin PR.
Endocrinology, Diabetes and Hypertension Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. pconlin@partners.org

Antihypertensive efficacy must be redefined beyond blood pressure (BP) lowering per se to include reducing the cardiovascular complications of hypertension. Treatment decisions should be based on results from large clinical trials with relevant clinical outcomes. Several recent morbidity and mortality trials with angiotensin II receptor antagonists (AIIAs) provide an evidence-based rationale for the use of AIIAs in patients with hypertension. Studies with AIIAs in comparison to conventional antihypertensive agents showed improved morbidity and mortality outcomes in patients with hypertension and left ventricular hypertrophy (losartan) and diabetes mellitus (losartan and irbesartan). Trials with some members of the AIIA class (candesartan and valsartan) have not demonstrated such benefits in comparison to conventional agents, possibly due to differences in BP control during the trials. The results of these AIIA outcome trials have impacted on recently issued clinical guidelines for management of hypertension.

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Adv Ther. 2004 Nov-Dec;21(6):357-69.
Therapeutic profile of manidipine and lercanidipine in hypertensive patients.
Casiglia E, Mazza A, Tikhonoff V, Basso G, Martini B, Scarpa R, Pessina AC.
Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy.

Manidipine and lercanidipine are considered effective and safe in the treatment of chronic arterial hypertension and are equipotent in reducing blood pressure (BP) levels. Their main side effect is ankle-foot edema. After a 2-week placebo run-in period, these 2 drugs were compared in a controlled parallel-group study lasting 3 months, involving 53 patients with mild-to-moderate essential hypertension (26 assigned to manidipine and 27 to lercanidipine). At the end of the active treatment period, BP was significantly reduced in comparison with the end of the placebo phase in both the manidipine and the lercanidipine groups, without significant differences between the 2 drugs. Daytime BP was significantly reduced by 5.5%/5.6% with manidipine and by 3.8%/6.6% with lercanidipine, while smaller reductions were seen at nighttime. The smoothness index was the same with both drugs. Unlike lercanidipine, manidipine significantly reduced both basal (-30%) and minimal vascular resistance (-39%), qualifying it as a potent vasodilator. Despite vasodilation, heart rate was not increased but was even slightly reduced by treatment. Ankle-foot edema was observed with both drugs but was less pronounced with manidipine, probably because of greater postcapillary dilatation. In conclusion, manidipine and lercanidipine are both effective and safe in mild-to-moderate essential hypertension, although the former seems to have a more favorable tolerability profile than the latter.

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J Hypertens. 2005 Feb;23(2):445-453.
Controlled-release nifedipine and candesartan low-dose combination therapy in patients with essential hypertension: the NICE Combi (Nifedipine and Candesartan Combination) Study.
Hasebe N, Kikuchi K; for the NICE Combi Study Group.
First Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan bSee Appendix.

OBJECTIVE: To compare the clinical efficacy of low-dose controlled-release (CR) nifedipine (20 mg/day) plus candesartan (8 mg/day) combination therapy with that of up-titrated candesartan (12 mg/day) monotherapy. DESIGN: Randomized, double-blind study. SETTING: Outpatient study. PATIENTS AND PARTICIPANTS: Patients with essential hypertension, who did not achieve their target blood pressure with baseline treatment of candesartan 8 mg/day for 8 weeks. MAIN OUTCOME MEASURES: Blood pressure, pulse pressure, urinary microalbumin excretion. RESULTS: Blood pressure was significantly reduced in both groups (P < 0.05), but the reduction was significantly greater in the combination therapy group (12.1 +/- 1.4/8.7 +/- 0.9 mmHg) than in the up-titrated monotherapy group (4.1 +/- 1.4/4.6 +/- 0.9 mmHg) (P < 0.0001). The reduction in pulse pressure was significantly greater in the combination therapy group (3.3 +/- 1.2 mmHg) than in the up-titrated monotherapy group (0.7 +/- 1.2 mmHg) (P = 0.0031). Urinary microalbumin excretion decreased significantly in the combination therapy group (from 61.9 to 40.5 mg/g creatinine; P < 0.05), but not in the up-titrated monotherapy group. CONCLUSIONS: These findings suggest that the low-dose combination therapy of nifedipine CR and candesartan is superior to the up-titrated monotherapy of candesartan in terms of blood pressure control and renal protection in patients with essential hypertension.

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Coron Artery Dis. 2005 Feb;16(1):67-73.
The vascular effects of doxazosin in hypertension complicated by metabolic syndrome.
Dell'omo G, Penno G, Pucci L, Pellegrini G, Scotti A, Prato SD, Pedrinelli R.
aDipartimento Cardio Toracico bDipartimento di Endocrinologia e Metabolismo, Universita' di Pisa, Pisa, Italy cLaboratorio Analisi Chimiche e Microbiologiche, Azienda Ospedaliera Pisana dItalfarmaco Spa, Milano, Italy.

AIMS: To evaluate the vascular effects of doxazosin, an alpha-1 antagonist, in hypertensive patients with metabolic syndrome in whom the drug has previously been shown to exert beneficial metabolic actions on lipids and insulin metabolism. EXPERIMENTAL PROTOCOL: Twelve untreated non-diabetic hypertensive patients with National Cholesterol Education Program (NCEP) ATP-III defined metabolic syndrome were assigned to three-months of treatment with doxazosin (5.5+/-1.9 mg/die). Study variables were measured at baseline and after treatment. End-points: forearm blood flow (strain-gauge plethysmography) responses to graded intra-arterial acetylcholine and sodium nitroprusside infusion to test endothelium-dependent and independent vasodilatation respectively. Minimum forearm vascular resistance, the ratio of mean blood pressure and post-ischaemic maximal blood flow, as an index of arteriolar structure; transcapillary albumin escape rate (the 1-h decay rate of I-albumin, 6-8 muC ev) as a measure of systemic capillary permeability. Lipids, fasting and post-glucose insulin were measured at baseline and after treatment. RESULTS: Doxazosin reduced blood pressure, augmented acetylcholine-mediated vasodilatation, decreased minimum resistance and, although not to a statistically significant extent, transvascular albumin leakage increased high-density lipoprotein (HDL) cholesterol while triglycerides and post-stimulative hyperinsulinemia decreased. CONCLUSIONS: Doxazosin improved endothelial-mediated vasomotor function and reversed abnormal arteriolar structure in hypertensive patients with metabolic syndrome while improving lipid profile and blunting post-glucose hyperinsulinemia.

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Am J Ther. 2005 January/February;12(1):3-8.
Regression of Left Ventricular Hypertrophy With Moexipril, an Angiotensin-Converting Enzyme Inhibitor, in Hypertensive Patients.
Sayegh F, Topouchian J, Hlawaty M, Olzewska M, Asmar R.
L'Institut Cardio Vasculaire, Paris, France.

Left ventricular hypertrophy (LVH) is a common complication of essential hypertension and an independent risk factor for the development of cardiovascular disease. Therefore, antihypertensive treatment should decrease blood pressure (BP) and reverse LVH. However, antihypertensive drugs have been shown to have different effects on LVH despite similar effects on BP reduction. Although lowering BP produces a beneficial effect on LVH per se, metaanalyses of clinical trials have indicated that angiotensin-converting enzyme (ACE) inhibitors decrease left ventricular mass (LVM) to a greater extent than do some other antihypertensives. The aim of this study was to evaluate the effect of a 24-week treatment with the ACE inhibitor moexipril (15 mg once daily) on the regression of LVH in hypertensive patients. This was a multicenter, international, single-blind, single-group, nonrandomized study. After a wash-out placebo period of 2 weeks, 15 mg moexipril once daily was administered for 24 weeks followed by a 2-week follow-up placebo period. Subjects with mild to moderate essential hypertension were screened; those with LVH [defined as an LVM indexed for body surface area (LVMIs) >111 g/m in men and LVMIs >106 g/m in women] were eligible to participate in this study. Echocardiograms were recorded on videotape and sent to a centralized laboratory for reading by 2 independent experts blinded for treatment, center, and visit; the mean values of these readings were calculated and used for analysis. Valid echocardiographic data were obtained from 72 patients (50 males, 22 females) with a mean age of 49 +/- 11 years. Analysis showed significant decrease of LVMIs (121 +/- 20 versus 103 +/- 17 g/m; P < 0.001) and BP (152 +/- 12/96 +/- 9 versus 140 +/- 13/86 +/- 9 mm Hg; P < 0.001) with moexipril. For patients who met LVMI inclusion criteria after centralized, blinded readings, the decrease from baseline in LVMIs was 23.4 g/m. The decrease in LVMIs was independent from the regression to the mean phenomenon as observed from the follow-up placebo period. Moexipril 15 mg once daily administered for 24 weeks resulted in a significant reversal of LVH in patients with essential hypertension. The result compares favorably with results previously obtained in trials of similar duration with other ACE inhibitors.

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J Hum Hypertens. 2005 Jan 20; [Epub ahead of print]
Current status of angiotensin receptor blockers for the treatment of cardiovascular diseases: focus on telmisartan.
Chrysant SG, Chrysant GS, Desai A.
1Cardiology, University of Oklahoma, Oklahoma Cardiovascular and Hypertension Center, Oklahoma City, OK, USA.

Poorly controlled hypertension is a major risk for cardiovascular morbidity and mortality, strokes, heart failure and renal failure. Despite these devastating complications, blood pressure control of </=140/90 mmHg, which is above the current standard, is very poor worldwide, accounting for 34% of hypertensive patients in the United States, and 6% in other countries. The reasons for this poor control of blood pressure include lack of aggressive treatment by physicians, especially for the systolic blood pressure, drug selection and patient compliance. The blood pressure follows a circadian rhythm and is the highest between 0600 to 1200 h, when most complications occur. Long-acting drugs that extend their action to cover this vulnerable period are preferable, especially those that block the renin-angiotensin-aldosterone system, such as ACE inhibitors and angiotensin receptor blockers, and are the most effective in controlling blood pressure and preventing or reducing its cardiovascular and renal complications. With respect to the angiotensin receptor blockers, telmisartan has been demonstrated by several studies to be the longest acting among its class of drugs and to effectively prevent the early morning rise of blood pressure.Journal of Human Hypertension advance online publication, 20 January 2005; doi:10.1038/sj.jhh.1001808.

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Hypertension. 2005 Jan 17; [Epub ahead of print]
Antihypertensive Therapy Increases Cerebral Blood Flow and Carotid Distensibility in Hypertensive Elderly Subjects.
Lipsitz LA, Gagnon M, Vyas M, Iloputaife I, Kiely DK, Sorond F, Serrador J, Cheng DM, Babikian V, Cupples LA.
Hebrew Rehabilitation Center for Aged.

Many physicians are reluctant to lower blood pressure to recommended levels in elderly hypertensive patients because of concern about producing cerebral hypoperfusion. Because hypertension is associated with potentially reversible structural and functional alterations in the cerebral circulation that may improve with treatment, we investigated whether long-term pharmacological reduction of systolic blood pressure will improve, rather than worsen, cerebral blood flow and its regulation. Three groups of elderly subjects 65 years of age or older were studied prospectively: normotensive subjects (N=19), treated hypertensive subjects with systolic pressure <140 mm Hg (N=18), and uncontrolled hypertensive subjects with systolic pressure >160 mm Hg at entry into the study (N=14). We measured beat-to-beat blood flow velocity in the middle cerebral artery (transcranial Doppler ultrasonography), finger arterial pressure (photoplethysmography), and pulsatile distensibility of the carotid artery (duplex Doppler ultrasonography) at baseline and after 6 months of observation or antihypertensive therapy. After baseline hemodynamic measurements, uncontrolled hypertensive subjects underwent aggressive treatment with lisinopril with or without hydroclorothiazide or, if not tolerated, nifedipine or an angiotensin receptor blocker to bring their systolic pressure <140 mm Hg for 6 months. The other 2 groups were observed for 6 months. After 6 months of successful treatment, uncontrolled hypertensive subjects had significant increases in cerebral blood flow velocity and carotid distensibility that was not seen in the other groups. Treatment reduced cerebrovascular resistance and did not impair cerebral autoregulation. Therefore, judicious long-term treatment of systolic hypertension in otherwise healthy elderly subjects does not cause cerebral hypoperfusion.

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Cochrane Database Syst Rev. 2005 Jan 25;1:CD005182.
Interventions used to improve control of blood pressure in patients with hypertension.
Fahey T, Schroeder K, Ebrahim S.
Division of Community Health Sciences, University of Dundee, MacKenzie Building, Kirsty Semple Way, Dundee, UK, DD2 4AD.

BACKGROUND: It is well recognized that patients with high blood pressure (hypertension) in the community frequently fail to meet treatment goals- a condition labeled as "uncontrolled" hypertension. The optimal way in which to organize and deliver care to patients who have hypertension so that they reach treatment goals has not been clearly identified. OBJECTIVES: To determine the effectiveness of interventions to improve control of blood pressure in patients with elevated blood pressure. To evaluate the ability of reminders to improve the follow-up of patients with elevated blood pressure. SEARCH STRATEGY: All-language search of all articles (any year) in the Cochrane Controlled Trials Register (CCTR), Medline and Embase from June 2000. SELECTION CRITERIA: Randomised controlled trials (RCTs) of patients with hypertension that evaluated the following interventions: (1) self-monitoring(2) educational interventions directed to the patient(3) educational interventions directed to the health professional(4) health professional (nurse or pharmacist) led care(5) organisational interventions that aimed to improve the delivery of care(6) appointment reminder systemsOutcomes assessed were: (1) mean systolic and diastolic blood pressure(2) control of blood pressure (3) proportion of patients followed up at clinic DATA COLLECTION AND ANALYSIS: Two authors extracted data independently and in duplicate and assessed each study according to the criteria outlined by the Cochrane Collaboration Handbook. MAIN RESULTS: 59 RCTs met our inclusion criteria. The methodological quality of included studies was variable. An organized system of regular review linked to vigorous antihypertensive drug therapy was shown to reduce blood pressure (weighted mean difference -8.2/-4.2 mmHg, -11.7/-6.5 mmHg, -10.6/-7.6 mmHg for 3 strata of entry blood pressure) and all-cause mortality at five years follow-up (6.38% versus 7.78%, difference 1.4%) in a single large RCT- the Hypertension Detection and Follow-Up study. Other interventions had variable effects. Self-monitoring was associated with moderate net reduction in diastolic blood pressure (weighted mean difference (WMD): -2.03 mmHg, 95%CI: -2.69 to -1.38 mmHg, respectively. Appointment reminders increased the proportion of individuals who attended for follow-up. RCTs of educational interventions directed at patients or health professionals were heterogeneous but appeared unlikely to be associated with large net reductions in blood pressure by themselves. Health professional (nurse or pharmacist) led care may be a promising way of delivering care, with the majority of RCTs being associated with improved blood pressure control, but requires further evaluation. AUTHORS' CONCLUSIONS: Family practices and community-based clinics need to have an organized system of regular follow-up and review of their hypertensive patients. Antihypertensive drug therapy should be implemented by means of a systematic stepped care approach when patients do not reach target blood pressure levels.

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Curr Treat Options Cardiovasc Med. 2004 Dec;6(6):451-458.
Pulmonary Arterial Hypertension: New Management Options.
Huffman MD, McLaughlin VV.
University of Michigan Medical Center, Division of Cardiovascular Medicine, Department of Internal Medicine, 1500 East Medical Center Drive, L3119 Women's Hospital, Ann Arbor, MI 48109-0273, USA. vmclaugh@umich.edu.

The past decade has realized remarkable advances in the treatment of pulmonary arterial hypertension (PAH), a progressive and potentially fatal disease. A small proportion of patients will have a dramatic hemodynamic response to acute vasodilator testing performed at the time of right heart catheterization and may be candidates for calcium channel blocker therapy. The vast majority of patients with PAH will not benefit from calcium channel blockers and should be treated with one of the three US Food and Drug Administration-approved therapies for PAH; bosentan, treprostinil, or epoprostenol. Because of the ease of administration relative to other therapies, the majority of patients with functional class III symptoms should be treated with the oral nonselective endothelin antagonist bosentan. Randomized controlled trials with treprostinil have demonstrated improvements in exercise endurance and hemodynamics. Patients who are critically ill, with functional class IV symptoms, should be started on epoprostenol because it is the most rapidly effective therapy. Intravenous epoprostenol improves exercise endurance, quality of life, hemodynamics, and survival in PAH. Investigational therapies on the horizon include phosphodiesterase inhibitors, prostacyclin analogues with alternative delivery routes (eg, inhaled, oral), and selective endothelin A receptor antagonists. The future of PAH therapy will likely include combinations of these therapies based on the multiple mechanisms of action.

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Curr Cardiol Rep. 2004 Nov;6(6):421-6.
Combination drug treatment of hypertension: have we come full circle?
Taylor AA.
Section on Hypertension and Clinical Pharmacology, Department of Medicine, Baylor College of Medicine, 6565 Fannin, MS F504, Houston, TX 77030-2704, USA. ataylor@bcm.tmc.edu.

Only 30% of hypertensive patients achieved and maintained adequate blood pressure control on a single drug in recent clinical trials. For the majority of patients who require two or more drugs to lower blood pressure to the currently recommended goals of 140/90 mm Hg or to 130/80 if they are diabetic or have chronic kidney disease, combinations of two or more drugs in a single pill offers an attractive alternative to taking multiple single drugs each day. Research has shown that the simpler the drug regimen the more likely patients are to be compliant in taking medications. Because a reduction in cardiovascular risk is linked to the extent to which elevated blood pressure is reduced, this benefit is not realized by patients who either discontinue their medications or are noncompliant. Carefully selected low doses of two antihypertensive drugs combined in a single pill offers other advantages including greater efficacy compared with high-dose monotherapy, a lower incidence of adverse effects, improved persistence in taking medications, fewer patient visits, and reduced cost to the health care system.

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J Hypertens. 2004 Nov;22(11):2043-8.
Lifestyle interventions or drugs for patients with essential hypertension: a systematic review.
Nicolson DJ, Dickinson HO, Campbell F, Mason JM.
National Guidelines Research and Development Unit, Centre for Health Services Research, 21 Claremont Place, University of Newcastle, Newcastle Upon Tyne, NE2 4AA, UK.

OBJECTIVE: To compare the effectiveness of lifestyle and drug interventions for treating patients with essential hypertension. METHODS: Systematic review of randomized controlled trials (RCTs), with 8 or more weeks follow-up, enrolling patients with blood pressure of at least 140/85 mmHg, which directly compared lifestyle and drug interventions. Planned outcome measures were cardiovascular morbidity and mortality and blood pressure. RESULTS: We found five RCTs meeting our inclusion criteria and additionally included one quasi-randomized trial. These trials enrolled between 27 and 64 participants, mean age 55 years, with follow-up of less than 1 year; none reported cardiovascular outcomes. The lifestyle and drug interventions and patient populations were heterogeneous. Overall, the trials were of poor quality and had inconsistent results. Although dietary interventions did not always lower blood pressure as much as antihypertensive drugs, secondary analysis suggested that they might be better at lowering cholesterol levels. CONCLUSIONS: In the short term, lifestyle treatment may be effective at reducing blood pressure for some individuals. A healthier diet, by lowering blood pressure and cardiovascular risk, may reduce, delay or remove the need for long-term drug therapy in some patients. However, further comparisons of lifestyle and drug interventions for hypertension are required, with larger clinical trials of longer duration and better quality. Future trials should aim to identify the characteristics of patients most likely to benefit from lifestyle changes.

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Cochrane Database Syst Rev. 2004 Oct 18(4):CD003562.
Sildenafil for pulmonary hypertension.
Kanthapillai P, Lasserson T, Walters E.
Luton and Dunstable NHS Trust, Lewsey Road,, Luton, Hertfordshire, UK, LU4 0DZ.

BACKGROUND: Pulmonary Hypertension (PH) can be either of unknown aetiology (primary pulmonary hypertension (PPH)) or due to a known underlying cause (secondary pulmonary hypertension (SPH). Pulmonary arteriolar vasoconstriction is considered to be an important characteristic of PH. Therapies which aim to vasodilate are used to treat pulmonary hypertension. OBJECTIVES: To determine the clinical efficacy of sildenafil, a vasodilator which works through inhibition of the enzyme phosphodiesterase type V (PDE5I), administered via any route to people with pulmonary hypertension in primary or secondary forms. SEARCH STRATEGY: Electronic databases were searched with pre-defined search terms. Searches were current as of November 2003. SELECTION CRITERIA: Randomised controlled trials were considered for inclusion in the review. We included studies which assessed the effects of sildenafil in participants with PPH and SPH. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed and extracted data from clinical trials. Data were entered in RevMan Analyses 1.0.2. Continuous data were pooled with an estimate on either WMD (weighted mean difference) or SMD (standardised mean difference) scales. Dichotomous data were pooled and a RR (relative risk) was calculated. MAIN RESULTS: Four studies recruiting 77 participants met the inclusion criteria of the review. Two studies assessed the acute effects of sildenafil. Two small crossover study assessed the effects of long term administration. The 'acute effect' studies indicated that sildenafil has a pulmonary vasodilatory effect. The two crossover studies showed improvement in symptoms. One study showed improvement in fatigue domains from a validated health status questionnaire. Both crossover studies reported that the drug was well tolerated. REVIEWERS' CONCLUSIONS: The validity of the observed effects is undermined by small participant numbers and inadequate exploration of the different disease etiologies. The effects on long term outcome such as NYHA functional class, symptoms, mortality and exercise capacity require further validation. More studies of adequate size are required before the long term effects of sildenafil on clinically important outcomes can be established.

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Ann Intern Med. 2004 Oct 19;141(8):614-27.
Systematic review: antihypertensive drug therapy in black patients.
Brewster LM, van Montfrans GA, Kleijnen J.
Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.

BACKGROUND: Hypertension occurs more frequently and is generally more severe in black persons than in white persons, leading to excess morbidity and mortality. PURPOSE: To systematically review the efficacy of different antihypertensive drugs in reducing blood pressure, morbidity, and mortality in hypertensive black adults. DATA SOURCES: The following databases were searched from their inception through November 2003: MEDLINE, EMBASE, LILACS (Literatura Latino-Americana y del Caribe en Ciencias de la Salud), African Index Medicus, and the Cochrane Library. PubMed was also searched from September 2003 through March 2004. Searches were conducted without language restriction. STUDY SELECTION: Randomized, controlled trials of drugs versus placebo (blood pressure outcomes) or drugs versus placebo or other drugs (morbidity and mortality outcomes). DATA EXTRACTION: 2 reviewers independently extracted data. DATA SYNTHESIS: The efficacy of beta-blockers in reducing systolic blood pressure and the efficacy of angiotensin-converting enzyme inhibitors in achieving diastolic blood pressure goals did not significantly differ from that of placebo (weighted mean difference for beta-blockers, -3.53 mm Hg [95% CI, -7.51 to 0.45 mm Hg]; relative risk for angiotensin-converting enzyme inhibitors, 1.35 [CI, 0.81 to 2.26]). In the pooled analyses, other reviewed drugs (calcium-channel blockers, diuretics, central sympatholytics, alpha-blockers, and angiotensin II receptor blockers) were more effective than placebo in reducing blood pressure, but only calcium-channel blockers remained effective in all prespecified subgroups, including patients with a baseline diastolic blood pressure of 110 mm Hg or greater. Main morbidity and mortality outcomes did not differ significantly between treatment groups when drugs were combined to reach blood pressure goals. However, trial results indicated a greater occurrence of diabetes with diuretics and a higher risk for cardiovascular events with drug regimens that included angiotensin-converting enzyme inhibitors. LIMITATIONS: This meta-analysis evaluated the blood pressure lowering-efficacy of monotherapy only. CONCLUSIONS: Drugs differ in their efficacy for reducing blood pressure in black patients, but there is no solid evidence that efficacy for reducing morbidity and mortality outcomes differs once patients achieve the blood pressure goal.

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Practitioner. 2004 Oct;248(1663):720, 722, 724 passim.
Hypertension in pregnancy.
Meher S, Neilson J.
University of Liverpool.

Formal assessment of the risk of pre-eclampsia should be made early in pregnancy and antenatal care planned accordingly. Recommendations will emerge by the end of this year in a consensus statement (PRECOG guidelines) prepared by clinicians and the lay organisation Action on Pre-eclampsia (APEC) www.apec.org.uk. Some hospitals complement clinical risk assessment with Doppler screening of uterine artery waveforms in mid-pregnancy. Severe pre-eclampsia often takes an explosive course, evolving over a period of hours. Recognition may, therefore, not be amenable to intermittent blood pressure recording and urine testing, but requires women reporting relevant symptoms and GPs being sensitive to the possible significance of complaints such as vomiting and epigastric pain. Severe hypertension demands urgent antihypertensive treatment in hospital. Magnesium sulphate now has an accepted role in the prevention of eclampsia. Possible prevention of pre-eclampsia by antioxidant therapy is the subject of a clinical trial. Low-dose aspirin has a modest but beneficial effect in high-risk women. Delivery remains the definitive treatment for pre-eclampsia, but there may be initial deterioration after birth, especially in the HELLP syndrome.

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Kardiologiia. 2004;44(3):47-51.
[Efficacy and tolerability of felodipine based antihypertensive therapy in hospitalized patients with hypertension.]
[Article in Russian]
Kotovskaia IuV, Bagmanova NKh, Milto AS, Riabova AV, Plavunov NF, Kobalova ZhD.
Russian University of Peoples Friendship; ul. Vavilova, 61, 117292 Moscow, Russia.

AIM: To compare efficacy and tolerability of felodipine based antihypertensive therapy with those of standard hospital treatment of hypertension. MATERIAL: Inhospital patients were randomized 1:2 to standard antihypertensive therapy or to therapy which included felodipine (n=50 and 100, 36 and 35% men, mean age 66.0+/-8.4 and 64.3+/-8.1 years, initial blood pressure 162.4+/-9.3/99.3+/-6.4 and 163.2+/-10.3/98.2+/-6.5 mm Hg, respectively). Felodipine was used: (1) as first drug with subsequent addition of other drugs as required; (2) after cessation of previously ineffective therapy; (3) in cases of intolerance to previous therapy, (4) as supplementation to previously insufficiently effective therapy. Results. At discharge in felodipine group 6, 25, 29 and 40% of patients received mono- (felodipine 10 mg/day), 2, 3 and 4 component therapy, respectively. In standard treatment group all patients received combination therapy with 3 (48%) or 4 (52%) drugs. Felodipine group compared with group of standard therapy was characterized by less frequent correction of antihypertensive therapy (0.8+/-0.6 and 2.2+/-0.9, p<0.05), smaller number of drugs used (3.03+/-0.95 and 3.52+/-0.5, p<0.01), more frequently achievement of target blood pressure level (88 and 64%, p=0.0075), less pronounced difference between morning and evening self-measured blood pressure. CONCLUSION: The use of felodipine in hospitalized patients with hypertension allowed achieving target blood pressure with fewer drugs. Felodipine was safe and well tolerated.

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Am J Hypertens. 2004 Oct;17(10):928-35.
Antihypertensive and renoprotective efficacy and safety of losartan. A long-term study in children with renal disorders.
Ellis D, Moritz ML, Vats A, Janosky JE.
Division of Pediatric Nephrology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA. ellisd@chplink.chp.edu

BACKGROUND: Hypertension is a major risk factor for progressive renal failure. We assessed the long term efficacy and safety of losartan in lowering blood pressure (BP) and in preserving renal function in hypertensive children with chronic renal disorders. METHODS: Losartan was used in 45 consecutive hypertensive children with chronic renal parenchymal disorders and mean glomerular filtration rate (GFR) 99.4 mL/min/1.73 m(2). Of the children, 21 had hypertension alone (H) and 24 had both hypertension and proteinuria (H+P). Assessment was done at baseline and at preselected time points: visit I, <0.25 years; visit II, >/=0.25 and <0.5 year;visit III, 0.5 to 1.0 year; and visit IV >1 year. Both BP control and GFR were the principal outcome measures, and proteinuria was a secondary outcome measure. RESULTS: The mean age was 12.85 years and follow-up was 2.42 years (visit IV). Compared with baseline the systolic, diastolic, and mean arterial BP (MABP) fell by 9 to 12 mm Hg (all P < .01) in visit I. Diastolic BP and MABP remained significantly lower in all visits (P < .05 to .001), whereas systolic BP was not statistically lower in visit II. In visit IV the proportion of normotensive children increased significantly compared with baseline (P < .03 for systolic BP, P < .0004 for diastolic BP). In the H+P subgroup, optimal reduction in proteinuria ranging from 66% to 71% occurred in visits II to IV (all P < .01). Mean GFR declined at a rate of 9.3 mL/min/1.73 m(2) /year before starting losartan, and 1.4 mL/min/1.73 m(2) /year subsequently (P = NS). On long term follow-up, GFR fell by 15.9 mL/min/1.73 m(2) in the H subgroup and by 5.5 mL/min/1.73 m(2) in the H+P subgroup (P = NS). There was no correlation between BP measures and GFR or between the magnitude of BP lowering and proteinuria. Adverse effects (one serious) led to discontinuation of losartan in five children (11%). CONCLUSIONS: Losartan therapy was associated with prolonged and sustained antihypertensive and renoprotective benefits in children with a variety of chronic renal parenchymal disorders. Such benefit may be more pronounced in children with combined hypertension and proteinuria. The agent was well tolerated in the majority of the children.

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Cleve Clin J Med. 2004 Sep;71(9):745-53.
The DASH diet for high blood pressure: from clinical trial to dinner table.
Karanja N, Erlinger TP, Pao-Hwa L, Miller ER 3rd, Bray GA.
Kaiser Permanente Center for Health Research, Portland, OR 97227, USA. njeri.karanja@kpchr.org

Three recent studies show that a diet rich in fruits, vegetables, whole grains, and lowfat dairy products and low in fat, refined carbohydrates, and sodium can lower blood pressure either alone or in combination with other lifestyle changes. These studies have greatly expanded our knowledge of nonpharmacologic interventions to prevent and manage hypertension. They also underscore the need for diet and lifestyle counseling in the primary care setting.

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Hypertens Res. 2004 Aug;27(8):545-50.
Practical Efficacy of Telmisartan for Decreasing Morning Home Blood Pressure and Pulse Wave Velocity in Patients with Mild-to-Moderate Hypertension.
Uchida H, Nakamura Y, Kaihara M, Sugimoto T, Norii H, Sasaki M, Sato H, Makino H.
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry.

The current guideline-recommended blood pressure values are difficult to maintain in general practice, partly due to the lack of ideal anti-hypertensive agents. Since morning hypertension has a high correlation with cardiovascular events, expectations that telmisartan, a long-acting angiotensin-II type-1 receptor blocker (ARB), can improve cardiovascular mortality are high. In this study, the efficiency of telmisartan in reducing morning hypertension and pulse wave velocity (PWV) as a practical surrogate endpoint was investigated. Seventeen unsupervised and 7 untreated hypertensive patients were prescribed telmisartan 40 mg/day for 3 months. Medication already prescribed upon enrollment in this study was continued, with the exception of ARBs (all of which turned out to be losartan 50 mg/day), which were discontinued and replaced with telmisartan. Morning home blood pressure (MHBP), office blood pressure (OBP), and brachial-ankle PWV (baPWV) were investigated in a prospective fashion. A stratified analysis was performed regarding previous use (group L) or non-use (group N) of losartan. Over a 3-month period, telmisartan was found to significantly reduce both OBP (from 153+/-13/85+/-9 to 141+/-17/80+/-7 mmHg (p <0.01)) and MHBP (from 153+/-23/93+/-11 to 137+/-22/82+/-10 mmHg (p <0.001)). Surprisingly, 7 patients (70%) from group L achieved an OBP of less than 140/90 mmHg by simply changing their medication to telmisartan. Furthermore, baPWV fell significantly from 1,892+/-334 cm/s to 1,672+/-324 cm/s (p <0.01), which was greater than the change in baPWV estimated by OBP reduction. Here it must be mentioned that there were no significant differences between group L and group N in the courses of blood pressures and baPWV. In conclusion, telmisartan 40 mg/day was found to be effective for reducing MHBP and arterial wall stiffness in patients with mild-to-moderate hypertension, and thus may also be effective for improving cerebrocardiovascular mortality.

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Curr Hypertens Rep. 2004 Aug;6(4):300-6.
Combined Antihypertensive and Lipid-lowering Treatment.
Cesari M, Pessina AC.
Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padova, via Giustiniani, 2, 35126 Padova, Italy. mcesari@hotmail.com

Hypertension and hypercholesterolemia are frequently associated, and their treatment is proven to reduce cardiovascular risk. Current guidelines on cardiovascular prevention strongly recommend treating both disorders. Unfortunately, the low treatment and control rates, combined with the high prevalence of both conditions, still contribute to the high burden of cardiovascular disease in Western countries. In the past 5 years, many studies evaluating the benefit of combined antihypertensive and lipid-lowering treatment on endothelial dysfunction, coronary atherosclerosis, hypertension control, and on primary and secondary prevention of cardiovascular events have been published. In this article, we discuss and critically evaluate the available evidence on the potential benefits of combined antihypertensive and lipid-lowering treatment.

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Curr Hypertens Rep. 2004 Aug;6(4):272-9.
Hypertension management in patients with diabetic nephropathy.
McCall AL.
University of Virginia Health System, Center for Diabetes & Hormone Excellence, Endocrinology Division, 450 Ray C. Hunt Drive, PO Box 801407, Charlottesville, VA 22908, USA. alm3j@virginia.edu

Treatment of hypertension, to reverse and delay proteinuria progression and kidney failure, is the primary focus of medical management in patients with diabetic nephropathy. The initial choice for hypertension treatment in those with early nephropathy involves agents that block the renin-angiotensin system. However, it is not clear what the best choices for further drug therapy management are, because there are few data concerning the impact that antihypertensive drug combinations have on hard clinical outcomes, such as preventing the need for dialysis, and death. Patients usually require several drugs for controlling hypertension, which becomes harder to control as nephropathy progresses. In this review, it is suggested that quantitatively tracking proteinuria to guide therapy and a broad focus on the cardiovascular and renal end points are important for best outcomes in patients. Strategies may vary based on stage of disease, comorbidities, and age. Therapies not directed specifically at hypertension may also significantly aid hypertension management in prevention of progressive nephropathy, comorbidities, and mortality.

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Curr Hypertens Rep. 2004 Aug;6(4):267-72.
Combination Therapy As First-line Treatment for Hypertension.
Gavras I, Rosenthal T.
Hypertension and Atherosclerosis Section, Boston University School of Medicine, 715 Albany Street, W508, Boston, MA 02118, USA. igavras@bu.edu

With the cut-off point between "normal" and "high" blood pressure (BP) being pushed increasingly downward, especially for patients with multiple cardiovascular risk factors, most hypertensives need more than one antihypertensive agent to reach their target BP. In this article, we examine the rationale for combining drugs from different classes that have synergistic or additive effects and properties that might offset one another's adverse hemodynamic and/or metabolic reactions. We suggest circumstances in which the initiation of therapy with a fixed two-drug combination might be preferable to the usual practice of starting with monotherapy followed by upward titration and addition of other agents, and we briefly review the existing fixed drug combinations. We end with the intriguing and provocative notion of the future "polypill," a fixed combination of agents addressing various components of the metabolic syndrome as well as other coexisting common risk factors in both high-risk patients with conditions requiring polypharmacy and in healthy, asymptomatic individuals.

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Curr Hypertens Rep. 2004 Aug;6(4):279-87.
Mineralocorticoid receptor antagonists and hypertension: is there a rationale?
Gumieniak O, Williams GH.
Endocrine-Hypertension Division, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, RFB-2, Boston, MA 02115, USA. gwilliams@partners.org

Accumulating evidence indicates that aldosterone is involved in cardiovascular disease by inducing inflammation in the presence of moderate amounts of salt in the diet. Spironolactone and eplerenone are the mineralocorticoid receptor (MR) antagonists currently available for the treatment of hypertension. They have similar safety and antihypertensive efficacy. The advantage of eplerenone is the lower incidence of anti-androgenic and progestational side effects. The rationale for using MR blockade in the treatment of hypertension is threefold: the evidence of antihypertensive efficacy, the phenomenon of "aldosterone escape" occurring with angiotensin-converting enzyme inhibitor and angiotensin-receptor blockade therapy, and the compelling evidence that MR antagonism reduces target-organ damage in hypertensive patients and improves survival in patients with cardiovascular disease. Thus, blockade of the MR may be very useful in many patients with hypertension, particularly those at risk for or having evidence of target-organ damage.

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Am J Geriatr Cardiol. 2004 Jul-Aug;13(4):197-207.
Angiotensin II Receptor Blockers in Older Patients.
Weber MA.
State University of New York Downstate College of Medicine, Brooklyn, NY.

Older patients with hypertension are often inadequately treated due to misconceptions regarding reasonable goal blood pressures or concerns about treatment side effects. Adequately treating hypertension can yield impressive benefits in terms of improved morbidity and enhanced quality of life in persons of any age. Antagonists of the renin-angiotensin-aldosterone system are especially effective in older persons, many of whom have concomitant conditions such as diabetes mellitus, renal dysfunction, and other cardiovascular risk factors. Treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers has been shown to improve many of the complications of hypertension, including left ventricular hypertrophy and renal disease. Results of recent key studies such as Losartan Intervention For Endpoint Reduction in Hypertension (LIFE), Valsartan in Heart Failure Trial (Val-HeFT), Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM), and Valsartan in Acute Myocardial Infarction (VALIANT) add to the evidence that angiotensin II receptor blockers are well suited for the treatment of hypertension in older patients. These trials also indicate that they are appropriate therapy for heart failure patients and for patients who have experienced acute myocardial infarction, particularly those who are unable to tolerate an angiotensin-converting enzyme inhibitor.

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Drugs Aging. 2004;21(9):565-81.
Use of calcium channel antagonists for the treatment of hypertension in the elderly.
Steffen HM.
Clinic IV for Internal Medicine, University of Cologne, Cologne, Germany.

Systolic blood pressure and pulse pressure increase continuously throughout adult life and the prevalence of arterial hypertension rises accordingly, reaching 53-78% among those aged 65-74 years. Estimates of the prevalence of isolated systolic hypertension in the elderly range from 34-65%, with more women than men affected. It has been shown that within all age groups a difference in usual systolic blood pressure of 20mm Hg or a difference in usual diastolic blood pressure of 10mm Hg is associated with an approximately 2-fold difference in the risk of dying from stroke or ischaemic heart disease. Intervention trials using predominantly diuretics and/or beta-adrenoceptor antagonists have proven the efficacy and tolerability of antihypertensive treatment in elderly patients.For many years there have been ongoing discussions about the safety of calcium channel antagonists, especially in patients with diabetes mellitus. However, according to a recently published large prospective, randomised, double-blind, controlled clinical trial with more than 33 000 patients enrolled, no indications for increased total mortality, cancer rate or gastrointestinal bleeding for participants on amlodipine, a long-acting dihydropyridine calcium channel antagonist, were found. With calcium channel antagonists, protective effects against cardiovascular disease have been proven in large trials with elderly patients, particularly against stroke. There is good evidence to suggest that calcium channel antagonists may be superior to other antihypertensive agents in diabetic patients with isolated systolic hypertension. These agents are well tolerated and probably delay the progression of dementia. The lack of adverse metabolic effects that, in the case of a diuretic-based regimen, may have important long-term implications concerning cardiovascular risk, make calcium channel antagonists an attractive choice when antihypertensive treatment decisions need to be made in a predominantly overweight or obese elderly population.

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Cochrane Database Syst Rev. 2004;3:CD003186.
Antiplatelet agents and anticoagulants for hypertension.
Lip G, Felmeden D.
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Dudley Road, Birmingham, UK, B18 7QH.

BACKGROUND: Although elevated systemic blood pressure results in high intravascular pressure, the main complications, coronary heart disease (CHD), ischaemic strokes and peripheral vascular disease (PVD), are related to thrombosis rather than haemorrhage. Some complications related to elevated blood pressure, heart failure or atrial fibrillation, are themselves associated with stroke and thromboembolism. It therefore seemed plausible that use of antithrombotic therapy may be particularly useful in preventing thrombosis-related complications of elevated blood pressure. OBJECTIVES: To conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with blood pressure, including those with elevations in both systolic and diastolic blood pressure, isolated elevations of either systolic or diastolic blood pressure, to address the following hypotheses: (i) antiplatelet agents reduce total deaths and/or major thrombotic events when compared to placebo or other active treatment; and (ii) oral anticoagulants reduce total deaths and/or major thromboembolic events when compared to placebo or other active treatment. SEARCH STRATEGY: Reference lists of papers resulting from this search, electronic database searching (MEDLINE, EMBASE, DARE), and abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. Relevant authors of these studies were contacted to obtain further data. SELECTION CRITERIA: Randomised controlled trials (RCTs) in patients with elevated blood pressure were included if they were of at least 3 months in duration and compared antithrombotic therapy with control or other active treatment. DATA COLLECTION AND ANALYSIS: Data were independently collected and verified by two reviewers. Data from different trials were pooled where appropriate. MAIN RESULTS: The ATC meta-analysis of antiplatelet therapy for secondary prevention in patients with elevated blood pressure reported an absolute reduction in vascular events of 4.1% as compared to placebo. Data on the patients with elevated blood pressure from the 29 individual trials included in this meta-analysis was requested but could not be obtained. Three additional trials met the inclusion criteria and are reported on here. Acetylsalicylic acid (ASA) did not reduce stroke or 'all cardiovascular events' compared to placebo in primary prevention patients with elevated blood pressure and no prior cardiovascular disease. Based on one large trial (HOT trial), ASA taken for 5 years reduced myocardial infarction (ARR, 0.5%, NNT 200 for 5 years), increased major haemorrhage (ARI, 0.7%, NNT 154), and did not reduce all cause mortality or cardiovascular mortality. There was no significant difference between ASA and clopidogrel for the composite endpoint of stroke, myocardial infarction or vascular death in one trial (CAPRIE 1996). In two small trials warfarin alone or in combination with ASA did not reduce stroke or coronary events. REVIEWERS' CONCLUSIONS: For primary prevention in patients with elevated blood pressure, anti-platelet therapy with ASA cannot be recommended since the magnitude of benefit, a reduction in myocardial infarction, is negated by a harm of similar magnitude, an increase in major haemorrhage. For secondary prevention in patients with elevated blood pressure (ATC meta-analysis: APTC 1994) antiplatelet therapy is recommended because the magnitude of the absolute benefit is many times greater. Warfarin therapy alone or in combination with aspirin in patients with elevated blood pressure cannot be recommended because of lack of demonstrated benefit. Glycoprotein IIb/IIIa inhibitors as well as ticlopidine and clopidogrel have not been sufficiently evaluated in patients with elevated blood pressure. Further trials of antithrombotic therapy with complete documentation of all benefits and harms are required in patients with elevated blood pressure.

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Semin Dial. 2004 Jul-Aug;17(4):295-8.
Hypertension control with daily dialysis.
Saad E, Charra B, Raj DS.
Division of Nephrology, University of New Mexico, Albuquerque, New Mexico.

ABSTRACT Hypertension is present in 60-90% of patients on maintenance hemodialysis (HD) and it is an important cause of cardiovascular (CV) mortality and morbidity. Frequent and prolonged HD has been uniformly shown to control hypertension in end-stage renal disease (ESRD) patients more effectively than conventional HD. The etiology of hypertension is predominantly volume dependent, but in a subset of patients increased renin, sympathetic overactivity, and endothelial dysfunction may play a role. Intradialytic hypotension precludes attainment of dry weight and hence optimal control of hypertension in conventional HD is challenging. Frequent and prolonged dialysis with gentle and persistent ultrafiltration allows time for refilling of the intravascular compartment and permits normalization of extracellular volume. It is also possible that intensive dialysis enables removal of pressor molecules and improves endothelial function. Improved blood pressure control translates into regression of left ventricular hypertrophy in patients on daily HD. Thus prolonged and frequent dialysis permits better control of hypertension via volume and volume-independent mechanisms and also improves cardiac geometry.

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Semin Dial. 2004 Jul-Aug;17(4):288-94.
Drug therapy for hypertension in hemodialysis patients.
Horl MP, Horl WH.
University Hospital Benjamin Franklin, Free University Berlin, Germany.

ABSTRACT The majority of end-stage renal disease (ESRD) patients are hypertensive. Drug therapy for hypertension in hemodialysis (HD) patients includes all classes of antihypertensive drugs, with the sole exception of diuretics. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers may decrease morbidity and mortality by reducing the mean arterial pressure (MAP), aortic pulse wave velocity, and aortic systolic pressure augmentation, as well as left ventricular hypertrophy (LVH) and probably reduction of C-reactive protein (CRP) and oxidant stress. Potential risk factors include hyperkalemia, anaphylactoid reaction with AN69 membranes (particularly ACE inhibitors), and aggravation of renal anemia. beta-blockers decrease not only mortality, blood pressure (BP), and ventricular arrhythmias, but also improve left ventricular function in ESRD patients. Nonselective beta-blockers can cause an increase in serum potassium (particularly during fasting or exercise). Lisinopril and atenolol have a predominant renal excretion and therefore a prolonged half life in ESRD patients. Thus thrice-weekly supervised administration of these drugs after HD can enhance BP control. The use of calcium channel blockers is also associated with lower total and cardiovascular-specific mortality in HD patients. Minoxidil is a very potent vasodilator that is generally reserved for dialysis patients with severe hypertension. Hypertensive dialysis patients who are noncompliant with their medications may benefit from transdermal clonidine therapy once a week. The majority of dialysis patients need a combination of several antihypertensive drugs for adequate BP control.

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J Clin Hypertens (Greenwich). 2004 Jul;6(7):383-90.
Comprehensive lifestyle modification and blood pressure control: a review of the PREMIER trial.
McGuire HL, Svetkey LP, Harsha DW, Elmer PJ, Appel LJ, Ard JD.
Division of Nephrology, Duke University Medical Center, Durham, NC. mcgui020@mc.duke.edu

The PREMIER trial assessed the aggregate effect on blood pressure (BP) of nationally recommended lifestyle modifications in free-living adults with high-normal (stage 1) hypertension. Participants (N=810) were randomized to the advice-only group; the established group (consisting of weight loss, increased physical activity, and reduced sodium and alcohol intake); or the established plus Dietary Approaches to Stop Hypertension (DASH) diet group (consisting of the established interventions in addition to the DASH dietary pattern). The primary outcome was change in systolic BP at 6 months. Net of advice only, mean systolic BP declined by 3.7 mm Hg for members of the established group (p<0.001) and 4.3 mm Hg for the established plus DASH group (p<0.001). The prevalence of hypertension decreased from a baseline of 38% to 17% in the established group (p=0.01) and to 12% in the established plus DASH group (p<0.001) compared with a decrease to 26% in the advice-only group. The PREMIER trial demonstrated that persons with above-optimal BP and stage 1 hypertension can make multiple lifestyle changes leading to better control of BP.

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J Clin Hypertens (Greenwich). 2004 Jul;6(7):373-81.
Effect of the dietary approaches to stop hypertension diet and reduced sodium intake on blood pressure control.
Svetkey LP, Simons-Morton DG, Proschan MA, Sacks FM, Conlin PR, Harsha D, Moore TJ.
the Duke Hypertension Center and The Sarah W. Steadman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC. svetk001@mc.duke.edu

The authors hypothesized that the Dietary Approaches to Stop Hypertension (DASH) diet and reduced sodium intake would control stage 1 hypertension and reduce high-normal blood pressure (BP) to optimal levels. Adults with systolic BP 120-159 mm Hg and diastolic BP 80-95 mm Hg were randomly assigned to receive the DASH diet or a typical American (control) diet, consuming three different sodium intakes (higher=142 mmol/d, intermediate=107 mmol/d, and lower=65 mmol/d) for 30 days each. BP control was defined as systolic BP <140 mm Hg and diastolic BP <90 mm Hg. Among subjects with hypertension at baseline, at higher sodium intake the DASH diet increased BP control two-fold over control (63% vs. 32%; 95% confidence interval, 1.4-2.9). Reducing sodium intake in the control diet group increased BP control 2.3-fold (74% vs. 32%; 95% confidence interval, 1.7-3.2). The maximum BP control rate (84%) was achieved with the DASH/lower sodium diet. BP became normal or optimal in 71% of persons consuming the control/lower sodium diet and 77% of persons consuming the DASH/lower sodium diet. Both the DASH diet and reduced sodium intake improved BP control.

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Z Kardiol. 2004 Jul;93(7):503-13.
[Obesity and cardiovascular diseases-theoretical background and therapeutic consequences]
[Article in German]
Voller H, Schmailzl KJ, Bjarnason-Wehrens B.
Klinik am See, Fachklinik fur kardiovaskulare Erkrankungen, Kardiologie, Seebad 84, 15562, Rudersdorf/Berlin, Germany, heinz.voeller@klinikamsee.com

In the normal population, the prevalence of obesity is almost 20%. It is a condition influenced by genetic factors, so that individual behavior cannot be regarded as its sole cause. The amount of food is essentially determined by the hormone leptin, the feedback regulation of which can be disturbed by a modification of the molecule or a mutation of the receptor. A further important determinant is energy consumption, which is subject to large individual variations, which partly result from thermogenesis. With regard to the fat distribution, it is concentrated on the trunk in the android form as compared to the hips in the gynecoid form. The android form is subject to a higher incidence of cardiovascular morbidity and mortality. The indirect determination of body fat by measuring the body mass index (weight [kg]/body weight [m(2)]) is hence less reliable than measuring the waist (women > 80 cm, men > 94 cm).The effects of generalized obesity on cardiovascular function are chiefly an increase of blood volume and an eccentric left ventricular hypertrophy. This first of all results in diastolic dysfunction, which can give rise to a disturbance of systolic function in left ventricular dilatation. Concentric hypertrophy develops in the presence of arterial hypertension. This is twice as frequent in obese patients than in the normal population, which is due to increased activity of the sympathetic nervous system and stimulation of the renin-angiotensin system. A disturbance of lipid metabolism is observed four to six times more frequently. The qualitative change in LDL fraction with a raised concentration of low density LDL particles appears to be of crucial importance. With increasing fat mass, the sensitivity to insulin is lowered, so that in obesity the risk of developing diabetes mellitus type 2 is tripled.Since there has been a dramatic increase in the numbers of overweight children and adolescents (from 10.5% to 15.5% within the past five years), prevention programs should be started in good time. A reduction in calorie intake and an altered dietary composition (55% complex carbohydrates, 30% fat and 15% to 20% protein) on the one hand, and increased physical activity on the other hand continue to be the central components. The latter is especially effective when it regularly gives rise to an increased turnover of fatty acids as a result of an increased energy metabolism at moderate intensity. This leads to adaptation, i. e. an increase in the activity of lipoprotein lipase.If prevention programs and/or changes in lifestyle do not give rise to the desired weight reduction, medication is indicated in some adults. Sibutramine (Reductil((R))) and orlistate (Xenical((R))) lead to an additional weight loss of up to 10%. However, consistent treatment of any cardiovascular risk factors present is more important. Treatment of arterial hypertension is of greatest prognostic significance, especially in concomitant diabetes mellitus. In individual cases and after thorough discussion of indication surgical options should be considered.

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Pneumologie. 2004 Jul;58(7):505-9.
[Cardiovascular diseases and sleep-disordered breathing]
[Article in German]
Hein H.
Krankenhaus Grosshansdorf, Zentrum fur Pneumologie und Thoraxchirurgie (Arztlicher Direktor: Prof. Dr. med. H. Magnussen), Grosshansdorf. Holger.Hein@t-online.de

About 1.9 % of the population suffer from an obstructive sleep apnea syndrome (OSAS). At the age of between 30 and 60 years it occurs in 3 %. Patients with OSAS develop more frequently such disorders as arteriosclerosis, cardiac arrhythmias and arterial hypertension. A host of pathophysiological changes can be diagnosed. The elevated sympathic activity, recurrent hypoxemias, stress, disturbances in the microvascular milieu, endothelial dysfunction, elevated oxidative capacity as well as a reduced vascular reagibility are deemed to be factors connected to arteriosclerosis. Different biochemical markers, which are seen as risk factors or as markers of cardiovascular diseases, are altered in patients with OSAS (high-sensitive CRP, Interleukin(IL)-6, IL-8, IL-10, TNF-alpha, VGEF, ICAM-1, VCAM-1 and L-Selectin). Patients with OSAS exhibit signs of an impaired insulin sensitivity. Disturbances in microcirculation are also evident. Patients with OSAS have, compared to patients without sleep apnea, elevated blood pressure measurements, even given other common risk factors. The incidence of coronary heart diseases is increased in patients with OSAS. Morbidity and mortality, especially of arteriosclerotic diseases are elevated. Many of the aforementioned disturbances can be improved by a CPAP-therapy.

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Am Fam Physician. 2004 Jul 1;70(1):133-40.
Omega-3 fatty acids.
Covington MB.
University of Maryland School of Medicine, Center for Integrative Medicine, Baltimore, Maryland 21207, USA. mcovington@compmed.umm.edu

Omega-3 fatty acids have been shown to significantly reduce the risk for sudden death caused by cardiac arrhythmias and all-cause mortality in patients with known coronary heart disease. Fatty fish, such as salmon and tuna, and fish oil are rich sources of the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. Flaxseed, canola oil, and walnuts also are good dietary sources of omega-3 fatty acids. In addition to being antiarrhythmic, the omega-3 fatty acids are antithrombotic and anti-inflammatory. In contrast, omega-6 fatty acids, which are present in most seeds, vegetable oils, and meat, are prothrombotic and proinflammatory. Omega-3 fatty acids also are used to treat hyperlipidemia, hypertension, and rheumatoid arthritis. There are no significant drug interactions with omega-3 fatty acids. The American Heart Association recommends consumption of two servings of fish per week for persons with no history of coronary heart disease and at least one serving of fish daily for those with known coronary heart disease. Approximately 1 g per day of eicosapentaenoic acid plus docosahexaenoic acid is recommended for cardioprotection. Higher dosages of omega-3 fatty acids are required to reduce elevated triglyceride levels (2 to 4 g per day) and to reduce morning stiffness and the number of tender joints in patients with rheumatoid arthritis (at least 3 g per day). Modest decreases in blood pressure occur with significantly higher dosages of omega-3 fatty acids.

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Am J Hypertens. 2004 Jul;17(7):590-6.
Amlodipine/benazepril combination therapy for hypertensive patients nonresponsive to benazepril monotherapy.
Chrysant SG, Bakris GL.
Oklahoma Cardiovascular and Hypertension Center and the University of Oklahoma School of Medicine, Oklahoma City, Oklahoma 73132, USA. schrysant@yahoo.com

BACKGROUND: Most patients with hypertension require two or more antihypertensive medications to achieve blood pressure (BP) goals. This double-blind study compared the efficacy and safety of high-dose combinations of amlodipine besylate (5 mg and 10 mg) and benazepril hydrochloride (40 mg) to benazepril hydrochloride (40 mg) alone in hypertensive patients not adequately controlled with benazepril hydrochloride (40 mg) monotherapy. METHODS: After a 2-week washout period and a 4-week lead-in period with benazepril 40 mg daily, patients with a mean sitting diastolic BP > or =95 mm Hg (i.e., nonresponders to benazepril 40 mg) were randomly assigned to active treatment with either a combination of amlodipine 5 mg and benazepril 40 mg for 4 weeks followed by a forced titration to amlodipine 10 mg and benazepril 40 mg for an additional 4 weeks, or to benazepril 40 mg alone for 8 weeks. RESULTS: The mean reduction in sitting BP from baseline (on benazepril) to endpoint (after 8 weeks of treatment) was 17/14 mm Hg with amlodipine/benazepril and 5/7 mm Hg with benazepril (P <.0001). The percentage of patients who met the diastolic BP response criteria (<90 mm Hg at endpoint or > or =10 mm Hg decrease from baseline) was 80% in the amlodipine/benazepril group and 45% in the benazepril group (P <.0001). The incidence of adverse events was infrequent and comparable for both treatment groups. CONCLUSION: High-dose amlodipine/benazepril combination therapy (5 mg/40 mg and 10 mg/40 mg) is an effective, safe, and well-tolerated treatment option for hypertensive patients who do not respond adequately to benazepril alone.

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Z Geburtshilfe Neonatol. 2004 Jun;208(3):79-90.
[Inhaled nitric oxide in neonatology: state of the art]
[Article in German]
Wirbelauer J, Speer CP.
Universitats-Kinderklinik, Wurzburg. wirbelauer_j@klinik.uni-wuerzburg.de

In the late 1970 s it was demonstrated that nitric oxide (NO) was involved in the regulation of vasomotor tone. In Europe inhaled NO (iNO) was approved as a therapy option for the treatment of pulmonary hypertension in term and slightly preterm (> 34 weeks of gestation) neonates. Therapy by iNO mainly reduces the necessity for treatment by extracorporeal membrane oxygenation. However, the mortality of the underlying disease is not affected. According to our current knowledge iNO therapy for term and slightly preterm (> 34 weeks of gestation) neonates does not represent an additional risk factor for the neurological development. Today, iNO therapy constitutes the gold standard for pulmonary hypertension in new-born babies. However, the 30 % non-responders warrant a continued search for alternative treatment concepts. Prophylactic therapy according to a risk profile has not yet proved to be meaningful. An indication for the treatment of preterm neonates of less than 34 weeks of gestation has not yet been confirmed.

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Clin Ther. 2004 Jun;26(6):855-65.
Comparison of valsartan 160 mg with lisinopril 20 mg, given as monotherapy or in combination with a diuretic, for the treatment of hypertension: the Blood Pressure Reduction and Tolerability of Valsartan in Comparison with Lisinopril (PREVAIL) study.
Malacco E, Santonastaso M, Vari NA, Gargiulo A, Spagnuolo V, Bertocchi F, Palatini P; Blood Pressure Reduction and Tolerability of Valsartan in Comparison with Lisinopril Study.
Division of Internal Medicine, L. Sacco Hospital, University of Milan, Milan, Italy.

BACKGROUND: The goal of antihypertensive therapy is to provide good blood pressure (BP) control without eliciting adverse effects. OBJECTIVE: This study compared the risk-benefit profile of the angiotensin II receptor blocker valsartan with that of the angiotensin-converting enzyme inhibitor lisinopril in patients with mild to severe hypertension. The primary objective was to show that the equipotent BP-lowering effect of the valsartan-based treatment is accompanied by a better tolerability profile. METHODS: This 16-week, randomized, double-blind, parallel-group study was conducted at 88 outpatient centers across Italy. After a 2-week placebo run-in period, patients aged > or = 18 years with mild to severe hypertension (systolic BP [SBP], 160-220 mm Hg; diastolic BP [DBP], 95-110 mm Hg) were eligible. Patients were randomized to receive once-daily, oral, self-administered treatment with valsartan 160-mg capsules or lisinopril 20-mg capsules under double-blind conditions for 4 weeks. Responders continued monotherapy, whereas nonresponders had hydrochlorothiazide 12.5 mg added for the final 12 weeks of the study. The 2 primary variables used to assess the equivalence of therapeutic efficacy of the 2 regimens were sitting SBP and sitting DBP, which were measured at weeks 0 (baseline), 4, 8, and 16. The rate of drug-related adverse events (AEs) was used to assess whether 1 treatment had a better tolerability profile than the other. Tolerability was assessed by collecting information about AEs by means of questioning the patient or physical examination at each visit. RESULTS: A total of 1213 patients were enrolled (635 men, 578 women; mean [SD] age, 54.5 [10.1] years [range, 28-78 years]). The study was completed by 1100 patients (553 receiving valsartan and 547 receiving lisinopril). Fifty-one patients (8.4%) treated with valsartan and 62 (1.2%) treated with lisinopril withdrew, mainly because of AEs (9 [1.5%] and 23 patients [3.8%], respectively). The valsartan- and lisinopril-based treatments were similarly effective in reducing sitting BP, with mean SBP/DBP reductions of 31.2/15.9 mm Hg and 31.4/15.9 mm Hg, respectively. At the end of the study, BP was controlled in 82.7% of the patients receiving valsartan and 81.6% of those receiving lisinopril. AEs were experienced by 5.1% of the patients treated with valsartan and 10.7% of those treated with lisinopril (P=.0001), with dry cough observed in 1.0% and 7.2% of patients, respectively (P<0.001). CONCLUSIONS: Valsartan and lisinopril were both highly effective in controlling BP in these patients with mild to severe hypertension, but valsartan was associated with a significantly reduced risk for AEs, especially cough.

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Herz. 2004 Jun;29(4):401-5.
Hypertension and exercise. Exercise regimes for the hypertensive patient.
Thiele H, Pohlink C, Schuler G.
Klinik fur Innere Medizin/Kardiologie, Universitat Leipzig-Herzzentrum, Leipzig, thielh@medizin.uni-leipzig.de

Physical exercise is of paramount therapeutic importance in nonpharmacological interventions of arterial hypertension. The extent and the effects of exercise on blood pressure lowering are analyzed according to the actual literature. Suitable and nonsuitable activities are considered. Dynamic isotonic endurance training is more effective than static isometric exercise. A rather low or moderate extent of endurance training lowers the systolic and diastolic blood pressure by approximately 5-11 mmHg and 3-8 mmHg, respectively. This effect of exercise can be achieved besides the favorable effects on other cardiovascular risk factors. Intensity of exercise should be monitored by the heart rate. The mean intensity should not exceed 70% of the maximal heart rate. An initial ergometry might be suitable for the planning of training recommendations.

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Can J Clin Pharmacol. 2004 Spring;11(1):E41-E44. Epub 2004 Apr 01.
Thiazide diuretics in the management of hypertension.
Khan NA, Campbell NR.
Division of General Internal Medicine, University of British Columbia, Vancouver, Canada.

Hypertension is highly prevalent in Canada, affecting more than 20% of all adults. Thiazide diuretics have been shown in numerous studies to be effective agents for controlling blood pressure and reducing cardiovascular disease and death in hypertensive patients. Thiazide diuretics are recommended as initial first line therapy for uncomplicated hypertension in the 2003 Canadian Hypertension recommendations. However, these agents are underutilized and in Canada, the proportion of persons with hypertension treated with diuretics is declining. To improve understanding of thiazide diuretic use, this document outlines the clinical pharmacology of thiazide diuretics, evidence for effectiveness in treating hypertension, as well as the side effects and controversies surrounding their use.

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Mt Sinai J Med. 2004 Mar;71(2):103-14.
Current medical treatment of pulmonary arterial hypertension.
Sulica R, Poon M.
Mount Sinai Pulmonary Hypertension Program, Cardiology Division, Box 1033, Mount Sinai School of Medicine, 1 East 100th Street, New York, NY 10029, USA.

Primary pulmonary hypertension is a rare disease of the pulmonary vasculature manifested by dyspnea on exertion, syncope, and signs and symptoms of right heart failure. In the absence of adequate treatment, primary pulmonary hypertension has a grave prognosis, with a median survival of 2.8 years. Pulmonary arterial hypertension develops in association with known risk factors and predisposing clinical conditions, and shares many clinical, pathological and therapeutic characteristics with primary pulmonary hypertension. Therapeutic choices in pulmonary arterial hypertension depend on the etiology of the disease, severity of functional impairment and hemodynamic response following acute vasodilator administration during right heart catheterization. Agents currently approved for the specific treatment of pulmonary arterial hypertension are continuous intravenous epoprostenol, subcutaneous treprostinil and oral bosentan. A small group of patients who demonstrate true acute vasoreactivity at right heart catheterization may be chronically treated with oral calcium channel blockers. In addition, most patients with pulmonary hypertension receive conventional treatment, represented by anticoagulants, diuretics, inotropic medication or oxygen supplementation. Treatment of pulmonary arterial hypertension has significantly altered the natural course of the disease, with pronounced symptomatic, functional and survival benefit. Current clinical research focuses on the discovery of new targets of therapy and the use of a combination treatment approach, which will offer hope and valuable insight into the pathogenetic basis of this devastating illness.

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Med Clin North Am. 2004 Jan;88(1):223-38.
Primary prevention of essential hypertension.
Krousel-Wood MA, Muntner P, He J, Whelton PK.
Clinical Outcomes Research, Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, LA 70121, USA. mawood@ochsner.org

The best approach to the primary prevention of hypertension is a combination of lifestyle changes: weight loss in overweight persons; increased physical activity; moderation of alcohol intake; and consumption of a diet that is higher in fruits, vegetables, and low-fat dairy products and lower in sodium content than the average American diet (Table 3). Recent randomized controlled trials have demonstrated that these lifestyle changes can be sustained over long periods of time (more than 3 years) and can have blood pressure-lowering effects as large as those seen in drug studies. Hypertension is an important preventable risk factor for cardiovascular disease, the leading cause of mortality in the United States. To achieve the Healthy People 2010 goal of reducing the proportion of adults with hypertension from 28% to 16%, concerted efforts must be directed toward primary prevention strategies. Lifestyle modifications including weight loss, increased physical activity, and dietary changes in individuals have been shown to reduce the incidence of hypertension and should be recommended for all persons and especially those with prehypertension. In addition, timely adoption of prevention strategies to reduce the incidence of hypertension and its subsequent complications in the general population may interrupt the costly cycle of hypertension and prevent the reductions in quality of life associated with this chronic disease.

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Kardiologiia. 2004;44(2):35-9.
[Efficacy of nondrug correction of hypertension in general medical practice]
[Article in Russian]
Frolova OV, Plavinskii OL, Moiseeva OE, Kuznetsova OIu, Filatov ON.
St-Petersburg Medical Academy of Postgraduate Medical Education; ul. Kirochnaya 41, 193015 St-Petersburg, Russia.

Effectiveness of nondrug correction of elevated blood pressure was assessed in a group of hypertensives selected from participants of a study of prevalence of cardiovascular risk factors conducted in one of Saint Petersburg districts. Patients were divided into 3 subgroups in which the following interventions were used: diet with decreased sodium content, aerobic physical exercise, or combination of these methods. Blood pressure lowering achieved with these methods (-11 mm Hg systolic and -6.8 mm Hg diastolic) was maintained throughout 2 years of observation.

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JAMA 2003 Apr 23-30;289(16):2083-93
Effects of comprehensive lifestyle modification on blood pressure control: main results of the
PREMIER clinical trial.
Appel LJ, Champagne CM, Harsha DW, Cooper LS, Obarzanek E, Elmer PJ, Stevens VJ, Vollmer WM, Lin PH, Svetkey LP, Stedman SW, Young DR; Writing Group of the PREMIER Collaborative Research Group.
Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Md 21205-2233, USA. lappel@jhmi.edu

CONTEXT: Weight loss, sodium reduction, increased physical activity, and limited alcohol intake are established recommendations that reduce blood pressure (BP). The Dietary Approaches to Stop Hypertension (DASH) diet also lowers BP. To date, no trial has evaluated the effects of simultaneously implementing these lifestyle recommendations. OBJECTIVE: To determine the effect on BP of 2 multicomponent, behavioral interventions. DESIGN, SETTING, AND PARTICIPANTS: Randomized trial with enrollment at 4 clinical centers (January 2000-June 2001) among 810 adults (mean [SD] age, 50 [8.9] years; 62% women; 34% African American) with above-optimal BP, including stage 1 hypertension (120-159 mm Hg systolic and 80-95 mm Hg diastolic), and who were not taking antihypertensive medications. INTERVENTION: Participants were randomized to one of 3 intervention groups: (1) "established," a behavioral intervention that implemented established recommendations (n = 268); (2) "established plus DASH,"which also implemented the DASH diet (n = 269); and (3) an "advice only" comparison group (n = 273). MAIN OUTCOME MEASURES: Blood pressure measurement and hypertension status at 6 months. RESULTS: Both behavioral interventions significantly reduced weight, improved fitness, and lowered sodium intake. The established plus DASH intervention also increased fruit, vegetable, and dairy intake. Across the groups, gradients in BP and hypertensive status were evident. After subtracting change in advice only, the mean net reduction in systolic BP was 3.7 mm Hg (P<.001) in the established group and 4.3 mm Hg (P<.001) in the established plus DASH group; the systolic BP difference between the established and established plus DASH groups was 0.6 mm Hg (P =.43). Compared with the baseline hypertension prevalence of 38%, the prevalence at 6 months was 26% in the advice only group, 17% in the established group (P =.01 compared with the advice only group), and 12% in the established plus DASH group (P<.001 compared with the advice only group; P =.12 compared with the established group). The prevalence of optimal BP (<120 mm Hg systolic and <80 mm Hg diastolic) was 19% in the advice only group, 30% in the established group (P =.005 compared with the advice only group), and 35% in the established plus DASH group (P<.001 compared with the advice only group; P =.24 compared with the established group). CONCLUSION: Individuals with above-optimal BP, including stage 1 hypertension, can make multiple lifestyle changes that lower BP and reduce their cardiovascular disease risk.

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JAMA 2003 Apr 23-30;289(16):2073-82
Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial.
Black HR, Elliott WJ, Grandits G, Grambsch P, Lucente T, White WB, Neaton JD, Grimm RH Jr, Hansson L, Lacourciere Y, Muller J, Sleight P, Weber MA, Williams G, Wittes J, Zanchetti A, Anders RJ; CONVINCE Research Group.
Rush Medical College of Rush University, Chicago, IL 60612, USA. hblack@rush.edu

CONTEXT: Hypertensive patients are often given a calcium antagonist to reduce cardiovascular disease risk, but the benefit compared with other drug classes is controversial. OBJECTIVE: To determine whether initial therapy with controlled-onset extended-release (COER) verapamil is equivalent to a physician's choice of atenolol or hydrochlorothiazide in preventing cardiovascular disease. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized clinical trial conducted at 661 centers in 15 countries. A total of 16 602 participants diagnosed as having hypertension and who had 1 or more additional risk factors for cardiovascular disease were enrolled between September 1996 and December 1998 and followed up until December 31, 2000. After a mean of 3 years of follow-up, the sponsor closed the study before unblinding the results. INTERVENTION: Initially, 8241 participants received 180 mg of COER verapamil and 8361 received either 50 mg of atenolol or 12.5 mg of hydrochlorothiazide. Other drugs (eg, diuretic, beta-blocker, or an angiotensin-converting enzyme inhibitor) could be added in specified sequence if needed. MAIN OUTCOME MEASURES: First occurrence of stroke, myocardial infarction, or cardiovascular disease-related death. RESULTS: Systolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the COER verapamil group and by 13.5 and 7.1 mm Hg for partcipants assigned to the atenolol or hydrochlorothiazide group. There were 364 primary cardiovascular disease-related events that occurred in the COER verapamil group vs 365 in atenolol or hydrochlorothiazide group (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.88-1.18; P =.77). For fatal or nonfatal stroke, the HR was 1.15 (95% CI, 0.90-1.48); for fatal or nonfatal myocardial infarction, 0.82 (95% CI, 0.65-1.03); and for cardiovascular disease-related death, 1.09 (95% CI, 0.87-1.37). The HR was 1.05 (95% CI, 0.95-1.16) for any prespecified cardiovascular disease-related event and 1.08 (95% CI, 0.93-1.26) for all-cause mortality. Nonstroke hemorrhage was more common with participants in the COER-verapamil group (n = 118) compared with the atenolol or hydrochlorothiazide group (n = 79) (HR, 1.54 [95% CI, 1.16-2.04]; P =.003). More cardiovascular disease-related events occurred between 6 AM and noon in both the COER verapamil (99/277) and atenolol or hydrochlorothiazide (88/274) groups; HR, 1.15 (95% CI, 0.86-1.53). CONCLUSIONS: The CONVINCE trial did not demonstrate equivalence of a COER verapamil-based antihypertensive regimen compared with a regimen beginning with a diuretic or beta-blocker. When considered in the context of other trials of calcium antagonists, these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or beta-blocker treatment.

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Br J Biomed Sci 2003;60(1):5-8
Vitamin E prevents extensive lipid peroxidation in patients with hypertension.
Brockes C, Buchli C, Locher R, Koch J, Vetter W.
University Hospital, Division of Hypertension, Ramistr, 100, CH-8091 Zurich, Switzerland. christiane.brockes@epost.de

Oxidative modification of low-density lipoprotein (LDL) increases atherogenic potential to induce the accumulation of lipids and cells in the vascular wall. Previous studies reveal that hypertensive patients have a higher susceptibility to LDL oxidation. As animal models indicate that vitamin E protects LDL from oxidation, here we study the influence of vitamin E on the resistance of LDL to oxidation (lag time) in 47 subjects (31 normotensive, 16 hypertensive) before and after oral administration of vitamin E (400 IE) daily for two months. LDL was isolated and oxidised by incubation with copper ions. The time course of oxidation was measured by continuous photometric monitoring of diene formation at 234 nm. At the beginning of this study, normotensive subjects showed a lag time of 108 +/- 26 minutes and hypertensive patients a lag time of 85 +/- 24 minutes (P<0.05). Vitamin E caused a significant increase in the lag time in both groups: normotensive subjects 128 +/- 33, hypertensives patients 114 +/- 27 minutes (P<0.01). At completion of the study, lag times in both groups were similar (P=not significant). The data presented here suggests that vitamin E protects against the increased risk of vascular disease in patients with hypertension by reducing the susceptibility to oxidative modification of LDL. Vitamin E may therefore act as an inhibitor of atherogenesis.

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J Am Coll Cardiol 2003 Apr 2;41(7):1148-55
Efficacy and tolerability of eplerenone and losartan in hypertensive black and white patients.
Flack JM, Oparil S, Pratt JH, Roniker B, Garthwaite S, Kleiman JH, Yang Y, Krause SL, Workman D, Saunders E.
Department of Internal Medicine, Wayne State University, Detroit, Michigan 48201, USA. JFlack@intmed.wayne.edu

OBJECTIVES: The purpose of this study was to evaluate the efficacy and tolerability of monotherapy with the selective aldosterone blocker eplerenone in both black and white patients with hypertension. BACKGROUND: Essential hypertension and cardiovascular-renal-target organ damage is more prevalent in black than white adults in the U.S. METHODS: Black (n = 348) and white (n = 203) patients with mild-to-moderate hypertension were randomized to double-blind treatment with eplerenone 50 mg, the angiotensin II receptor antagonist losartan 50 mg, or placebo once daily. Doses were increased if blood pressure remained uncontrolled. The primary end point was change in mean diastolic blood pressure (DBP) after 16 weeks of therapy. RESULTS: Adjusted mean changes from baseline in DBP were -5.3 +/- 0.7, -10.3 +/- 0.7, and -6.9 +/- 0.6 mm Hg in the placebo, eplerenone-treated, and losartan-treated groups, respectively (mean +/- SE, p < 0.001 eplerenone vs. placebo, p < 0.001 eplerenone vs. losartan). In black patients, DBP decreased by -4.8 +/- 1.0, -10.2 +/- 0.9, and -6.0 +/- 0.9 mm Hg for the placebo, eplerenone-treated, and losartan-treated groups, respectively (mean +/- SE, p < 0.001 eplerenone vs. placebo, p < 0.001 eplerenone vs. losartan), whereas in white patients, DBP decreased by -6.4 +/- 1.0, -11.1 +/- 1.1, and -8.4 +/- 1.0 mm Hg, respectively (p = 0.001 eplerenone vs. placebo, p = 0.068 for eplerenone vs. losartan). For reduction of systolic blood pressure (SBP), eplerenone was superior to placebo and losartan in all patients combined and in black patients, and was superior to placebo in white patients. Eplerenone was as effective as losartan in reducing SBP and DBP in the high renin patient, but more effective than losartan in the low renin patient. Similarly, eplerenone was at least as effective as losartan in patients with differing baseline levels of aldosterone. Both eplerenone and losartan were well tolerated. CONCLUSIONS: The antihypertensive effect of eplerenone was equal in black and white patients and was superior to losartan in black patients.

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Metabolism 2003 Mar;52(3):261-3
Antihypertensive treatment and homocysteine concentrations.
Westphal S, Rading A, Luley C, Dierkes J.
Institute of Clinical Chemistry, Magdeburg, Germany.

Thiazides and angiotensin-converting enzyme (ACE) inhibitors are first-choice drugs for lowering elevated blood pressure and hence risk of cardiovascular disease. Homocysteine (tHcy) is another and independent cardiovascular risk factor and has been reported to be elevated in patients on antihypertensive therapy. As these studies reported only associations, a preliminary, randomized, prospective treatment study was performed in 40 hypertensive patients. We investigated the major determinants of tHcy concentrations after treatment with hydrochlorothiazide (HCT) or captopril: vitamins B6, B12, folic acid, and creatinine and cystatin C as parameters of renal function. A total of 21 Patients were treated with HCT and 19 with captopril, for, respectively, 31 and 29 days. HCT, but not captopril, raised tHcy by 16% (P =.003) and also creatinine and cystatin C (P =.025 and P =.004, respectively). This tHcy increase may offset the desired cardioprotection conferred by lowering the blood pressure. Copyright 2003, Elsevier Science (USA). All rights reserved.

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Curr Hypertens Rep 2003 Apr;5(2):122-5
Aldosterone and specific aldosterone receptor antagonists in hypertension and cardiovascular disease.
Bravo EL.
Department of Nephrology and Hypertension, Cleveland Clinic Foundation, 9500 Euclid Avenue - Desk A51, OH 44195, USA. bronofs@ccf.org

Recent preclinical and clinical studies indicate that aldosterone, independent of angiotensin II and elevated blood pressure, may play a role in health and disease. In addition to its role in fluid and electrolyte balance and circulatory homeostasis, more recent studies have identified aldosterone as a critical mediator of vascular damage. In animal studies, aldosterone is implicated in cardiac and vascular fibrosis, renal disease, and cerebrovascular damage. These lesions are prevented by specific aldosterone receptor blockade. In clinical studies, aldosterone receptor antagonism is associated with decreased hospitalization, symptomatology, and mortality, and improvement of endothelial dysfunction in patients with chronic heart failure. A better understanding of aldosterone's actions in nonepithelial tissues should pave the way to better protection of organs at risk such as the kidneys, heart, and brain.

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Clin Ther 2003 Jan;25(1):35-57
Effect of amlodipine on systolic blood pressure.
Levine CB, Fahrbach KR, Frame D, Connelly JE, Estok RP, Stone LR, Ludensky V.
MetaWorks Inc., Medford, Massachusetts 02155, USA.

BACKGROUND: Systolic hypertension is the most common form of hypertension, particularly in people aged >60 years. Caused by decreased compliance of large arteries, systolic hypertension is an independent risk factor for cardiovascular disease. Recent studies have demonstrated that it is more important to control systolic blood pressure (SBP) than diastolic blood pressure (DBP). OBJECTIVE: The objective of this study was to perform a systematic literature review to examine the effectiveness of amlodipine in lowering SBP in a variety of patient subgroups and clinical settings. METHODS: The literature review methodology included identifying, selecting, appraising, extracting, and synthesizing primary research studies. Following an a priori protocol, published literature was searched from 1980 to 2001 using 3 electronic databases. A manual review of the reference lists of recent review articles and all accepted studies was performed. Parallel-group, randomized, controlled trials that included at least 10 adults with baseline hypertension (SBP>or=140 mm Hg, DBP>or=90 mm Hg, or both), included at least 1 arm randomized to initial treatment with amlodipine monotherapy, had a minimum treatment duration of 8 weeks, and reported baseline and end-point blood pressure were included. RESULTS: Of 696 citations identified, 85 primary studies met all inclusion criteria. Comparable treatment arms were pooled, and weightd mean SBP was calculated. In the amlodipine monotherapy arms, which included >5000 patients, SBP decreased by a mean of 17.5 mm Hg from baseline. The effect of amlodipine in reducing SBP was greater in elderly patients (age>or=60 years) and patients with author-defined isolated systolic hypertension. The dose was titrated to achieve the target blood pressure in 73 of 89 amlodipine treatment arms, whereas 16 treatment arms reported fixed doses. The median daily dose was 5 mg (range, 1.25-15 mg) in both the fixed-dose and dose-titration groups. CONCLUSIONS: In this review of the published literature, amlodipine monotherapy was effective in reducing SBP. Antihypertensive agents such as amlodipine warrant consideration for the management of patients with inadequately controlled SBP.

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Ned Tijdschr Geneeskd 2003 Jan 18;147(3):96-9
[Treatment of hypertension: angiotensin-II antagonists potentially better than beta-blockers in the occurrence of cardiovascular and cerebrovascular damage; the LIFE study in perspective]
[Article in Dutch]
de Boer RA, van Veldhuisen DJ, Gans RO, Gansevoort RT.
Thoraxcentrum, afd. Cardiologie, Academisch Ziekenhuis, Postbus 30.001, 9700 RB Groningen.

Current clinical guidelines state that only beta-blockers, diuretics, calcium channel antagonists and ACE inhibitors should be used for initial pharmacotherapy for uncomplicated hypertension. On basis of experience, efficacy and costs beta-blockers and diuretics are first choice. However, the importance of the renin-angiotensin-aldosterone-system in the pathophysiology of hypertensive end-organ damage is increasingly recognised nowadays, and modulation of this system may therefore exert favourable effects on cardiovascular and cerebrovascular complications. In the LIFE study, a recently published double-blinded, randomised trial, the angiotensin-II receptor (A-II) antagonist losartan was compared with the beta-blocker atenolol in patients with essential hypertension and left ventricular hypertrophy (LVH). Patients randomised to the A-II antagonist suffered statistically significantly fewer clinical end-points, specifically fewer cerebrovascular accidents, whereas both treatments resulted in a similar decrease in blood pressure. In the subset of diabetic patients, the use of the A-II antagonist yielded an even more favourable outcome. In our opinion, it should now also be permitted to prescribe A-II antagonists as initial pharmacotherapy for patients with uncomplicated essential hypertension. It might be considered to prescribe A-II antagonists as preferred treatment for patients with essential hypertension and known LVH, especially in diabetic patients.

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Int J Clin Pharmacol Ther 2003 Jan;41(1):22-9
Comparison of talinolol and atenolol effects on blood pressure in relation to lipid and glucose metabolic parameters. Results from the TALIP study.
Sourgens H, Schmidt J, Derendorf H.
Applied Pharmacology, Dresden, Germany.

AIMS: The primary objective of this double-blind, randomized, parallel-group study was to compare the influence ofthe selective beta1-receptor antagonists talinolol (100 mg) and atenolol (50 mg) on the lipid metabolism in hyperlipemic patients with mild to moderate hypertension after 12 weeks of treatment. As a secondary endpoint, the influence of the drug on blood pressure, pulse rate as well as glucose metabolism were examined. Furthermore, pharmacokinetic parameters were assessed. PATIENTS: Of the 198 patients recruited for the study, 166 were randomized to receive atenolol (n = 83) or talinolol (n = 83) for up to 12 weeks, 149 patients received the study medication for up to 48 weeks under double-blind conditions. RESULTS: There was no difference between the antihypertensive effect of both beta1-selective antagonists in patients with mild to moderate hypertension. No clinically relevant differences between the 2 drugs were observed for LDL cholesterol, HDL cholesterol, total cholesterol and triglycerides in the rather low doses given. However, there was evidence for a decrease in LDL cholesterol following treatment with talinolol, but not following treatment with atenolol, in patients with the highest initial blood pressure and in those with normalized blood pressure after 12 weeks of treatment. Parameters of glucose metabolism were not adversely affected by both drugs. Stable pharmacokinetics were observed over the 12-week administration, and steady state conditions were achieved after a 1-week treatment with both active compounds in the target population. Data indicate that once-a-day dosing can be performed with less fluctuation between peak and trough for talinolol in comparison to atenolol. Both treatments were well tolerated.

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Rev Med Liege 2003 Jan;58(1):47-52
[Clinical study of the month. Which initial antihypertensive? Results from the ALLHAT trial]
[Article in French]
Scheen AJ, Krzesinski JM.
Service de Diabetologie, Nutrition et Maladies metaboliques, Service de Medecine interne generale, Departement de Medecine, CHU Ourthe-Ambleve.

Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality, but the optimal first-step therapy is still controversial. The "Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial" (ALLHAT) should give such an answer. It is a randomised, double-blind, trial designed to determine whether treatment with either a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease (CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic. A total of 33,357 participants aged 55 years or older with mild to moderate hypertension and at least 1 other CHD risk factor were randomly assigned to receive chlorthalidone (12.5 to 25 mg/day; n = 15,255), amlodipine (2.5 to 10 mg/day; n = 9,048) or lisinopril (10 to 40 mg; n = 9,054). The primary outcome combined both fatal CHD and non-fatal myocardial infarction, analyzed by intent-to-treat. Secondary outcomes were all-causes mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina without hospitalization, heart failure and peripheral arterial disease). Chlorthalidone was slightly more effective in reducing systolic pressure while amlodipine reduced slightly more effectively diastolic blood pressure. After a mean follow up of 4.9 years, no differences were observed between the three treatments regarding both the primary outcome and the total mortality. Secondary outcomes were similar when comparing amlodipine vs chlorthalidone. A moderately higher 6-year incidence rate of clinically detected heart failure was observed with amlodipine, but without significant influence on mortality. For lisinopril vs chlorthalidone, lisinopril had slightly higher 6-year rates of combined CVD, stroke and heart failure. In conclusion, thiazide-type diuretics are superior in preventing one or more major forms of CVD and offer the advantage to be cheaper. They should be preferred for first-step antihypertensive therapy. However, to reach the recommended blood pressure target, most patients should receive a combination of antihypertensive compounds. Such a combination should always comprise a diuretic agent, in absence of contra-indications

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N Engl J Med 2003 Feb 13;348(7):583-92
A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly.
Wing LM, Reid CM, Ryan P, Beilin LJ, Brown MA, Jennings GL, Johnston CI, McNeil JJ, Macdonald GJ, Marley JE, Morgan TO, West MJ; Second Australian National Blood Pressure Study Group.
School of Medicine, Flinders University, Adelaide, Australia.

BACKGROUND: Treatment of hypertension with diuretics, beta-blockers, or both leads to improved outcomes. It has been postulated that agents that inhibit the renin-angiotensin system confer benefit beyond the reduction of blood pressure alone. We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting-enzyme (ACE) inhibitors with the outcomes in those treated with diuretic agents. METHODS: We conducted a prospective, randomized, open-label study with blinded assessment of end points in 6083 subjects with hypertension who were 65 to 84 years of age and received health care at 1594 family practices. Subjects were followed for a median of 4.1 years, and the total numbers of cardiovascular events in the two treatment groups were compared with the use of multivariate proportional-hazards models. RESULTS: At base line, the treatment groups were well matched in terms of age, sex, and blood pressure. By the end of the study, blood pressure had decreased to a similar extent in both groups (a decrease of 26/12 mm Hg). There were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group (56.1 per 1000 patient-years) and 736 cardiovascular events or deaths from any cause in the diuretic group (59.8 per 1000 patient-years; the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [95 percent confidence interval, 0.79 to 1.00]; P=0.05). Among male subjects, the hazard ratio was 0.83 (95 percent confidence interval, 0.71 to 0.97; P=0.02); among female subjects, the hazard ratio was 1.00 (95 percent confidence interval, 0.83 to 1.21; P=0.98); the P value for the interaction between sex and treatment-group assignment was 0.15. The rates of nonfatal cardiovascular events and myocardial infarctions decreased with ACE-inhibitor treatment, whereas a similar number of strokes occurred in each group (although there were more fatal strokes in the ACE-inhibitor group). CONCLUSIONS: Initiation of antihypertensive treatment involving ACE inhibitors in older subjects, particularly men, appears to lead to better outcomes than treatment with diuretic agents, despite similar reductions of blood pressure. Copyright 2003 Massachusetts Medical Society

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Hypertension 2003 Mar;41(3):422-30
DASH diet lowers blood pressure and lipid-induced oxidative stress in obesity.
Lopes HF, Martin KL, Nashar K, Morrow JD, Goodfriend TL, Egan BM.
Department of Pharmacology, Medical University of South Carolina, 96 Jonathan Lucas St, CSB 826H, Charleston, SC 29425, USA.

Evidence suggests that obesity may raise blood pressure (BP) through oxidative stress-sensitive mechanisms and that the Dietary Approaches to Stop Hypertension combination diet (DASH-CD) may decrease BP by enhancing antioxidant capacity. To address this question, 12 obese patients with high-normal-to-stage 1 hypertension (hypertensives) and 12 lean normotensives were studied on their usual diets and after following the DASH-CD and a low-antioxidant diet in random sequence for 4 weeks each. Acute oxidative stress was induced by a 4-hour infusion of intralipid and heparin. Ferric-reducing activity of plasma (FRAP) and plasma F2-isoprostanes were measured as biomarkers of antioxidant capacity and oxidative stress, respectively. BP was lower in obese hypertensives on the DASH-CD than on the usual and low-antioxidant diets (-8.1+/-1.5/-7.4+/-1.6 mm Hg, P<0.05). BP did not change significantly in lean normotensives after 4 weeks on the DASH-CD but tended to rise on the low-antioxidant diet. FRAP on usual diets was higher in lean subjects than in obese subjects. FRAP increased in obese but not lean volunteers on the DASH-CD compared with usual diet, and the group difference disappeared. F2-isoprostanes increased from baseline during intralipid and heparin in both groups on the low-antioxidant diet but not in obese hypertensives on the DASH-CD. Among free-living obese hypertensives, the DASH-CD raises antioxidant capacity, lowers BP, and reduces oxidative stress induced by acute hyperlipidemia. The findings are consistent with evidence that elevated BP in obese subjects may reflect an imbalance between antioxidant capacity and oxidative stress that is improved by the DASH-CD.

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Ugeskr Laeger 2003 Jan 27;165(5):456-9
[The effect of losartan versus atenolol on cardiovascular morbidity and mortality in patients with hypertension and ECG-verified left ventricular hypertrophy in the LIFE-study]
[Article in Danish]
Ibsen H, Pedersen OL, Dahlof B, Kjeldsen SE, Lindholm LH.
Medicinsk Afdeling M, Amtssygehuset i Glostrup.

INTRODUCTION: Left ventricular hypertrophy is a strong independent predictor of risk of cardiovascular morbidity and death. The aim of the LIFE-study was to establish whether treatment with the angiotensin-II AT 1-receptor antagonist, losartan, reduced cardiovascular events more effectively than treatment with the betablocker atenolol in patients with hypertension and left ventricular hypertrophy. MATERIAL AND METHODS: The LIFE-study included 9193 patients with essential hypertension and ECG-verified left ventricular hypertrophy, age range 55-80 years, systolic blood pressure in sitting position 160-200 mmHg and/or diastolic blood pressure 95-115 mmHg. Patients were randomized to double-blind treatment with losartan versus atenolol. They were followed for at least four years and until 1040 patients had a primary cardiovascular event (cardiovascular death, myocardial infarction or stroke). RESULTS: Blood pressure fell by 30.2/16.6 and 29.1/16.8 mmHg in the losartan and the atenolol group, respectively. The primary composite endpoint occurred in 508 losartan and 588 atenolol patients (relative risk 0.87, p = 0.021). A total of 232 and 309, respectively, had fatal or non-fatal stroke (relative risk 0.75, p = 0.001). There was no difference in myocardial infarction. New-onset diabetes was 25% less frequent on losartan. Side effects were less on losartan compared to atenolol. DISCUSSION: Losartan prevents to a higher degree cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated.

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Dtsch Med Wochenschr 2003 Mar 14;128(11):541-4
[Lowering of blood pressure, blood pressure amplitude and heart rate by treatment with valsartan or valsartan/hydrochlorothiazide. Results of an open observation study of 11,447 hypertensives]
[Article in German]
Weisser B, Vetter H, Mengden T.
Medizinische Poliklinik, Universitat Bonn. b.weisser@uni-bonn.de

OBJECTIVE: This trial investigated the decrease of blood pressure, safety and tolerability of valsartan, an angiotensin-receptor blocker, alone or combined with the diuretic hydrochlorothiazide. In addition, the effect on pulse pressure, heart rate and mean blood pressure were recorded as independent markers of cardiovascular risk. PATIENTS AND METHODS: 12278 hypertensive patients were treated for 12 weeks with valsartan alone or combined with hydrochlorothiazide in a multi-centre open trial. Previously established antihypertensive treatment was continued. Systolic and diastolic pressure, pulse pressure and resting heart rate were recorded at the start of the trial and at 1, 4 and 12 weeks thereafter. RESULTS: Data on 11447 were complete enough to be evaluated (54% males, 46% females; mean age 60.8 years). 44% of the patients were at the same time receiving other antihypertensive drugs at the start of the trial, but the numbers so treated decreased during the trial period. Systolic pressure was reduced by 27.8 mmHg. diastolic pressure by 14.7 mmHg, with a calculated reduction of pulse pressure from 71.5 to 58.7 mmHg. Heart rate was reduced by 3.4 beats. The treatment had to be stopped prematurely in 2.3% of patients because of side effects. There were no severe or life-threatening side effects. CONCLUSION: Treatment with valsartan alone or combined with hydrochlorothiazide provides effective blood pressure reduction and is well tolerated. This trial suggests that, in addition to the fall in blood pressure, the independent risk factors of cardiovascular disease, pulse pressure and resting heart rate, were also reduced during administration of valsartan.

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Ter Arkh 2002;74(12):34-7
[Functional and biochemical characteristics of the vasodilator effects of nebivolol in patients with
arterial hypertension]
[Article in Russian]
Gel'tser BI, Kotel'niko v VN, Savchenko SV.

AIM: To examine nebivolol-induced changes in endothelial vasomotor function and blood concentrations of nitric oxide (NO) metabolites in patients with arterial hypertension (AH). MATERIALS AND METHODS: The impact of 8-week nebivolol monotherapy on 24-hour blood pressure (BP) monitoring, ECG, autonomic heart regulation, changes in endothelium-dependent vasodilation (EDVD) and endothelium-independent vasodilation, on the plasma concentration of NO metabolites, and on the endothelial responsiveness index (ERI) were studied in 30 patients with stages I-II AH. RESULTS: Nebivolol provides a sufficient 24-hour BP monitoring, reduced heart rate, the incidence of supraventricular arrhythmias, and left ventricular myocardial mass with the optimization of autonomic cardiac regulation. The agent recovers NO-ergic regulation of endothelial vasomotor function in patients with AH by normalizing the basal level of NO and EDVD. The study of plasma NO metabolites before and during reactive hyperemia test with ERI calculation substantially extends an idea of the mechanisms of EDVD and supplements the diagnostic potentialities of this method. CONCLUSION: Dysfunction of the vascular endothelial NO-producing system occurs in patients with AH. In addition to its positive effect on 24-hour BP profile and myocardial morphofunctional parameters, nebivolol restores the NO-ergic regulation of endothelial vasomotor function in patients with AH, by potentiating NO expression, and modulates steady-state vasodilation.

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Rev Med Chir Soc Med Nat Iasi 2002 Jan-Mar;106(1):137-41
[Our experience in the surgical treatment of the arterial hypertension due to endocrine disturbances]
[Article in Romanian]
Scripcariu V, Dragomir C, Dolinescu C.
Clinica a III-a Chirurgicala, Facultatea de Medicina, Universitatea de Medicina si Farmacie Gr.T. Popa Iasi.

This study is trying to expose our experience in the surgical treatment for adrenal tumors which produce arterial hypertension, experience gained over a period of 25 years. There were 93 adrenalcctomies carried out for these kinds of lesions, out of a total of 125 surgical procedures on the adrenal glands. Best results were obtained for phaeochromocytomas and also for tumors that produce primary hyperaldosteronism. Real advances have been done in the field of adrenal glands diseases by diagnosis and treatment but minimal invasive surgery is best used for all adrenal lesions but phaeochromocytomas in which this approach has to be very well judged.

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Rev Med Chir Soc Med Nat Iasi 2002 Apr-Jun;107(2):258-63
[The beneficial effect of physical training in hypertension]
[Article in Romanian]
Chiriac S, Dima-Cozma C, Georgescu T, Turcanu D, Pandele GI.
Facultatea de Medicina Clinica a VI-a Medicala, Universitatea de Medicina Gr.T. Popa Iasi.

Hypertension is present in epidemic proportion and is associated with a markedly increased risk of developing numerous cardiovascular disorders. All current treatment guidelines emphasise the role of nonpharmacological interventions, physical activity included, in the treatment of mild to moderate hypertension. A large number of studies have demonstrated that regular exercise reduces the incidence of hypertension. In addition to preventing hypertension, regular exercise has been found to lower blood pressure (10 mmHg average reduction in both systolic and diastolic pressure), improve lipoprotein-lipid profiles and insulin sensitivity. As part of the initial treatment, exercise is recommended for 12 months in patients with stage 1 hypertension, with no other coronary risk factors and no evidence of cardiovascular disease, and for as long as 6 months in those with other risk factor, but not diabetes. In patients with diabetes, cardiovascular disease or with stage 2 or 3 hypertension, drug therapy should be initiated first. Dynamic exercise of moderate intensity, 50-75% VO2max, (e.g. brisk walking, cycling) for 50-60 minutes, 3-5 times per week, is preferable to vigorous exercise because it appears to be more effective in lowering blood pressure. In addition to reducing hypertension, physical activity improves other cardiovascular risk factors.

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Przegl Lek 2002;59 Suppl 3:25-30
[The therapeutic possibilities of the regression of the vascular changes in hypertension]
[Article in Polish]
Kawecka-Jaszcz K, Styczkiewicz K.
I Klinika Kardiologii, Instytutu Kardiologii Collegium Medicum, Uniwersytetu Jagiellonskiego, 31-501 Krakow, ul. Kopernika 17. mckaweck@cyf-kr.edu.pl

Arterial hypertension has an important functional and morphological influence on the arterial system. The evaluation of functional and morphological changes is based upon such terms as compliance, stiffness, distensibility in the former and intima-media thickness (IMT), number and kind of atheromatous plaques in the latter case. Functional changes in the large arteries can be modified by antihypertensive and hypolipemic agents. The IMT as a non-invasive marker of vascular wall injury is increasingly frequently used in the studies. It has been identified as a significant predictor of coronary and cerebral vascular complications. Most studies on hypolipemic therapy demonstrate that the progression of IMT is slowed down. Ca-antagonists, ACE inhibitors and beta blockers are the most frequently studied agents with respect to their influence on IMT in the following patient populations: hypertensives, patients with coronary artery disease, at high cardiovascular risk and asymptomatic subjects with carotid plaque. The present paper summarises the results of these studies. The findings of the ELSA trial, the largest study evaluating the effects of therapy on IMT are noteworthy. It has been demonstrated that lacidipine has a better antiatheromatous effect than atenolol, which is independent of its hypotensive properties. Non-invasive, relatively easy ultrasound measurement of IMT in the carotid artery is an important tool to detect atheromatous lesions and because of its prognostic value. It may also serve as a predictor of cardiovascular complications, which helps in the process of therapeutic decision-making.

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Can J Cardiol 2002 Dec;18(12):1317-27
Combination therapy as first-line treatment of arterial hypertension.
Ruzicka M, Leenen FH.
University of Ottawa Centre for Kidney Diseases, Canada.

Mild to moderate hypertension still remains poorly controlled. This relates to multiple factors including low antihypertensive efficacy of single drug therapies, reluctance of primary care physicians to modify or titrate initially chosen therapy to obtain target blood pressure and poor compliance with medication. Evidence discussed in the present paper points to superior control of blood pressure by combinations of low doses of two drugs compared with monotherapy in regular doses. This superior effectiveness of combined therapy relates to a better antihypertensive efficacy and higher response rates in the low range of doses as the result of complementary mechanisms of antihypertensive effects. It is associated with better tolerance as the result of a lower rate of side effects in the low range of dosing, improved compliance from better tolerance and simple drug regimen, and lower cost. Increased use of fixed, low dose combination therapies can be expected to result in better control of arterial hypertension in the population. Given the evidence for superior antihypertensive efficacy and better tolerability, and the absence of harm from fixed, low dose drug combinations per se, this alternative deserves more consideration in the guidelines of major hypertension organizations.

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Can J Cardiol 2002 Dec;18(12):1285-93
Differential effects of once-daily antihypertensive drugs on blood pressure, left ventricular mass and sympathetic activity: Nifedipine-GITS versus felodipine-ER versus enalapril.
Leenen FH, Myers MG, Joyner CD, Toal CB.
University of Ottawa Heart Institute, Canada. fleenen@ottawaheart.ca

BACKGROUND: Recent meta-analyses suggest that once-daily dihydropyridines and angiotensin-converting enzyme inhibitors cause similar decreases in left ventricular (LV) mass for comparable decreases in blood pressure (BP). However, some dihydropyridines, such as felodipine-extended release (ER), still increase sympathetic activity and may, therefore, be less effective in decreasing LV mass. OBJECTIVES: To evaluate the effects of long term antihypertensive treatment with nifedipine-gastrointestinal therapeutic system (GITS) and felodipine-ER compared with enalapril on LV mass relative to the extent of BP control (assessed by 24 h ambulatory BP monitoring) and sympathetic activity (assessed by plasma catecholamine concentrations). PATIENTS AND METHODS: Enalapril was started at 10 mg/day, felodipine-ER at 5 mg/day and nifedipine-GITS at 30 mg/day, all once daily. Doses were increased to 20 mg/day, 10 mg/day or 60 mg/day, respectively, if the office BP remained 160/90 mmHg or greater at the end of the dosing interval. Evaluable echocardiograms were obtained for 116 patients at the end of the study (30 weeks of treatment). RESULTS: On 24 h ambulatory BP monitoring, nifedipine-GITS caused a consistent decrease in BP throughout the 24 h dosing interval, whereas felodipine-ER caused a more marked fall in BP during the day, and enalapril's effects diminished during the night and had disappeared by the morning. Only felodipine-ER significantly increased supine and standing plasma noradrenaline by more than 50% similarly after six, 18, and 30 weeks of treatment. In BP responders (decrease in systolic BP 10 mmHg or greater), enalapril and nifedipine-GITS caused clear decreases in LV mass by 12 to 16 g/m2, whereas felodipine-ER was less effective (decrease by only 6 g/m2, P<0.01 versus enalapril). CONCLUSIONS: Once-daily dihydropyridines should not be regarded as one homogeneous class and, compared with felodipine-ER, nifedipine-GITS exhibits a better profile regarding 24 h BP control, sympathetic activation and regression of LV mass.

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J Assoc Physicians India 2002 Oct;50:1236-9
An open comparative clinical trial to assess the efficacy and safety of losartan versus enalapril in mild to moderate hypertension.
Chowta KN, Chowta MN, Bhat P, Adhikari PM.
Department of Medicine, Kasturba Medical College, Mangalore.

OBJECTIVES: To compare the efficacy and safety of losartan with enalapril, in mild to moderate hypertension. METHODS: An open, enalapril controlled study was conducted in 30 patients with mild to moderate hypertension. Losartan 50 mg was administered to patients for eights weeks. Throughout the study blood pressure was measured every two weeks. Routine laboratory investigations were performed before entering the trial, fourth week and at the end of the study. Adverse effects were recorded. After eight weeks losartan was stopped and enalapril 10 mg daily was administered to the same patients after two weeks washout period. The same methodology that was followed for losartan trial was repeated for enalapril trial also. RESULTS: Losartan treatment resulted in a highly significant reduction in the mean sitting diastolic blood pressure. Comparison with enalapril showed that both drugs are equally efficacious in reducing blood pressure in mild to moderate hypertension. The percentage of responders was slightly more with losartan than enalapril (86.7% vs 76.7%). Adverse events reported with losartan were mild. Enalapril also was well tolerated like losartan but there was high incidence of dry cough, which was reported in nine patients (30%). CONCLUSIONS: Losartan is an effective antihypertensive drug with an excellent safety and tolerability profile. It shows similar blood pressure lowering efficacy to that of enalapril. In contrast to enalapril, losartan does not cause dry cough.

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Ann Cardiol Angeiol (Paris) 2002 Dec;51(6):341-5
[Cardio-vascular effects of sildenafil: new data]
[Article in French]
Danchin N.
Departement de cardiologie, hopital europeen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France. nicolas.danchin@egp.ap-hop-paris.fr

Sildenafil is an inhibitor of phosphodiesterase 5, which has important vasodilatory properties. Though sildenafil provokes a decrease in systemic arterial pressure, its safety has been confirmed in large series of patients on several kinds of anti-hypertensive therapy. Likewise, post-marketing surveys, in the US or United Kingdom, have recorded a number of cardio-vascular deaths following sildenafil administration which was lower than expected, provided the contra-indication with the concomitant use of nitrates is observed. In patients with known or suspected coronary artery disease, sildenafil does not modify the tolerance or results of echocardiographic exercise testing. However, sildenafil does increase coronary flow reserve, both in narrowed or normal coronary arteries, with no sign of a "steal" phenomenon. Because of its capacity to retard the degradation of cGMP, by the inhibition of phosphodiesterase 5, the effect of sildenafil in primary pulmonary hypertension has been evaluated in several studies: acutely, sildenafil decreases pulmonary artery pressure, either alone or in combination with inhaled iloprost or NO. On the same line, sildenafil decreases hypoxia-induced pulmonary hypertension in normal volunteers. These findings, together with reports of long-term improvement in symptoms and levels of pulmonary artery pressure in patients with primary pulmonary hypertension, will warrant further trials to document its potential role in this otherwise severe disease.

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J Cardiovasc Nurs 2002 Jul;16(4):50-63; quiz 75-6
The cardiovascular effects of soy products.
Hasler CM.
Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois, USA.

In human clinical intervention trials, soy product consumption reduced levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C). In October 1999, the US Food and Drug Administration approved a health claim for the relationship between consumption of soy protein and reduced risk of coronary heart disease. This article provides an overview of the cardiovascular effects of various soy products, including their effects on blood lipids, LDL-C oxidation, blood pressure, and vascular reactivity. Potential mechanisms of effect are discussed, emphasizing human clinical intervention trials. Soy consumption improves plasma lipids, although this effect appears to be more pronounced in individuals with elevated cholesterol. Soy and its associated isoflavones also reduce LDL oxidation and improve vascular reactivity.

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J Cardiovasc Nurs 2002 Jul;16(4):9-20
Coenzyme Q10 and cardiovascular disease: a review.
Sarter B.
Department of Nursing, University of Southern California, Los Angeles, California, USA.

This article provides a comprehensive review of 30 years of research on the use of coenzyme Q10 in prevention and treatment of cardiovascular disease. This endogenous antioxidant has potential for use in prevention and treatment of cardiovascular disease, particularly hypertension, hyperlipidemia, coronary artery disease, and heart failure. It appears that levels of coenzyme Q10 are decreased during therapy with HMG-CoA reductase inhibitors, gemfibrozil, Adriamycin, and certain beta blockers. Further clinical trials are warranted, but because of its low toxicity it may be appropriate to recommend coenzyme Q10 to select patients as an adjunct to conventional treatment.

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