Acute and Short-Term Autonomic and Hemodynamic Responses to Transcranial Direct Current Stimulation in Patients With Resistant Hypertension.

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.

ACUTE TRANSCRANIAL DIRECT CURRENT STIMULATION (tDCS) IMPROVES VENTILATORY VARIABILITY AND AUTONOMIC MODULATION IN RESISTANT HYPERTENSIVE PATIENTS.

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.

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.

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.

Central blood pressure and aortic pulse wave reflection in water-exercised postmenopausal hypertensive women: A cross-sectional study.

Exercise training has been associated with the attenuation of cardiovascular impairment after menopause. This study aimed to compare central and peripheral blood pressure and aortic pulse wave reflection in sedentary and trained (aerobic exercise in the water) hypertensive postmenopausal women. Hypertensive postmenopausal women were divided into sedentary (SED, n = 53) and trained groups (TR, n = 31). Self-reporting from the trained group presented a mean of 1.7 ± 0.3 years of exercise practice in the water. Central blood pressure and amplification indexes (AIx) were obtained by the applanation tonometry of radial and aortic arteries. No changes were observed in systolic blood pressure (SBP) in the TR group than the SED group; however, office diastolic blood pressure (DBP) was reduced compared to the SED group. Central blood pressure and augmentation index (AIx@75%) values were similar in the SED and TR groups. These data suggest that self-reported long-term exercise training in the water could not improve central hemodynamic variables in postmenopausal hypertensive women compared to sedentary ones. However, it should be emphasized that DBP levels were reduced in trained subjects, which might reduce cardiovascular outcomes.

Acute effects of pharmacotherapies in blood pressure in normotensive moderate smokers.

This study was designed to evaluate the changes in arterial blood pressure (BP) and heart rate (HR) in moderate smokers during smoking abstinence after 7 days of treatment with bupropion alone, transdermal nicotine or bupropion combined with transdermal nicotine. Twenty-four healthy moderate smokers (12 female/12 male; 40+/-7 years) were evaluated randomly on five occasions and their systolic, diastolic, mean arterial blood pressure (MAP) and HR were measured by a Finapres device for 10 h, immediately after smoking interruption. All of the 24 smokers participated on five protocols during 7 days: control group (C) - no drugs; placebo group (PL); bupropion group (BUP) 150-300 mg; transdermal nicotine group (TN) - 21 mg; and BUP+TN-nicotine patch. Concomitantly, the subjects were evaluated by ABPM (ambulatory BP monitoring). All of BP parameters monitored shown significant statistical differences in the BUP, TN and BUP+TN groups compared with the controls (p<0.05), when measured by Finapres. The HR remained unaltered in all of the groups. No significant differences were seen in the BP or HR during the 24-h ABPM. These findings indicate that in moderate smokers, bupropion, transdermal nicotine or bupropion associated with transdermal nicotine caused an elevation in the BP after acute smoking interruption.

A Proposed Inflammatory Score of Circulating Cytokines/Adipokines Associated with Resistant Hypertension, but Dependent on Obesity Parameters.

BACKGROUND: There is evidence that subclinical systemic inflammation is present in resistant hypertension (RHTN). OBJECTIVE: The aim of the study was to develop an integrated measure of circulating cytokines/adipokines involved in the pathophysiology of RHTN. METHODS: RHTN (n = 112) and mild to moderate hypertensive (HTN) subjects (n=112) were studied in a cross-sectional design. Plasma cytokines/adipokines (TNF-alpha, interleukins [IL]-6, -8, -10, leptin and adiponectin) values were divided into tertiles, to which a score ranging from 1 (lowest tertile) to 3 (highest tertile) was assigned. The inflammatory score (IS) of each subject was the sum of each pro-inflammatory cytokine scores from which anti-inflammatory cytokines (adiponectin and IL-10) scores were subtracted. The level of significance accepted was alpha = 0.05. RESULTS: IS was higher in RHTN subjects compared with HTN subjects [4 (2-6) vs. 3 (2-5); p = 0.02, respectively]. IS positively correlated with body fat parameters, such as body mass index (r = 0.40; p < 0.001), waist circumference (r = 0.30; p < 0.001) and fat mass assessed by bioelectrical impedance analysis (r = 0.31; p < 0.001) in all hypertensive subjects. Logistic regression analyses revealed that IS was an independent predictor of RHTN (OR = 1.20; p = 0.02), independent of age, gender and race, although it did not remain significant after adjustment for body fat parameters. CONCLUSION: A state of subclinical inflammation defined by an IS including TNF-alpha, IL-6, IL-8, IL-10, leptin and adiponectin is associated with obese RHTN. In addition, this score correlates with obesity parameters, independently of hypertensive status. The IS may be used for the evaluation of conditions involving low-grade inflammation, such as obesity-related RHTN. Indeed, it also highlights the strong relationship between obesity and inflammatory process.

Metabolic Syndrome-Related Features in Controlled and Resistant Hypertensive Subjects.

BACKGROUND: Metabolic syndrome (MetS) is widespread among hypertensive patients. Clinical features and potential biomarkers of MetS in the presence of hypertension and resistant hypertension (RHTN) represent a great area of interest for investigation. OBJECTIVE: The purpose of this study was to evaluate the prevalence of MetS and the clinical features associated with it in resistant and mild to moderate hypertensives. METHODS: This cross-sectional study included 236 patients, (i) 129 mild to moderate hypertensive patients and (ii) 107 patients with RHTN. We measured blood pressure (BP) and adipokines levels, and performed bioelectrical impedance analysis. Microalbuminuria (MA), cardiac hypertrophy and arterial stiffness were also assessed. The significance level of alpha = 0.05 was adopted. RESULTS: We found a MetS prevalence of 73% in resistant and 60% in mild-to-moderate hypertensive patients. In a multiple regression analysis, MA (odds ratio = 8.51; p = 0.01), leptin/adiponectin ratio (LAR) (odds ratio = 4.13; p = 0.01) and RHTN (odds ratio = 3.75; p = 0.03) were independently associated with the presence of MetS apart from potential confounders. CONCLUSIONS: Our findings suggest that both resistant and controlled hypertensive subjects have a high prevalence of MetS. In addition, MetS-related metabolic derangements may cause early renal and hormonal changes. Finally, LAR may be useful as a reliable biomarker for identifying those hypertensive subjects who are at risk for developing MetS.

[Venous endothelial dysfunction in Chagas' disease patients without heart failure]. / Disfunção endotelial venosa em pacientes com doença de Chagas sem insuficiência cardíaca.

OBJECTIVE: To analyze the venous endothelial function in Chagas' disease patients without heart failure. METHODS: The Chagas' disease Group (G1) was composed by 14 women and 2 men aged 46 +/- 2.7 and the Control Group (G0) by 7 women and 1 man matched by age, weight and height. Dorsal Hand Vein Compliance Technique was used to evaluate the venous endothelial function. Crescent doses of phenylephrine were infused to get a 70% pre-constriction of the vein; after that, acetylcholine and sodium nitroprusside were respectively administrated to analyze the endothelium-dependent and -independent venodilation. RESULTS: No significant systemic hemodynamic changes were observed in both groups during the experiment. The necessary phenylephrine dose to reach 70% pre-constriction of the vein was significantly higher in the G1 (1116 +/- 668.2 ng/ml) compared to G0 (103 +/- 28 ng/ml) p = 0.05. The endothelium-dependent venous dilation was significantly lower in G1 (65.5 +/- 8%) compared to G0 (137 +/- 20%) p = 0.009. No difference was observed in the endothelium-independent venous dilatation between groups. CONCLUSION: Patients with Chagas' disease without heart failure presented venous endothelial dysfunction.

I RBH - First Brazilian Hypertension Registry.

BACKGROUND: A registry assessing the care of hypertensive patients in daily clinical practice in public and private centers in various Brazilian regions has not been conducted to date. Such analysis is important to elucidate the effectiveness of this care. OBJECTIVE: To document the current clinical practice for the treatment of hypertension with identification of the profile of requested tests, type of administered treatment, level of blood pressure (BP) control, and adherence to treatment. METHODS: National, observational, prospective, and multicenter study that will include patients older than 18 years with hypertension for at least 4 weeks, following up in public and private centers and after signing a consent form. The study will exclude patients undergoing dialysis, hospitalized in the previous 30 days, with class III or IV heart failure, pregnant or nursing, with severe liver disease, stroke or acute myocardial infarction in the past 30 days, or with diseases with a survival prognosis < 1 year. Evaluations will be performed at baseline and after 1 year of follow-up. The parameters that will be evaluated include anthropometric data, lifestyle habits, BP levels, lipid profile, metabolic syndrome, and adherence to treatment. The primary outcomes will be hospitalization due to hypertensive crisis, cardiocirculatory events, and cardiovascular death, while secondary outcomes will be hospitalization for heart failure and requirement of dialysis. A subgroup analysis of 15% of the sample will include noninvasive central pressure evaluation at baseline and study end. The estimated sample size is 3,000 individuals for a prevalence of 5%, sample error of 2%, and 95% confidence interval. RESULTS: The results will be presented after the final evaluation, which will occur at the end of a 1-year follow-up. CONCLUSION: The analysis of this registry will improve the knowledge and optimize the treatment of hypertension in Brazil, as a way of modifying the prognosis of cardiovascular disease in the country.

Nebivolol reduces central blood pressure in stage I hypertensive patients: experimental single cohort study.

CONTEXT AND OBJECTIVES: Assessment of central blood pressure (BP) has grown substantially over recent years because evidence has shown that central BP is more relevant to cardiovascular outcomes than peripheral BP. Thus, different classes of antihypertensive drugs have different effects on central BP despite similar reductions in brachial BP. The aim of this study was to investigate the effect of nebivolol, a ß-blocker with vasodilator properties, on the biochemical and hemodynamic parameters of hypertensive patients. DESIGN AND SETTING: Experimental single cohort study conducted in the outpatient clinic of a university hospital. METHODS: Twenty-six patients were recruited. All of them underwent biochemical and hemodynamic evaluation (BP, heart rate (HR), central BP and augmentation index) before and after 3 months of using nebivolol. RESULTS: 88.5% of the patients were male; their mean age was 49.7 ± 9.3 years and most of them were overweight (29.6 ± 3.1 kg/m2) with large abdominal waist (102.1 ± 7.2 cm). There were significant decreases in peripheral systolic BP (P = 0.0020), diastolic BP (P = 0.0049), HR (P < 0.0001) and central BP (129.9 ± 12.3 versus 122.3 ± 10.3 mmHg; P = 0.0083) after treatment, in comparison with the baseline values. There was no statistical difference in the augmentation index or in the biochemical parameters, from before to after the treatment. CONCLUSIONS: Nebivolol use seems to be associated with significant reduction of central BP in stage I hypertensive patients, in addition to reductions in brachial systolic and diastolic BP.

Hipertensão arterial resistente (HAR) / Resistant arterial hypertension (RAH)

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. Nesta definição está incluído o subgrupo de pacientes hipertensos resistentes, cuja PA é controlada com quatro ou mais medicamentos anti-hipertensivos, chamada de HAR controlada (HAR-C). A classificação da doença em HAR-C e HAR não controlada (HAR-NC), incluindo a HAR refratária (HAR-Ref), um fenótipo extremo de HAR-NC em uso de cinco ou mais anti-hipertensivos, é uma proposta que ganha espaço na literatura. Diante da suspeita clínica de HAR, é necessário verificar a confirmação diagnóstica, e a primeira etapa na investigação é a exclusão das causas de pseudorresistência, tais como falta de adesão ao tratamento (farmacológico e não farmacológico), posologia inadequada, técnica imprópria de aferição da PA e efeito do avental branco. O MAPA e o monitoramento residencial da pressão arterial (MRPA) são os exames para confirmação do controle inadequado da PA. Uma vez afastada a pseudorresistência, confirma-se a existência da HAR e inicia-se uma investigação diagnóstica com exames específicos, conforme a orientação das Diretrizes de Hipertensão em relação ao comprometimento de lesões em órgãos-alvo e hipertensão secundária. A ocorrência de comorbidades associadas deve ser detectada com exames especializados de acordo com a suspeita clínica. O objetivo do tratamento medicamentoso na HAR é detectar as causas do não controle e encontrar a melhor combinação de fármacos, visando o alcance das metas pressóricas com menor ocorrência de efeitos adversos e maior adesão. Em geral, busca-se otimizar o tratamento tríplice com os fármacos preferenciais, que são: IECA ou BRA, BCC di-hidropiridínico e DT.

Resistant hypertension (RHTN) is defined as blood pressure (BP) persistently above the recommended target values despite the use of three antihypertensive agents of different classes, including one blocker of the renin- angiotensin system (angiotensin-converting enzyme inhibitor [ACEI] or angiotensin receptor blocker [ARB]), one long- acting calcium channel blocker (CCB), and one long-acting thiazide diuretic (TD) at maximum recommended and tolerated doses, administered with appropriate frequency and doses and with proven adherence. The definition above includes a subgroup of patients with RHTN whose BP is controlled with four or more antihypertensive medications, known as controlled RHTN (C-RHTN). On clinical suspicion of RHTN, diagnostic confirmation is required, and the first step in the investigation is the exclusion of causes of pseudoresistance, such as lack of treatment adherence (pharmacological and non-pharmacological), inadequate dosing, improper BP measurement technique, and white-coat effect. Lack of BP control should be confirmed by ABPM and home blood pressure monitoring (HBPM). Secondary hypertension (SecH) is defined as increased BP due to an identifiable cause. Patients with RH should be investigated for the most prevalent causes of "non-endocrine" and "endocrine" SecH after exclusion of use of medications that may interfere with BP values: antiinflammatory drugs, glucocorticoids, nasal decongestants, appetite suppressants, antidepressants, immunosuppressants, erythropoietin, contraceptives, and illicit drugs. The objective of pharmacological treatment in RHTN is to identify the causes of lack of control and find the best combination of drugs, aiming at achieving the target BP with few adverse effects and greater adherence. In general, triple treatment optimization is attempted with preferred drugs, namely, ACEIs or ARBs, dihydropyridine CCBs, and TDs

A Proposed Inflammatory Score of Circulating Cytokines/Adipokines Associated with Resistant Hypertension, but Dependent on Obesity Parameters / Proposta de um Escore Inflamatório de Citocinas e Adipocinas Plasmáticas Associado à Hipertensão Resistente, mas Dependente dos Parâmetros de Obesidade

Abstract Background: There is evidence that subclinical systemic inflammation is present in resistant hypertension (RHTN). Objective: The aim of the study was to develop an integrated measure of circulating cytokines/adipokines involved in the pathophysiology of RHTN. Methods: RHTN (n = 112) and mild to moderate hypertensive (HTN) subjects (n=112) were studied in a cross-sectional design. Plasma cytokines/adipokines (TNF-alpha, interleukins [IL]-6, -8, -10, leptin and adiponectin) values were divided into tertiles, to which a score ranging from 1 (lowest tertile) to 3 (highest tertile) was assigned. The inflammatory score (IS) of each subject was the sum of each pro-inflammatory cytokine scores from which anti-inflammatory cytokines (adiponectin and IL-10) scores were subtracted. The level of significance accepted was alpha = 0.05. Results: IS was higher in RHTN subjects compared with HTN subjects [4 (2-6) vs. 3 (2-5); p = 0.02, respectively]. IS positively correlated with body fat parameters, such as body mass index (r = 0.40; p < 0.001), waist circumference (r = 0.30; p < 0.001) and fat mass assessed by bioelectrical impedance analysis (r = 0.31; p < 0.001) in all hypertensive subjects. Logistic regression analyses revealed that IS was an independent predictor of RHTN (OR = 1.20; p = 0.02), independent of age, gender and race, although it did not remain significant after adjustment for body fat parameters. Conclusion: A state of subclinical inflammation defined by an IS including TNF-alpha, IL-6, IL-8, IL-10, leptin and adiponectin is associated with obese RHTN. In addition, this score correlates with obesity parameters, independently of hypertensive status. The IS may be used for the evaluation of conditions involving low-grade inflammation, such as obesity-related RHTN. Indeed, it also highlights the strong relationship between obesity and inflammatory process.

Resumo Fundamento: Evidências indicam que a inflamação sistêmica subclínica está presente na hipertensão arterial resistente (HAR). Objetivo: Desenvolver uma medida que integra citocinas envolvidas na fisiopatologia da HAR. Métodos: Indivíduos com HAR (n = 112) e indivíduos com hipertensão leve a moderada (HT) (n = 112) foram estudados em delineamento transversal. Valores de citocinas/adipocinas plasmáticas [TNF-alfa, interleucinas (IL)-6, -8, -10, leptina e adiponectina] foram divididos em tercis, e lhes atribuído um escore variando de 1 (tercil mais baixo) a 3 (tercil mais alto). O escore inflamatório (EI) de cada participante foi calculado como a soma do escore de cada citocina pró-inflamatória da qual subtraiu-se o escore de cada citocina anti-inflamatória (adiponectina e IL-10). O nível de significância aceito foi alfa = 0,05. Resultados: O EI foi mais alto nos indivíduos com HAR em comparação a indivíduos com HT [4 (2-6) vs. 3 (2-5); p = 0,02, respectivamente]. O EI correlacionou-se positivamente com parâmetros de gordura corporal, tais como índice de massa corporal (r = 0,40; p < 0,001), circunferência da cintura (r = 0,30; p < 0,001) e massa gorda avaliada por bioimpedância (r = 0,31; p < 0,001) em todos os indivíduos hipertensos. Análises de regressão logística mostraram que o EI foi um preditor independente de HAR (OR = 1,20; p = 0,02), independentemente de idade, sexo e raça; porém, o modelo perdeu significância estatística após ajuste para os parâmetros de gordura corporal. Conclusão: Um estado de inflamação subclínica definida pelo EI incluindo TNF-alfa, IL-6, IL-8, IL-10, leptina e adiponectina está associado com indivíduos obesos com HAR. Além disso, o escore correlaciona-se com parâmetros de obesidade, independentemente do grau de hipertensão. O EI pode ser usado na avaliação de condições que envolvem inflamação subclínica, tal como HAR relacionada à obesidade. O estudo também destaca a forte relação entre obesidade e inflamação.

Neuropatia autonômica cardiovascular em pacientes com diabetes mellitus: perspectivas atuais / Cardiovascular autonomic neuropathy in patients with diabetes mellitus: current outlook

A neuropatia autonômica cardíaca (NAC) é uma complicação comum do diabetes mellitus (DM) e frequentemente, subdiagnosticada. A NAC está associada ao aumento da mortalidade, cardiovascular e renal, doença renal crônica e maior morbidade em pacientes com DM. Apesar dessas consequências, muitas vezes, a NAC permanece sem diagnóstico por um período prolongado. Isso geralmente porque a doença é assintomática até a fase avançada, bem como pela falta de informações e de estratégias de triagem. Clinicamente NAC se manifesta por distúrbios funcionais ou condições clínicas que envolvem desajuste das atividades reflexas cardiovasculares, tais como taquicardia em repouso, intolerância ao exercício, hipotensão ortostática, instabilidade cardiovascular intraoperatória, disfunção elétrica do coração traduzida por arritmias e isquemia miocárdica silenciosa. Essas alterações comprometem a qualidade de vida e a sobrevida dos pacientes. A NAC, segundo sua evolução, pode ser subdividida em subclínica (fase em que predominam alterações funcionais reversíveis) e clínica (quando as alterações neuronais estruturais estão plenamente estabelecidas). A avaliação da integridade do sistema nervoso autonômico é realizada por meio de exploração da atividade parassimpática, analisando o comportamento da frequência cardíaca (FC) em resposta à respiração profunda, ortostatismo ou manobra de Valsalva. A atividade simpática é explorada por meio de aferição da pressão arterial em resposta a mudança de postura (ortostatismo) e esforço isométrico. A análise da variabilidade da frequência cardíaca (VFC), no domínio do tempo, no domínio da frequência e por métodos gráficos complementam essa avaliação. Neste artigo de revisão, analisamos recentes informações sobre a epidemiologia, manifestações clínicas, diagnóstico, e tratamentos da NAC

Cardiac autonomic neuropathy (CAN) is a common and often-underdiagnosed complication of diabetes mellitus (DM). CAN is associated with increased mortality, cardiovascular disease, chronic kidney disease, and morbidity in patients with DM, but despite these significant consequences CAN often remains undiagnosed for a prolonged period. This is commonly due to the disease being asymptomatic until the later stages, as well as a lack of easily available screening strategies. Clinically, CAN is manifested by functional disorders or clinical conditions that involve maladjustment of cardiovascular reflex activities, such as tachycardia at rest, exercise intolerance, orthostatic hypotension, intraoperative cardiovascular instability, electrical dysfunction of the heart translated by arrhythmias and silent myocardial ischemia. These changes compromise patients' quality of life and survival. CAN, according to its evolution, can be subdivided into subclinical (phase in which reversible functional changes predominate) and clinical (when structural neuronal changes are fully established). The assessment of the integrity of the autonomic nervous system is performed by exploring parasympathetic activity, analyzing the heart rate in response to deep breathing, orthostatism or Valsalva maneuver. Sympathetic activity is explored by measuring blood pressure in response to a change in posture (orthostatism) and isometric effort. The analysis of heart rate variability (HRV), in the time domain, in the frequency domain and by graphic methods, complement this assessment. In this article, we review the latest developments in the epidemiology, pathogenesis, diagnosis, consequences, and treatments of CAN in patients with DM.

Metabolic Syndrome-Related Features in Controlled and Resistant Hypertensive Subjects / Características Relacionadas à Síndrome Metabólica em Indivíduos com Hipertensão Controlada e Hipertensão Resistente

Abstract Background: Metabolic syndrome (MetS) is widespread among hypertensive patients. Clinical features and potential biomarkers of MetS in the presence of hypertension and resistant hypertension (RHTN) represent a great area of interest for investigation. Objective: The purpose of this study was to evaluate the prevalence of MetS and the clinical features associated with it in resistant and mild to moderate hypertensives. Methods: This cross-sectional study included 236 patients, (i) 129 mild to moderate hypertensive patients and (ii) 107 patients with RHTN. We measured blood pressure (BP) and adipokines levels, and performed bioelectrical impedance analysis. Microalbuminuria (MA), cardiac hypertrophy and arterial stiffness were also assessed. The significance level of alpha = 0.05 was adopted. Results: We found a MetS prevalence of 73% in resistant and 60% in mild-to-moderate hypertensive patients. In a multiple regression analysis, MA (odds ratio = 8.51; p = 0.01), leptin/adiponectin ratio (LAR) (odds ratio = 4.13; p = 0.01) and RHTN (odds ratio = 3.75; p = 0.03) were independently associated with the presence of MetS apart from potential confounders. Conclusions: Our findings suggest that both resistant and controlled hypertensive subjects have a high prevalence of MetS. In addition, MetS-related metabolic derangements may cause early renal and hormonal changes. Finally, LAR may be useful as a reliable biomarker for identifying those hypertensive subjects who are at risk for developing MetS.

Resumo Fundamentos: A síndrome metabólica (SM) é comum em pacientes hipertensos. As características clínicas e os potenciais biomarcadores da SM na presença de hipertensão e hipertensão resistente (HR) representam uma ampla área de interesse a ser investigada. Objetivo: O objetivo deste estudo foi avaliar a prevalência de SM e as características clínicas associadas à síndrome em indivíduos com hipertensão resistente e leve a moderada. Métodos: Este estudo transversal incluiu 236 pacientes, (i) 129 pacientes com hipertensão leve a moderada e (ii) 107 pacientes com HR. Medimos a pressão arterial (PA), parâmetros bioquímicos e os níveis de adipocinas dos pacientes, além de microalbuminúria (MA), hipertrofia cardíaca e rigidez arterial. Foi adotado o nível de significância de alfa 0,05. Resultados: A SM esteve presente em 73% dos pacientes com HR e 60% daqueles com hipertensão leve a moderada. Na análise de regressão múltipla, a MA (odds ratio = 8,51; p = 0,01), a razão leptina/adiponectina (RLA) (odds ratio = 4,13; p = 0,01) e a HR (odds ratio = 3,75; p = 0,03) foram independentemente associadas com a presença de SM, excluindo-se potenciais fatores de confusão. Conclusões: Nossos resultados sugerem que tanto hipertensos resistentes como hipertensos controlados apresentam alta prevalência de SM. Além disso, distúrbios metabólicos relacionados à SM podem causar alterações precoces renais e hormonais, e a RLA parece ser útil como biomarcador confiável para identificar indivíduos hipertensos em risco de desenvolverem SM.

Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats.

High systolic blood pressure caused by endothelial dysfunction is a comorbidity of metabolic syndrome that is mediated by local inflammatory signals. Insulin-induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin-stimulated serine/threonine kinase (AKT) and is severely impaired in obese, hypertensive rodents and humans. Neutralisation of circulating tumor necrosis factor-α (TNFα) with infliximab improves glucose homeostasis, but the consequences of this pharmacological strategy on systolic blood pressure and eNOS activation are unknown. To address this issue, we assessed the temporal changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab. We also assessed the activation of critical proteins that mediate insulin activity and TNFα-mediated insulin resistance in the aorta and cardiac left ventricle. Our data demonstrate that infliximab prevents the upregulation of both systolic pressure and left ventricle hypertrophy in SHR. These effects paralleled an increase in AKT/eNOS phosphorylation and a reduction in the phosphorylation of inhibitor of nuclear factor-κB (Iκß) and c-Jun N-terminal kinase (JNK) in the aorta. Overall, our study revealed the cardiovascular benefits of infliximab in SHR. In addition, the present findings further suggested that the reduction of systolic pressure and left ventricle hypertrophy by infliximab are secondary effects to the reduction of endothelial inflammation and the recovery of AKT/eNOS pathway activation.

Não adesão ao tratamento farmacológico anti-hipertensivo como causa de controle inadequado da hipertensão arterial / Non-adherence to antihypertensive drug treatment as cause of inadequate Blood Pressure control

A hipertensão arterial tem impacto no desenvolvimento de danos em órgãos-alvo e forte relação com eventos cardiovasculares. Apresenta ainda uma prevalência alta na população mundial e, sobretudo, na brasileira. Embora muitos tratamentos estejam disponíveis, uma parte da população não atinge as metas pressóricas, sendo a não adesão ao tratamento uma das principais causas dessa falha. A adesão farmacológica é um passo importante na consolidação dos tratamentos crônicos. Além disso, os impactos em mortalidade, em economia e em saúde pública tornam esse tema digno de atenção, uma vez que o tratamento realizado corretamente pode diminuir custos de saúde e atuar efetivamente na prevenção de danos causados por progressão e descontrole da doença. Portanto, esta revisão tem como objetivo fornecer um sucinto panorama atual da adesão ao tratamento e principalmente seu impacto sobre o descontrole pressórico e consequentes malefícios à saúde individual e pública.

Hypertension has an impact on the development of target organ damage and a close relationship with cardiovascular events. Also, it has a high worldwide prevalence, including Brazilian population. Although many treatments are available, a portion of the patients does not reach blood pressure goals, and non adherence to treatment is pointed as one of the main causes of this failure. Pharmacological adherence is an important step in chronic diseases treatment. In addition, the impacts in mortality, economy and public health make this issue worthy of attention, since the correct treatment can reduce health costs and act effectively in the prevention of damages caused by the progress and improper control of the disease. This review aims to provide a current overview on adherence and mainly its impact on blood pressure control and consequent harm to individual and public health.

Near-fatal pulmonary embolism in an experimental model: hemodynamic, gasometric and capnographic variables.

INTRODUCTION: Experimental studies on pulmonary embolism (PE) are usually performed under mechanical ventilation. Most patients with suspicion of PE enter the Emergency Services in spontaneous breathing and environmental air. Thus, under these conditions, measurements of hemodynamic, gasometric and capnographic variables contribute largely to a more specific comprehension of cardiopulmonary and gasometric alterations in the acute phase of the disease. Studies which evaluated animals under conditions are lacking. OBJECTIVE: This study aimed to submit animals under spontaneous ventilation and without supplemental oxygen to PE. METHODS: PE was induced in six pigs using autologous blood clots, and cardiorespiratory and gasometric records were performed before and after PE. The values of "near fatal" mean pulmonary arterial pressure (MPAP) were previously determined. RESULTS: The presence of obstructive shock could be evidenced by increased MPAP (from 17.8 ± 3.5 to 41.7 ± 3.3 mmHg) (P<0.0001) and decreased cardiac output (from 4.9 ± 1.0 to 2.7 ± 1.0 L/min) (P<0.003). Consequently, metabolic acidosis occurred (Lac art) (from 2.4 ± 0.6 to 5.7 ± 1.8 mmol/L)(P<0.0001). It was observed hypoxemia (from 73.5 ± 12.7 to 40.3 ± 4.6 mmHg) (P<0.0001); however, PaCO2 did not vary (from 44.9 ± 4.4 to 48.2 ± 6.0 mmHg) (NS). There were significant increases in both P(a-et)CO2 (from 4.8 ± 2.8 to 37.2 ± 5.8 mmHg) and P(A-a)O2 (from 8.2 ± 8.9 to 37.2 ± 10.3 mmHg) (both P<0.0001). There was also a significant increase in the total alveolar minute volume (from 4.0 ± 0.9 to 10.6 ± 2.9 L/min) (P<0.0001). CONCLUSIONS: In this model, the near fatal MPAP was from 2 to 2.5 times the basal MPAP; and the capnographic variables, associated with arterial and venous gasometry, showed effective in discriminating an acute obstructive profile.