Novel Class of Central Renin Angiotensin Aldosterone System Inhibitor: Firibastat

Hypertension is one of the most important risk factors for the development of ischemic heart diseases, stroke, disability, vascular demen?a, heart failure, renal dysfunc?on, re?nopathy, and premature death. Despite the use of two or more blood pressure lowering medica?ons, a considerable propor?on of pa?ents show poor control. Current an?hypertensive medica?ons show the limita?on of use and effect in obese popula?on, certain races like black popula?on and also in renal impairment. Thus, there is an impending need to develop novel classes of an?hypertensive agents ac?ng on new targets with diversified mechanisms of ac?on to more effec?vely manage raised blood pressure. With the introduc?on of the recent concept of overac?ve brain renin angiotensin system in cardiovascular disorders, a?empts have been made to iden?fy a molecule with the poten?al of inhibi?ng aminopep?dases involved in the forma?on of Angiotensin III. A novel aminopep?dase A inhibitor, also a prodrug Firibastat is currently undergoing development in Phase III clinical trials for hypertension as well as chronic heart failure. We hereby, provide an updated summary of evidence generated so far with Firibastat and also a glimpse into the therapeu?c poten?al of this novel candidate extending beyond the spectrum of essen?al hypertension

Denervação de artéria renal em paciente com hipertensão arterial refratária / Renal denervation in patient with refrataryarterial hypertension

Caso clínico de uma paciente com quadro de hipertensão arterial refratária, sendo inicialmente atribuída como etiologia a displasia de artéria renal. Os níveis pressóricos mantiveram elevados após a angioplastia de artéria renal, mantendo descontrole pressórico apesar do uso de 10 classes de anti-hipertensivos. Foi indicada a denervação de artéria renal e após tal, foi possível redução das medicações e êxito no controle de seus níveis tensionais. Destaca-se a importância do adequado diagnóstico de hipertensão arterial refratária, a exclusão de hipertensão secundária, somado à otimização terapêutica e indicação de procedimentos quando necessário, tendo como objetivo o melhor controle pressórico e consequente redução de lesões de órgãos-alvo e eventos cardiovasculares graves (AU).

It will be explained the patient clinical case of with refractory hypertension, which was initially attributed to renal artery dysplasia, but after the renal artery angioplasty, remained with high blood pressure levels despite adequate anti-hypertensive drugs administration. Renal denervation was indicated and after medications was reduced, with adequate blood pressure level control. It emphasizes the importance of secondary hypertension diagnosis, therapeutic optimization and specific therapies, if necessary, with the aim to take blood pressure control and the consequent reduction of target-organ damage and severe vascular events (AU).

Estratificação de Risco e Avaliação da Atividade Simpática Cardíaca Utilizando Imagem Miocárdica com [123I] MIBG na Denervação Renal / Risk Stratification and Cardiac Sympathetic Activity Assessment Using Myocardial [123I] MIBG Imaging in Renal Denervation

Resumo A hiperativação do sistema nervoso simpático desempenha um papel central na fisiopatologia da hipertensão. O objetivo deste estudo foi avaliar a atividade simpática cardíaca e investigar o papel da cintigrafia miocárdica com metaiodobenzilguanidina com 123I ([123I] MIBG) na estratificação de risco cardiovascular de pacientes com hipertensão resistente tratados com denervação renal (DR). Dezoito pacientes foram incluídos neste estudo prospectivo (média de idade de 56 ± 10 anos, 27,8% mulheres). Ecocardiograma transtorácico, análise geral do sangue e cintilografia miocárdica com [(123I) MIBG] foram realizados antes e seis meses após a DR. Um paciente era considerado respondedor (R) se uma diminuição ≥ 5 mmHg na pressão arterial sistólica (PAS) média ambulatorial fosse observada no seguimento de seis meses. 66,7% dos pacientes foram R (diminuição na PAS de 20,6 ± 14,5 mmHg, vs. menos 8 ± 11,6 mmHg em não-respondedores (NR), p = 0,001). A relação coração-mediastino (RCM) inicial foi significativamente menor na linha basal no grupo R (1,6 ± 0,1 vs. 1,72 ± 0,1, p <0,02), mas semelhante em seis meses. Considerando os dois momentos no tempo, o grupo R teve valores iniciais de RCM mais baixos do que o grupo NR (p <0,05). Tanto o RCM tardio quanto a taxa de washout foram idênticos e nenhuma correlação significativa entre a resposta à DR ou qualquer índice de imagem com MIBG foi encontrada. A denervação renal efetivamente reduziu a pressão arterial na maioria dos pacientes, mas a imagem com [123I] MIBG não foi útil na previsão da resposta. Entretanto, houve evidência de overdrive do sistema nervoso simpático e, tanto a RCM inicial quanto tardia estavam reduzidas em geral, provavelmente colocando essa população em um risco maior de eventos adversos.

Abstract Hyperactivation of the sympathetic nervous system plays a central role in the pathophysiology of hypertension. The aim of this study was to assess cardiac sympathetic activity and investigate the role of myocardial123I-labelled meta-iodo benzyl guanidine ([123I] MIBG) scintigraphy in cardiovascular risk stratification of patients with resistant hypertension treated with renal denervation (RDN). Eighteen patients were included in this prospective study (mean age 56 ± 10 years old, 27.8% females). Transthoracic echocardiogram, general blood analysis and myocardial ([123I] MIBG scintigraphy were performed before and six-months after RDN. A patient was considered a responder (R) if a drop ≥ 5mmHg on mean systolic ambulatory blood pressure (BP) monitoring was observed at the six-month follow-up. 66.7% of patients were R (drop in systolic BP of 20.6 ± 14.5mmHg, vs minus 8 ± 11.6mmHg in non-responders (NR), p=0.001). Early heart-mediastinum ratio (HMR) was significantly lower at baseline in the R group (1.6 ± 0.1 vs 1.72 ± 0.1, p<0.02) but similar at six months. Considering both instants in time, the R group had lower early HMR values than the NR group (p<0.05). Both the late HMR and the washout rate were identical and no significant correlation between response to RDN or any MIBG imaging index was found. Renal denervation effectively lowered blood pressure in the majority of patients but [123I] MIBG was not useful in predicting the response. However, there was evidence of sympathetic overdrive and, both early and late HMR were overall reduced, probably putting this population at a higher risk of adverse events.

DOENÇA CORONARIANA SINTOMÁTICA EM IDOSA COM HIPERTENSÃO ARTERIAL RESISTENTE VERDADEIRA / SYMPTOMATIC CORONARY DISEASE IN ELDERLY WOMAN WITH TRUE RESISTANT ARTERIAL HYPERTENSION

Caso clínico de uma paciente idosa, com diagnóstico de hipertensão arterial há mais de 10 anos previamente controlada evoluindo com sintomas sugestivos de doença arterial coronariana sintomática em conjunto com descontrole da hipertensão arterial. Durante o seguimento foi possível confirmar o diagnóstico de hipertensão arterial resistente não controlada e a possível associação com descompensação da doença coronariana na forma de equivalente anginoso. Após ajuste medicamentoso, levando em consideração o risco cardiovascular individual da paciente e a avaliação geriátrica, as metas pressóricas e o controle sintomático da lesão de órgão-alvo foram alcançados com sucesso. Destaca-se a importância do diagnóstico preciso da hipertensão arterial resistente assim como seu controle, em especial na população idosa onde a prevalência de comorbidades e lesões de órgão alvos é maior

Clinical case of an elderly patient, diagnosed with hypertension for more than 10 years, previously controlled, evolving with symptoms suggestive of symptomatic coronary artery disease simultaneously with uncontrolled hypertension. During follow-up, it was possible to confirm the diagnosis of uncontrolled resistant arterial hypertension and the possible association with decompensated coronary disease in the form of anginal equivalent. After medication adjustment, taking into account the patient's individual cardiovascular risk and geriatric assessment, blood pressure goals and symptomatic control of target organ damage were successfully achieved, emphasizing the importance of accurate diagnosis of resistant hypertension as well as its control in particular in the elderly population, where the prevalence of comorbidities and target organ damage is higher

Hipertensão resistente em paciente com diagnótico de hiperaldosteronismo primário: resposta ao eplerenone / Resistant hypertension in a patient with primary hypereraldosteronism diagnosis: response to eplerenone

A maioria dos pacientes com hipertensão arterial (HA) não tem etiologia clara e é classificada como hipertensão primária. No entanto, 5% a 10% desses pacientes podem ter hipertensão secundária, o que indica presença de uma causa subjacente e potencialmente reversível. Em adultos com 65 anos ou mais, estenose da artéria renal aterosclerótica, insuficiência renal e hipotireoidismo são causas comuns. A hipertensão secundária deve ser considerada na presença de sintomas e sinais sugestivos, como hipertensão grave ou resistente, idade de início inferior a 30 anos (especialmente antes da puberdade), hipertensão maligna ou acelerada e aumento agudo da pressão arterial a partir de leituras previamente estáveis. Outras causas subjacentes da hipertensão secundária incluem hiperaldosteronismo, apneia obstrutiva do sono, feocromocitoma, síndrome de Cushing, doença da tireoide, coarctação da aorta e uso de certos medicamentos. A hipertensão arterial resistente (HAR) é definida quando a pressão arterial (PA) permanece acima das metas recomendadas com o uso de três anti-hipertensivos de diferentes classes, incluindo um bloqueador do sistema renina- -angiotensina (inibidor da enzima conversora da angiotensina [IECA] ou bloqueador do receptor de angiotensina [BRA]), um bloqueador dos canais de cálcio (BCC) de ação prolongada e um diurético tiazídico (DT) de longa ação em doses máximas preconizadas e toleradas, administradas com frequência, dosagem apropriada e comprovada adesão. Hipertensão arterial acompanhada de supressão da atividade da renina plasmática (ARP) e aumento da excreção de aldosterona caracteriza a síndrome de aldosteronismo primário. Esse quadro foi descrito, pela primeira vez em 1955 por Conn, em um paciente hipertenso grave hipocalêmico e com secreção elevada de aldosterona, que submetido à adrenalectomia direita resultou em cura da HA

Patients with arterial hypertension have no clear etiology and are classified as primary hypertension. However, 5% to 10% of these with hypertension may have the secondary form of disease, which indicates the presence of an underlying and potentially reversible cause. In adults aged 65 and over, the common causes of secondary hypertension are atherosclerotic renal artery stenosis, renal failure and hypothyroidism. Secondary hypertension should be considered in the presence of suggestive symptoms and signs, such as severe or resistant hypertension, age at onset less than 30 years (especially before puberty), malignant or accelerated hypertension and acute increase in blood pressure from previously stable readings. Other underlying causes of secondary hypertension include hyperaldosteronism, obstructive sleep apnea, pheochromocytoma, Cushing's syndrome, thyroid disease, coarctation of the aorta and use of others medications. Resistant arterial hypertension is defined when blood pressure remains above the recommended targets with the use of three antihypertensives of different classes, including a blocker of the renin-angiotensin system (inhibitor of the angiotensin-converting enzyme or angiotensin receptor blocker ), a calcium channel blocker and a thiazide diuretic in maximum recommended and tolerated doses, administered frequently, appropriate dosage and proven adherence. Arterial hypertension accompanied by suppression of plasma renin activity and increased aldosterone excretion characterizes the primary aldosteronism syndrome. This condition was described in 1955 by Conn, in a severe hypohypokalemic hypertensive patient with high aldosterone secretion, who underwent right adrenalectomy resulted in a cure for the hypertension

Meta-analysis for clinical efficacy of traditional Chinese medicine in treating resistant hypertension / 中国中药杂志

To systematically evaluate the efficacy and safety of traditional Chinese medicine in treating patients with resistant hypertension. CNKI, Wanfang, VIP, CBM, PubMed, Web of Science, Cochrane Library, EMbase and other databases were retrieved by computers to screen out the randomized controlled trial of traditional Chinese medicine in treating resistant hypertension. Cochrane Handbook was used to evaluate the quality of the included literature, RevMan 5.3 and Stata 12.0 was used for Meta-analysis. Finally, 11 literatures meeting the criteria were included, involving 1 023 patients. The results of Meta-analysis showed that the combined therapy of standard triple antihypertensive regimen with traditional Chinese medicine could further reduce systolic blood pressure of patients with resistant hypertension(MD=-16.69, 95%CI[-22.21,-11.16], P<0.000 01), reduce diastolic blood pressure(MD=-7.51, 95%CI[-8.26,-6.76], P<0.000 01), improve the effective rate of anti-hypertension(OR=5.16, 95%CI[3.01, 8.84], P<0.000 01), improve the up-to-standard rate of blood pressure(OR=3.01, 95%CI[1.49, 6.09], P=0.002), and improve the effectiveness of clinical symptoms(OR=4.48, 95%CI[2.31, 8.68], P<0.000 01), with no significant effect on creatinine level(MD=-2.51, 95%CI[-6.91, 1.89], P=0.26). The results of this study indicated that the combined therapy of standard triple antihypertensive regimen with traditional Chinese medicine could further improve the clinical efficacy in patients with resistant hypertension with a good safety, but more high-quality clinical studies are still needed to verify this conclusion.

Effectiveness of a 12-week physical exercise programme on blood pressure in adults with true resistant hypertension and high risk of obstructive sleep apnoea: a study protocol for a pre-post test non randomised clinical trial

Background:Resistant hypertension, a special phenotype of hypertension, is associated with increased cardiovascular risk. Exercise and physical activity are recommended as non-pharmacological interventions to manage blood pressure in hypertension. Little is known about the effectiveness of exercise in resistant hypertension. A bidirectional relationship has been identified between resistant hypertension and obstructive sleep apnoea but the literature pertaining to the benefit of exercise for populations with both conditions, is minimal. This study aims to identify the effectiveness of exercise in reducing blood pressure in a cohort of adults with resistant hypertension and high risk of obstructive sleep apnoea.Methods:Dunedin based adults with resistant hypertension and high risk of obstructive sleep apnoea will be recruited from the community and health centres to participate in the study. Consenting volunteers (no. of fourteen) will participate in a 12-week exercise programme including aerobic and strength training. The primary outcome measure will be 24h ambulatory blood pressure while the secondary outcomes will be anthropometrics, activity parameters, sleep parameters, cardiac structure and function, and quality of life. The measurements at the end ofthe 12-week exercise programme will be compared with baseline to determine the effectiveness of exercise in reducing blood pressure in the cohort with resistant hypertension and risk of obstructive sleep apnoea. Conclusions: Exercise and physical activity are recommended to manage hypertension. Therefore, it is anticipated that the exercise programme will have a positive effect on the blood pressure of the participants. The findings have potential to change the direction of research in the area by fillingthe knowledge gaps.Trial Registration:The Ministry of Health, New Zealand (Ethics Ref: 18/CEN/257), Trial registry: ACTRN12618001881224p).

Espironolactona ou clonidina como quarto fármaco na hipertensão resistente? / Spironolactone or clonidine as the fourth drug to treat resistant hypertension?

A hipertensão arterial resistente (HAR) é definida como a ausência de controle pressórico nas medidas de pressão arterial (PA) de consultório a despeito do uso de três ou mais anti-hipertensivos em doses adequadas, incluindo-se preferencialmente um diurético, ou o controle pressórico atingido às custas do uso de quatro ou mais medicamentos. O uso de espironolactona, um antagonista dos receptores de aldosterona, como quarto fármaco no tratamento da HAR é indicado pelas principais diretrizes sobre o assunto, e tem a sua eficácia comprovada em ensaios clínicos e meta análises. Um estudo comparou o uso de clonidina, um agonista adrenérgico alfa-2, como quarto fármaco para tratamento da HAR em comparação com a espironolactona. Embora o desfecho primário (taxa de controle da PA no consultório ou na medida ambulatorial da PA) tenha sido similar com as duas medicações, a espironolactona mostrou maior redução na PA de 24h quando comparada à clonidina. Neste contexto, a clonidina pode ser uma alternativa à espironolactona, particularmente em grupos específicos de pacientes que tenham contraindicação ao uso de espironolactona, como os que apresentam hipercalemia ou doença renal crônica pré dialítica.

Resistant Hypertension (RH) is defined as the absence of blood pressure (BP) control despite the use of three antihypertensive drugs in adequate doses, or the achievement of BP control with the use of four or more medications. The use of spironolactone, an antagonist of aldosterone receptors, as the fourth medication in the treatment of RH is recommended by current Management of Hypertension Guidelines, and its efficacy has been proved in clinical trials and meta-analysis. One clinical trial compared the use of clonidine, an adrenergic alpha-2 agonist, versus spironolactone as an option as the fourth drug in the treatment of RH. The results showed similar rates of the primary outcome (BP control at the office and at ambulatory monitoring) with both drugs, although spironolactone promoted greater reduction in 24h BP when compared with clonidine. In this context, clonidine can be used as an alternative to spironolactone, particularly among specific groups of patients that have contraindications to the use of spironolactone, such as patients with hyperkalemia or end stage renal disease.

Comparison of medical therapy with renal denervation in patients with resistant hypertension

Introduction: Catheter-based renal denervation selectively reduces renal sympathetic efferent activity and is accompanied by an increase in renal blood flow and reduction in plasma renin activity. Thus, ablation of afferent and efferent renal nerves in patients with treatment-resistant hypertension probably leads to reductions in blood pressure. Material and methods: The present study conducted a non-randomized case-control study and enrolled 15 patients who underwent renal denervation therapy for resistant hypertension as cases and 16 patients who were on medical management for resistant hypertension served as controls. Results: It was found that catheter based renal denervation is safe, significantly reduces blood pressure at 1 month, 3 months and 6 months of follow-up without any major adverse events. It was observed that a significant BP reduction when compared to patients only on medical therapy. The mean number of drugs decreased significantly in the denervation group in follow-up. Conclusions: Though the present study showed a significant BP reduction in patients with renal denervation, a significant effect on BP was not observed in a large randomized trial simplicity HTN-3 and major criticism was on the trials design and neuroscience failings. Even today the clinical dilemma is still continuing and further evaluation in rigorously designed clinical trials are necessary to validate alternative methods of renal denervation or to confirm previously reported benefits of renal denervation. The current study anticipate that future trials will also address the effectiveness of renal denervation in disease states other than hypertension.

Prevalence and clinical profile of patients with resistant hypertension

Objective: To find prevalence and clinical profile of patients with resistant hypertension. Methods: In a Prospective Observational Study, 100 Hypertensive patients were evaluated in Hypertension OPD, Medical OPD, and Medical Wards. Hypertensive Patient on more than 3 drugs with uncontrolled BP were included for this study. Patients were subjected to Clinical examination, Laboratory investigations and Ultrasound. BP is recorded in all 4 limbs with appropriate cuff size, Patients drug history (Both antihypertensive and other medications for concomitant illness will be enquired), Physical activity and Drug compliance were enquired. Result: Among the 100 patients studied, 18% patients were found to have Resistant hypertension. Of this, 5 patients were in incorrect drug combination, 7 patients were not drug compliant, 12 patients had Uncontrolled Diabetes, 15 patients had Dyslipidemia, 6 patients had Medical Renal disease, 2 patients had Fatty Liver, 1 patient had Contracted Kidney and 1 patient had Aortailiac Thrombosis. Conclusion: Incorrect Drug prescription, non-adherence to drugs and metabolic factors played a major role in resistant hypertension in the present study group.

Resistant and refractory hypertension: two sides of the same disease? / Hipertensão resistente e refratária: duas faces de uma mesma doença?

Abstract Refractory hypertension (RfH) is an extreme phenotype of resistant hypertension (RH), being considered an uncontrolled blood pressure besides the use of 5 or more antihypertensive medications, including a long-acting thiazide diuretic and a mineralocorticoid antagonist. RH is common, with 10-20% of the general hypertensives, and its associated with renin angiotensin aldosterone system hyperactivity and excess fluid retention. RfH comprises 5-8% of the RH and seems to be influenced by increased sympathetic activity. RH patients are older and more obese than general hypertensives. It is strongly associated with diabetes, obstructive sleep apnea, and hyperaldosteronism status. RfH is more frequent in women, younger patients and Afro-americans compared to RFs. Both are associated with increased albuminuria, left ventricular hypertrophy, chronic kidney diseases, stroke, and cardiovascular diseases. The magnitude of the white-coat effect seems to be higher among RH patients. Intensification of diuretic therapy is indicated in RH, while in RfH, therapy failure imposes new treatment alternatives such as the use of sympatholytic therapies. In conclusion, both RH and RfH constitute challenges in clinical practice and should be addressed as distinct clinical entities by trained professionals who are capable to identify comorbidities and provide specific, diversified, and individualized treatment.

Resumo A Hipertensão Arterial Refratária (HARf) representa um fenótipo extremo da hipertensão arterial resistente (HAR), sendo considerada a falência ao tratamento apesar do uso de 5 ou mais classes de anti-hipertensivos, incluindo um diurético tiazídico de longa ação e um antagonista mineralocorticoide. A HAR é comum (10-20%) entre os hipertensos em geral, sendo decorrente de hiperatividade do Sistema Renina Angiotensina Aldosterona e retenção hidrossalina. Aqueles com HARf correspondem a 5-8% dos resistentes e parecem sofrer maior influência catecolaminérgica. Os resistentes tendem a ter maior idade, ao sobrepeso e à obesidade. Comorbidades incluem diabetes, apneia obstrutiva do sono e status de hiperaldosteronismo. Refratários são afro-americanos em maior proporção, mais jovens e, predominantemente, mulheres. Ambos são fortemente associados à elevada albuminúria, HVE, doenças cardio e cerebrovasculares, além da doença renal crônica. O fenômeno do jaleco branco parece ser mais evidente nos resistentes. Quanto ao tratamento, a intensificação da terapia diurética está indicada nos resistentes, enquanto na HARf, a falência à terapia impôs novas alternativas de tratamento ("simpaticolíticas"). Em conclusão, tanto a HAR quanto a HARf constituem-se desafios na prática clínica e devem ser abordadas como entidades clínicas distintas por profissionais especialistas que identifiquem comorbidades e venham a prover um tratamento específico, diversificado e individualizado.

Hipertensión resistente en un paciente con aldosteroninsmo primario. Una presentación clínica inusual

En este reporte se presenta el caso de una paciente con hipertensión resistente que requería triple terapia antihipertensiva. Presentaba episodios súbitos de hipertensión, de predominio nocturno, cefalea, disnea, palpitaciones, dolor precordial, y se documentó ultrasonográficamente una masa suprarrenal izquierda. Estas manifestaciones clínicas podrían corresponder a hipertensión endocrina debida a feocromocitoma. No obstante, las pruebas de laboratorio mostraron hipocalemia, elevación de la aldosterona plasmática y supresión de la actividad de renina plasmática. Estos resultados fueron consistentes con aldosteronismo primario. Con la resección laparoscópica del adenoma suprarrenal, se normalizaron las cifras tensionales y las concentraciones de aldosterona y actividad de renina plasmática.

In this report we present a case of a patient with resistant hypertension treated with triple antihypertensive medication. The patient suffered of sudden episodes of nocturnal hypertension, headache, dyspnoea, palpitations, precordial pain and a left suprarenal mass was found in the abdominal ultrasound. These findings suggested endocrine hypertension due to pheochromocytoma.However, the laboratory tests showed hypokalemia, high plasma aldosterone concentrations and suppressed plasma renin activity. This results were consistent with primary aldosteronism. After the laparoscopic removal of the suprarenal adenoma blood pressure, plasma aldosterone concentrations and plasma renine activity returned to normal.

Parâmetros hemodinâmicos centrais estão alterados em hipertensos resistentes / Central hemodynamic parameters are changed in resistant hypertensive individuals

Objetivo: Correlacionar a excreção de sódio urinário 24 h, pressão arterial e parâmetros de rigidez arterial em indivíduos hipertensos. Casuística e Métodos: Foram avaliados 53 pacientes, submetidos a exames para medição da pressão arterial, em consultório e 24 h, e parâmetros de rigidez arterial, utilizando-se do equipamento Mobil O Graph®. Os pacientes foram divididos nos grupos Hipertensos Controlados e Hipertensos Resistentes. Foi realizado teste t não pareado com significância p < 0,05. Resultados: Média de idade foi de 64,32 anos; peso de 77,56 kg; altura de 1,61 m; e IMC de 29,68 kg/m2 . Hipertensos resistentes (25 indivíduos) possuem pressão arterial sistólica (p < 0,0001), pressão arterial diastólica (p = 0,004), pressão arterial sistólica 24 h (p < 0,0001), pressão arterial diastólica 24 h (p = 0,002), pressão de pulso (p < 0,0001), pressão arterial sistólica central (p = 0,0003) e pressão arterial diastólica central (p = 0,021) mais elevadas que hipertensos controlados (28 indivíduos). Conclusão: Pressões arteriais periférica e central são maiores em hipertensos resistentes do que em controlados. Excreção de Sódio não se relacionou com variáveis hemodinâmicas. Idade está relacionada com a elevação da pressão arterial central e da velocidade da onda de pulso. Augmentation index está relacionado com pressão arterial central.

Objective: Correlate daily sodium excreted in urine 24h, arterial blood pressure and arterial stiffness in patients with arterial hypertension. Patients and Methods: 53 patients were studied by non-invasive exam to measure their arterial pressure, arterial pressure in 24h and others parameters of arterial stiffness, using the device Mobil O Graph®. Patients were divided in two groups: controlled hypertensive patients and resistant hypertensive patients. Non-paired student t-test was applied, adopted value p < 0.05. Results: Mean age considering all patients were 64.32 years-old; weight were 77.56 kg; height were 1.61 m; and BMI were 29.68 kg/m2 . Resistant hypertensive individuals (N = 25) have systolic blood pressure (p < 0.0001), diastolic blood pressure (p = 0.004), systolic blood pressure 24h (p < 0.0001), diastolic blood pressure 24h (p = 0.002), pulse pressure (p < 0.0001), central systolic blood pressure (p = 0.0003) e central diastolic blood pressure (p = 0.021) higher than controlled hypertensive individuals (N = 28). Conclusion: Peripheral blood pressure, central blood pressure and pulse pressure are higher in resistant hypertensive patients than controlled hypertensive patients are. Sodium excretion is not relationated with hemodynamic parameters. Age is relationated with central blood pressure and pulse wave velocity. Augmentation index is relationated with central blood pressure.

Resistant Hypertension: A Clinical Case / Hipertensión resistente: un caso clínico / Hipertensão resistente: um caso clínico

Abstract Introduction: Secondary hypertension corresponds to 15 % of the causes of arterial hypertension, and among them, primary hyperaldosteronism presents a variable incidence of about 3 % in hypertensive patients. It has a slightly higher prevalence in women, between 30 and 60 years, and is usually unilateral. Case presentation: The authors describe the clinical case of a patient, followed by a severe hypertension medicated with four antihypertensive drugs for tension stabilization, maintaining systolic arterial tensions superior to 170 mmHg. In the aetiological study of hypertension, analytical alterations suggested hyperaldosteronism and a nodular lesion was detected in the left adrenal gland. The patient was submitted to surgery and excision of the lesion was done with histological confirmation of the diagnosis of corticomedullary adenoma of the adrenal gland. The patient presented improvement of the tension profile, with need to suspend two of the four antihypertensive drugs and to reduce the dose of the remaining ones. Conclusion: A tumor of the adrenal cortex producing aldosterone is the main cause of primary hyperaldosteronism and should always be excluded when the presence of difficult to control, severe hypertension is detected, since the standard treatment is surgical, leading to a stabilization of the tension pattern after a few months.

Resumen Introducción: la hipertensión secundaria corresponde al 15 % de las causas de hipertensión arterial, y entre ellas, el hiperaldosteronismo primario presenta una incidencia variable de sobre 3 % en pacientes hipertensos. Tiene una prevalencia ligeramente mayor en mujeres, entre 30 y 60 años, y generalmente es unilateral. Presentación del caso: los autores describen el caso clínico de un paciente, seguido por una hipertensión resistente medicada con cuatro fármacos antihipertensivos para la estabilización de la tensión, con mantenimiento de las tensiones arteriales sistólicas superiores a 170 mmHg. Las alteraciones analíticas en el estudio etiológico de la hipertensión sugirieron hiperaldosteronismo y una lesión nodular en la glándula suprarrenal izquierda. El paciente fue sometido a cirugía y se realizó la escisión de la lesión con confirmación histológica del diagnóstico de adenoma corticomedular de la glándula suprarrenal. El paciente presentó una mejora en el perfil de tensión, con la necesidad de suspender dos de los cuatro fármacos antihipertensivos y reducir la dosis de los restantes. Discusión: un tumor de la corteza suprarrenal que produce la aldosterona es la principal causa de hiperaldosteronismo primario y siempre debe excluirse cuando se presenta hipertensión grave, difícil de controlar, ya que el tratamiento estándar es quirúrgico y conduce a una estabilización del patrón de tensión después de unos meses.

Resumo Introdução: a hipertensão secundária corresponde ao 15 % das causas de hipertensão arterial, e entre elas, o hiperaldosteronismo primário apresenta uma incidência variável de sobre 3 % em pacientes hipertensos. Tem uma prevalência ligeiramente maior em mulheres, entre 30-60 anos, e geralmente é unilateral. Apresentação do caso: os autores descrevem o caso clínico de um paciente, seguido por uma hipertensão resistente medicada com quatro fármacos anti-hipertensivos para a estabilização da tensão, com manutenção das tensões arteriais sistólicas a 170 mmHg. As alterações analíticas no estudo etiológico da hipertensão sugeriram hiperaldosteronismo e uma lesão nodular na glândula suprarrenal esquerda. O paciente foi submetido a cirurgia e se realizou a incisão da lesão com confirmação histológica do diagnóstico de adenoma córtico-medular da glândula suprarrenal. O paciente apresentou uma melhora no perfil de tensão, com a necessidade de suspender dois dos quatro fármacos anti-hipertensivos e reduzir a dose dos restantes. Discussão: um tumor do córtex suprarrenal que produz a aldosterona é a principal causa de hiperaldosteronismo primário e sempre deve excluir-se quando se apresenta hipertensão grave, difícil de controlar, pois o tratamento standard é cirúrgico e conduz a uma estabilização do patrão de tensão depois de uns meses.

Blood pressure-lowering efficacy of Spironolactone in patients with Resistant Hypertension: A meta-analysis

Introduction@#Resistant hypertension (RH) is defined as a blood pressure (BP) reading that remains above goal despite concurrent use of three optimally dosed antihypertensives of different classes, including a diuretic. Spironolactone, a mineralocorticoid receptor antagonist, has shown significant benefit in reduction of BP in recent trials and is used empirically as an add-on therapy for RH. The researchers’ objective is to evaluate the BP-lowering efficacy of spironolactone in patients with resistant hypertension.@*Methods@#A meta-analysis was performed on randomized controlled trials (RCTs) comparing office or home BP reduction using spironolactone with placebo or an alternative drug regimen on top of standard-triple drug therapy among patients with RH. The study was conducted in reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).@*Results@#Five RCTs were included comprising a total of 662 patients. Three of these studies were found to have low risk of bias while two had unclear risk of bias. Compared to placebo, the addition of spironolactone significantly decreased office systolic BP (weighted mean difference [WMD]= -16.33, 95% confidence interval [CI]=-24.68 to -7.97, P=0.0001) and office diastolic BP (WMD=-6.12, 95% CI= -9.35 to -2.89, P=0.0002). Compared to an alternative drug regimen, additional spironolactone resulted in a significantly greater reduction in office systolic BP (WMD=-4.58mmHg, 95% CI=-7.19, -1.97, P= 0.0006) and home systolic BP (WMD= -4.33, 95% CI= 5.55, -3.12, P< 0.00001); while the addition of spironolactone had no significant difference compared to an alternative drug regimen in reducing office diastolic BP (WMD=-3.35, 95% CI=-12.08 to +5.38, P=0.45) and home diastolic BP (WMD= 0.00, 95 % CI=-0.73 to 0.73, P=1.0).@*Conclusion@#Spironolactone, when added to triple-drug anti-hypertensive therapy, showed significant reduction of systolic office and home BP. It should be considered as the add-on medication of choice for BP reduction in patients with RH.

Papel de la espironolactona en el tratamiento de la hipertensión arterial resistente / Role of spironolactone in the treatment of resistant hypertension

Resumen Este artículo aporta herramientas útiles para el diagnóstico y el diagnóstico diferencial de la hipertensión arterial resistente. En él, se refieren las recomendaciones de las principales guías internacionales de tratamiento respecto de las cifras meta de presión arterial, la incapacidad o falla del tratamiento triple en un amplio porcentaje de pacientes y los factores para la elección racional del cuarto agente para la institución de un tratamiento cuádruple. Esta elección se basa en la capacidad de la espironolactona -antagonista de los receptores de aldosterona- para inhibir los efectos nocivos de la aldosterona que dificultan el control de la presión arterial e incrementan el riesgo cardiovascular en un alto porcentaje de pacientes.

Abstract This article provides useful tools for the diagnosis and differential diagnosis of resistant hypertension. Here, we refer the recommendations of the main international guidelines of management respect to the target goals of the blood pressure, the failure of triple therapy in a large percentage of patients and the factors for the rational choice of the fourth agent for the institution of a quadruple therapy. This choice is based on the ability of spironolactone, antagonist of aldosterone receptors, to inhibit the deleterious effects of aldosterone that difficult the control of blood pressure and increase the cardiovascular risk in a high percentage of patients.

Diagnosis and management of primary aldosteronism

ABSTRACT Primary aldosteronism (PA) is the most common form of secondary hypertension (HTN), with an estimated prevalence of 4% of hypertensive patients in primary care and around 10% of referred patients. Patients with PA have higher cardiovascular morbidity and mortality than age- and sex-matched patients with essential HTN and the same degree of blood pressure elevation. PA is characterized by an autonomous aldosterone production causing sodium retention, plasma renin supression, HTN, cardiovascular damage, and increased potassium excretion, leading to variable degrees of hypokalemia. Aldosterone-producing adenomas (APAs) account for around 40% and idiopathic hyperaldosteronism for around 60% of PA cases. The aldosterone-to-renin ratio is the most sensitive screening test for PA. There are several confirmatory tests and the current literature does not identify a "gold standard" confirmatory test for PA. In our institution, we recommend starting case confirmation with the furosemide test. After case confirmation, all patients with PA should undergo adrenal CT as the initial study in subtype testing to exclude adrenocortical carcinoma. Bilateral adrenal vein sampling (AVS) is the gold standard method to define the PA subtype, but it is not indicated in all cases. An experienced radiologist must perform AVS. Unilateral laparoscopic adrenalectomy is the preferential treatment for patients with APAs, and bilateral hyperplasia should be treated with mineralocorticoid antagonist (spironolactone or eplerenone). Cardiovascular morbidity caused by aldosterone excess can be decreased by either unilateral adrenalectomy or mineralocorticoid antagonist. In this review, we address the most relevant issues regarding PA screening, case confirmation, subtype classification, and treatment.

Effect of the continuous positive airway pressure on refractory hypertension in patients with obstructive sleep apnea hypopnea syndrome / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the effect of continuous positive airway pressure(CPAP) on blood pressure in patients with obstructive sleep apnea hypopnea syndrome(OSAHS) and refractory hypertension.METHODS Fifty five OSAHS patients with refractory hypertension were treated with CPAP.Ambulatory blood pressure monitoring was performed to the patients before and 6 months after the treatment.RESULTS After treatment,the blood pressure of all the patients decreased at different degrees.The mean of 24 h systolic blood pressure(SBP) and 24 h diastolic blood pressure(DBP) decreased from (136.4±2.8)mmHg and (85.6± 1.7)mmHg to (126.9± 1.0)mmHg and (76.8± 1.3)mmHg,the differences were statistically significant(P＜0.05).The mean decrease of 24 h SBP and DBP were (9.6 ± 3.0)mmHg and (8.7± 2.0)mmHg.The decrease value of 24 h SBP and DBP were concerned with apnea and hypopnea index.The numbers of antihypertensive drugs decreased in 31 patients.CONCLUSION After CPAP treatment,the blood pressure of the patients with OSAHS and refractory hypertension dropped significantly,and the varieties of antihypertensive drugs taken in these patients were reduced significantly.

Renal sympathetic denervation guided by monitoring fractional flow reserve with pressure guide wire in pigs / 第二军医大学学报

Objective To explore the feasibility of the catheter-based renal sympathetic denervation (RDN) guided by monitoring fractional flow reserve (FFR) with pressure guide wire. Methods Eleven minipigs were allocated into RDN group (n=8) and sham operation group (n=3). Before ablation, the angiography of bilateral renal arteries was conducted. Ablation catheter and FFR pressure guide wire were implanted in the renal arteries guided by 7F guided catheter. Then renal arteries were observed by X-ray. The FFR value (renal artery pressure/aortic pressure) was monitored by electric stimulation (20 Hz). When the FFR value had significant change, the target was to be ablated (50°C, 10 W, 60 s). The ablation was considered effective once there was no change of the above indicators after a second stimulation immediately following ablation. Results Renal artery ablation was successfully completed in all the 8 pigs of RDN group. FFR values were monitored before and after ablation, and the results showed that the FFR values were significantly decreased upon stimulation before RDN (0.73±0.07 vs 0.98±0.02, P<0.01), and the FFR values were almost unchanged immediately after ablation (0.97±0.03 vs 0.95±0.02,P=0.25), which was not observed in the sham operation group. Conclusion There is significant difference in the FFR values of the target following stimulation before and after RDN. The FFR pressure guide wire-mediated target ablation may become a new operation mode, with its effectiveness and mechanism needed to be further verified.