Mercedes Mayos

Long-term effect of continuous positive airway pressure in hypertensive patients with sleep apnea.

RATIONALE Continuous positive airway pressure (CPAP) is the current treatment for patients with symptomatic obstructive sleep apnea (OSA). Its use for all subjects with sleep-disordered breathing, regardless of daytime symptoms, is unclear. OBJECTIVES This multicenter controlled trial assesses the effects of 1 year of CPAP treatment on blood pressure (BP) in nonsymptomatic, hypertensive patients with OSA. METHODS We evaluated 359 patients with OSA. Inclusion criteria consisted of an apnea-hypopnea index (AHI) greater than 19 hour(-1), an Epworth Sleepiness Scale score less than 11, and one of the following: under antihypertensive treatment or systolic blood pressure greater than 140 or diastolic blood pressure greater than 90 mm Hg. Patients were randomized to CPAP (n = 178) or to conservative treatment (n = 181). BP was evaluated at baseline and at 3, 6, and 12 months of follow-up. MEASUREMENTS AND MAIN RESULTS Mean (SD) values were as follows: age, 56 +/- 10 years; body mass index (BMI), 32 +/- 5 kg x m(-2); AHI, 45 +/- 20 hour(-1); and Epworth Sleepiness Scale score, 7 +/- 3. After adjusting for follow-up time, baseline blood pressure values, AHI, time with arterial oxygen saturation less than 90%, and BMI, together with the change in BMI at follow-up, CPAP treatment decreased systolic blood pressure by 1.89 mm Hg (95% confidence interval: -3.90, 0.11 mm Hg; P = 0.0654), and diastolic blood pressure by 2.19 mm Hg (95% confidence interval: -3.46, -0.93 mm Hg; P = 0.0008). The most significant reduction in BP was in patients who used CPAP for more than 5.6 hours per night. CPAP compliance was related to AHI and the decrease in Epworth Sleepiness Scale score. CONCLUSIONS In nonsleepy hypertensive patients with OSA, CPAP treatment for 1 year is associated with a small decrease in BP. This effect is evident only in patients who use CPAP for more than 5.6 hours per night. Clinical trial registered with www.clinicaltrials.gov (NCT00127348).

Continuous positive airway pressure as treatment for systemic hypertension in people with obstructive sleep apnoea: randomised controlled trial

Objective To assess the effect of continuous positive airway pressure (CPAP) on 24 hour ambulatory blood pressure monitoring values in a large number of patients with untreated systemic hypertension of new onset and obstructive sleep apnoea. Design Multicentre, double blind, randomised, placebo controlled trial. Setting Eleven general hospitals in Spain between 2004 and 2007. Participants 340 patients recently diagnosed as having systemic hypertension by a general practitioner (systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or both) and an apnoea-hypopnoea index per hour of sleep of >15 events/hour. Intervention Patients were assigned to CPAP (n=169) or sham CPAP (n=171) for three months. Main outcome measurements Net changes in the different 24 hour ambulatory blood pressure monitoring values from baseline to three months of optimal or sham CPAP. Results 277 (81%) of the 340 patients randomised were men; the patients had a mean age of 52.4 (SD 10.5) years, a body mass index of 31.9 (5.7), an Epworth sleepiness scale score of 10.1 (4.3), an apnoea-hypopnoea index of 43.5 (24.5). No differences between groups were seen at baseline. Compared with placebo and analysed by intention to treat, the mean 24 hour ambulatory blood pressure of the CPAP group decreased by 1.5 (95% confidence interval: 0.4 to 2.7) mm Hg (P=0.01). The mean 24 hour ambulatory blood pressure monitoring measures decreased by 2.1 mm Hg (0.4 to 3.7) mm Hg (P=0.01) for systolic pressure and 1.3 (0.2 to 2.3) mm Hg (P=0.02) for diastolic blood pressure. Mean nocturnal blood pressure decreased by 2.1 (0.5 to 3.6) mm Hg (P=0.01). Conclusions CPAP produced a statistically significant reduction in blood pressure in patients with systemic hypertension and obstructive sleep apnoea. This reduction is small and did not achieve the 3 mm Hg drop in mean 24 hour ambulatory blood pressure that the trial was powered to detect. Consequently, these results may have uncertain clinical relevance. However, taking into account the prevalence of hypertension and the likelihood of comorbidities, the decrease in blood pressure, although minimal, may be beneficial. Trial registration Clinical trials NCT00202527.

Obstructive sleep apnoea and metabolic impairment in severe obesity

Obstructive sleep apnoea (OSA) seems to worsen metabolism. This effect has not been evaluated in morbid obesity (MO). We hypothesised that the metabolic profile is more impaired in MO patients with OSA than in those without, and investigated whether any specific metabolic dysfunction is related to OSA in MO. A prospective multicentre cross-sectional study was conducted in consecutive subjects before bariatric surgery. OSA was defined as apnoea/hypopnoea index (AHI) ≥15 by overnight polysomnography. Anthropometrical, blood pressure (BP) and fasting blood measurements were obtained the morning after. Metabolic syndrome (MetS) was defined according to National Cholesterol Education Program Adult Treatment Panel III modified criteria. 159 patients were studied: 72% were female and 72% had OSA. MetS prevalence was 70% in OSA versus 36% in non-OSA (p<0.001). As AHI severity increased, metabolic parameters progressively worsened, even in those without type 2 diabetes (DM2). AHI was independently associated with systolic and diastolic BP, triglycerides and the percentage of glycosylated haemoglobin (HbA1c) in the total sample, and with systolic BP, high-density lipoprotein cholesterol and HbA1c in those samples without DM2. OSA increased the adjusted odds ratio of having MetS by 2.8 (95% CI 1.3–6.2; p=0.009). In MO, OSA is associated with major metabolic impairment caused by higher BP and poorer lipid and glucose control, independent of central obesity or DM2.

A Randomized Controlled Trial of Continuous Positive Airway Pressure on Glucose Tolerance in Obese Patients with Obstructive Sleep Apnea.

STUDY OBJECTIVES Obstructive sleep apnea (OSA) is associated with an increased prevalence of metabolic syndrome (MetS), even in patients with morbid obesity. Our goal was to address whether continuous positive airway pressure (CPAP) treatment improved glucose metabolism in this population. METHODS A prospective randomized controlled trial was performed in severe OSA patients with morbid obesity without diabetes in two university referral hospitals. Patients received conservative (CT) versus CPAP treatment for 12 weeks. MetS components, homeostasis model assessment of insulin resistance (HOMA-IR) and oral glucose tolerance were assessed at baseline and after treatment. RESULTS A total of 80 patients completed the study (42 CPAP and 38 CT patients). After 12 w of CPAP treatment, weight loss was similar in both groups and physical activity, prevalence of MetS, and HOMA-IR did not change in either group. In the CPAP group impaired glucose tolerance (IGT) reversed in nine patients and IGT developed in none, whereas IGT reversed in five patients and IGT developed in five patients in the CT group (P = 0.039 in the Fisher test). Changes in 2-h plasma glucose after glucose load were greater in the CPAP group than in the CT group (CPAP: -0.5 ± 1.5 versus CT: 0.33 ± 1.9, P = 0.007). CONCLUSIONS The improvement of glucose tolerance in morbidly obese patients with severe obstructive sleep apnea, without changes in homeostasis model assessment of insulin resistance, supports an improvement in peripheral insulin resistance after continuous positive airway pressure treatment. CLINICAL TRIALS REGISTRATION NCT 01029561.

Obstructive sleep apnoea in the elderly: role of continuous positive airway pressure treatment

CPAP is effective in elderly patients with severe OSA in clinical and neurocognitive terms improving quality of life http://ow.ly/KHfh9 Almost all the information about the effect of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnoea (OSA) comes from clinical trials involving only middle-aged patients. The objective of this study was to assess the effect of CPAP treatment in elderly patients with severe OSA on clinical, quality-of-life and neurocognitive spheres. We performed an open-label, randomised, multicentre clinical trial in a consecutive clinical cohort of 224 elderly (≥70 years old) patients with confirmed severe OSA (apnoea–hypopnea index ≥30) randomised to receive CPAP (n=115) or no CPAP (n=109) for 3 months. A sleep study was performed by either full polysomnography or respiratory polygraphy. CPAP titration was performed by an autoCPAP device. The primary endpoint was quality of life (Quebec Sleep Questionnaire) and secondary endpoints included sleep-related symptoms, presence of anxiety/depression, office-based blood pressure and some neurocognitive tests. The mean±sd age was 75.5±3.9 years. The CPAP group achieved a greater improvement in all quality-of-life domains (p<0.001; effect size: 0.41–0.98), sleep-related symptoms (p<0.001; effect size 0.31–0.91) as well as anxiety (p=0.016; effect size 0.51) and depression (p<0.001; effect size: 0.28) indexes and some neurocognitive tests (digit symbol test (p=0.047; effect size: 0.20) and Trail Making Test A (p=0.029; effect size: 0.44)) in an intention-to-treat analysis. In conclusion, CPAP treatment resulted in an improvement in quality of life, sleep-related symptoms, anxiety and depression indexes and some neurocognitive aspects in elderly people with severe OSA.

Sleep hypoventilation due to increased nocturnal oxygen flow in hypercapnic COPD patients.

Background and objective:  Several COPD treatment guidelines recommend increasing oxygen flow during sleep to avoid nocturnal desaturation. However, such an increase could have deleterious clinical and gas exchange effects. The objective of this study was to evaluate short‐term gas exchange alterations produced by increasing the nocturnal oxygen flow rate.

Effectiveness of home single-channel nasal pressure for sleep apnea diagnosis.

INTRODUCTION Home single-channel nasal pressure (HNP) may be an alternative to polysomnography (PSG) for obstructive sleep apnea (OSA) diagnosis, but no cost studies have yet been carried out. Automatic scoring is simpler but generally less effective than manual scoring. OBJECTIVES To determine the diagnostic efficacy and cost of both scorings (automatic and manual) compared with PSG, taking as a polysomnographic OSA diagnosis several apnea-hypopnea index (AHI) cutoff points. METHODS We included suspected OSA patients in a multicenter study. They were randomized to home and hospital protocols. We constructed receiver operating characteristic (ROC) curves for both scorings. Diagnostic efficacy was explored for several HNP AHI cutoff points, and costs were calculated for equally effective alternatives. RESULTS Of 787 randomized patients, 752 underwent HNP. Manual scoring produced better ROC curves than automatic for AHI < 15; similar curves were obtained for AHI ≥ 15. A valid HNP with manual scoring would determine the presence of OSA (or otherwise) in 90% of patients with a polysomnographic AHI ≥ 5 cutoff point, in 74% of patients with a polysomnographic AHI ≥ 10 cutoff point, and in 61% of patients with a polysomnographic AHI ≥ 15 cutoff point. In the same way, a valid HNP with automatic scoring would determine the presence of OSA (or otherwise) in 73% of patients with a polysomnographic AHI ≥ 5 cutoff point, in 64% of patients with a polysomnographic AHI ≥ 10 cutoff point, and in 57% of patients with a polysomnographic AHI ≥ 15 cutoff point. The costs of either HNP approaches were 40% to 70% lower than those of PSG at the same level of diagnostic efficacy. Manual HNP had the lowest cost for low polysomnographic AHI levels (≥ 5 and ≥ 10), and manual and automatic scorings had similar costs for higher polysomnographic cutoff points (AHI ≥ 15) of diagnosis. CONCLUSION Home single-channel nasal pressure (HNP) is a cheaper alternative than polysomnography for obstructive sleep apnea diagnosis. HNP with manual scoring seems to have better diagnostic accuracy and a lower cost than automatic scoring for patients with low apnea-hypopnea index (AHI) levels, although automatic scoring has similar diagnostic accuracy and cost as manual scoring for intermediate and high AHI levels. Therefore, automatic scoring can be appropriately used, although diagnostic efficacy could improve if we carried out manual scoring on patients with AHI < 15. CLINICAL TRIALS INFORMATION Clinicaltrials.gov identifier: NCT01347398.

Predicting nocturnal hypoventilation in hypercapnic chronic obstructive pulmonary disease patients undergoing long-term oxygen therapy.

Background: Chronic obstructive pulmonary disease (COPD) patients are very sensitive to changes in pulmonary mechanics and central ventilation control during sleep and may develop significant gas exchange alterations with increased hypoxemia and hypercapnia. Oxygen therapy improves nocturnal desaturation but can worsen hypoventilation. Objectives: To analyze the prevalence of nocturnal hypoventilation (NHV) in hypercapnic COPD patients and to determine predictive factors for this phenomenon. Methods: This was a prospective multicenter study which enrolled 80 clinically stable COPD patients with hypercapnic respiratory failure who fulfilled the conventional criteria for long-term oxygen therapy (LTOT). All patients had undergone pulmonary function testing, blood gas analysis, and respiratory polygraphy. Arterial blood gas samples were obtained while patients were awake and during sleep. NHV was considered when an increase in PaCO2 >10 mm Hg was observed in any nocturnal arterial blood gas sample as compared to the awake levels. Results: Seventeen patients (21%) developed NHV. NHV was associated with the values of BMI, hemoglobin, hematocrits, DLCO, and PaO2 reached after oxygen administration. In the logistic regression analysis BMI (OR 1.26, 95% CI 1.068–1.481; p = 0.006) and the diurnal increase of PaO2 after O2 (OR 0.89, 95% CI 0.807–0.972; p = 0.010) were the variables that best discriminated with a sensitivity of 82% and a specificity of 78%. Conclusions: NHV is a relatively common finding in stable hypercapnic COPD patients undergoing LTOT and it is related to a higher BMI and lower PaO2 after oxygen administration.

Optimizing screening of severe obstructive sleep apnea in patients undergoing bariatric surgery

BACKGROUND Obstructive sleep apnea is common in patients waiting for bariatric surgery (BS). International consensuses have recommended assessment of obstructive sleep apnea in the preoperative evaluation to avoid perioperative complications. Polysomnography is the standard diagnostic method but is expensive and time-consuming. The aim of our study was to detect those patients who merit treatment before BS using a simple predictor model. The study was conducted at 3 university hospitals (Hospital de Bellvitge, Hospital de la Santa Creu i Sant Pau, Hospital Clinic de Barcelona). METHODS A prospective cross-sectional study was conducted of 136 consecutive bariatric subjects. The outcome variable was severe obstructive sleep apnea, defined as an apnea-hypoapnea index of ≥30 events/hr by polysomnography. The predictors evaluated were anthropometric and clinical in the first model, with an oxygen desaturation index of ≥3% added to the second model. Predictive models were constructed using multivariate logistic regression analysis. The best model was selected according to the area under the receiver operating characteristic curve. RESULTS The first model identified 4 independent factors: age, waist circumference, systolic blood pressure, and witnessed apnea episodes, with a sensitivity of 78%, specificity of 68%, and area under the receiver operating characteristic curve of .83 (95% confidence interval .76-.90, P < .001). The second model identified 2 independent factors (witness apnea episodes, oxygen desaturation index of ≥3%), with a sensitivity of 91%, specificity of 85%, and area under the receiver operating characteristic curve of .94 (95% confidence interval .89-.98, P < .001). The 2-step model predictive values were sensitivity of 90%, specificity of 91%, and accuracy of 90% (95% confidence interval 84-94%). After applying the first model and then the second, 45% of subjects would have been ruled out (15% and 30%, respectively) and 55% would require additional sleep management before BS. CONCLUSION The proposed model could be useful for improving the management of complex patients before BS and optimizing limited polysomnography resources.

Impact of OSA on Biological Markers in Morbid Obesity and Metabolic Syndrome

BACKGROUND AND OBJECTIVE There is compelling evidence that obstructive sleep apnoea (OSA) can affect metabolic syndrome (MetS) and cardiovascular risk, but the intermediate mechanisms through which it occurs have not been well defined. We explored the impact of OSA in morbidly obese patients with MetS on adipokines, pro-inflammatory markers, endothelial dysfunction, and atherosclerosis markers. METHODS We included 52 morbidly obese patients in an observational study matched for age, gender and central obesity in 3 groups (OSA-MetS, Non-OSA-MetS, and Non OSA-non-MetS). Anthropometrical, blood pressure, and fasting blood measurements were obtained the morning after an overnight polysomnography. VEGF, soluble CD40 ligand (sCD40L), TNF-α, IL-6, leptin, adiponectin, and chemerin were determined in serum by ELISA. OSA was defined as apnea/ hypopnea index ≥ 15 and MetS by NCEP-ATP III. RESULTS Cases and control subjects did not differ in age, BMI, waist circumference, and gender (43 ± 10 years, 46 ± 5 kg/m(2), 128 ± 10 cm, 71% females). The cases had severe OSA with 47 (32-66) events/h, time spent < 90% SpO2 7% (5%-31%). All groups presented similar serum cytokines, adipokines, VEGF, and sCD40L levels. CONCLUSIONS In a morbidly obese population with established MetS, the presence of OSA did not determine any differences in the studied mediators when matched by central obesity. Morbidly obese NonOSA-NonMetS had a similar inflammatory, adipokine VEGF, and sCD40L profile as those with established MetS, with or without OSA. Obesity itself could overwhelm the effect of sleep apnea and MetS in the studied biomarkers. CITATION Salord N; Gasa M; Mayos M; Fortuna-Gutierrez AM; Montserrat JM; Sánchez-de-la-Torre M; Barceló A; Barbé F; Vilarrasa N; Monasterio C. Impact of OSA on biological markers in morbid obesity and metabolic syndrome.