RESUMO

Apparent resistant hypertension (aTRH) is a significant public health issue. Once low adherence to antihypertensive treatment has been ruled out and true resistant hypertension is diagnosed, aldosterone-direct-renin-ratio (ADRR) aids in the screening of an aldosterone-producing adenoma (APA) and primary aldosteronism (PA). Once PA and other secondary causes have been ruled out, the values of aldosterone and renin allow patients to be classified into phenotypes such as low renin hypertension (LRH), Liddle's-like (LLph), and primary hyperaldosteronism (PAph). These classifications could aid in the treatment decision-making process. However, optimal cut-off points for these classifications remain uncertain. This study aims to assess the prevalence of these phenotypes and the behavior of different cut-offs of the ADRR in an Afro-Colombian population with apparent resistant hypertension, as well to describe their sodium consumption. Afro-descendant individuals 18 years of age or older, diagnosed with resistant hypertension and attending to a primary care center in Colombia were recruited as volunteers. As part of the study, their plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured. The phenotypes were categorized into three groups based on multiple cut-off points from different authors: low renin and low aldosterone phenotype (LLph), low renin and high aldosterone phenotype (PAph), and high renin and high aldosterone phenotype, referred to as the renal phenotype (Rph). The prevalence of ADRR values exceeding the cut-off and phenotypes were calculated. A linear regression model was derived to assess the effect of sodium consumption with PAC, PRC and ADRR. A total of 88 patients with aTRH were included. Adherence to at least 3 antihypertensive medications was 62.5%. The median age was 56 years (IQR 48-60), 44% were female, and 20% had diabetes. The study found that the prevalence of ADRR values exceeding the cut-off ranged from 4.5 to 23%, while low-renin hypertension (LRH) varied from 15 to 74%, Rph was found in approximately 30 to 34% of patients, PAph in 30 to 51%, and the LLph in 15 to 41%, respectively, depending on the specific cut-off value by different authors. Notably, sodium consumption was associated with lower aldosterone (ß - 0.15, 95% CI [- 0.27, - 0.03]) and renin concentrations (ß - 0.75, 95% CI [- 1.5, - 0.02]), but ADRR showed no significant association with sodium consumption. There were no significant differences in prevalences between the groups taking < 3 vs ≥ 3 antihypertensive medications. Altered aldosterone-direct-renin-ratio, low renin hypertension, Liddle's-like, and primary hyperaldosteronism are prevalent phenotypes in patients within Afro-Colombian patients with apparent treatment-Resistant hypertension.

Assuntos

Aldosterona , Anti-Hipertensivos , Hipertensão , Fenótipo , Renina , Humanos , Renina/sangue , Aldosterona/sangue , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/sangue , Feminino , Pessoa de Meia-Idade , Masculino , Adulto , Anti-Hipertensivos/uso terapêutico , Hiperaldosteronismo/sangue , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/tratamento farmacológico , Hiperaldosteronismo/epidemiologia , População Negra , Idoso , Resistência a Medicamentos

RESUMO

PURPOSE OF REVIEW: Resistant Hypertension (RH) poses a significant public health challenge, contributing to increased mortality, cardiovascular events and organ damage. Both clinical and experimental research are striving for higher standards in a translational manner to integrate new findings and confirm hypotheses. Considering that many are the aspects of RH that are still under investigation, this review aims to shed light on the advances made in experimental research concerning RH. It seeks to underscore the pivotal role of experimental studies in shaping clinical practices and also explore future perspectives. RECENT FINDINGS: It is important to emphasize the significance of experimental models, primarily for advancing our understanding: experimental models have greatly contributed to our comprehension of the underlying mechanisms in RH, including factors like sympathetic activation, endothelial dysfunction and structural vessel abnormalities. Secondly, for assessing treatment approaches: animal models have also played a crucial role in evaluating the potential effectiveness of diverse treatment approaches for RH. These encompass both pharmacological options, involving combinations of established drugs or novel pharmaceuticals, and non-pharmacological alternatives, which include surgical procedures like renal denervation, medical devices like baroreceptor stimulators, and lifestyle modifications. The most lacking component in translational research is the fact that there is no well-established animal model that perfectly replicates RH. Consequently, alternative strategies, including the combination of models, must be considered. What remains clear is that the development of animal models closely mimicking RH holds the promise of providing valuable insights into the essential mechanisms and responses necessary to combat or slow the global progression of RH.

Assuntos

Anti-Hipertensivos , Modelos Animais de Doenças , Hipertensão , Humanos , Hipertensão/terapia , Hipertensão/fisiopatologia , Hipertensão/tratamento farmacológico , Animais , Anti-Hipertensivos/uso terapêutico , Resistência a Medicamentos

RESUMO

INTRODUCTION: New therapies for resistant hypertension (RH), including renal denervation (RDN), have been studied. AIM: Access the safety and effectiveness of radiofrequency-based RDN vs pharmacological treatment for RH. METHODS: A thorough literature search was conducted across PubMed, EMBASE, and the Cochrane databases, focusing on studies that compared the effects of radiofrequency-based RDN versus pharmacological treatment for RH. Treatment effects for binary and continuous endpoints were pooled and used, respectively, odds-ratio (OR) and mean differences (MD) with 95% confidence intervals (CI) to analyze continuous outcomes. RESULTS: In the 10 included studies, involving 1.182 patients, 682 received radiofrequency-based RDN. The follow-up period ranged from 6 to 84 months. Analysis revealed that the RDN group had a significant reduction in office systolic blood pressure (BP) (MD - 9.5 mmHg; 95% CI - 16.81 to - 2.29; P = 0.01), office diastolic BP (MD - 5.1 mmHg; 95% CI - 8.42 to - 2.80; P < 0.001), 24 h systolic BP (MD - 4.8 mmHg; 95% CI - 7.26 to - 2.42; P < 0.001). For 24 h diastolic BP RDN did not have a significant reduction (MD - 2.3 mmHg; 95% CI - 4.19 to - 0.52; P = 0.012). The heterogeneity between the studies was high, visible in the funnel and Baujat plots. The OR was non-significant for non-serious adverse events, but also clinically significant for hypertensive crises and strokes for the RDN group. CONCLUSIONS: While the pharmacological regimen of 3 or more anti-hypertensive, including a diuretic, still be the first-line option for RH treatment, our results support that radiofrequency-based RDN is superior in reducing global BP and is safe.

Assuntos

Anti-Hipertensivos , Pressão Sanguínea , Ablação por Cateter , Resistência a Medicamentos , Hipertensão , Rim , Simpatectomia , Humanos , Resultado do Tratamento , Hipertensão/fisiopatologia , Hipertensão/cirurgia , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Pressão Sanguínea/efeitos dos fármacos , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Ablação por Cateter/efeitos adversos , Rim/inervação , Pessoa de Meia-Idade , Simpatectomia/efeitos adversos , Simpatectomia/métodos , Feminino , Masculino , Idoso , Fatores de Risco , Artéria Renal/inervação , Artéria Renal/cirurgia , Fatores de Tempo , Adulto

RESUMO

This review provides an overview of the efficacy and safety of renal sympathetic denervation as a therapeutic approach for resistant hypertension. While the initial enthusiasm was sparked by the results of early clinical trials, it was dampened by the findings of the Symplicity HTN-3 study. However, recent advances in catheter technology and more refined patient selection criteria have yielded more promising results. Subsequent studies, such as SPYRAL HTN-OFF MED and RADIANCE II, demonstrated significant reductions in blood pressure, even in patients with mild to moderate hypertension. Despite the lack of robust data on major clinical outcomes, investigations into the time in therapeutic range for patients undergoing renal sympathetic denervation suggested potential cardiovascular benefits. Nevertheless, further research is needed to thoroughly understand the long-term impact, assess cost-effectiveness, and accurately identify which patient subgroups may derive the greatest benefits from this therapy.

---

Esta revisión brinda una síntesis de la eficacia y la seguridad de la denervación simpática renal como enfoque terapéutico para la hipertensión resistente. A pesar del entusiasmo inicial generado por los resultados de los primeros ensayos clínicos, la eficacia de esta terapia se vio comprometida por los hallazgos negativos del estudio Symplicity HTN-3. Sin embargo, recientes avances en la tecnología de catéteres y una refinada selección de los pacientes han proporcionado resultados más prometedores. Estudios posteriores, como SPYRAL HTN-OFF MED y RADIANCE II, demostraron reducciones significativas en la presión arterial, incluso en pacientes con hipertensión de leve a moderada. A pesar de la falta de datos sólidos sobre desenlaces clínicos importantes, las investigaciones sobre el tiempo en rango terapéutico de los pacientes sometidos a denervación simpática renal sugirieron posibles beneficios cardiovasculares. No obstante, se requiere una mayor investigación para comprender a fondo el impacto a largo plazo, evaluar la relación costo-efectividad y determinar con precisión qué subgrupos de pacientes podrían obtener los mayores beneficios de esta terapia.

Assuntos

Hipertensão , Rim , Simpatectomia , Humanos , Simpatectomia/métodos , Hipertensão/cirurgia , Rim/inervação

RESUMO

OBJECTIVE: Reducing maternal morbidity and mortality has been a challenge for low and middle-income countries, especially in the setting of hypertensive disorders of pregnancy. Improved strategies for treating obstetric patients with resistant hypertension are needed. We sought to explore whether hemodynamic parameters may be used to identify patients that develop resistant hypertension in pregnancy. METHODS: Retrospective cohort study among pregnant patients with gestational hypertension or preeclampsia that experienced severe blood pressure elevations. Hemodynamic variables were evaluated, including cardiac output (CO), and total peripheral resistance (TPR). The primary endpoint was resistant hypertension. An exploratory logistic regression was performed to evaluate the association between the hemodynamic profile and the development of resistant hypertension. Adverse maternal and fetal outcomes were additionally described according to the presence of resistant hypertension. RESULTS: Fifty-seven patients with severe pregnancy hypertension were included, of whom 34 developed resistant hypertension (59.7%). The resistant hypertension group, in comparison to those without resistant hypertension, presented with a hypodynamic profile characterized by reduced CO < 5 L/min (41.2% vs. 8.7%, p: 0.007), and increased TPR > 1400 dyn-s/cm5 (64.7% vs. 39.1%, p: 0.057). Logistic regression analysis revealed an association between a hypodynamic profile and resistant hypertension (OR 3.252, 95% CI 1.079-9.804; p = 0.035). Newborns of the resistant hypertension group had more frequent low birth weight (<2500 g), low Apgar scores, ICU admissions, and acute respiratory distress syndrome. CONCLUSION: Patients experiencing hypertensive crisis during pregnancy and exhibiting a hypodynamic profile (TPR ≥1400 dyn·s/cm5 and CO ≤ 5 L/min) developed higher rates of resistant hypertension.

Assuntos

Hipertensão Induzida pela Gravidez , Crise Hipertensiva , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Recém-Nascido , Estudos Retrospectivos , Hemodinâmica

RESUMO

Resistant hypertension (RH) is characterized by being difficult to control, even with the use of various antihypertensive drugs and is associated with target organ lesions and other comorbidities. Thus, new treatment alternatives such as transcutaneous electrical nerve stimulation (TENS) can offer benefits to resistant hypertensive patients by reducing blood pressure (BP) in a non-invasive way and without the need for the association of more antihypertensive drugs. In this case, a patient with RH was submitted to three weekly applications of TENS on the stellate ganglion lasting 40 min each for 1 month. Peripheral and central hemodynamic assessments were performed by 24-h ambulatory BP monitoring (ABPM) before and after TENS applications. After completion of the TENS applications, significant reductions in office systolic (SBP) and diastolic BP (DBP) were observed. There was also a decrease in peripheral SBP and DBP in the 24-h ABPM and sleep and SBP during wakefulness. Additionally, central parameters including central SBP and pulse wave velocity presented a significant reduction in the 24-h ABPM, during the wakefulness and sleep. TENS is able to attenuate the sympathetic hyperactivity present in RH cases and decrease the peripheral and central hemodynamic parameters of a resistant hypertensive patient.

Assuntos

Hipertensão , Estimulação Elétrica Nervosa Transcutânea , Humanos , Anti-Hipertensivos/uso terapêutico , Análise de Onda de Pulso , Hipertensão/diagnóstico , Hipertensão/terapia , Hipertensão/complicações , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial

RESUMO

Cardiac innervation by the parasympathetic nervous system (PNS) and the sympathetic nervous system (SNS) modulates the heart rate (HR) (chronotropic activity) and the contraction of the cardiac muscle (inotropic activity). The peripheral vasculature is controlled only by the SNS, which is responsible for peripheral vascular resistance. This also mediates the baroreceptor reflex (BR), which in turn mediates blood pressure (BP). Hypertension (HTN) and the autonomic nervous system (ANS) are closely related, such that derangements can lead to vasomotor impairments and several comorbidities, including obesity, hypertension, resistant hypertension, and chronic kidney disease. Autonomic dysfunction is also associated with functional and structural changes in target organs (heart, brain, kidneys, and blood vessels), increasing cardiovascular risk. Heart rate variability (HRV) is a method of assessing cardiac autonomic modulation. This tool has been used for clinical evaluation and to address the effect of therapeutic interventions. The present review aims (a) to approach the heart rate (HR) as a CV risk factor in hypertensive patients; (b) to analyze the heart rate variability (HRV) as a "tool" to estimate the individual risk stratum for Pre-HTN (P-HTN), Controlled-HTN (C-HTN), Resistant and Refractory HTN (R-HTN and Rf-HTN, respectively), and hypertensive patients with chronic renal disease (HTN+CKD).

RESUMO

The prognostic importance of obstructive sleep apnea (OSA) severity and other polysomnographic parameters in patients with resistant hypertension (RHT) has never been evaluated. We aimed to assess it in a prospective cohort of 422 individuals with RHT. OSA presence/severity was ascertained by complete polysomnography (PSG) at baseline. Multivariable Cox regressions assessed the risks associated with OSA severity and other PSG parameters (apnea-hypopnea index, sleep duration, nocturnal hypoxemia and periodic limb movements) for the primary (total cardiovascular events [CVEs] and all-cause mortality) and secondary outcomes (major CVEs). In the subgroup of patients with moderate/severe OSA, the risks associated with CPAP treatment were also estimated in relation to untreated individuals. One-hundred and eighty-six participants (44%) had no/mild OSA and 236 (56%) had moderate/severe OSA, and 67 of them were CPAP-treated. Over a mean follow-up of 5 years, there were 46 CVEs (37 major ones) and 44 all-cause deaths. Neither the presence of moderate/severe or severe OSA, nor being untreated during follow-up, was associated with significant excess risks for any outcome in relation to the subgroup with no/mild OSA. Similarly, no other PSG-derived parameter predicted any adverse outcome. Otherwise, CPAP treatment was associated with non-significant risk reductions of 37% for total CVEs, 49% for major CVEs and 63% for all-cause mortality in relation to those who remained untreated during follow-up. In conclusion, the presence/severity of OSA and its related PSG parameters were not associated with worse cardiovascular/mortality prognosis in patients with RHT. However, CPAP treatment might be protective in individuals with moderate/severe OSA.

Assuntos

Hipertensão , Apneia Obstrutiva do Sono , Humanos , Estudos Prospectivos , Prognóstico , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , Hipertensão/complicações , Pressão Positiva Contínua nas Vias Aéreas

RESUMO

PURPOSE: To evaluate (i) the outcome of swallowing therapy program on the rehabilitation of oropharyngeal dysphagia in resistant hypertensive patients with obstructive sleep apnea (OSA) and (ii) the association between the clinical and anthropometric characteristics of these individuals and this outcome. METHODS: This was a prospective interventional study in which resistant hypertensives diagnosed with OSA by polysomnography and dysphagia by fiberoptic endoscopic evaluation of swallowing (FESS) participated. All participants underwent a FEES and assessment of the risk of dysphagia (Eating Assessment Tool, EAT-10) and swallowing-related quality of life (Swal-QoL) before and after the intervention. The therapeutic program was performed daily by the participants, with weekly speech-therapist supervision for eight weeks, including the following strategies: Masako, chin tuck against resistance, and expiratory muscle training. RESULTS: A total of 26 (78.8%) of the participants exhibited improvement in the degree of dysphagia in the intervention outcome. After the intervention, there was a statistically significant improvement in the level of penetration-aspiration (p = 0.007), the degree of pharyngeal residue (p = 0.001), the site of onset of the pharyngeal phase (p = 0.001), and the severity of dysphagia (p = 0.001) compared to before intervention. The EAT-10 score was 2 (0-6) before and 0 (0-3) after intervention (p = 0.023). Swal-QoL had a score on the symptom frequency domain of 92.8 (75-100) before and 98.2 (87.5-100) after intervention (p = 0.002). CONCLUSIONS: Resistant hypertensive patients with OSA showed improved swallowing performance after swallowing therapy program.

Assuntos

Transtornos de Deglutição , Apneia Obstrutiva do Sono , Humanos , Deglutição/fisiologia , Transtornos de Deglutição/terapia , Transtornos de Deglutição/complicações , Qualidade de Vida , Fonoterapia , Estudos Prospectivos , Fala , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/diagnóstico

RESUMO

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.

Assuntos

Bisoprolol , Hipertensão , Humanos , Pessoa de Meia-Idade , Bisoprolol/efeitos adversos , Sistema Renina-Angiotensina , Anti-Hipertensivos/efeitos adversos , Monitorização Ambulatorial da Pressão Arterial , Estudos Prospectivos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Pressão Sanguínea , Néfrons

RESUMO

Previously, we demonstrated that acute transcranial direct current stimulation (tDCS) reduced blood pressure (BP) and improved autonomic modulation in hypertensives. We hypothesized that acute and short-term tDCS intervention can promote similar benefits in resistant hypertensive patients (RHT). We assessed the impact of one (acute intervention) and ten (short-term intervention) tDCS or SHAM (20 min, each) sessions on BP, pulse interval (PI) and systolic blood pressure variabilities, humoral mechanisms associated with BP regulation, and cytokines levels. True RHT subjects (n = 13) were randomly submitted to one and ten SHAM and tDCS crossing sessions (1 week of "washout"). Hemodynamic (Finometer®, Beatscope), office BP, and autonomic variables (accessed through spectral analysis of the pulse-to-pulse BP signal, in the time and frequency domain - Fast Fourrier Transform) were measured at baseline and after the short-term intervention. 24 h-ambulatory BP monitoring was measured after acute and short-term protocols. Acute intervention: tDCS reduced BP, cardiac output, and increase high-frequency band of PI (vagal modulation to the heart). Short-term protocol: tDCS did not change BP and cardiac output parameters. In contrast, central systolic BP (-12%), augmentation index (-31%), and pulse wave velocity (34%) were decreased by the short-term tDCS when compared to SHAM. These positive results were accompanied by a reduction in the low-frequency band (-37%) and an increase of the high-frequency band of PI (+62%) compared to SHAM. These findings collectively indicate that short-term tDCS concomitantly improves resting cardiac autonomic control and pulse wave behavior and reduces central BP in RHT patients, https://ensaiosclinicos.gov.br/rg/RBR-8n7c9p.

RESUMO

Systemic blood pressure (BP) may oscillate for homeostatic needs (equilibrium by constancy) or just as shifts in other intrinsic and extrinsic variables known as allostatic changes. This transitory pressure often rises alerts physicians to out-of-control hypertension or even hypertensive crisis. There is a very complex theory underlying these stochastic phenomena, which physicists and mathematicians translate into a single word: chaos. These changes happen according to a stochastic probabilistic pattern that presumes chaotic but somewhat predictable and nonlinear modeling of BP-related dynamics as a mathematical approach. Based on the chaos theory, small changes at the initial BP (baseline overtime) values could disturb the homeostasis leading to extreme BP chaotic shifts. These almost insignificant oscillations may also affect other variables and systems, leading to the misdiagnosis of hypertension, "out-of-control" BP levels, and resistant hypertension (RHT). Thus, these unpredictable and transient increases in BP values may be improperly diagnosed as the white coat and masked or resistant hypertension. Indeed, the interference of the chaos in any phenotype of (true or false) hard to control BP is not considered in clinical settings. This review provides some basic concepts on chaos theory and BP regulation. Besides pseudoresistant hypertension (lack of adherence, circadian variations, and others (white-coat, masked, early morning effects or hypertension), chaotic changes can be responsible for out-of-control hypertension.

Assuntos

Hipertensão , Hipertensão Mascarada , Hipertensão do Jaleco Branco , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão Mascarada/diagnóstico , Hipertensão do Jaleco Branco/diagnóstico

RESUMO

PURPOSE OF REVIEW: Resistant hypertension (R-HTN) is related to worse cardiovascular, renal outcomes, and death compared to non R-HTN. We aimed to review the burden of R-HTN across the world, focusing on its prevalence, associated factors and outcomes, and the impact of treatment. RECENT FINDINGS: R-HTN prevalence among hypertensive individuals varies around 10-20%, depending on the population and definition applied. R-HTN consistently relates to older age, chronic kidney disease, obesity, and obstructive sleep apnea - which are increasing in prevalence with global population aging. As such, R-HTN prevalence is also expected to rise. Infrequent use of ambulatory blood pressure monitoring to identify at higher risk individuals and poor adherence to treatment are still barriers in the approach of R-HTN. Available evidence suggests that 10-20% of patients with hypertension have R-HTN. However, the prevalence of true R-HTN using contemporaneous standardized definitions is still unknown. Novel strategies to address clinicians, patients and health system barriers to treatment inertia and adherence are fundamental to reduce the burden of R-HTN.

Assuntos

Hipertensão , Insuficiência Renal Crônica , Apneia Obstrutiva do Sono , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Masculino , Prevalência , Insuficiência Renal Crônica/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia

RESUMO

PURPOSE OF REVIEW: To perform a narrative systematic review on refractory hypertension (RfHT) with particular emphasis on prognosis. RECENT FINDINGS: There were 37 articles on RfHT, 13 non-systematic reviews, and 24 original studies. RfHT, a recently described extreme phenotype of anti-hypertensive treatment failure, shall be defined as uncontrolled out-of-office blood pressure (BP) levels despite the use of at least 5 anti-hypertensive drugs, including a long-acting diuretic and a mineraloreceptor antagonist. Its prevalence ranges from 0.5 to 4.3% of general treated hypertensives and between 3.6 and 51.4% of patients with resistant hypertension (RHT). RfHT is associated with younger age, African ancestry, obesity, hypertension-mediated organ damage and clinical cardiovascular diseases, and with some comorbidities, such as diabetes and obstructive sleep apnea. Its physiopathological mechanisms probably involve sympathetic overactivity and not volume overload. Patients with RfHT have a worse prognosis than non-refractory RHT individuals, with higher risks of adverse cardiovascular and renal outcomes and of mortality. RfHT represents a rare but true extreme phenotype of anti-hypertensive treatment failure distinct from RHT and with a significantly worse prognosis. Identifying such individuals is important to tailor specific interventions.

Assuntos

Hipertensão , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Diuréticos/uso terapêutico , Humanos , Prognóstico

RESUMO

Approximately 12-18% of hypertensive patients are diagnosed with resistant hypertension (RH). The risk of having worse cardiovascular outcomes is twice higher in those patients. The low effectiveness of conventional antihypertensive drugs in RH emphasizes the need to evaluate complementary drug therapies to achieve blood pressure (BP) control. Previous studies have demonstrated that phosphodiesterase 5 (PDE-5) inhibitors improve hemodynamics and reduce BP on essential hypertension. So, the authors aimed to summarize current clinical trials-based evidence published concerning the use of PDE-5 inhibitors on BP, cardiovascular function, and hemodynamics of patients with RH. We searched MEDLINE, EMBASE, LILACS, ClinicalTrials.gov, and WHO International Clinical Trials Registry databases on May 15th, 2020 using pre-defined search terms. Two independent reviewers assessed and extracted data from clinical trials that evaluated the effect of PDE-5 inhibitors on BP. We have included five articles in this systematic review. Four of them developed a single-day protocol, while one has developed a 14-day study. The main findings indicate that PDE-5 inhibitors ameliorate BP, vascular hemodynamics, and diastolic function parameters. Some data demonstrated improvement of endothelial function, but it was not a consensus. The side effects seemed to be limited and well-tolerated. In brief, our systematic review highlights the potential of PDE-5 inhibitors as a therapeutic alternative in addition to the multiple-drug regime for RH. Larger studies are still needed to determine whether the beneficial effects of PDE-5 inhibitors on RH would be maintained with chronic administration.

Assuntos

Hipertensão/tratamento farmacológico , Inibidores da Fosfodiesterase 5/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Diástole/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Inibidores da Fosfodiesterase 5/metabolismo

RESUMO

Here, we assessed the impact of one session of transcranial direct current stimulation (tDCS) or SHAM (20 min, each) on ventilatory responses to cardiopulmonary exercise test, central and peripheral blood pressure (BP), and autonomic modulation in resistant hypertensive (RHT) patients. RHT subjects (n = 13) were randomly submitted to SHAM and tDCS crossing sessions (1 week of "washout"). Patients and a technician who set the tDCS/Sham room up were both blind. After brain stimulation, patients were submitted to a cardiopulmonary exercise test to evaluate ventilatory and cardiovascular response to exercise. Hemodynamic (Finometer®, Beatscope), and autonomic variables were measured at baseline (before tDCS/Sham) and after incremental exercise. RESULTS: Our study shows that tDCS condition improved heart rate recovery, VO2 peak, and vagal modulation (after cardiopulmonary exercise test); attenuated the ventilatory variability response, central and peripheral blood pressure well as sympathetic modulation (after cardiopulmonary exercise test) in comparison with SHAM. These data suggest that acute tDCS sessions prevented oscillatory ventilation behavior during the cardiopulmonary exercise test and mitigated the increase of systolic blood pressure in RHT patients. After the exercise test, tDCS promotes better vagal reentry and improved autonomic modulation, possibly reducing central blood pressure and aortic augmentation index compared to SHAM. Brazilian Registry of Clinical Trials (ReBEC): https://ensaiosclinicos.gov.br/rg/RBR-8n7c9p.

Assuntos

Sistema Nervoso Autônomo/fisiologia , Pressão Sanguínea/fisiologia , Aptidão Cardiorrespiratória/fisiologia , Hipertensão/terapia , Ventilação Pulmonar/fisiologia , Estimulação Transcraniana por Corrente Contínua , Idoso , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade

RESUMO

Resistant arterial hypertension (RAH) is strongly associated with obstructive sleep apnea (OSA). Individuals with OSA may have subclinical swallow impairment, diagnosed by instrumental assessments, such as videofluoroscopy and fiberoptic endoscopic evaluation of swallowing (FEES). However, few studies have evaluated this population and included a control group of individuals without OSA. To evaluate, through FEES, the swallowing characteristics of resistant hypertensive patients with and without OSA and to investigate the association between the signs of swallow impairment and OSA. This was an observational study in which individuals with RAH underwent baseline polysomnography and were diagnosed with and without OSA. All participants underwent an initial assessment with the collection of demographic characteristics and FEES. Individuals were divided into 2 groups based on the presence or absence of OSA. Seventy-nine resistant hypertensive patients were evaluated: 60 with OSA (19 with mild OSA, 21 with moderate OSA, and 20 with severe OSA) and 19 without OSA. The most prevalent swallowing differences between groups with and without OSA were piecemeal deglutition, in 61.7% and 31.6%, respectively (p = 0.022); spillage, in 58.3% and 21.1% (p = 0.005); penetration/aspiration, in 55% and 47.4% (p = 0.561); and pharyngeal residue, in 51.5% and 26.3% (p = 0.053). The prevalence of swallow impairment among the participants in this study was 58.3% and 47.4% in the groups with OSA and without OSA, respectively (p = 0.402). This study shows a high prevalence of swallow impairment both in hypertensive patients with OSA and without OSA. The characteristics of swallowing associated with hypertensive patients with OSA are spillage, piecemeal deglutition, and the onset of the pharyngeal phase in the hypopharynx.

Assuntos

Transtornos de Deglutição , Hipertensão , Apneia Obstrutiva do Sono , Deglutição , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Humanos , Hipertensão/complicações , Sono , Apneia Obstrutiva do Sono/complicações

RESUMO

BACKGROUND: The available antihypertensive drugs are effective and well tolerated agents. However, only about half of patients with treated hypertension achieve appropriate blood pressure control. Genetic and non-genetic factors contribute to the interindividual variability of the therapeutic response. OBJECTIVE: This review constitutes a comprehensive update of the pharmacogenomics of antihypertensive drugs and their clinical implications in Brazil. RESULTS: Twenty-five studies explored the influence of gene variants on drug response in patients with primary, resistant, or gestational hypertension. Variants in BDKRB2, NOS3, PRKCA, and VEGFA influenced the response to enalapril in patients with primary hypertension. AGT and MMP2 variants were associated with a high risk of resistance to antihypertensive treatment, whereas NOS2 variants were related to low risk. Moreover, NAT2 slow acetylators showed an increased response to hydralazine in patients with resistant hypertension. HMOX1, NAMPT, MMP9, NOS3, and TIMP1 variants might be markers of drug responsiveness in hypertensive or preeclamptic pregnant women. Power and replication of studies, polygenic nature of the response to therapy, and treatment with multiple drugs were important challenges to identify genetic predictors of antihypertensive response in Brazil. CONCLUSION: Pharmacogenomic studies in Brazilian cohorts provide some evidence of variants, mainly in pharmacodynamics genes, which influence the response to antihypertensive drugs. However, some findings are limited by cohort size or therapeutic scheme and may be influenced by interactions with other genetic and non-genetic factors. Therefore, further investigations are needed to elucidate the contribution of pharmacogenomics to the efficacy and safety of antihypertensive therapy.

Assuntos

Anti-Hipertensivos , Hipertensão , Farmacogenética , Feminino , Humanos , Gravidez , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Brasil/epidemiologia , Hipertensão/tratamento farmacológico , Hipertensão/genética

RESUMO

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).

Assuntos

Humanos , Feminino , Pessoa de Meia-Idade , Artéria Renal/cirurgia , Artéria Renal/inervação , Hipertensão Renal