Effect of high-intensity interval training on obstructive sleep apnea severity: A randomized controlled trial.

Vigorous physical activity has been associated with a reduced risk of developing obstructive sleep apnea (OSA). However, whether high-intensity interval training (HIIT) reduces OSA severity remains unclear. Thus, this study aimed to investigate the impact of 12 weeks of HIIT on the apnea-hypopnea index (AHI) and sleep parameters in participants with moderate-severe OSA. In this randomized controlled trial, 36 adults (19 males; 52.2 ± 9.8 years; body mass index = 34.2 ± 5.8) with moderate to severe OSA (AHI = 42.0 ± 22.9 e/h) were randomly assigned to HIIT [5 periods of 4 min of walking or running on a treadmill at 90-95 % of maximum heart rate (HRmax) interspersed with 3 min of walking at 50-55 % of HRmax performed three times per week for 12 weeks] or a control group (CG; stretching exercises performed two times per week for 12 weeks). Sleep parameters were assessed at baseline and after 12 weeks through overnight polysomnography. Generalized estimated equations assessed differences between groups over time. There was not group × time interaction for body mass index between groups (p = 0.074). However, significant group × time interactions were observed for AHI (CG change = 8.2 ± 3.7, HIIT change = -8.6 ± 4.8; p = 0.005), SaO2 minimum (CG change = -1.6 ± 1.6 %, HIIT change = 0.4 ± 2.3 %; p = 0.030), total sleep time (CG change = -31.5 ± 19.5 min, HIIT change = 33.7 ± 19.3 min; p = 0.049), and sleep efficiency (CG change = -3.2 ± 4.4 %, HIIT change = 9.9 ± 3.5 %; p = 0.026). Moreover, there was a significant time × group interaction for maximum oxygen consumption (VO2max; CG change = -1.1 ± 1.0 mL/kg/min, HIIT change = 4.8 ± 0.9 mL/kg/min; p < 0.001)]. However, In patients with OSA, 12 weeks of HIIT decreases sleep apnea severity, improves sleep quality, and cardiorespiratory fitness. CLINICAL TRIAL REGISTRATION: (Registro Brasileiro de Ensaios Clínicos [ReBec]): # RBR-98jdt3.

Sleep quality in COPD patients: correlation with disease severity and health status / Qualidade do sono em pacientes com DPOC: correlação com gravidade da doença e estado de saúde

To evaluate clinical predictors of poor sleep quality in COPD patients with and without obstructive sleep apnea (OSA). Methods: Consecutive stable patients with COPD were evaluated for OSA by means of overnight polysomnography; for sleep quality by means of the Pittsburgh Sleep Quality Index (PSQI); and for disease impact by means of the COPD Assessment Test. COPD severity was graded in accordance with the 2020 GOLD guidelines. Predictors of poor sleep quality were evaluated by multivariate logistic regression analysis. Results: We studied 51 patients with COPD alone and 51 patients with COPD and OSA. Both groups had similar age (66.2 ± 9.2 years vs. 69.6 ± 10.7, p = 0.09) and airflow limitation (p = 0.37). Poor sleep quality was present in 74.8% of the study participants, with no significant difference between COPD patients with and without OSA regarding PSQI scores (p = 0.73). Polysomnography showed increased stage 1 non-rapid eye movement sleep and arousal index, as well as reduced sleep efficiency and stage 3 non-rapid eye movement sleep, in the group of patients with COPD and OSA (p < 0.05). Independent predictors of poor sleep quality were GOLD grade C/D COPD (OR = 6.4; 95% CI, 1.79-23.3; p < 0.01), a COPD Assessment Test score ≥ 10 (OR = 12.3; 95% CI, 4.1-36.5; p < 0.01), and lowest SaO2 < 80% (p < 0.0001). Conclusions: Poor sleep quality is quite common in patients with COPD and is associated with severe COPD and poor health status, having a negative impact on overall quality of life. Despite changes in polysomnography, OSA appears to have no impact on subjective sleep quality in COPD patients.

Avaliar os preditores clínicos de má qualidade do sono em pacientes com DPOC, com e sem apneia obstrutiva do sono (AOS). Métodos: Pacientes estáveis consecutivos com DPOC foram avaliados quanto à AOS por meio de polissonografia noturna; quanto à qualidade do sono por meio do Índice de Qualidade do Sono de Pittsburgh (IQSP) e quanto ao impacto da doença por meio do Teste de Avaliação da DPOC. A gravidade da DPOC foi classificada conforme as diretrizes de 2020 da GOLD. Os preditores de má qualidade do sono foram avaliados por meio de análise de regressão logística multivariada. Resultados: Foram estudados 51 pacientes com DPOC apenas e 51 pacientes com DPOC e AOS. Ambos os grupos eram semelhantes quanto à idade (66,2 ± 9,2 anos vs. 69,6 ± 10,7, p = 0,09) e limitação do fluxo aéreo (p = 0,37). Sono de má qualidade esteve presente em 74,8% dos participantes, sem diferença significativa entre os pacientes com DPOC, com e sem AOS, quanto à pontuação no IQSP (p = 0,73). A polissonografia mostrou aumento do estágio 1 do sono non-rapid eye movement e do índice de despertares, bem como redução da eficiência do sono e do estágio 3 do sono non-rapid eye movement nos pacientes com DPOC e AOS (p < 0,05). Os preditores independentes de má qualidade do sono foram DPOC grau C/D da GOLD (OR = 6,4; IC95%: 1,79-23,3; p < 0,01), pontuação ≥ 10 no Teste de Avaliação da DPOC (OR = 12,3; IC95%: 4,1-36,5; p < 0,01) e menor SaO2 < 80% (p < 0,0001). Conclusões: O sono de má qualidade é bastante comum em pacientes com DPOC e apresenta relação com DPOC grave e estado de saúde ruim, além de ter impacto negativo na qualidade de vida global. Não obstante as alterações na polissonografia, a AOS aparentemente não tem impacto na qualidade do sono referida por pacientes com DPOC.

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.

Effects of isometric handgrip training in patients with cardiovascular disease: rationale and design of the ISOPRESS network

Meta-analytical studies have indicated that isometric handgrip training promotes significant reduction in blood pressure in hypertensive patients with similar or greater decreases in blood pressure than observed after aerobic and dynamic resistance training. However, several gaps in the literature still need to be addressed. Thus, we designed the ISOPRESS network group, which consists of a task force of different research groups aimed at analyzing the effects of isometric handgrip training on different contexts, parameters, and populations. Thus, the aim of this study was to describe the rationale and design behind the ISOPRESS, presenting the methods employed. The ISOPRESS questions involve whether isometric handgrip training is effective in hypertensives in different settings (ISOPRESS 1 - unsupervised training and ISOPRESS 2 - public health system), whether it works in patients with other cardiovascular diseases (ISOPRESS 3 - obstructive sleep apnea and ISOPRESS 4 - peripheral artery disease) and what are the mechanisms underlying the effects of isometric handgrip training in hypertensives (ISOPRESS 5 - neural mechanism). The study will yield information on the effectiveness of isometric handgrip training in different settings and patients with other cardiovascular diseases. Finally, it will help to understand the mechanisms involved in reducing blood pressure in hypertensives.(AU)

Lysyl Oxidase as a Serum Biomarker of Liver Fibrosis in Patients with Severe Obesity and Obstructive Sleep Apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with the progression of nonalcoholic fatty liver disease (NAFLD). We hypothesized that the hypoxia of OSA increases hepatic production of lysyl oxidase (LOX), an enzyme that cross-links collagen, and that LOX may serve as a biomarker of hepatic fibrosis. DESIGN: Thirty-five patients with severe obesity underwent liver biopsy, polysomnography, and serum LOX testing. A separate group with severe OSA had serum LOX measured before and after 3 mo of CPAP or no therapy, as did age-matched controls. LOX expression and secretion were measured in mouse hepatocytes following exposure to hypoxia. SETTING: The Johns Hopkins Bayview Sleep Disorders Center, and the Hypertension Unit of the Heart Institute at the University of São Paulo Medical School. MEASUREMENTS AND RESULTS: In the bariatric cohort, the apnea-hypopnea index was higher in patients with hepatic fibrosis than in those without fibrosis (42.7 ± 30.2 events/h, versus 16.2 ± 15.5 events/h; P = 0.002), as was serum LOX (84.64 ± 29.71 ng/mL, versus 45.46 ± 17.16 ng/mL; P < 0.001). In the sleep clinic sample, patients with severe OSA had higher baseline LOX than healthy controls (70.75 ng/mL versus 52.36 ng/mL, P = 0.046), and serum LOX decreased in patients with OSA on CPAP (mean decrease 20.49 ng/mL) but not in untreated patients (mean decrease 0.19 ng/mL). Hypoxic mouse hepatocytes demonstrated 5.9-fold increased LOX transcription (P = 0.046), and enhanced LOX protein secretion. CONCLUSIONS: The hypoxic stress of obstructive sleep apnea may increase circulating lysyl oxidase (LOX) levels. LOX may serve as a biomarker of liver fibrosis in patients with severe obesity and nonalcoholic fatty liver disease.

Impact of OSA on cardiovascular events after coronary artery bypass surgery.

BACKGROUND: The impact of OSA on new cardiovascular events in patients undergoing coronary artery bypass graft (CABG) surgery is poorly explored. METHODS: Consecutive patients referred for CABG underwent clinical evaluation and standard polysomnography in the preoperative period. CABG surgery data, including percentage of off-pump and on-pump CABG, number of grafts, and intraoperative complications, were collected. The primary end point was major adverse cardiac or cerebrovascular events (MACCEs) (combined events of all-cause death, myocardial infarction, repeated revascularization, and cerebrovascular events). Secondary end points included individual MACCEs, typical angina, and arrhythmias. Patients were evaluated at 30 days (short-term) and up to 6.1 years (long term) after CABG. RESULTS: We studied 67 patients (50 men; mean age, 58 ± 8 years; mean BMI, 28.5 ± 4.1 kg/m2). OSA (apnea-hypopnea index ≥ 15 events/h) was present in 56% of the population. The patients were followed for a mean of 4.5 years (range, 3.2-6.1 years). No differences were observed in the short-term follow-up. In contrast, MACCE (35% vs 16%, P = .02), new revascularization (19% vs 0%, P = .01), episodes of typical angina (30% vs 7%, P = .02), and atrial fibrillation (22% vs 0%, P = .0068) were more common in patients with than without OSA in the long-term follow-up. OSA was an independent factor associated with the occurrence of MACCE, repeated revascularization, typical angina, and atrial fibrillation in the multivariate analysis. CONCLUSIONS: OSA is independently associated with a higher rate of long-term cardiovascular events after CABG and may have prognostic and economic significance in CABG surgery.

Lack of reliable clinical predictors to identify obstructive sleep apnea in patients with hypertrophic cardiomyopathy

OBJECTIVE: Obstructive sleep apnea is common among patients with hypertrophic cardiomyopathy and may contribute to poor cardiovascular outcomes. However, obstructive sleep apnea is largely unrecognized in this population. We sought to identify the clinical predictors of obstructive sleep apnea among patients with hypertrophic cardiomyopathy. METHODS: Consecutive patients with hypertrophic cardiomyopathy were recruited from a tertiary University Hospital and were evaluated using validated sleep questionnaires (Berlin and Epworth) and overnight portable monitoring. Ninety patients (males, 51%; age, 46±15 years; body mass index, 26.6±4.9 kg/m2) were included, and obstructive sleep apnea (respiratory disturbance index ≥15 events/h) was present in 37 patients (41%). RESULTS: Compared with the patients without obstructive sleep apnea, patients with obstructive sleep apnea were older and had higher body mass index, larger waist circumference, larger neck circumference, and higher prevalence of atrial fibrillation. Excessive daytime sleepiness (Epworth scale) was low and similar in the patients with and without obstructive sleep apnea, respectively. The only predictors of obstructive sleep apnea (using a logistic regression analysis) were age ≥45 years (odds ratio [OR], 4.46; 95% confidence interval [CI 95%], 1.47-13.54; p = 0.008) and the presence of atrial fibrillation [OR, 5.37; CI 95%, 1.43-20.12; p = 0.013]. CONCLUSION: Consistent clinical predictors of obstructive sleep apnea are lacking for patients with hypertrophic cardiomyopathy, which suggests that objective sleep evaluations should be considered in this population, particularly among elderly patients with atrial fibrillation. .

Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension.

Recognition and treatment of secondary causes of hypertension among patients with resistant hypertension may help to control blood pressure and reduce cardiovascular risk. However, there are no studies systematically evaluating secondary causes of hypertension according to the Seventh Joint National Committee. Consecutive patients with resistant hypertension were investigated for known causes of hypertension irrespective of symptoms and signs, including aortic coarctation, Cushing syndrome, obstructive sleep apnea, drugs, pheochromocytoma, primary aldosteronism, renal parenchymal disease, renovascular hypertension, and thyroid disorders. Among 125 patients (age: 52±1 years, 43% males, systolic and diastolic blood pressure: 176±31 and 107±19 mm Hg, respectively), obstructive sleep apnea (apnea-hypopnea index: >15 events per hour) was the most common condition associated with resistant hypertension (64.0%), followed by primary aldosteronism (5.6%), renal artery stenosis (2.4%), renal parenchymal disease (1.6%), oral contraceptives (1.6%), and thyroid disorders (0.8%). In 34.4%, no secondary cause of hypertension was identified (primary hypertension). Two concomitant secondary causes of hypertension were found in 6.4% of patients. Age >50 years (odds ratio: 5.2 [95% CI: 1.9-14.2]; P<0.01), neck circumference ≥41 cm for women and ≥43 cm for men (odds ratio: 4.7 [95% CI: 1.3-16.9]; P=0.02), and presence of snoring (odds ratio: 3.7 [95% CI: 1.3-11]; P=0.02) were predictors of obstructive sleep apnea. In conclusion, obstructive sleep apnea appears to be the most common condition associated with resistant hypertension. Age >50 years, large neck circumference measurement, and snoring are good predictors of obstructive sleep apnea in this population.

Avanços recentes do impacto da apneia obstrutiva do sono na hipertensão arterial sistêmica / Recent advances of the impact of obstructive sleep apnea on systemic hypertension / Avances recientes del impacto de la Apnea Obstructiva del Sueño en la Hipertensión Arterial Sistémica

A apneia obstrutiva do sono (AOS) é uma condição clínica comum na população em geral, principalmente entre os pacientes portadores de doenças cardiovasculares. Mais do que um fenômeno local de obstrução das vias aéreas superiores, a AOS traz repercussões sistêmicas que podem incluir a hipóxia intermitente, a redução abrupta da pressão intratorácica e a ocorrência de microdespertares com fragmentação do sono. Nas últimas décadas, inúmeras evidências apontam de forma consistente a AOS como um importante fator envolvido na ocorrência de doenças cardiovasculares. Particularmente, a relação entre a AOS e a hipertensão arterial sistêmica (HAS) é a que encontra um maior conjunto de evidências. Atualmente, encontram-se dados que consideram a AOS uma importante causa secundária de HAS. Mais do que isso, a AOS está independentemente associada a um pior controle pressórico, alteração do descenso noturno da pressão arterial e à presença de lesões de órgãos-alvo, tais como a hipertrofia do ventrículo esquerdo e a microalbuminúria. Estudos randomizados sugerem que o tratamento da AOS, especialmente com a pressão positiva contínua de vias aéreas superiores (CPAP), considerado o tratamento padrão para a AOS, promove redução significante da pressão arterial nas 24 horas, efeito esse mais significante no subgrupo de pacientes com HAS não controlada e nos pacientes com HAS resistente. A despeito de todas essas evidências, a AOS ainda continua sendo subdiagnosticada. O objetivo desta revisão é discutir os recentes avanços nos mecanismos fisiopatológicos, na apresentação clínica e no tratamento da AOS, e o benefício sobre a pressão arterial.

Obstructive sleep apnea (OSA) is a common clinical condition in the general population, especially among patients with cardiovascular diseases. More than just a local phenomenon of upper respiratory tract obstruction, OSA leads to systemic consequences that may include intermittent hypoxia, sudden reduction of the intrathoracic pressure, and the occurrence of micro-awakenings with sleep fragmentation. In the past decades, innumerous evidences have consistently pointed to OSA as an important factor related to the presence of cardiovascular diseases. In particular, the relationship between OSA and systemic hypertension (SH) is the one supported by the largest body of evidence. Currently, there are data suggesting that OSA is an important secondary cause of SH. More importantly, OSA is independently associated with poorer blood pressure control, changes in sleep dip, and presence of target-organ damage such as left ventricular hypertrophy and microalbuminuria. Randomized studies suggest that the management of OSA, especially with continuous positive airway pressure (CPAP) - which is considered the standard treatment for OSA - promotes a significant 24-hour blood pressure reduction, and this effect is more significant in the subgroup of patients with uncontrolled SH and drug-resistant SH. Despite all those evidences, OSA has still been underdiagnosed. The objective of this review is to discuss the recent advances in the pathophysiological mechanisms, clinical presentation, and treatment of OSA, as well as the benefits this treatment can bring on blood pressure.

La apnea obstructiva del sueño (AOS) es una condición clínica común en la población en general, principalmente entre los pacientes portadores de enfermedades cardiovasculares. Más que un fenómeno local de obstrucción de las vías aéreas superiores, la AOS trae repercusiones sistémicas que pueden incluir la hipoxia intermitente, la reducción abrupta de la presión intratorácica y la ocurrencia de microdespertares con fragmentación del sueño. En las últimas décadas, innúmeras evidencias señalan de forma consistente la AOS como un importante factor envuelto en la ocurrencia de enfermedades cardiovasculares. Particularmente, la relación entre la AOS y la Hipertensión Arterial Sistémica (HAS) es la que encuentra un mayor conjunto de evidencias. Actualmente, se encuentran datos que consideran la AOS una importante causa secundaria de HAS. Más que eso, la AOS está independientemente asociada a un peor control presórico, alteración del descenso nocturno de la presión arterial y a la presencia de lesiones de órganos-blanco, tales como la hipertrofia del ventrículo izquierdo y la microalbuminuria. Estudios randomizados sugieren que el tratamiento de la AOS, especialmente con la presión positiva continua de vías aéreas superiores (CPAP), considerado el tratamiento estándar para la AOS, promueve reducción significativa de la presión arterial en las 24 horas, efecto ese más significativo en el subgrupo de pacientes con HAS no controlada y en los pacientes con HAS resistente. A despecho de todas esas evidencias, la AOS aun continúa siendo subdiagnosticada. El objetivo de esta revisión es discutir los recientes avances en los mecanismos fisiopatológicos, en la presentación clínica y en el tratamiento de la AOS, y el beneficio sobre la presión arterial.

Apneia do sono e arritmias cardíacas / Sleep apnea and cardiac arrhythmias

A apneia obstrutiva do sono é muito comum na população em geral, sendo ainda mais comum entre os pacientes com doença cardiovascular estabelecida. A apneia obstrutiva do sono é considerada fator de risco para o desenvolvimento de hipertensão arterial sistêmica, insuficiência cardíaca, infarto do miocárdio, acidente vascular encefálico e arritmias cardíacas. Dentre as arritmias mais comuns e associadas com apneia obstrutiva do sono destacamos a fibrilação atrial, as bradiarritmias e as arritmias ventriculares. Diversos mecanismos fisiopatológicos, incluindo as vias neural, humoral hemodinâmica e metabólica, são responsáveis pelos efeitos negativos da apneia obstrutiva do sono nas doenças cardiovasculares. Evidências científicas atuais sugerem que os cardiologistas identifiquem os subgrupos de pacientes portadores de alto risco para apneia obstrutiva do sono, sua referência para a polissonografia e a indicação do tratamento com pressão positiva contínua em vias aéreas (CPAP). A identificação e o tratamento da apneia obstrutiva do sono melhoram a qualidade de vida dos pacientes e podem prevenir os efeitos negativos da apneia obstrutiva do sono nas arritmias cardíacas.

Síndrome da apnéia obstrutiva do sono, obesidade e hipertensão / Obstructive sleep apnea syndrome, obesity, and hypertension

A síndrome da apnéia obstrutiva do sono é uma entidade muito prevalente e ainda pouco diagnosticada em individuos obesos e em hipertensos. Caracteriza-se por episódios recorrentes de cessação do fluxo aéreo decorrente do colapso inspiratório das vias aéreas durante o sono, frequentemente acompanhada por queda da saturação arterial de oxigênio e/ou despertares breves. As alterações hemodinâmicas e metabólicas causadas por esses fenômenos contribuem para o desenvolvimento da hipertensão arterial e suas consequências para o sistema cardiovascular. Discutiremos nesta breve revisão os princípios fisiopatólogicos envolvidos na síndrome de apnéia obstrutiva do sono e da obesidade na gênese da hipertensão arterial, como também as peculiaridades de seu tratamento com base nas mais recentes evidências clínicas.