Effect of CPAP treatment on BP in resistant hypertensive patients according to the BP dipping pattern and the presence of nocturnal hypertension.

High heterogeneity in the blood pressure (BP) response to continuous positive airway pressure (CPAP) exists in patients with resistant hypertension (RH). Only nondipper normotensive and hypertensive patients exhibited BP reductions when treated with CPAP; the baseline BP dipping pattern has been proposed as a predictor of BP response to CPAP but has never been explored in patients with RH. This study aimed to assess the effect of CPAP on BP in subjects with RH with respect to BP dipping pattern or nocturnal hypertension. This is an ancillary study of the SARAH study. RH subjects with an apnea/hypopnea index (AHI) ≥ 15/h and who received CPAP treatment for 1 year were included. Subjects underwent a sleep study and ambulatory BP monitoring (ABPM) at baseline and at the 1-year follow-up. Eighty-nine RH subjects were included. The subjects were mainly male (77.5%) and obese, with a mean age of 66 years (25th-75th percentile; 59.0; 70.0) and an AHI of 32.7/h (25th-75th percentile; 25.0; 54.7). A total of 68.5% of participants were nondippers, and 71.9% had nocturnal hypertension. After 1 year of CPAP, no significant differences in ABPM parameters were observed between dippers and nondippers. According to nighttime BP, subjects with nocturnal normotension did not show significant changes in ABPM parameters, while nocturnal hypertensive subjects achieved a significant reduction in mean nighttime BP of -4.38 mmHg (-7.10 to -1.66). The adjusted difference between groups was 3.04 (-2.25 to 8.34), which was not significant. This study shows that the BP response to CPAP in patients with RH does not differ according to the BP dipping pattern (dipper and nondipper) and suggests a differential response according to the presence of nocturnal hypertension (ClinicalTrials.gov: NCT03002558).

Rationale and Methodology of the SARAH Trial: Long-Term Cardiovascular Outcomes in Patients With Resistant Hypertension and Obstructive Sleep Apnea / Justificación y metodología del ensayo clínico SARAH: evolución cardiovascular a largo plazo en pacientes con hipertensión resistente y apnea obstructiva del sueño

Introduction: Patients with resistant hypertension (RH) have a high risk of developing cardiovascular events; therefore, new therapeutic approaches to better control blood pressure may be useful in improving cardiovascular outcomes. The prevalence of obstructive sleep apnea (OSA) is very high among patients with RH. Continuous positive airway pressure (CPAP) has been shown to be an effective treatment for reducing blood pressure in patients with RH. Nevertheless, the long-term effect of CPAP treatment on cardiovascular outcomes has not been explored. The main objective of the SARAH study is to assess the impact of OSA and its treatment on cardiovascular outcomes (morbidity and mortality) in patients with RH. Methods: This study is a multi-center, prospective, observational cohort study. A total of 1371 patients with RH will be enrolled in the study and followed once a year for five years. At inclusion, ambulatory blood pressure monitoring (ABPM) and a sleep study will be performed in all subjects. Socio-demographic, clinical and cardiovascular variables will be collected at baseline and follow-up. Subsequently, subjects with OSA will be managed according to local standard practice. Based on the OSA diagnosis and its treatment, three cohorts of subjects with RH will be defined: non-OSA, treated OSA and non-treated OSA. Conclusions: This study will contribute to elucidating the long-term impact of OSA treatments on blood pressure control and cardiovascular outcomes in patients with RH. These results will contribute to improve the cardiovascular prognosis of patients with RH

Introducción: Los pacientes con hipertensión resistente (HR) tienen un elevado riesgo de desarrollar eventos cardiovasculares; así, las nuevas estrategias terapéuticas para el control de la presión arterial podrían ser útiles para mejorar los resultados cardiovasculares. La prevalencia de la apnea obstructiva del sueño (AOS) es muy elevada entre los pacientes con HR. Se ha demostrado que la presión positiva continua en la vía aérea (CPAP) constituye un tratamiento efectivo para reducir la presión arterial en pacientes con HR. Sin embargo, todavía no se han estudiado los efectos a largo plazo del tratamiento con CPAP sobre los resultados cardiovasculares. El principal objetivo del estudio SARAH es evaluar el impacto de la AOS y su tratamiento en los resultados cardiovasculares (morbilidad y mortalidad) en pacientes con HR. Métodos: Este es un estudio observacional prospectivo multicéntrico en el que se incluirán 1.371 pacientes con HR, a los cuales se les realizará seguimiento una vez al año durante 5 años. En el momento de la inclusión se realizará a todos los pacientes monitorización ambulatoria de la presión arterial (MAPA), así como un estudio de sueño. Se recogerán las variables sociodemográficas, clínicas y cardiovasculares tanto al inicio del estudio como durante el seguimiento. Posteriormente, los individuos con AOS serán tratados de acuerdo con la práctica clínica estándar de cada centro. Se definirán 3 grupos en función del diagnóstico de AOS y su tratamiento: sin AOS, con AOS en tratamiento, con AOS sin tratar. Conclusiones: Este estudio contribuirá a averiguar el impacto a largo plazo del tratamiento de la AOS en el control de la presión arterial y los resultados cardiovasculares en pacientes con HR. Asimismo, estos resultados contribuirán a mejorar el pronóstico cardiovascular de los pacientes con HR

Rationale and Methodology of the SARAH Trial: Long-Term Cardiovascular Outcomes in Patients With Resistant Hypertension and Obstructive Sleep Apnea.

INTRODUCTION: Patients with resistant hypertension (RH) have a high risk of developing cardiovascular events; therefore, new therapeutic approaches to better control blood pressure may be useful in improving cardiovascular outcomes. The prevalence of obstructive sleep apnea (OSA) is very high among patients with RH. Continuous positive airway pressure (CPAP) has been shown to be an effective treatment for reducing blood pressure in patients with RH. Nevertheless, the long-term effect of CPAP treatment on cardiovascular outcomes has not been explored. The main objective of the SARAH study is to assess the impact of OSA and its treatment on cardiovascular outcomes (morbidity and mortality) in patients with RH. METHODS: This study is a multi-center, prospective, observational cohort study. A total of 1371 patients with RH will be enrolled in the study and followed once a year for five years. At inclusion, ambulatory blood pressure monitoring (ABPM) and a sleep study will be performed in all subjects. Socio-demographic, clinical and cardiovascular variables will be collected at baseline and follow-up. Subsequently, subjects with OSA will be managed according to local standard practice. Based on the OSA diagnosis and its treatment, three cohorts of subjects with RH will be defined: non-OSA, treated OSA and non-treated OSA. CONCLUSIONS: This study will contribute to elucidating the long-term impact of OSA treatments on blood pressure control and cardiovascular outcomes in patients with RH. These results will contribute to improve the cardiovascular prognosis of patients with RH.

El síndrome de apneas-hipoapneas del sueño (SAHS) grave incrementa la excreción urinaria de eritropoyetina. Efecto del tratamiento con CPAP / Increased Urinary Erythropoietin Excretion in Severe Sleep Apnea-Hipoapnea Syndrome: The Effect of CPAP

Introducción: La hipoxia tisular estimula la producción de eritropoyetina (EPO) que tiene como principal función estimular la eritropoyesis. El SAHS es una entidad caracterizada por la presencia de episodios repetidos de hipoxemia durante el sueño. Objetivo: Analizar si dicha hipoxemia es un estímulo suficiente para incrementar la excreción urinaria de EPO. Si la respuesta fuera positiva, valorar si el tratamiento con presión continua positiva de la vía aérea (CPAP) la inhibiría. Métodos: Se han estudiado 25 sujetos con sospecha de SAHS, a los que se les realizó un estudio polisomnográfico. En todos ellos se determinaron los niveles de EPO en la primera orina de la mañana (uEPO), así como los niveles de creatinina y hemoglobina en sangre. En los pacientes con SAHS grave se repitieron las mismas determinaciones tras el tratamiento con CPAP. Resultados: Doce sujetos fueron diagnosticados de SAHS grave (media ± SD, IAH de 53,1 ± 22,7). La creatinina y la hemoglobina fueron normales en todos los sujetos. La uEPO fue cuatro veces superior en el grupo SAHS respecto a los controles (1,32 ± 0,83 vs. 0,32 ± 0,35 IU/l, p < 0,002). El tratamiento con CPAP descendió la uEPO hasta 0,61 ± 0,49 IU/l (p < 0,02), acercándose al valor de los sujetos sanos. No se observó una relación dosis-respuesta entre la gravedad de las alteraciones de la PSG y los valores de uEPO. Conclusiones: Los pacientes con SAHS grave muestran un incremento en su excreción de uEPO, que se normaliza tras el tratamiento con CPAP

Introduction: Tissue hypoxia stimulates the production of erythropoietin (EPO), the main effect of which is, in turn, to stimulate erythropoiesis. Sleep apnea-hypopnea syndrome (SAHS) is an entity characterized by repeated episodes of hypoxemia during sleep. Objective: To analyze whether hypoxemia stimulated increased urinary excretion of EPO, and if so, to evaluate if treatment with continuous positive airway pressure (CPAP) can inhibit this phenomenon. Methods: We studied 25 subjects with suspected SAHS who underwent a polysomnography study (PSG). EPO levels in first morning urine (uEPO) and blood creatinine and hemoglobin were determined in all patients. Patients with severe SAHS repeated the same determinations after CPAP treatment. Results: Twelve subjects were diagnosed with severe SAHS (mean ± SD, AHI 53.1 ± 22.7). Creatinine and hemoglobin levels were normal in all subjects. uEPO was 4 times higher in the SAHS group than in the control group (1.32 ± 0.83 vs. 0.32 ± 0.35 UI/l, p <.002). CPAP treatment reduced uEPO to 0.61 ± 0.9 UI/l (p <.02), levels close to those observed in healthy subjects. No dose-response relationship was observed between severity of PSG changes and uEPO values. Conclusions: Patients with severe SAHS show increased uEPO excretion, but this normalizes after treatment with CPAP

Increased Urinary Erythropoietin Excretion in Severe Sleep Apnea-Hipoapnea Syndrome: The Effect of CPAP. / El síndrome de apneas-hipoapneas del sueño (SAHS) grave incrementa la excreción urinaria de eritropoyetina. Efecto del tratamiento con CPAP.

INTRODUCTION: Tissue hypoxia stimulates the production of erythropoietin (EPO), the main effect of which is, in turn, to stimulate erythropoiesis. Sleep apnea-hypopnea syndrome (SAHS) is an entity characterized by repeated episodes of hypoxemia during sleep. OBJECTIVE: To analyze whether hypoxemia stimulated increased urinary excretion of EPO, and if so, to evaluate if treatment with continuous positive airway pressure (CPAP) can inhibit this phenomenon. METHODS: We studied 25 subjects with suspected SAHS who underwent a polysomnography study (PSG). EPO levels in first morning urine (uEPO) and blood creatinine and hemoglobin were determined in all patients. Patients with severe SAHS repeated the same determinations after CPAP treatment. RESULTS: Twelve subjects were diagnosed with severe SAHS (mean ± SD, AHI 53.1 ± 22.7). Creatinine and hemoglobin levels were normal in all subjects. uEPO was 4 times higher in the SAHS group than in the control group (1.32 ± 0.83 vs. 0.32 ± 0.35 UI/l, p <.002). CPAP treatment reduced uEPO to 0.61 ± 0.9 UI/l (p <.02), levels close to those observed in healthy subjects. No dose-response relationship was observed between severity of PSG changes and uEPO values. CONCLUSIONS: Patients with severe SAHS show increased uEPO excretion, but this normalizes after treatment with CPAP.

Impacto a largo plazo del tratamiento con presión positiva continua en la vía aérea superior sobre la incidencia de arritmias y la variabilidad de frecuencia cardiaca en pacientes con apnea del sueño / Long-term Impact of Continuous Positive Airway Pressure Therapy on Arrhythmia and Heart Rate Variability in Patients With Sleep Apnea

Introducción: La disfunción del sistema nervioso autonómico produce alteraciones en la variabilidad de la frecuencia cardiaca y aumenta la incidencia de arritmias. Analizamos este fenómeno fisiopatológico en pacientes con síndrome de apnea/hipoapnea del sueño severo y el impacto sobre el mismo del tratamiento con presión positiva continua en la vía aérea (CPAP). Métodos: Pacientes consecutivos con síndrome de apnea/hipoapnea del sueño severo de reciente diagnóstico fueron prospectivamente considerados para inclusión. Se analizó la incidencia de arritmias y la variabilidad de la frecuencia cardiaca (obtenidos mediante registro Holter de 24 horas) antes de iniciarse tratamiento con CPAP y tras un año del mismo. Resultados: Se incluyeron 26 pacientes. El tiempo de uso de CPAP durante el registro Holter fue de 6,6 ± 1,8 horas. Tras inicio de CPAP, se apreció una reducción marginalmente significativa en la FC media (80 ± 9 a 77 ± 11 lpm, p = 0,05). El uso de CPAP se asoció a una modulación parcial y exclusivamente en horas de vigilia de los parámetros de modulación parasimpáticar-MSSD (p = 0,047) y HF (p = 0,025) y de modulación simpática LF (p = 0,049). Ninguno de estos revirtió completamente a la normalidad (p < 0,001). Se observó una reducción de los episodios no sostenidos de taquicardia auricular (p = 0,024), sin efecto demostrativo sobre otras arritmias. Conclusiones: El tratamiento con CPAP se asocia a una mejora solo parcial y diurna de la variabilidad de la frecuencia cardiaca y disminuye la incidencia de taquicardia auricular. Ambos efectos podrían influir en la morbimortalidad cardiovascular de los pacientes con síndrome de apnea/hipoapnea del sueño

Introduction: Autonomic dysfunction can alter heart rate variability and increase the incidence of arrhythmia. We analyzed the impact of continuous positive airway pressure (CPAP) on this pathophysiological phenomenon in patients with severe sleep apnea-hypopnea syndrome. Methods: Consecutive patients with recently diagnosed severe sleep apnea-hypopnea syndrome were prospectively considered for inclusion. Incidence of arrhythmia and heart rate variability (recorded on a 24-hour Holter monitoring device) were analyzed before starting CPAP therapy and 1 year thereafter. Results: A total of 26 patients were included in the study. CPAP was administered for 6.6 ± 1.8 hours during Holter monitoring. After starting CPAP, we observed a marginally significant reduction in mean HR (80 ± 9 to 77 ± 11 bpm, p = .05). CPAP was associated with partial modulation (only during waking hours) of r-MSSD (p = .047) and HF (p = .025) parasympathetic parameters and LF (p = .049) sympathetic modulation parameters. None of these parameters returned completely to normal levels (p < .001). The number of unsustained episodes of atrial tachycardia diminished (p = .024), but no clear effect on other arrhythmias was observed. Conclusions: CPAP therapy only partially improves heart rate variability, and exclusively during waking hours, and reduces incidence of atrial tachycardia, both of which can influence cardiovascular morbidity and mortality in sleep apnea-hypopnea syndrome patients

Long-term Impact of Continuous Positive Airway Pressure Therapy on Arrhythmia and Heart Rate Variability in Patients With Sleep Apnea.

INTRODUCTION: Autonomic dysfunction can alter heart rate variability and increase the incidence of arrhythmia. We analyzed the impact of continuous positive airway pressure (CPAP) on this pathophysiological phenomenon in patients with severe sleep apnea-hypopnea syndrome. METHODS: Consecutive patients with recently diagnosed severe sleep apnea-hypopnea syndrome were prospectively considered for inclusion. Incidence of arrhythmia and heart rate variability (recorded on a 24-hour Holter monitoring device) were analyzed before starting CPAP therapy and 1 year thereafter. RESULTS: A total of 26 patients were included in the study. CPAP was administered for 6.6 ± 1.8 hours during Holter monitoring. After starting CPAP, we observed a marginally significant reduction in mean HR (80 ± 9 to 77 ± 11 bpm, p=.05). CPAP was associated with partial modulation (only during waking hours) of r-MSSD (p=.047) and HF (p=.025) parasympathetic parameters and LF (p=.049) sympathetic modulation parameters. None of these parameters returned completely to normal levels (p<.001). The number of unsustained episodes of atrial tachycardia diminished (p=.024), but no clear effect on other arrhythmias was observed. CONCLUSIONS: CPAP therapy only partially improves heart rate variability, and exclusively during waking hours, and reduces incidence of atrial tachycardia, both of which can influence cardiovascular morbidity and mortality in sleep apnea-hypopnea syndrome patients.

Obstructive sleep apnea in patients with typical atrial flutter: prevalence and impact on arrhythmia control outcome.

BACKGROUND: The clinical yield of cavotricuspid isthmus (CTI) radiofrequency ablation of atrial flutter (AF) is limited by a high incidence of atrial fibrillation (AFib) in the long term. Among other acknowledged variables, the association of obstructive sleep apnea (OSA) could favor incomplete arrhythmia control in this setting. We assessed the impact of CPAP in reducing the occurrence of AFib after CTI ablation. METHODS: Consecutive patients with AF who were undergoing CTI ablation were screened for OSA. Relationship of the following variables with the occurrence of AFib during follow-up (12 months) was investigated: CPAP initiation, hypertension, BMI, underlying structural heart disease, left atrial diameter, and AFib documentation prior to ablation. RESULTS: We prospectively included 56 patients (mean age: 66 (± 11) years; 12 female patients), of whom 46 (82%) had OSA and 25 (45%) had severe OSA. Twenty-one patients (38%) had AFib during follow-up after CTI ablation. Both freedom from AFib prior to ablation and CPAP initiation in those patients without previously documented AFib at inclusion were associated with a reduction of AFib episodes during follow-up (P = .019 and P = .025, respectively). Inversely, CPAP was not protective from AFib recurrence when this arrhythmia was documented prior to ablation (P = .25). CONCLUSIONS: OSA is a prevalent condition in patients with AF. Treatment with CPAP is associated with a lower incidence of newly diagnosed AFib after CTI ablation. Screening for OSA in patients with AF appears to be a reasonable clinical strategy.

Physical activity and its determinants in severe chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have a limited exercise capacity. Surprisingly, little is known about their levels of physical activity practice. We assessed the levels and determinants of physical activity practice in severe COPD patients. METHODS: A cross-sectional systematic sample of 346 COPD patients was recruited during 1 yr in four tertiary hospitals of the Barcelona area of Spain. Patients answered a questionnaire, which included physical activity assessment, and performed spirometric tests and blood gases. RESULTS: Seventy-eight percent of patients walked daily whereas 17% did not practice any physical activity. Median energy expenditure in physical activity was 109 kcal x d(-1) (IQR 24-239). The following factors were independently associated with a lower physical activity level in a logistic regression analysis: female sex (OR 2.92, 95% CI 1.11-7.70), older age (1.04, 1.01-1.07 per year), higher socioeconomic status (2.23, 1.24-4.02), diabetes (2.66, 1.40-5.06), lower physical and mental quality of life (0.93, 0.90-0.96 and 0.96, 0.93-0.98, respectively, per unit), and long-term oxygen therapy (2.07, 1.19-3.60). Neither FEV1, previous COPD admissions, body mass index, nor other treatments were related to physical activity practice. CONCLUSIONS: In conclusion, one third of severe COPD patients in our study reported a level of physical activity lower than the equivalent to walking less than 15 min x d(-1). Apart from sociodemographic variables, comorbidity, health-related quality of life, and long-term oxygen therapy were the only factors independently associated with a low level of physical activity.

Health-related quality of life and mortality in male patients with chronic obstructive pulmonary disease.

To assess whether generic and specific health-related quality of life (HRQL) are independently associated with total and specific mortality in patients with chronic obstructive pulmonary disease (COPD), we followed until 1999 a cohort of 321 male patients with COPD, recruited in 1993-1994 at outpatient respiratory clinics. Baseline characteristics recorded under stable clinical conditions included forced spirometry, arterial blood gas tensions, dyspnea scales, 11 comorbid conditions, St. George's Respiratory Questionnaire (SGRQ), and SF-36 Health Survey. Vital status was assessed through reinterviews, the Mortality Register, and clinical records. Subjects who died (106) were older (69.8 versus 62.5 years) (p < 0.001), had lower body mass index (BMI) (25.4 versus 27.1) (p < 0.01), were more impaired in the clinical characteristics studied (%FEV(1), 34.0 versus 51.0) (p < 0.001), and had long-term oxygen therapy more frequently (31% versus 7%) (p < 0.001). Survival was shorter when worse HRQL was reported. SGRQ total and SF-36 physical summary scores were independently associated with total and respiratory mortality in Cox models, including age, FEV(1), and BMI. The total mortality-standardized hazard ratios for both HRQL measures were 1.3, whereas those for FEV(1) were 1.6. HRQL measures provide independent and relevant information on the health status of male patients with COPD. Their use should be considered for a more thorough evaluation and staging of patients with COPD.