Non-invasive brain stimulation for the management of arterial hypertension

The neural control of the cardiovascular system is a complex process that involves many structures at different levels of nervous system. Several cortical areas are involved in the control of systemic blood pressure, such as the sensorimotor cortex, the medial prefrontal cortex and the insular cortex. Non-invasive brain stimulation techniques - repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) - induce sustained and prolonged functional changes of the human cerebral cortex. rTMS and tDCS has led to positive results in the treatment of some neurological and psychiatric disorders. Because experiments in animals show that cortical modulation can be an effective method to regulate the cardiovascular system, non-invasive brain stimulation might be a novel tool in the therapeutics of human arterial hypertension. We here review the experimental evidence that non-invasive brain stimulation can influence the autonomic nervous system and discuss the hypothesis that focal modulation of cortical excitability by rTMS or tDCS can influence sympathetic outflow and, eventually, blood pressure, thus providing a novel therapeutic tool for human arterial hypertension. (C) 2009 Published by Elsevier Ltd.

Prevalence of Arterial Hypertension Among Seventh-Day Adventists of the Sao Paulo State Capital and Inner Area

Background: Inadequate life habits are known to favor hypertension, and Adventists recommend healthy life habits. Objective: To assess the prevalence of hypertension among Seventh-Day Adventists from the inner Sao Paulo state and Sao Paulo state capital. Methods: This study assessed 264 Adventists (mean age, 41.17 +/- 15.27 years; women, 59.8%) with a high religiosity level assessed by use of the Duke University Religion Index. Blood pressure was measured with a validated automatic device. The significance level adopted was p < 0.05. Results: The total prevalence of hypertension was 22.7% (27.4% in the inner state and 15% in the capital). The Adventists from the capital differed from those of inner state as follows (p < 0.05), respectively: higher education (62% vs 36.6%); employed by a third party (44%) vs self-employed (40.9%); family income (8.39 +/- 6.20 vs 4.59 +/- 4.75 minimum wages); individual income (4.54 +/- 5.34 vs 6.35 +/- 48; couple responsible for family income (35% vs 39.6%); vegetarianism (11% vs 3%); blood pressure (115.38 +/- 16.52/68.74 +/- 8.94 vs 123.66 +/- 19.62/74.88 +/- 11.85 mmHg); white ethnicity (65% vs 81.1%); married (53% vs 68.9%); lower tangible support in the social aspect (15.7 +/- 5.41 vs 16.9 +/- 4.32); and recalling the last time one's blood pressure was measured (65% vs 48.8%). On multivariate analysis, hypertension associated with the following: 1) vegetarianism (OR 0.051; 95% CI: 0.004-0.681); 2) educational level (OR 5.317; 95% CI: 1.674-16.893); 3) recalling the last time one's blood pressure was measured (OR 2.725; 95% CI: 1.275-5.821); 4) being retired (OR 8.846; 95% CI: 1.406-55.668); and 5) being responsible for family income (OR 0.422; 95% CI: 0.189-0.942). Conclusion: The prevalence of hypertension among Adventists was lower as compared with that reported in Brazilian studies, and it was lower in the Sao Paulo state capital as compared with that in the inner Sao Paulo state, possibly because of the better socioeconomic conditions and life habits of the former. (Arq Bras Cardiol 2012; 98(4): 329-337)

The Role of Target Therapies in Schistosomiasis-Associated Pulmonary Arterial Hypertension

Background: Schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) may be one of the most prevalent forms of pulmonary arterial hypertension (PAH) worldwide. However, the clinical and hemodynamical response to specific PAH therapy in Sch-PAH is not known. Methods: We retrospectively analyzed the charts of all patients with Sch-PAH who initiated specific PAH treatment between June 2003 and June 2010 in a single PAH reference center in Sao Paulo, Brazil. Clinical and hemodynamical data were retrospectively collected and evaluated in two periods: baseline and posttreatment. Results: The study population consisted of 12 patients with Sch-PAH. They were treated with phosphodiseterase-5 inhibitors (seven patients), endothelin receptor antagonists (four patients), or combination therapy (one patient). Mean treatment period was 34.9 +/- 15.5 months. Patients with Sch-PAH presented significant improvements in terms of functional class, 6-min walk test distance (439 +/- 85 to 492 +/- 79 m, P = .032), cardiac index (2.66 +/- 0.59 to 3.08 +/- 0.68 L/min/m(2), P = .028), and indexed pulmonary vascular resistance (20.7 +/- 11.6 to 15.9 +/- 9 W/m(2), P = .038) with the introduction of specific PAH treatment. Conclusions: We conclude that specific PAH therapy may be of benefit to patients with Sch-PAH, considering clinical, functional, and hemodynamic parameters. CHEST 2012; 141(4):923-928

Cardiac Magnetic Resonance Imaging: What Can It Add to Our Knowledge of the Right Ventricle in Pulmonary Arterial Hypertension?

Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature characterized by vasoconstriction and vascular remodeling leading to a progressive increase in pulmonary vascular resistance (PVR). It is becoming increasingly recognized that it is the response of the right ventricle (RV) to the increased afterload resulting from this increase in PVR that is the most important determinant of patient outcome. A range of hemodynamic, structural, and functional measures associated with the RV have been found to have prognostic importance in PAH and, therefore, have potential value as parameters for the evaluation and follow-up of patients. If such measures are to be used clinically, there is a need for simple, reproducible, accurate, easy-to-use, and noninvasive methods to assess them. Cardiac magnetic resonance imaging (CMRI) is regarded as the "gold standard" method for assessment of the RV, the complex structure of which makes accurate assessment by 2-dimensional methods, such as echocardiography, challenging. However, the majority of data concerning the use of CMRI in PAH have come from studies evaluating a variety of different measures and using different techniques and protocols, and there is a clear need for the development of standardized methodology if CMRI is to be established in the routine assessment of patients with PAH. Should such standards be developed, it seems likely that CMRI will become an important method for the noninvasive assessment and monitoring of patients with PAH. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110[suppl]:25S-31S)

Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension

Objective: To assess safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension (PAH). Background: Sitaxsentan is a highly selective endothelin-A receptor antagonist that was recently withdrawn by the manufacturer because of a pattern of idiosyncratic liver injury. Methods: Before sitaxsentan withdrawal, this 18-week double-blind, placebo-controlled study randomized patients with PAH to receive placebo or sitaxsentan 50 or 100 mg once daily. The primary efficacy endpoint was change from baseline in 6-min walk distance (6MWD) at week 18. Changes in World Health Organization (WHO) functional class and time to clinical worsening (TTCW) were secondary endpoints. The primary efficacy analysis was powered for sitaxsentan 100 mg versus placebo. Results: Of 98 randomized patients, 61% were WHO functional class II at baseline. Improvement from baseline to week 18 in 6MWD occurred with sitaxsentan 100 but not 50 mg; a strong placebo effect was observed. At week 18, WHO functional class was improved or maintained in more patients receiving sitaxsentan 100 mg than placebo (P = 0.038); 0% versus 12% of patients deteriorated, respectively. TTCW was not significantly different for 100-mg sitaxsentan patients than placebo (P = 0.090). Adverse events (AEs) occurring more frequently with sitaxsentan (50 or 100 mg) included headache, peripheral edema, dizziness, nausea, extremity pain, and fatigue; most AEs were of mild or moderate severity. Conclusion: Sitaxsentan 100 mg improved functional class but not 6MWD in PAH patients who were mostly WHO functional class II at baseline. No patient receiving sitaxsentan 100 mg experienced clinical worsening; sitaxsentan was well tolerated. (C) 2011 Elsevier Ltd. All rights reserved.

Assessment of cardiovascular risk of patients with arterial hypertension of a public health unit

OBJECTIVE: To assess the cardiovascular risk, using the Framingham risk score, in a sample of hypertensive individuals coming from a public primary care unit. METHODS: The caseload comprised hypertensive individuals according to criteria established by the JNC VII, 2003, of 2003, among 1601 patients followed up in 1999, at the Cardiology and Arterial Hypertension Outpatients Clinic of the Teaching Primary Care Unit, at the Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. The patients were selected by draw, aged over 20 years, both genders, excluding pregnant women. It was a descriptive, cross-sectional, observational study. The Framingham risk score was used to stratify cardiovascular risk of developing coronary artery disease (death or non-fatal acute myocardial infarction). RESULTS: Age range of 27-79 years ( = 63.2 ± 9.58). Out of 382 individuals studied, 270 (70.7%) were female and 139 (36.4%) were characterized as high cardiovascular risk for presenting diabetes mellitus, atherosclerosis documented by event or procedure. Out of 243 stratified patients, 127 (52.3%) had HDL-C < 50 mg/dL; 210 (86.4%) had systolic blood pressure > 120 mmHg; 46 (18.9%) were smokers; 33 (13.6%) had a high cardiovascular risk. Those added to 139 enrolled directly as high cardiovascular risk, totaled up 172 (45%); 77 (20.2%) of medium cardiovascular risk and 133 (34.8%) of low risk. The highest percentage of high cardiovascular risk individuals was aged over 70 years; those of medium risk were aged over 60 years; and the low risk patients were aged 50 to 69 years. CONCLUSION: The significant number of high and medium cardiovascular risk individuals indicates the need to closely follow them up.

Late evaluation of the relationship between morphological and functional renal changes and hypertension after non-operative treatment of high-grade renal injuries

Objective: To evaluate the anatomical and functional renal alterations and the association with post-traumatic arterial hypertension. Methods: The studied population included patients who sustained high grades renal injury (grades III to V) successfully non-operative management after staging by computed tomography over a 16-year period. Beyond the review of medical records, these patients were invited to the following protocol: clinical and laboratory evaluation, abdominal computed tomography, magnetic resonance angiography, DMSA renal scintigraphy, and ambulatory blood pressure monitoring. The hypertensive patients also were submitted to dynamic renal scintigraphy (Tc-99m EC), using captopril stimulation to verify renal vascular etiology. Results: Of the 31 patients, there were thirteen grade III, sixteen grade IV (nine lacerations, and seven vascular lesions), and two grade V injuries. All the patients were asymptomatic and an average follow up post-injury of 6.4 years. None had abnormal BUN or seric creatinine. The percentage of renal volume reduction correlates with the severity as defined by OIS. There was no evidence of renal artery stenosis in Magnetic Resonance angiography (MRA). DMSA scanning demonstrated a decline in percentage of total renal function corresponding to injury severity (42.2 +/- 5.5% for grade III, 35.3 +/- 12.8% for grade IV, 13.5 +/- 19.1 for grade V). Six patients (19.4%) had severe compromised function (< 30%). There was statistically significant difference in the decrease in renal function between parenchymal and vascular causes for grade IV injuries (p < 0.001). The 24-hour ambulatory blood pressure monitoring detected nine patients (29%) with post-traumatic hypertension. All the patients were male, mean 35.6 years, 77.8 % had a familial history of arterial hypertension, 66.7% had grade III renal injury, and average post-injury time was 7.8 years. Seven patients had negative captopril renography. Conclusions: Late results of renal function after conservative treatment of high grades renal injuries are favorable, except for patients with grades IV with vascular injuries and grade V renal injuries. Moreover, arterial hypertension does not correlate with the grade of renal injury or reduction of renal function.

Phenylephrine-induced hypertension during transient middle cerebral artery occlusion alleviates ischemic brain injury in spontaneously hypertensive rats

Arterial hypertension is a major risk factor for ischemic stroke. However, the management of preexisting hypertension is still controversial in the treatment of acute stroke in hypertensive patients. The present study evaluates the influence of preserving hypertension during focal cerebral ischemia on stroke outcome in a rat model of chronic hypertension, the spontaneously hypertensive rats (SHR). Focal cerebral ischemia was induced by transient (1 h) occlusion of the middle cerebral artery, during which mean arterial blood pressure was maintained at normotension (110-120 mm Hg, group 1, n=6) or hypertension (160-170 mm Hg, group 2, n=6) using phenylephrine. T2-, diffusion- and perfusion-weighted MRI were performed serially at five different time points: before and during ischemia, and at 1, 4 and 7 days after ischemia. Lesion volume and brain edema were estimated from apparent diffusion coefficient maps and T2-weighted images. Regional cerebral blood flow (rCBF) was measured within and outside the perfusion deficient lesion and in the corresponding regions of the contralesional hemisphere. Neurological deficits were evaluated after reperfusion. Infarct volume, edema, and neurological deficits were significantly reduced in group 2 vs. group 1. In addition, higher values and rapid restoration of rCBF were observed in group 2, while rCBF in both hemispheres was significantly decreased in group 1. Maintaining preexisting hypertension alleviates ischemic brain injury in SHR by increasing collateral circulation to the ischemic region and allowing rapid restoration of rCBF. The data suggest that maintaining preexisting hypertension is a valuable approach to managing hypertensive patients suffering from acute ischemic stroke. Published by Elsevier B.V.

Sildenafil vs. Sodium Nitroprusside for the Pulmonary Hypertension Reversibility Test Before Cardiac Transplantation

Background: Pulmonary hypertension is associated with a worse prognosis after cardiac transplantation. The pulmonary hypertension reversibility test with sodium nitroprusside (SNP) is associated with a high rate of systemic arterial hypotension, ventricular dysfunction of the transplanted graft and high rates of disqualification from transplantation. Objective: This study was aimed at comparing the effects of sildenafil (SIL) and SNP on hemodynamic, neurohormonal and echocardiographic variables during the pulmonary reversibility test. Methods: The patients underwent simultaneously right cardiac catheterization, echocardiography, BNP measurement, and venous blood gas analysis before and after receiving either SNP (1 - 2 mu g/kg/min) or SIL (100 mg, single dose). Results: Both drugs reduced pulmonary hypertension, but SNP caused a significant systemic hypotension (mean blood pressure - MBP: 85.2 vs. 69.8 mm Hg; p < 0.001). Both drugs reduced cardiac dimensions and improved left cardiac function (SNP: 23.5 vs. 24.8%, p = 0.02; SIL: 23.8 vs. 26%, p < 0.001) and right cardiac function (SIL: 6.57 +/- 2.08 vs. 8.11 +/- 1.81 cm/s, p = 0.002; SNP: 6.64 +/- 1.51 vs. 7.72 +/- 1.44 cm/s, p = 0.003), measured through left ventricular ejection fraction and tissue Doppler, respectively. Sildenafil, contrary to SNP, improved venous oxygen saturation, measured on venous blood gas analysis. Conclusion: Sildenafil and SNP are vasodilators that significantly reduce pulmonary hypertension and cardiac geometry, in addition to improving biventricular function. Sodium nitroprusside, contrary to SIL, was associated with systemic arterial hypotension and worsening of venous oxygen saturation. (Arq Bras Cardiol 2012;99(3):848-856)

Pulmonary hypertension diagnosed by right heart catheterisation in sickle cell disease

Recent studies have recognised the importance of pulmonary hypertension (PH) in sickle cell disease (SCD). The aim of this study was to determine the prevalence and prognostic impact of PH and its features in patients with SCD. 80 patients with SCD underwent baseline clinical evaluation, laboratory testing, 6-min walk tests (6MWTs) and echocardiography. Patients with a peak tricuspid regurgitant jet velocity (TRV) of >= 2.5 m.s(-1) were further evaluated through right heart catheterisation (RHC) to assure the diagnosis of PH. Our study evidenced a 40% prevalence of patients with elevated TRV at echocardiography. RHC (performed in 25 out of 32 patients) confirmed PH in 10% (95% CI 3.4-16.5%) of all patients, with a prevalence of post-capillary PH of 6.25% (95% CI 0.95-11.55%) and pre-capillary PH of 3.75% (95% CI -0.4-7.9%). Patients with PH were older, had worse performance in 6MWTs, and more pronounced anaemia, haemolysis and renal dysfunction. Survival was shorter in patients with PH. Our study reinforced the use of echocardiography as a screening tool for PH in SCD and the mandatory role of RHC for proper diagnosis. Our findings confirmed the prognostic significance of PH in SCD as its association to pronounced haemolytic profile.

Comparison of two experimental models of pulmonary hypertension

Objective: To compare two models of pulmonary hypertension (monocrotaline and monocrotaline+pneumonectomy) regarding hemodynamic severity, structure of pulmonary arteries, inflammatory markers (IL-1 and PDGF), and 45-day survival. Methods: We used 80 Sprague-Dawley rats in two study protocols: structural analysis; and survival analysis. The rats were divided into four groups: control; monocrotaline (M), pneumonectomy (P), and monocrotaline+pneumonectomy (M+P). In the structural analysis protocol, 40 rats (10/group) were catheterized for the determination of hemodynamic variables, followed by euthanasia for the removal of heart and lung tissue. The right ventricle (RV) was dissected from the interventricular septum (IS), and the ratio between RV weight and the weight of the left ventricle (LV) plus IS (RV/LV+IS) was taken as the index of RV hypertrophy. In lung tissues, we performed histological analyses, as well as using ELISA to determine IL-1 and PDGF levels. In the survival protocol, 40 animals (10/group) were followed for 45 days. Results: The M and M+P rats developed pulmonary hypertension, whereas the control and P rats did not. The RV/LV+IS ratio was significantly higher in M+P rats than in M rats, as well as being significantly higher in M and M+P rats than in control and P rats. There were no significant differences between the M and M+P rats regarding the area of the medial layer of the pulmonary arteries; IL-1 and PDGF levels; or survival. Conclusions: On the basis of our results, we cannot conclude that the monocrotaline+pneumonectomy model is superior to the monocrotaline model.

Prevalência de hipertensão arterial em Adventistas do Sétimo Dia da capital e do interior paulista

FUNDAMENTO: Sabe-se que hábitos de vida inadequados favorecem a hipertensão, e os adventistas preconizam hábitos saudáveis. OBJETIVO: Avaliar a prevalência da hipertensão nos adventistas do sétimo dia na capital e no interior paulistas. MÉTODOS: Foram estudados 264 adventistas (41,17 ± 15,27 anos, 59,8% mulheres, com alto nível de religiosidade avaliada pela escala Duke-DUREL). A medida da pressão arterial foi realizada com aparelho automático validado. Nível de significância adotado foi p < 0,05. Resultados: A prevalência total de hipertensão foi 22,7%, (27,4% no interior e 15% na capital). Os adventistas da capital diferiram dos do interior (p < 0,05), respectivamente, quanto: escolaridade superior (62% vs 36,6%); ter vínculo empregatício (44%) vs autônomos (40,9%); renda familiar (8,39 ± 6,20 vs 4,59 ± 4,75 salários mínimos) e renda individual (4,54 ± 5,34 vs 6,35 ± 48 salários mínimos); casal responsável pela renda familiar (35% vs 39,6%); vegetarianismo (11% vs 3%); pressão arterial (115,38 ± 16,52/68,74 ± 8,94 vs 123,66 ± 19,62/74,88 ± 11,85 mmHg); etnia branca (65% vs 81,1%); casados (53% vs 68,9%); menor apoio social no domínio material (15,7 ± 5,41 vs 16,9 ± 4,32) e lembrar da última vez que mediu a pressão arterial (65% vs 48,8%). A análise multivariada associou hipertensão com: 1) vegetarianismo (OR 0,051, IC95% 0,004-0,681), 2) escolaridade (OR 5,317, IC95% 1,674-16,893), 3) lembrar quando mediu a pressão (OR 2,725, IC95% 1,275-5,821), 4) aposentado (OR 8,846, IC95% 1,406-55,668), 5) responsável pela renda familiar (OR 0,422, IC95% 0,189-0,942). CONCLUSÃO: A prevalência de hipertensão dos adventistas foi menor se comparada com estudos nacionais, sendo menor na capital em relação ao interior possivelmente por melhores condições socioeconômicas e hábitos de vida.

Ausência de estreita associação entre qualidade de vida e capacidade de exercício na hipertensão arterial pulmonar

FUNDAMENTO: Na hipertensão arterial pulmonar (HAP) a qualidade de vida relacionada saúde (QVRS) tem sido investigada em curtos períodos de tempo (semanas), mas pouco se sabe sobre a perspectiva do paciente no médio e longo prazo. OBJETIVO: Analisar o estado de pacientes em terapias específicas de HAP durante um ano de observação, em termos de QVRS, e investigar se possíveis associações entre a capacidade de exercício (CE) e a QVRS persistem no médio prazo. MÉTODOS: Trinta e quatro pacientes em terapias para a HAP (bosentan e/ou sildenafil) foram selecionados (idade de 14 a 58 anos, mediana de 35,5 anos, classe funcional II ou III), e avaliados no momento basal, e 3, 6, 9 e 12 meses depois, usando o teste de caminhada de 6 minutos e questionário SF-36 de QVRS. RESULTADOS: A distância percorrida nos seis minutos não mudou durante o acompanhamento (387 - 432 metros, valores da mediana, p=0.2775), o mesmo para a classe funcional e saturação periférica de oxigênio. Os escores SF-36 também se mantiveram estáveis, com a saúde física sempre pior que a saúde mental. Das 40 possíveis associações entre a CE e QVRS, apenas 12 foram significativas (30%, p<0,05). A previsão de uma QVRS severamente deprimida com base em uma distância percorrida de 235 metros foi específica em >90%, mas sensível em <43%. CONCLUSÃO: Os pacientes com HAP que se mantêm estáveis em termos da CE também parecem fazê-lo em termos de QVRS. Contudo, CE e QVRS não têm ligação consistente com o tempo, e devem ser analisadas como diferentes perspectivas no paciente individual.

Componentes da síndrome metabólica na hipertensão arterial

Este estudo teve como objetivo identificar e comparar a prevalência da síndrome metabólica entre hipertensos e normotensos. Os aspectos adotados para a definição de síndrome metabólica foram os definidos pelo National Cholesterol Education Program/Adults Treatment Painel (NCEP-ATP III). Os dados referentes aos perfis clínicos e bioquímicos foram processados no programa SPSS para cálculo de frequências absolutas e porcentagens. Utilizou-se o teste t de Student para comparações das médias, sendo as diferenças consideradas estatisticamente significantes para p<0,05. A amostra foi composta por 93 participantes normotensos e 168 hipertensos. Identificou-se a presença de síndrome metabólica em 60,7% dos hipertensos e 18,3% dos normotensos. Os portadores de hipertensão arterial apresentam diferença significante nos valores de pressão arterial (p<0,001), circunferência abdominal (p<0,001), glicemia (p<0,05) e triglicérides plasmáticos (p<0,05). A frequência dos riscos cardiometabólicos associados à síndrome metabólica é maior na presença de doença hipertensiva.

Functional Limitation and Intermittent Claudication: Impact of Blood Pressure Measurements

Background: Arterial hypertension is an important risk factor for Lower-Limb Occlusive Arterial Disease (LLOAD). However, the correlation between blood pressure and pulse pressure (PP) with LLOAD severity and functional impairment resulting from this disease is not well established in the Brazilian population. Objective: To verify whether there is a correlation between blood pressure, PP, LLOAD severity and functional capacity in patients with symptomatic LLOAD. Methods: A total of 65 patients (62.2 + 8.1 years, 56.9% males) were evaluated. They were divided into two groups: normal (A) and high (B) blood pressure. LLOAD severity was assessed using the ankle-brachial index (ABI) and functional capacity by the total and pain-free walking distance at the 6-minute walking test (6MWT). Results: Group A consisted of 17 (26.1%) patients. The systolic (SBP), diastolic blood pressure (DBP), and PP were, respectively, 125.4 +/- 11.7, 74.5 +/- 9.1 and 50.9 +/- 10.0 mmHg in group A and 160.7 +/- 19.6, 90.0 +/- 12.2 and 70.7 +/- 20.2 mmHg in group B. The ABI was significantly lower in group B (0.66 +/- 0.12 vs. 0.57 +/- 0.13, p < 0.05). SBP and PP correlated with LLOAD severity and the distances walked at the 6MWT. Patients with PP > 40 mmHg walked shorter distances. Conclusion: SBP and PP significantly correlated with the distances walked in the 6MWT, suggesting they are clinical markers of functional capacity impairment in patients with symptomatic LLOAD. (Arq Bras Cardiol 2012; 98(2): 161-166)