The effect of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea and uncontrolled hypertension - Study design and challenges during the COVID-19 pandemic

OBJECTIVES: To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic. METHODS: MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and ≥80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index ≥15 events/hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658. RESULTS: The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities. CONCLUSIONS: The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP.

Applicability of the Test of Variables of Attention - T.O.V.A. in Brazilian adults / Aplicabilidade do teste de variáveis de atenção - T.O.V.A. em adultos brasileiros

ABSTRACT: The functioning of attention is complex, a primordial function in several cognitive processes and of great interest to neuropsychology. The Test of Variables of Attention (T.O.V.A) is a continuous computerized performance test that evaluates some attention components such as response time to a stimulus and errors due to inattention and impulsivity. Objective: 1) To evaluate the applicability of T.O.V.A in Brazilian adults; 2) To analyze the differences in performance between genders, age ranges, and levels of education; 3) To examine the association between T.O.V.A variables and other attention and cognitive screening tests. Methods: The T.O.V.A was applied to 63 healthy adults (24 to 78 years of age) who also underwent the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Digit Span and Digit Symbol (Wechsler Intelligence Scale for Adults ­ WAIS-III) and the Trail Making Test. Results: The T.O.V.A was little influenced by age or education, but was influenced by gender. The correlations between some T.O.V.A variables and the Digit Symbol and Trail Making test were weak (r-values between 0.2 and 0.4), but significant (p<0.05). There was no correlation with the Digit Span test. Conclusion: The T.O.V.A showed good applicability and proved adequate for evaluating attentional processes in adults.

RESUMO: O funcionamento da atenção é complexo, função primordial em diversos processos cognitivos e de grande interesse para a neuropsicologia. O Teste de Variáveis de Atenção (T.O.V.A) é um teste computadorizado de desempenho contínuo que avalia alguns componentes de atenção, como tempo de resposta a um estímulo e erros por desatenção e impulsividade. Objetivo: 1) Avaliar a aplicabilidade do T.O.V.A em adultos brasileiros; 2) Analisar as diferenças de desempenho entre os gêneros, faixas etárias e níveis de escolaridade; 3) Examinar a associação entre as variáveis T.O.V.A e outros testes de atenção e triagem cognitiva. Métodos: O TOVA foi aplicado a 63 adultos saudáveis (24 a 78 anos) submetidos ao Mini-Exame do Estado Mental (MEEM), Montreal Cognitive Assessment (MoCA), Digit Span e Digit Symbol (Wechsler Intelligence Scale for Adults ­ WAIS-III) e o Trail Making Test. Resultados: T.O.V.A teve pouca influência da idade e escolaridade, mas foi influenciado pelo gênero. As correlações entre algumas variáveis T.O.V.A e o símbolo Digit e o teste Trail Making foram fracas (valores de r entre 0,2 e 0,4), mas significativas (p <0,05). Não houve correlação com o teste Digit Span. Conclusão: T.O.V.A apresentou boa aplicabilidade e foi adequado para avaliar os processos de atenção em adultos.

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users

OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. METHODS: Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. RESULTS: Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. CONCLUSIONS: Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population.

Impact of hypertension severity on arterial stiffness, cerebral vasoreactivity, and cognitive performance / Impacto da gravidade da hipertensão na rigidez arterial, vasorreatividade cerebral e desempenho cognitivo

ABSTRACT. Aging, hypertension (HTN), and other cardiovascular risk factors contribute to structural and functional changes of the arterial wall. Objective: To evaluate whether arterial stiffness (AS) is related to cerebral blood flow changes and its association with cognitive function in patients with hypertension. Methods: 211 patients (69 normotensive and 142 hypertensive) were included. Patients with hypertension were divided into 2 stages: HTN stage-1 and HTN stage-2. The mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA) and a battery of neuropsychological (NPE) tests were used to determine cognitive function. Pulse wave velocity was measured using the Complior®. Carotid properties were assessed by radiofrequency ultrasound. Central arterial pressure and augmentation index were obtained using applanation tonometry. Middle cerebral artery flow velocity was measured by transcranial Doppler ultrasonography. Results: Both arterial stiffness parameters and cerebral vasoreactivity worsened in line with HTN severity. There was a negative correlation between breath holding index (BHI) and arterial stiffness parameters. Cognitive performance worsened in line with HTN severity, with statistical difference occurring mainly between the HTN-2 and normotension groups on both the MMSE and MoCA. The same tendency was observed on the NPE tests. Conclusion: Hypertension severity was associated with higher AS, worse BHI, and lower cognitive performance.

RESUMO. A idade, hipertensão arterial (HA), e outros fatores de risco cardiovascular contribuem para as alterações estruturais e funcionais da parede arterial. Objetivo: Avaliar o quanto a rigidez arterial está relacionada com as alterações do fluxo sanguíneo cerebral e sua associação com a função cognitiva em pacientes com hipertensão. Métodos: Foram incluídos 211 pacientes (69 normotensos e 142 hipertensos). Os pacientes com hipertensão foram divididos em dois estágios: HA-1 e HA-2. O mini exame do estado mental (MEEM), Montreal Cognitive Assessment (MoCA) e uma bateria de testes neuropsicológicos foram usados para avaliar a função cognitiva. A velocidade da onda de pulso foi medida usando o Complior®. As propriedades da artéria carótida foram avaliadas usando o ultrassom de radiofrequência. A pressão arterial central e o índice de incremento foram obtidos usando a tonometria de aplanação. A velocidade de fluxo sanguíneo da arterial cerebral média foi medida pelo ultrassom com Doppler Transcraniano. Resultados: Tanto os parâmetros da rigidez arterial quanto a vasorreatividade cerebral foram piores com a gravidade da hipertensão. Houve uma correlação negativa entre o índice de apnéia e os parâmetros da rigidez arterial. O desempenho cognitivo foi pior com a gravidade de hipertensão arterial com diferença estatística ocorrendo principalmente entre os grupos HA-2 e normotensão tanto no MEEM quanto no MoCA. A mesma tendência foi observada em relação aos testes neuropsicológicos. Conclusão: A gravidade de hipertensão arterial foi associada com maior rigidez arterial, pior índice de apneia, e menor desempenho cognitivo.

The impact of metabolic syndrome on metabolic, pro-inflammatory and prothrombotic markers according to the presence of high blood pressure criterion

OBJECTIVES: We explored whether high blood pressure is associated with metabolic, inflammatory and prothrombotic dysregulation in patients with metabolic syndrome. METHODS: We evaluated 135 consecutive overweight/obese patients. From this group, we selected 75 patients who were not under the regular use of medications for metabolic syndrome as defined by the current Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults criteria. The patients were divided into metabolic syndrome with and without high blood pressure criteria (≥130/≥85 mmHg). RESULTS: Compared to the 45 metabolic syndrome patients without high blood pressure, the 30 patients with metabolic syndrome and high blood pressure had significantly higher glucose, insulin, homeostasis model assessment insulin resistance index, total cholesterol, low-density lipoprotein-cholesterol, triglycerides, uric acid and creatinine values; in contrast, these patients had significantly lower high-density lipoprotein-cholesterol values. Metabolic syndrome patients with high blood pressure also had significantly higher levels of retinol-binding protein 4, plasminogen activator inhibitor 1, interleukin 6 and monocyte chemoattractant protein 1 and lower levels of adiponectin. Moreover, patients with metabolic syndrome and high blood pressure had increased surrogate markers of sympathetic activity and decreased baroreflex sensitivity. Logistic regression analysis showed that high-density lipoprotein, retinol-binding protein 4 and plasminogen activator inhibitor-1 levels were independently associated with metabolic syndrome patients with high blood pressure. There is a strong trend for an independent association between metabolic syndrome patients with high blood pressure and glucose levels. CONCLUSIONS: High blood pressure, which may be related to the autonomic dysfunction, is associated with metabolic, inflammatory and prothrombotic dysregulation ...

Apneia do sono e aterosclerose / Sleep apnea and atherosclerosis

Evidências recentes sugerem que a apneia obstrutiva do sono está independentemente associada ao aumento da mortalidade por doenças cardiovasculares, incluindo infarto do miocárdio e acidente vascular cerebral. Uma vez que essas doenças estão intimamente ligadas à progressão da aterosclerose, essa observação sugere que a apneia obstrutiva do sono possa contribuir para a progressão da aterosclerose. Existem múltiplos mecanismos diretos e indiretos pelos quais a apneia obstrutiva do sono pode contribuir para a progressão da aterosclerose. A apneia obstrutiva do sono é uma causa reconhecida de hipertensão arterial secundária e pode contribuir para resistência à insulina, diabetes e dislipidemia, que são fatores de risco bem estabelecidos para aterosclerose. Além disso, há um crescente conjunto de evidências, tanto em modelos animais como em humanos, sugerindo que a apneia obstrutiva do sono desencadeia vários mecanismos associados com a progressão da aterosclerose, incluindo inflamação sistêmica, estresse oxidativo, ativação de células da musculatura lisa vascular, aumento da expressão de moléculas de adesão, ativação de monócitos/ linfócitos, aumento da carga lipídica em macrófagos, peroxidação lipídica...

Acute aerobic exercise reduces 24-h ambulatory blood pressure levels in long-term-treated hypertensive patients

BACKGROUND: Even with anti-hypertensive therapy, it is difficult to maintain optimal systemic blood pressure values in hypertensive patients. Exercise may reduce blood pressure in untreated hypertensive, but its effect when combined with long-term anti-hypertensive therapy remains unclear. Our purpose was to evaluate the acute effects of a single session of aerobic exercise on the blood pressure of long-term-treated hypertensive patients. METHODS: Fifty treated hypertensive patients (18/32 male/female; 46.5±8.2 years; Body mass index: 27.8±4.7 kg/m²) were monitored for 24 h with respect to ambulatory (A) blood pressure after an aerobic exercise session (post-exercise) and a control period (control) in random order. Aerobic exercise consisted of 40 minutes on a cycle-ergometer, with the mean exercise intensity at 60 percent of the patient's reserve heart rate. RESULTS: Post-exercise ambulatory blood pressure was reduced for 24 h systolic (126±8.6 vs. 123.1±8.7 mmHg, p=0.004) and diastolic blood pressure (81.9±8 vs. 79.8±8.5 mmHg, p=0.004), daytime diastolic blood pressure (85.5±8.5 vs. 83.9±8.8 mmHg, p=0.04), and nighttime S (116.8±9.9 vs. 112.5±9.2 mmHg, p<0.001) and diastolic blood pressure (73.5±8.8 vs. 70.1±8.4 mmHg, p<0.001). Post-exercise daytime systolic blood pressure also tended to be reduced (129.8±9.3 vs. 127.8±9.4 mmHg, p=0.06). These post-exercise decreases in ambulatory blood pressure increased the percentage of patients displaying normal 24h systolic blood pressure (58 percent vs. 76 percent, p=0.007), daytime systolic blood pressure (68 percent vs. 82 percent, p=0.02), and nighttime diastolic blood pressure (56 percent vs. 72 percent, p=0.02). Nighttime systolic blood pressure also tended to increase (58 percent vs. 80 percent, p=0.058). CONCLUSION: A single bout of aerobic exercise reduced 24h ambulatory blood pressure levels in long-term-treated hypertensive patients and increased the percentage of patients reaching normal...

Increased arterial distensibility and renovascular hypertension in Goldenhar syndrome

Relatamos a associação de hipertensão renovascular por estenose de artéria renal e a Sindrome de Goldenhar (variante da displasia oculoauriculovertebral) em uma paciente do sexo feminino de 13 anos de idade. Este é o primeiro relato de tratamento por angioplastia. Além disso, detectamos por métodos não invasivos um aumento da distensibilidade arterial, a despeito da hipertensão arterial. A similaridade destes achados com outras doenças genéticas sugere que as alterações vasculares presentes podem estar relacionadas à Síndrome de Goldenhar.

Distúrbios cognitivos no idoso hipertenso / Cognitive disturbances in the elderly hypertensive patient

A hipertensão arterial tem sido associada a declínio de habilidade cognitiva ao longo do tempo. Em indivíduos idosos, a maioria dos estudos tem demonstrado desempenho mais baixo em diferentes testes de capacidade cognitiva nos portadores de hipertensão, quando comparados com normotensos. As alterações da função cognitiva mais freqüentemente observadas em hipertensos idosos são diminuição do desempenho em testes de memória visual e verbal e de atividade psicomotora, e em alguns testes de inteligência. Embora a relação de causa-efeito permaneça ainda indefinida, correlações entre lesões da substância branca cerebral e pressão arterial elevada têm sido demonstradas por meio de estudos envolvendo novas técnicas de imagem cerebral. O tratamento medicamentoso da hipertensão no idoso pode ser importante para prevenir o declínio acelerado da cognição, como sugerido pelos ensaios randomizados mais recentes. A possibilidade dessa prevenção tem importância fundamental na preservação da boa qualidade de vida do indivíduo idoso.