Effect of Sequential Nephron Blockade versus Dual Renin-Angiotensin System Blockade Plus Bisoprolol in the Treatment of Resistant Hypertension, a Randomized Controlled Trial (Resistant Hypertension on Treatment - ResHypOT).

Introduction: Hypertension is the most important modifiable risk factor for cardiovascular disease and a leading public health concern. Objectives: The primary aim was to compare sequential nephron blockade (SNB) versus dual renin-angiotensin system blockade (DRASB) plus bisoprolol in patients with resistant hypertension to observe reductions in systolic and diastolic blood pressure (SBP and DBP) levels after 20 weeks of treatment. Material and Methods: This trial was an open-label, prospective, randomized, parallel-group, clinical study with optional drug up-titration. Participants were evaluated during five visits at 28-day intervals. Results: The mean age was 55.5 years in the SNB and 58.4 years in the DRASB + bisoprolol group (p=NS). Significant office BP reductions were observed in both groups. SNB group, SBP decreased from 174.5±21.0 to 127.0±14.74 mmHg (p<0.0001), and DBP decreased from 105.3±15.5 to 78.11±9.28 mmHg (p<0.0001). DRASB group, SBP decreased from 178.4±21.08 to 134.4 ± 23.25 mmHg (p<0.0001) and DBP decreased from 102.7±11.07 to 77.33±13.75 mmHg (p<0.0001). Ambulatory blood pressure monitoring (ABPM) showed also significant SBP and DBP reductions in both groups (p<0.0001). Conclusion: In patients with RHTN adherent to treatment, SNB and DRASB plus bisoprolol showed excellent therapeutic efficacy, although SNB was associated with earlier SBP reduction.

Linear and non-linear analyses of autonomic modulation in uncontrolled and controlled elderly resistant hypertensives.

Resistant hypertension (RHT) is associated with worse outcomes among patients, and sympathetic overactivity is a challenge in treating this clinical condition. Here, we evaluated the autonomic modulation (by linear and non-linear analyses), central blood pressure, and pulse wave velocity in controlled and uncontrolled RHT patients, as well as those in use of beta-blockers. We observed that uncontrolled RHT patients display, in addition to an increase in peripheral blood pressure, presented higher central blood pressure values concerning controlled RHT. Furthermore, despite the use of beta-blockers, both patients in the RHT + beta-blockers and uncontrolled RHT groups had negative changes in autonomic balance as compared with controlled RHT. These results reinforce the importance of autonomic nervous system interventions in managing arterial hypertension.

Qual o papel do bloqueio sequencial do néfron na hipertensão resistente? / What is the role of sequential nephron blockade in resistant hypertension?

A hipertensão resistente (HAR) ocorre quando a pressão arterial (PA) permanece acima da meta recomendada após o uso de três fármacos anti-hipertensivos com ação sinérgica em suas doses máximas toleradas recomendadas, preferencialmente incluindo um diurético. A identificação da contribuição do volume intravascular e da renina sérica na manutenção dos níveis elevados da PA permite um tratamento mais eficaz da hipertensão, ao atuar sobre o controle do volume intravascular, equilíbrio de sódio e sobre os efeitos do sistema renina-angiotensina-aldosterona (SRAA) no rim. Bloqueio sequencial do néfron (BSN) consiste em um aumento progressivo na depleção de sódio usando um diurético tiazídico, um bloqueador do receptor mineralocorticoide (espironolactona), furosemida e, finalmente, amilorida. Os mecanismos de ação, as indicações e os efeitos adversos são discutidos na presente revisão.

Resistant hypertension (HAR) occurs when blood pressure (BP) remains above the recommended target after the use of three antihypertensive drugs with synergistic action at their maximum recommended tolerated doses, preferably including a diuretic. The identification of the contribution of intravascular volume and serum renin in maintaining high BP levels allows a more effective treatment of hypertension, by acting on the control of intravascular volume, sodium balance and on the effects of the renin-angiotensin-aldosterone system (RAS) in the kidney. Sequential nephron block (BSN) consists of a progressive increase in sodium depletion using a thiazide diuretic, a mineralocorticoid receptor blocker (spironolactone), furosemide and, finally, amiloride. Mechanisms of action, indications and adverse effects are discussed in the present review

Use of atypical antipsychotics and risk of hypertension: A case report and review literature.

Atypical antipsychotics is being considered in the treatment of "negative" symptoms of psychoses, such as schizophrenia. In this case report, we presented a case of a patient with psychiatric disorder who developed hypertension soon after starting using atypical antipsychotic. A 53-year-old woman had reported having episodes of tachycardia, nausea, headache and high blood pressure. At the time of the doctor's appointment, the blood pressure was 210/110 mmHg. According to the patient, she made use of simvastatin for dyslipidemia and started taking aripiprazole, an antipsychotic for approximately 40 days before the symptoms. The initial treatment was 20 mg of olmesartan, and examinations were requested. After 2 months, the patient returned with the examinations: altered serum lipids and the other results were normal. Ambulatory blood pressure monitoring showed an average of 24 h of 150/100 mmHg. Blood pressure was measured at the doctor's office; in regular use of 20 mg of olmesartan, it was 156/92 mmHg. The dosage of olmesartan was increased to 40 mg and 1.5 mg of indapamide was initiated. The patient returned after 20 days with a blood pressure of 146/90 mmHg. After approval from the psychiatrist, the Aripiprazole was stopped, and the patient returned 15 days later with blood pressure of 120/80 mmHg. The ambulatory blood pressure monitoring control showed an average of 24 h of 130/78 mmHg. The Dopamine receptors play a role in the regulation of the blood pressure and the alterations in this system can lead to hypertension. D1, D3 and D4 receptors interact with the renin-angiotensin-aldosterone system, while D2 and D5 interact with the sympathetic nervous system in the regulation of PA. The case reported and the literature review bring to light the discussion of the use of atypical antipsychotics and its adverse events. If necessary, the use of these drugs should be followed by careful monitoring of blood pressure.

Hipertensão e acidente vascular cerebral / Hypertension and cerebrovascular accident

Acidente vascular cerebral (AVC) é a principal causa de mortalidade cardiovascular no Brasil e a segunda no mundo. Manifesta-se por desenvolvimento rápido de déficit neurológico permanente ou transitório, decorrente da interrupção do fluxo sanguíneo encefálico por obstrução ou ruptura de vasos. A gravidade depende do tipo e da extensão anatômica da lesão. O conceito de AVC como emergência médica ainda não está bem estabelecido no Brasil e o consequente atraso do tratamento na fase aguda tem importante influência na mortalidade. Hipertensão arterial é o principal fator de risco modificável para AVC agudo e recorrente. Nesse contexto, diversos estudos focalizam o controle da PA como alvo principal da prevenção e recorrência do AVC e seus desfechos secundários. A redução da PA durante um evento cerebral agudo, geralmente é segura, entretanto sabe-se que não se acompanha de redução da mortalidade ou diminuição de incapacidade decorrentes do evento. Além disso, questiona-se o benefício da redução da PA sobre desfechos funcionais no AVC isquêmico. Em relação ao AVC hemorrágico, redução aguda e intensiva da PAS1 não demonstrou redução de mortalidade ou incapacidade, no entanto parece melhorar desfechos funcionais. Com o objetivo de oferecer a base adequada para discussão do tratamento anti-hipertensivo no AVC agudo e crônico iniciaremos a abordagem conceituando o AVC e a seguir serão apontados aspectos epidemiológicos, fisiopatológicos e finalmente terapêuticos.

Stroke, the main cause of cardiovascular mortality in Brazil and the second in the world, manifests by the rapid development of permanent or transitory neurological deficit caused by the interruption of cerebral blood flow due to the obstruction or rupture of vessels. Severity depends on the type and anatomical extent of the lesion. The concept of stroke as a medical emergency is still not well established in Brazil and so there is a consequent delay in acute treatment, which reflects on the mortality rate. Arterial hypertension is the main modifiable risk factor for acute and recurrent stroke. In this context, several studies focus on blood pressure (BP) control as the main target to prevent recurrent strokes and complications. The reduction of BP during an acute brain event is generally safe, but it is known that it is not accompanied by a reduction in the mortality or a decrease in disability related to the event. In addition, the benefit of BP reductions on functional outcomes in ischemic stroke is questioned. Regarding hemorrhagic stroke, acute and intensive reductions in systolic BP1 did not show a reduction in the mortality or disability, however, they seem to improve functional outcomes. In order to provide an adequate basis for the discussion of antihypertensive treatment in acute and chronic stroke, we will start the approach by conceptualizing stroke and then describe epidemiological, pathophysiological and finally therapeutic aspects.

Resistant Hypertension On Treatment (ResHypOT): sequential nephron blockade compared to dual blockade of the renin-angiotensin-aldosterone system plus bisoprolol in the treatment of resistant arterial hypertension - study protocol for a randomized controlled trial.

BACKGROUND: Resistant hypertension is characterized when the blood pressure (BP) remains above the recommended goal after taking three antihypertensive drugs with synergistic actions at their maximum recommended tolerated doses, preferably including a diuretic. Identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether acting on the control of intravascular volume or sodium balance, or acting on the effects of the renin-angiotensin-aldosterone system (RAAS) on the kidney. METHODS/DESIGN: This is a randomized, open-label, clinical trial is designed to compare sequential nephron blockade and its contribution to the intravascular volume component with dual blockade of the RAAS plus bisoprolol and the importance of serum renin in maintaining BP levels. The trial has two arms: sequential nephron blockade versus dual blockade of the RAAS (with an angiotensin converting enzyme (ACE) inhibitor plus a beta-blocker) both added-on to a thiazide diuretic, a calcium-channel blocker and an angiotensin receptor-1 blocker (ARB). Sequential nephron blockade consists in a progressive increase in sodium depletion using a thiazide diuretic, an aldosterone-receptor blocker, furosemide and, finally, amiloride. On the other hand, the dual blockade of the RAAS consists of the progressive addition of an ACE inhibitor until the maximum dose and then the administration of a beta-blocker until the maximum dose. The primary outcomes will be reductions in the systolic BP, diastolic BP, mean BP and pulse pressure (PP) after 20 weeks of treatment. The secondary outcomes will evaluate treatment safety and tolerability, biochemical changes, evaluation of renal function and recognition of hypotension (ambulatory BP monitoring (ABPM)). The sample size was calculated assuming an alpha error of 5% to reject the null hypothesis with a statistical power of 80% giving a total of 40 individuals per group. DISCUSSION: In recent years, the cost of resistant hypertension (RH) treatment has increased. Thus, identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether by acting on the control of intravascular volume or sodium balance, or by acting on the effects of the RAAS on the kidney. TRIAL REGISTRATION: Sequential Nephron Blockade vs. Dual Blockade Renin-angiotensin System + Bisoprolol in Resistant Arterial Hypertension (ResHypOT). ClinicalTrials.gov, ID: NCT02832973 . Registered on 14 July 2016. First received: 12 June 2016. Last updated: 18 July 2016.

Controle da pressão central em paciente obeso, após infarto do miocárdio / Control of central pressure in an obese patient, post myocardial infarction

Pacientes hipertensos com evento cardiovascular agudo requerem intervenção adequada com alcance precoce de metas pressóricas pré-definidas, para redução de risco absoluto e residual de desfechos fatais e não fatais. O presente caso clínico trata-se de um paciente obeso, hipertenso que apresentou infarto agudo do miocárdio submetido a cateterismo e angioplastia com sucesso primário. Após alta da Unidade Coronariana, na enfermaria evoluiu com elevação dos valores pressóricos. Foram realizados teste de bioimpedância (para verificar volumetria) e avaliação da pressão central por tonometria de aplanação da artéria radial com Sphygmocor. A conduta a seguir foi orientada pelos resultados dos paramentos hemodinâmicos e realizada a escolha da medicação ideal para o tratamento

Hypertensive patients with an acute cardiovascular event require adequate intervention with early reach of pre-defined blood pressure goals to reduce absolute and residual risk of fatal and nonfatal outcomes. The present case is a hypertensive patient who presented acute myocardial infarction undergoing catheterization and angioplasty with primary success. After discharge from the Coronary Unit, the ward evolved with elevation of blood pressure values. Bioimpedance test (to verify volumetry) and evaluation of the central pressure by tonometry of radial artery aplanation with Sphygmocor were performed. The following conduct was guided by the results of the hemodynamic parameters and the choice of the ideal medication for the treatment was made.

Effects of transcutaneous electrical nerve stimulation (TENS) on arterial stiffness and blood pressure in resistant hypertensive individuals: study protocol for a randomized controlled trial.

BACKGROUND: Resistant hypertension (RH) treatment requires an adequate and intense therapeutic approach. However, the results are not always satisfactory despite intensive treatment. Of the different pathophysiological mechanisms involved in the pathogenesis of RH, sympathetic overstimulation and therapies that block the sympathetic system have been widely studied. These approaches, however, are invasive and expensive. Another possible approach is by transcutaneous electrical nerve stimulation (TENS), a noninvasive method that modulates activity by using low-frequency transcutaneous electrical stimulation to inhibit primary afferent pathways. Thus, the current study will evaluate the effect of applying TENS in the cervicothoracic region of subjects with RH and will seek to develop a new low-cost and readily available therapy to treat this group of hypertensive individuals. METHODS/DESIGN: This is a randomized, single blind (subject), parallel-assignment study controlled with a sham group and including participants aged 40 to 70 years with resistant hypertension. The trial has two arms: the treatment and control (sham group). The treatment group will be submitted to the stimulation procedure (TENS). The sham group will not be submitted to stimulation. The primary outcomes will be a reduction in the peripheral blood pressure and adverse events. The secondary outcomes will be a reduction the central blood pressure. The study will last 30 days. The sample size was calculated assuming an alpha error of 5 % to reject the null hypothesis with a statistical power of 80 %, thereby resulting in 28 participants per group (intervention versus sham). DISCUSSION: In recent decades, RH has become very common and costly. Adequate control requires several drugs, and in many cases, treatment is not successful. Sympathetic nervous system inhibition by renal denervation and central inhibition have significant effects in reducing BP; however, these treatments are costly and invasive. Another type of sympathetic nervous system inhibition can also be noninvasively achieved by electric current. Therefore, the application of TENS may be a new therapeutic option for treating resistant hypertensive individuals. TRIAL REGISTRATION: Clinical Trials NCT02365974.

Chlorthalidone Plus Amiloride Reduces the Central Systolic Blood Pressure in Stage 1 Hypertension Patients.

BACKGROUND: Hypertension reduction strategies use blood pressure in the brachial artery as the primary endpoint. Individuals who achieve the target blood pressure reduction with antihypertensive treatment have residual cardiovascular risk attributed to the difference in pressure between the aorta and brachial artery. Antihypertensive treatment affects the intrinsic properties of the vascular wall and arterial stiffness markers and consequently the central pressure. Recent publications stress the importance of adequate control of the central compared to peripheral blood pressure. Related clinical implications suggest that individuals with normal peripheral but high central blood pressure should not receive antihypertensive drugs that act on the central pressure. Therefore, they are at greater cardiovascular risk. The aim of the study was to evaluate the effect of treatment with a thiazide diuretic versus losartan on the central blood pressure in stage 1 hypertensive patients. METHODS: Twenty-five patients were randomized to the chlorthalidone 25 mg/amiloride 5 mg group (q.d.) and 25 patients received losartan 50 mg (b.i.d). The central systolic blood pressure (CSBP) and augmentation index (AIx 75) were assessed using applanation tonometry. The paired t-test was used to compare the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), CSBP and AIx 75 between the thiazide and losartan groups at baseline and after 6 months of treatment. RESULTS: Significant reductions in CSBP (123.3 ± 14.2 vs. 113.4 ± 111.4, P = 0.0103) and AIx 75 (87.7 ± 9.6 vs. 83.8 ± 8.9, P = 0.0289) were observed after 6 months of drug treatment with chlorthalidone 25 mg/amiloride 5 mg (q.d.). The administration of losartan 50 mg (b.i.d) did not reduce the CSBP and there were insignificant changes in the AIx 75. CONCLUSIONS: Six-month treatment of chlorthalidone/amiloride but not losartan reduces the CSBP and AIx 75 in adults with stage 1 hypertension.