Wille Oigman

Results of Treatment With Telmisartan-Amlodipine in Hypertensive Patients

This randomized 4×4 factorial study determined the efficacy and safety of telmisartan (T) plus amlodipine (A) in hypertensive patients. Adults (N=1461) with stage 1 or 2 hypertension (baseline blood pressure [BP]: 153.2[12.1]/101.7[4.3] mm Hg) were randomized to 1 of 16 treatment groups with T 0, 20, 40, 80 mg and A 0, 2.5, 5, 10 mg for 8 weeks. In‐clinic BP reductions were greater with combination therapy than respective monotherapies. The greatest least‐square mean systolic/diastolic BP reductions were observed with T80 mg plus A10 mg (−26.4/−20.1 mm Hg; P<.05 compared with both monotherapies). BP control was also greatest in the T80‐mg plus A10‐mg group (76.5% [overall control] and 85.3% [diastolic BP control]), and BP response rates >90% with this combination. Peripheral edema was most common in the A10‐mg group (17.8%); however, this rate was notably lower when A was used in combination with T: 11.4% (T20/A10), 6.2% (T40/A10), and 11.3% (T80/A10).

Estudo `LOTHAR`: avaliação de eficácia e tolerabilidade da combinação fixa de anlodipino e losartana no tratamento da hipertensão arterial primária

OBJETIVO: O estudo LOTHAR avaliou a eficacia, tolerabilidade e os efeitos metabolicos em medio e longo prazo (um ano) da combinacao fixa de anlodipino e losartana versus anlodipino e losartana isoladamente. METODOS: Estudo multicentrico brasileiro, randomizado, duplo-cego e comparativo realizado com 198 pacientes com hipertensao arterial primaria em estagios 1 e 2. RESULTADOS: A combinacao fixa apresenta alta eficacia anti-hipertensiva que se mantem em longo prazo com percentual reduzido de escape do controle pressorico, inferior a dos dois regimes monoterapicos de comparacao. Em longo prazo, mais de 60% dos pacientes tratados com a combinacao fixa permaneceram com niveis da PAD < 85 mmHg e o efeito anti-hipertensivo quando avaliado pela MAPA persistiu nas 24 horas com relacao vale-pico de 76,7%. A frequencia de eventos adversos foi bastante reduzida neste grupo sendo a incidencia em longo prazo de edema de membros inferiores cerca de quatro vezes menor que a observada com o anlodipino isolado. A combinacao fixa nao alterou os metabolismos da glicose e dos lipides tanto em medio quanto em longo prazos. CONCLUSAO: Estes resultados nos permitem afirmar que a combinacao de anlodipino e losartana, a primeira combinacao fixa de um antagonista dos canais de calcio e um bloqueador do receptor da angiotensina II disponivel no mercado farmaceutico constitui-se em excelente opcao para o tratamento da hipertensao arterial em larga gama de pacientes hipertensos.

Cardiac fibrosis and vascular remodeling are attenuated by metformin in obese rats

BACKGROUND Human obesity has been associated with alterations of vascular structure, especially in large and medium arteries, but the effects of insulin-sensitizers are not well known. METHODS Twenty-five male Wistar rats received subcutaneous injections of monosodium glutamate (MSG) or an equivalent volume of vehicle from the second to the sixth day after birth, At 16 weeks of age, five MSG rats started receiving an oral treatment with metformin (300 mg/kg) which was maintained for six weeks, composing five groups: control 16 weeks (CON-16), MSG 16 weeks (MSG-16), control 22 weeks (CON-22), MSG 22 weeks (MSG-22), and MSG plus metformin 22 weeks (MET-22). Systolic blood pressure (BP) was verified weekly. The lumen diameter and media thickness, media cross-sectional area (CSA) and growth index of the intramyocardial arterioles were measured. Cardiac interstitial and perivascular collagen density were also evaluated. RESULTS Systolic BP was significantly increased in the MSG-22 comparing to MSG-16 group. Insulin resistance was confirmed by HOMA-IR index and metformin-treated group presented reduction of insulin levels at week 22. The morphology analysis showed greater media-to-lumen ratio and CSA in the obese groups, which were reduced by the metformin treatment. Connective tissue deposition in the perivascular region of the left ventricle was significantly higher in the obese groups which was attenuated by metformin. CONCLUSIONS Hypertrophic vascular remodeling and cardiac collagen deposition were significantly evident in MSG-induced obese rats. Metformin treatment was able to reduce insulin resistance and attenuated this adverse cardiac and vascular remodeling.

Treatment of essential hypertension does not normalize capillary rarefaction

OBJECTIVES To determine if capillary rarefaction persists when hypertension is treated with angiotensin converting enzyme inhibitor, thiazidic diuretic and/or beta-blocker, and to identify which microcirculatory alterations (structural and functional) persist after anti-hypertensive treatment. METHODS We evaluated 28 well-controlled essential hypertensive patients and 19 normotensive subjects. Nailfold videocapillaroscopy examination of the fourth finger of the left hand was used to determine the functional capillary densities at baseline, during post-occlusive hyperemia, and after venous congestion. Capillary loop diameters (afferent, apical and efferent) and red blood cell velocity were also quantified. RESULTS Compared with normotensive subjects, hypertensive patients showed lower mean functional capillary density at baseline (25.1±1.4 vs. 33.9±1.9 cap/mm2, p<0.01), during post-occlusive reactive hyperemia (29.3±1.9 vs. 38.2±2.2 cap/mm2, p<0.01) and during venous congestion responses (31.4±1.9 vs. 41.1±2.3 cap/mm2, p<0.01). Based on the density during venous congestion, the estimated structural capillary deficit was 25.1%. Mean capillary diameters were not different at the three local points, but red blood cell velocity at baseline was significantly lower in the hypertensive group (0.98±0.05 vs. 1.17±0.04 mm/s, p<0.05). CONCLUSIONS Patients treated for essential hypertension showed microvascular rarefaction, regardless of the type of therapy used. In addition, the reduced red blood cell velocity associated with capillary rarefaction might reflect the increased systemic vascular resistance, which is a hallmark of hypertension.

Brachial Flow-mediated Dilation Correlates With Vardenafil Response in Hypertensive Men With Vasculogenic Erectile Dysfunction

OBJECTIVES To investigate whether vasculogenic erectile dysfunction (ED) severity and the clinical response to vardenafil were associated with structural and functional vascular changes in patients with uncomplicated hypertension. METHODS Sexually active hypertensive men (n = 100), aged 50-70 years, completed the International Index of Erectile Function, Erection Function Domain (IIEF-EF) and were divided into 2 groups: 74 men with mild to moderate, moderate, or severe ED (IIEF-EF score ≤18) and without major cardiovascular disease and 26 controls (IIEF-EF score ≥25). Clinical and laboratory evaluations were performed, followed by measurement of the carotid intima-media thickness (IMT) and brachial flow-mediated dilation (FMD) before 4 attempts with 20 mg of vardenafil. The responders had ≥50% positive answers on sexual encounter profile question 3. RESULTS The carotid IMT was significantly greater and the FMD was significantly lower in patients with ED than in the control patients. The baseline IIEF-EF score correlated negatively with the carotid IMT (r = -0.48, P < .001) and with the Framingham score (r = -0.41, P < .001) among those with ED. After multivariate logistic regression analysis, the baseline IIEF score was independently and only associated with the carotid IMT (β = 6.105, P = .019). Responders were younger, had a lower cardiovascular risk profile and carotid IMT, and greater baseline IIEF-EF score and FMD than did the nonresponders. On logistic regression analysis, the response to vardenafil was independently associated with the brachial FMD (β = 1.085, P = .002). CONCLUSIONS In hypertensive men with vasculogenic ED and no other clinical evidence of arteriosclerosis, the ED severity correlated with the carotid IMT, and phosphodiesterase-5 effectiveness correlated with brachial FMD.

Amlodipine 2.5 mg once daily in older hypertensives: a brazilian multi-centre study

ObjectivesThe use of low-dose amlodipine has not yet been well established in the elderly. This study therefore aimed to evaluate the efficacy and tolerability of low-dose amlodipine in elderly patients with Joint National Committee VI stage I or II hypertension. Patients and methodsSixty-five hypertensive individuals (aged 66.3±5.3 years) received amlodipine 2.5 mg per day for 12 weeks before and after two periods of 4 weeks of placebo. At weeks 0, 12 and 16, patients were submitted to office, 24 h ambulatory blood pressure monitoring and home blood pressure measurement. ResultsOffice systolic and diastolic blood pressure showed decreases at weeks 8 (153±17, 90±9 mmHg) and 12 (152±16, 90±9 mmHg) compared with weeks 0 (164±16, 99±6 mmHg) and 16 (162±19, 95±9 mmHg). During ambulatory monitoring, a decrease was observed in the average 24 h systolic and diastolic pressure at week 12 (143±13, 86±7 mmHg) compared with weeks 0 (155±15, 93±6 mmHg) and 16 (152±16, 92±8 mmHg). A daytime and night-time reduction in systolic and diastolic pressure was observed on home blood pressure monitoring at week 12 (146±16/88±8, 144±16/93±8 mmHg) compared with weeks 0 (159±17/94±8, 161±19/93±8 mmHg) and 16 (153±16/93±8, 154±17/92±8 mmHg). Adverse reactions were infrequent. ConclusionsAmlodipine at a dose of 2.5 mg per day showed efficacy and good tolerability in elderly hypertensives.

Sodium and Hypertension Still a Controversy in 1986

SummaryInterpopulation studies support the hypothesis of a causal relationship between sodium consumption and arterial hypertension. However, although this association has been contradicted by intrapopulation studies, the correlation between sodium and hypertension appears to be genetically determined, as there are both sodium-sensitive and sodium-resistant individuals.Sodium is essential for the maintenance of extracellular and plasma volume equilibrium. It is controlled metabolically by the interaction of several biological systems such as the renin-angiotensin-aldosterone system, the sympathetic nervous system, and the kallikrein-kinin and prostaglandin systems. Thus, sodium has a definite role in the mechanism involved in the pathophysiology of the predominantly volume-dependent forms of arterial hypertension.Recently, different structural substances with natriuretic effects have been identified. Natriuretic hormone is a non-peptide substance which inhibits the Na,K-ATPase in response to extracellular volume increase. This hormone acts on the renal tubular cells reducing sodium reabsorption, and at an arteriolar level elevating peripheral resistance by increasing smooth muscle tension. Mammalian atria contain various precursors of biologically active peptides, with potent natriuretic and diuretic effects. They are released in response to volume loading and atrial stretch. Although some data suggest an important role for these natriuretic substances in fluid volume and blood pressure control, their place in physiology and in abnormal clinical states should be more definitively clarified in the next few years.RésuméLes études interpopulations renforcent l’hypothèse d’une relation causale entre la consommation de sodium et l’hypertension artérielle. Cette corrélation est contredite par les études intrapopulations, elle semble toutefois génétiquement déterminée puis qu’il existe à la fois des individus sodium-sensibles et des individus sodium-résistants.Le sodium est essentiel au maintien de l’équilibre des volumes extracellulaire et plasmatique. Il est métaboliquement contrôlé par l’interaction de plusiers systèmes biologiques tels que le système aldostérone-rénine-angiotensine, le système nerveux autonome, les systèmes prostaglandines et kallikréine-kinines. Ainsi, le sodium joue un rôle précis dans le mécanisme qui intervient dans la physiopathologie des hypertensions artérielles essentiellement volume-dépendantes.Récemment, on a identifié différentes substances natriurétiques. L’hormone natriurétique est une substance non peptidique qui inhibe la Na, K-A TPase en réponse à une augmentation du volume extracellulaire. Cette hormone agit sur les cellules tubulaires rénales provoquant une diminution de la réabsorption du sodium et au niveau artériolaire, élevant les résistances périphériques par augmentation de la contraction des muscles lisses. L’oreillette des mammifères contient divers précurseurs des peptides biologiquement actifs, qui majorent les effets natriurétique et diurétique. Ils sont libérés en réponse à un accroissement des volumes et à une distension auriculaires. Un certain nombre de données suggère que ces substances natriurétiques tiennent un rôle important dans le contrôle des volumes liquidiens et de la pression sanguine. Cependant, leur rôle exact dans la physiologie et les états cliniques pathologiques devraient être plus clairement précisé dans les prochaines années.ZusammenfassungBevölkerungsstudien stützen die Hypothese einer kausalen Beziehung zwischen Natriumverbrauch und arterieller Hypertonie. Wenn auch dieser Assoziation in Bevölkerungsstudien widersprochen wurde, scheint jedoch die Korrelation zwischen Natrium und Hypertonie genetisch bestimmt zu sein, da es sowohl Natrium-sensitive als auch Natrium-resistente Personen gibt.Natrium ist für die Aufrechterhaltung des Gleichgewichts von extrazellulärem und Plasma-Volumen erforderlich. Es wird metabolisch durch die Interaktion verschiedener biologischer Systeme, wie das Renin-Angiotensin-Aldosteron-System, das sympathische Nervensystem sowie das Kalikrein-Kinin und das Prostaglandin-System kontrolliert. Damit besitzt das Natrium eine definitive Rolle bei dem Mechanismus, der an der Pathophysiologie der vornehmlich Volumenabhängigen Formen der arteriellen Hypertonie beteiligt ist.Kürzlich wurden verschiedene strukturelle Substanzen mit natriuretischen Effekten identifiziert. Das natriuretische Hormon ist eine nicht peptidartige Substanz, die die Na, K-A TPase in Reaktion auf einen Anstieg des extrazellulären Volumens hemmt. Dies Hormon wirkt auf die Zellen der Nierentubuli, indem es die Natriumresorption reduziert und auf Höhe der Arteriolen den peripheren Widerstand durch Erhöhung des Tonus der glatten Muskulatur erhöht. Der Herzvorhof von Säugetieren enthält verschiedene Vorstufen von biologisch-aktiven Peptiden mit potenten natriuretischen und diuretischen Effekten. Sie werden als Reaktion auf eine Volumenüberladung und Dehnung des Vorhofs freigesetzt. Wenn auch einige Daten eine wichtige Rolle für diese natriuretische Substanzen bei der Kontrolle des Flüssigkeitsvolumens und Blutdrucks vermuten lassen, sollte ihre Bedeutung in der Physiologie und abnormen klinischen Zuständen in den nächsten paar Jahren definitiv geklärt werden.ResumenLos estudios interpoblación confirman la relación causal entre consumo de sodio e hipertensión arterial. Aunque esta asociación ha sido negada por otros estudios intrapoblación, la cor-relación entre sodio e hipertensión parece estar determinada genéticamente al haber individuos sodiosensibles y sodiorresistentes.El sodio es esencial para el mantenimiento del equilibrio del volumen extracelular y el plasmatico, controlado metabólicamente por la interaccion de varios sistemas biológicos, tales como el de renina-angiotensina-aldosterona, el sistema nervioso simpâtico y los sistemas calicreína-cinina y prostaglandina. Así pues, el sodio desempeña una función bien definida en el mecanismo fisiopatológico de las formas de hipertensión arterial, en su mayor parte dependientes del volumen.Recientemente se han identificado diferentes sustancias estructurales con efectos natriuréticos. La hormona natriurética es una sustancia no peptídica que inhibe la Na, K-A TPasa en respuesta al aumento de volumen extracelular. Esta hormona actúa sobre las células tubulares rénales reduciendo la reabsorción de sodio y elevando la resistencia periférica en las asteriolas por aumento de la tension del músculo liso. Las aurículas de mamífero contienen diversos precursores de péptidos biológicamente activos con potentes efectos natriuréticos y diuréticos, que se liberan en respuesta a la carga de volumen y a la dilatación auricular. Aunque algunos datos parecen confirmar la importancia de estas sustancias natriuréticas en el control del volumen líquido y de la presión arterial, su función en fisiología y en los estados clínicos anómalos debera determinarse con mayor precisión en el futuro.ResumoEstudos interpopulacionais sustentam a hipótese de que o consumo de sódio tem relação causal com a hipertensão arterial. Entretanto, embora os estudos intrapopulacionais tenham contradito uma tal associação, a correlação entre o sódio e hipertensão parece ser genéticamente determinada, uma vez que há indivíduos sensíveis e indivíduos resistentes ao sódio.O sódio é essencial para a manutenção do equiliíbrio do volume plasmático e extracelular. Ele é controlado metabolicamente pela interação de diversos sistemas biológicos, tais como o sistema renina-angiotensina-aldosterona, o sistema nervoso simpático e os sistemas calicreínaquinina e prostaglandina. Assim sendo, o sódio tem papel definido no mecanismo implicado na fisiopatologia das formas de hipertensão arterial predominantemente dependentes do volume.Recentemente, identificou-se diversas substâncias estruturais com efeitos natriuréticos. O hormônio natriurético é uma substância não-peptídica que inibe a Na-K-A TPase como reação a um aumento do volume extracelular. Este hormônio a tua nas células tubulares renais, reduzindo a reabsorção do sódio, e, num nível arteriolar, elevando a resistência periférica por meio de um aumento da tensão de músculo liso. Os átrios de mamíferos contêm diversos precursores de peptídeos biologicamente ativos, dotados de poderosos efeitos natriuréticos e diuréticos. Eles são liberados em reação ao aumento do volume e ao estiramento dos átrios. Embora alguns dados surgiram que estas substâncias natriuréticas tenham um papel importante no controle do volume de fluido e da pressão sanguínea, o seu desempenho nafisiologia e nos estados clínicos anormals deveria ser esclarecido de forma mais definida nos próximos anos.RiassuntoGli studi tra popolazioni confermano l’ipotesi di un rapporto causale ira consumo di sodio e ipertensione arteriosa. Tuttavia, sebbene questo rapporto sia stato smentito da studi intrapopolazione, la correlazione tra sodio e ipertensione appare geneticamente determinata, poichè vi sono sia individui sodio—sensibili che sodio-resistenti. Il sodio è essenziale per il mantenimento dell’equilibrio del volume plasmatico ed extracellulare. È controllato metabolicamente dall’inter azione di diversi sistemi biologici, come il sistema renina—angiotensina—aldosterone, il sistema nervoso simpatico e i sistemi callicreina—chinina e prostaglandinico. Pertanto il sodio ha un ruolo preciso nei meccanismi fisiopatologici delle forme di ipertensione arteriosa di tipo prevalentemente volume—dipendente. Recentemente sono state identificate differenti sostanze con effetti natriuretici. Vormone natriuretico è una sostanza non peptidica che inibisce la Na, K—ATPasi in risposta ad aumenti del volume extracellulare. Questo ormone agisce sulle cellule dei tubuli renali riducendo il riassorbimento di sodio e a livello arteriolare aumentando la tensione della muscolatura liscia. Gli atri dei mammiferi contengono vari precursori di peptidi biologicamente attivi, co

Efficacy and tolerability of telmisartan plus amlodipine in added-risk hypertensive patients

Abstract Objectives: Added-risk hypertensive patients with co-morbidities such as diabetes and metabolic syndrome often require two or more antihypertensives to achieve blood pressure (BP) targets. The aim of this sub-analysis was to determine the efficacy and safety of telmisartan 40 or 80 mg plus amlodipine 5 or 10 mg in patients with hypertension, stratified according to certain criteria such as type 2 diabetes mellitus and metabolic syndrome. Methods: Patients were treated for 8 weeks with telmisartan 20–80 mg plus amlodipine 2.5–10 mg. This post-hoc analysis included patients treated with higher doses, and stratified according to a number of sub-populations (age, race, diabetes, obesity, metabolic syndrome, elevated baseline systolic BP (SBP), renal impairment). Results: Eight weeks’ treatment with telmisartan plus amlodipine combinations provided consistent reductions in mean SBP/diastolic BP (DBP) across the different sub-populations, similar to the overall population. SBP/DBP reductions ranged from −13.5 to −34.7/−12.6 to −26.1 mmHg and BP goal rates (<140/90 mmHg) ranged from 29.8–100% for the four key dose combinations of telmisartan plus amlodipine. For the highest dose combination of telmisartan 80 mg plus amlodipine 10 mg, SBP/DBP reduction ranged from −19.1 to −34.7/−16.4 to −22.8 mmHg and goal attainment rate from 66.7% to 87.0%. Across the sub-populations, high SBP and DBP response rates were seen with combination treatment (83.3–97.7% and 75.0–95.7%, respectively, with telmisartan 80 mg plus amlodipine 10 mg). The combination was safe and well tolerated across all sub-populations and the incidence of peripheral oedema with telmisartan 40–80 mg plus amlodipine 10 mg was generally lower than with A10 monotherapy. Conclusions: Despite small patient numbers in some sub-populations and the post-hoc nature of the analysis, this does show that the combination of telmisartan plus amlodipine provides an effective, safe and well-tolerated antihypertensive treatment for added-risk hypertensive patients.

Oral magnesium supplementation improves endothelial function and attenuates subclinical atherosclerosis in thiazide-treated hypertensive women

Background: Epidemiological studies demonstrate an inverse association between serum magnesium and incidence of cardiovascular disease. Diuretics commonly cause hypomagneseamia. Method: We evaluated effects of magnesium supplementation on blood pressure (BP) and vascular function in thiazide-treated hypertensive women in a randomized, double-blind, clinical trial. Hypertensive women (40–65 years) on hydrochlorothiazide and mean 24-h BP at least 130/80 mmHg were divided into placebo and supplementation (magnesium chelate 600 mg/day) groups. Patients were evaluated for nutritional and biochemical parameters, office and ambulatory blood pressure monitoring, brachial flow-mediated dilatation (FMD), peripheral arterial tonometry, assessment of carotid intima–media thickness, central hemodynamic parameters and pulse wave velocity at inclusion and after 6-month follow-up. Results: The magnesium group had a significant reduction in SBP (144 ± 17 vs. 134 ± 14 mmHg, P = 0.036) and DBP (88 ± 9 vs. 81 ± 8 mmHg, P = 0.005) at 6 months, without effect on plasma glucose, lipids, or arterial stiffness parameters. The placebo group showed a significant increase in carotid intima-media thickness (0.78 ± 0.13 vs. 0.89 ± 0.14 mm, P = 0.033) without change in the magnesium group (0.79 ± 0.16 vs. 0.79 ± 0.19 mm, P = 0.716) after 6 months. The magnesium group demonstrated a significant increase in variation of FMD vs. the placebo group (+3.7 ± 2.1 vs. 2.4 ± 1.2%, P = 0.015). There was a significant correlation between the intracellular magnesium variation and FMD (r = 0.44, P = 0.011). Conclusion: Magnesium supplementation was associated with better BP control, improved endothelial function and amelioration of subclinical atherosclerosis in these thiazide-treated hypertensive women.

Early combination therapy with telmisartan plus amlodipine for rapid achievement of blood pressure goals

Rapid and sustained blood pressure (BP) goal attainment is important to reduce cardiovascular risk. Initial use of combination therapy may improve BP goal attainment.