Relación entre la apnea obstructiva del sueño y la diabetes mellitus tipo 2 / Relationship between obstructive sleep apnea and type 2 diabetes mellitus

Introducción: La asociación entre la apnea obstructiva del sueño (AOS) y el metabolismo de la glucosa sigue siendo controvertida. Este estudio investiga la relación entre la AOS y la diabetes mellitus tipo 2 (DM) y prediabetes (preDM) incidentes, así como el efecto del tratamiento con presión positiva continua en la vía aérea (CPAP) a largo plazo. Métodos: Estudio de seguimiento en cohorte retrospectiva clínica de pacientes con AOS y controles seleccionados de manera aleatoria. Los datos sobre DM incidente y preDM, así como de la CPAP se obtuvieron de los registros hospitalarios. La relación entre AOS basal y la DM incidente se examinó con modelos de regresión de Cox. Resultados: De un total de 356 pacientes, 169 con AOS y 187 controles fueron seguidos por una mediana de 98 meses; 47 enfermos (13,2%) desarrollaron DM y 43 (12,1%) preDM. La incidencia acumulada a los cinco años de DM fue de 10,7% (6,5-13,9%). De los sujetos con preDM en la muestra basal, 87% evolucionaron a DM incidente. Se demuestra que el índice de masa corporal (IMC), la hipoxia nocturna y el índice de apnea hipopnea (IAH) son factores de riesgo para el desarrollo de DM, y que la CPAP los disminuye. Conclusiones: Los pacientes con AOS tienen mayor probabilidad de desarrollar DM. Los factores de riesgo implicados son el IMC, la hipoxia nocturna y el IAH. El uso regular de CPAP a largo plazo se asoció con una disminución de estos. (AU)

Introduction: The association between obstructive sleep apnea (OSA) and glucose metabolism remains controversial. This study investigates the relationship between OSA and incident type 2 diabetes (DM) and prediabetes (preDM), as well as the effect of long-term CPAP (continuous positive airway pressure) treatment. Methods: Follow-up study in a retrospective clinical cohort of patients with OSA and randomly selected controls. Data on incident DM and preDM as well as CPAP were obtained from hospital records. The relationship between baseline OSA and incident DM was examined using COX regression models. Results: Three hundred and fifty-six patients, 169 with OSA and 187 controls were followed for a median of 98 months; 47 patients (13.2%) developed DM and 43 (12.1%) developed preDM. The 5-year cumulative incidence of DM was 10.7% (6.5–13.9%). 87% of subjects with preDM in the baseline sample progressed to incident DM. It is shown that body mass index (BMI), nocturnal hypoxia and apnea hypopnea index (AHI) are risk factors for the development of DM and that CPAP reduces this risk. Conclusions: Patients with OSA have a higher risk of developing DM. The risk factors involved are BMI, nocturnal hypoxia and AHI. Regular long-term CPAP use was associated with a decreased risk. (AU)

[Relationship between obstructive sleep apnea and type 2 diabetes mellitus]. / Relación entre la apnea obstructiva del sueño y la diabetes mellitus tipo 2.

INTRODUCTION: The association between obstructive sleep apnea (OSA) and glucose metabolism remains controversial. This study investigates the relationship between OSA and incident type 2 diabetes (DM) and prediabetes (preDM), as well as the effect of long-term CPAP (continuous positive airway pressure) treatment. METHODS: Follow-up study in a retrospective clinical cohort of patients with OSA and randomly selected controls. Data on incident DM and preDM as well as CPAP were obtained from hospital records. The relationship between baseline OSA and incident DM was examined using COX regression models. RESULTS: Three hundred and fifty-six patients, 169 with OSA and 187 controls were followed for a median of 98 months; 47 patients (13.2%) developed DM and 43 (12.1%) developed preDM. The 5-year cumulative incidence of DM was 10.7% (6.5-13.9%). 87% of subjects with preDM in the baseline sample progressed to incident DM. It is shown that body mass index (BMI), nocturnal hypoxia and apnea hypopnea index (AHI) are risk factors for the development of DM and that CPAP reduces this risk. CONCLUSIONS: Patients with OSA have a higher risk of developing DM. The risk factors involved are BMI, nocturnal hypoxia and AHI. Regular long-term CPAP use was associated with a decreased risk.

Effects of sacubitril-valsartan on central and obstructive apneas in heart failure patients with reduced ejection fraction.

OBJECTIVE: This study aimed to evaluate the effect of sacubitril-valsartan (SV) on central apneas (CA) and obstructive apneas (OA) in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: In patients with HFrEF, SV initiation was titrated to the highest tolerable dosage. Patients were evaluated with portable apnea monitoring, echocardiography, and cardiopulmonary exercise testing at baseline and 3 months later. RESULTS: Of a total of 18 patients, 9 (50%) had OA, 7 (39%) had CA, and 2 (11%) had normal breathing. SV therapy was related to a reduction in NT-pro BNP and an improvement in LV function after 3 months. Portable apnea monitoring revealed a significant decrease of the respiratory event index (REI) after treatment with SV (20 ± 23 events/h to 7 ± 7 events/h, p = 0.003). When subgrouping according to type of apneas, REI, and time spent below 90% saturation (T90) decreased in patients with CA and OA (all p < 0.05). CONCLUSION: In this prospective study, SV treatment for 3 months in patients with CA and OA is associated with a significant decrease in REI.

Cognition in Patients with Sleep-Disordered Breathing: Can Obstructive and Central Apneic Pauses Play a Different Role in Cognitive Impairment?

BACKGROUND: There are increasing data linking sleep apnea with cognitive impairment. We aimed to clarify the relationship between sleep-disordered breathing (SDB) and cognition. Detailed attention was assigned to the potential role of central versus obstructive apneic pauses in cognitive impairment. METHODS: Patients with suspected SDB were prospectively enrolled, and a complex sleep study was performed that included overnight polysomnography. A revised version of Addenbrooke's Cognitive Examination (ACE-R) was used to assess cognition, evaluating overall cognition and individual subdomains. RESULTS: A total number of 101 participants were included in the study. In multivariate binary logistic regression analysis, obstructive apnea index ([OAI], 95% CI: 1.009-1.057, p = 0.008) was the only significant contributor to the model predicting attention deficit. The proportion of N1 stage of NREM sleep was the only significant contributor to the model predicting impaired verbal fluency (95% CI: 1.004-1.081, p = 0.029). No significant differences in sleep-related indices were observed in the remaining ACE-R subdomains. CONCLUSION: Except for verbal fluency and attention, we failed to find any significant association of sleep-related indices with the impairment in different cognitive subdomains. Our data suggest that impairment observed in verbal fluency is associated with a higher proportion of shallow NREM sleep, and attention deficit is associated with higher OAI. Obstructive respiratory episodes seem to play a more important role in cognitive impairment when compared to central ones.

Speckle tracking echocardiography in heart failure development and progression in patients with apneas.

Obstructive (OA) and central apneas (CA) are highly prevalent breathing disorders that have a negative impact on cardiac structure and function; while OA promote the development of progressive cardiac alterations that can eventually lead to heart failure (HF), CA are more prevalent once HF ensues. Therefore, the early identification of the deleterious effects of apneas on cardiac function, and the possibility to detect an initial cardiac dysfunction in patients with apneas become relevant. Speckle tracking echocardiography (STE) imaging has become increasingly recognized as a method for the early detection of diastolic and systolic dysfunction, by the evaluation of left atrial and left and right ventricular global longitudinal strain, respectively. A growing body of evidence is available on the alterations of STE in OA, while very little is known with regard to CA. In this review, we discuss the current knowledge and gap of evidence concerning apnea-related STE alterations in the development and progression of HF.

Sacubitril-valsartan treatment is associated with decrease in central apneas in patients with heart failure with reduced ejection fraction.

BACKGROUND: To assess the impact of sacubitril-valsartan on apneic burden in patients with heart failure with reduced ejection fraction (HFrEF), 51 stable HFrEF patients planned for switching from an ACE-i/ARB to sacubitril-valsartan were prospectively enrolled. METHODS AND RESULTS: At baseline and after 6 months of treatment, all patients underwent echocardiography, 24-h cardiorespiratory monitoring, neurohormonal evaluation, and cardiopulmonary exercise testing. At baseline 29% and 65% of patients presented with obstructive and central apneas, respectively. After 6 months, sacubitril-valsartan was associated with a decrease in NT-proBNP, improvement in LV function, functional capacity and ventilatory efficiency. After treatment, the apnea-hypopnea index (AHI) decreased across the 24-h period (p < 0.001), as well as at daytime (p < 0.001) and at nighttime (p = 0.026), proportionally to baseline severity. When subgrouping according to the type of apneas, daytime, nighttime and 24-h AHI decreased in patients with central apneas (all p < 0.01). Conversely, in patients with obstructive apneas, the effect of drug administration was neutral at nighttime, with significant decrease only in daytime events (p = 0.007), mainly driven by reduction in hypopneas. CONCLUSIONS: Sacubitril-valsartan on top of medical treatment is associated with a reduction in the apneic burden among a real-life cohort of HFrEF patients. The most marked reduction was observed for central apneas.

Role of the Cyclooxygenase Pathway in the Association of Obstructive Sleep Apnea and Cancer.

The objective of this review is to examine the findings that link obstructive sleep apnea (OSA) with cancer and the role played by the cyclooxygenase (COX) pathway in this association. Epidemiological studies in humans suggest a link between OSA and increased cancer incidence and mortality. Studies carried out in animal models have shown that intermittent hypoxia (IH) induces changes in several signaling pathways involved in the regulation of host immunological surveillance that results in tumor establishment and invasion. IH induces the expression of cyclooxygenase 2 (COX-2) that results in an increased synthesis of prostaglandin E2 (PGE2). PGE2 modulates the function of multiple cells involved in immune responses including T lymphocytes, NK cells, dendritic cells, macrophages, and myeloid-derived suppressor cells. In a mouse model blockage of COX-2/PGE2 abrogated the pro-oncogenic effects of IH. Despite the fact that aspirin inhibits PGE2 production and prevents the development of cancer, none of the epidemiological studies that investigated the association of OSA and cancer included aspirin use in the analysis. Studies are needed to investigate the regulation of the COX-2/PGE2 pathway and PGE2 production in patients with OSA, to better define the role of this axis in the physiopathology of OSA and the potential role of aspirin in preventing the development of cancer.

Central and Obstructive Apneas in Heart Failure With Reduced, Mid-Range and Preserved Ejection Fraction.

Background: Although central apneas (CA) and obstructive apneas (OA) are highly prevalent in heart failure (HF), a comparison of apnea prevalence, predictors and clinical correlates in the whole HF spectrum, including HF with reduced ejection fraction (HFrEF), mid-range EF (HFmrEF) and preserved EF (HFpEF) has never been carried out so far. Materials and methods: 700 HF patients were prospectively enrolled and then divided according to left ventricular EF (408 HFrEF, 117 HFmrEF, 175 HFpEF). All patients underwent a thorough evaluation including: 2D echocardiography; 24-h Holter-ECG monitoring; cardiopulmonary exercise testing; neuro-hormonal assessment and 24-h cardiorespiratory monitoring. Results: In the whole population, prevalence of normal breathing (NB), CA and OA at daytime was 40, 51, and 9%, respectively, while at nighttime 15, 55, and 30%, respectively. When stratified according to left ventricular EF, CA prevalence decreased (daytime: 57 vs. 43 vs. 42%, p = 0.001; nighttime: 66 vs. 48 vs. 34%, p < 0.0001) from HFrEF to HFmrEF and HFpEF, while OA prevalence increased (daytime: 5 vs. 8 vs. 18%, p < 0.0001; nighttime 20 vs. 29 vs. 53%, p < 0.0001). In HFrEF, male gender and body mass index (BMI) were independent predictors of both CA and OA at nighttime, while age, New York Heart Association functional class and diastolic dysfunction of daytime CA. In HFmrEF and HFpEF male gender and systolic pulmonary artery pressure were independent predictors of CA at daytime, while hypertension predicted nighttime OA in HFpEF patients; no predictor of nighttime CA was identified. When compared to patients with NB, those with CA had higher neuro-hormonal activation in all HF subgroups. Moreover, in the HFrEF subgroup, patients with CA were older, more comorbid and with greater hemodynamic impairment while, in the HFmrEF and HFpEF subgroups, they had higher left atrial volumes and more severe diastolic dysfunction, respectively. When compared to patients with NB, those with OA were older and more comorbid independently from background EF. Conclusions: Across the whole spectrum of HF, CA prevalence increases and OA decreases as left ventricular systolic dysfunction progresses. Different predictors and specific clinical characteristics might help to identify patients at risk of developing CA or OA in different HF phenotypes.

Polysomnographic findings in Rett syndrome.

INTRODUCTION: Rett syndrome (RS) is a severe neurodevelopment disorder associated with abnormal breathing during wakefulness and disturbed nocturnal behaviour. Breathing abnormalities during daytime have been extensively reported but polysomnographic (PSG) findings have been poorly studied. MATERIALS AND METHODS: Consecutive patients with RS carrying distinct mutations in MECP2 gene, who underwent a PSG between October 2014 and January 2018, were included in the study. Clinical and PSG data were collected. RESULTS: Seventeen RS girls, mean age 9.5 ± 2.8 years, were included in the study. Mean total sleep time was 366 ± 102 min. Mean sleep efficiency was reduced (66 ± 19%) with only 3 girls presenting a sleep efficiency above 80%. Wake after sleep onset was increased (33 ± 20%) with an arousal index of 7 ± 6 events/hour. Sleep stages were altered with a normal N1 (2 ± 3%), a decreased N2 (34 ± 20%), an increase of N3 (51 ± 23%) and a decrease of REM sleep (12 ± 9%). Mean apnea hypopnea index (AHI) was increased at 19 ± 37 events/hour, with a predominance of obstructive events. Thirteen patients had an AHI > 1.5 event/hour. Four patients had an obstructive AHI >10 events/hour with one patient having associated tonsillar hypertrophy. Two patients had predominant severe central apneas (central AHI 53 and 132 events/hour) which resolved with noninvasive ventilation and nocturnal oxygen therapy respectively. CONCLUSION: Girls with RS have poor sleep quality with alterations in slow wave and REM sleep stages. Obstructive respiratory events are uncommon in patients without adenotonsillar hypertrophy. Central respiratory events are rare. Longitudinal studies should help understanding the natural history of sleep disturbances in RS and their relationship with the neurocognitive decline.

Estudios de sueño en niños con daño neurológico: ¿cuándo y por qué estudiar? / Sleep study in children with neurologic impairments: when and why need to study?

Sleep disordered breathing is frequent among children with neurologic impairments. underdiagnosis and misrecognition of this diseases seames to be important. In the present revision, major findings in children with cerebral palsy, neuromuscular disease and Down syndrome are summarized. Patients with cerebral palsy show several aspects which are associated and may worsen sleep disordered breathing. Children with neuromuscular diseases present with a characteristic pattern of sleep disordered breathing, which shows predominantely central hipopneas. On the other hand, patients with Down syndrome show a high prevalence of obstructive sleep apneas. Early recognition of sleep disordered breathing is important among children with neurologic impairments, as it may lead to an early treatment. The development of new screening methods for sleep disordered breathing maybe especially useful in children with underlying neurological diseases.

Los trastornos respiratorios del sueño (TRs) son frecuentes en niños con daño neurológico, existiendo un subdiagnóstico y desconocimiento importante de esta patología. En la presente revisión se resumen los hallazgos más importantes en niños con parálisis cerebral (PC), enfermedades neuromusculares (enm) y síndrome de Down. Los pacientes con PC presentan una serie de factores que empeoran y se asocian a los TRs. los niños con enm muestran un patrón de TRs característico, en el cual predomina la presencia de hipopneas centrales. Los pacientes con síndrome de Down, por otra parte, presentan una alta prevalencia de apneas obstructivas del sueño. El reconocimiento precoz de los TRs es fundamental en los niños con daño neurológico, ya que pudiera permitir un tratamiento precoz. El desarrollo de nuevos exámenes de pesquisa podría ser útil para la pesquisa precoz de los TRs en niños con daño neurológico de base.