Alberto Alonso-Fernández

Effects of CPAP on oxidative stress and nitrate efficiency in sleep apnoea: a randomised trial

Background: Previous studies have presented contradictory data concerning obstructive sleep apnoea syndrome (OSAS), lipid oxidation and nitric oxide (NO) bioavailability. This study was undertaken to (1) compare the concentration of 8-isoprostane and total nitrate and nitrite (NOx) in plasma of middle-aged men with OSAS and no other known co-morbidity and healthy controls of the same age, gender and body mass index; and (2) test the hypothesis that nasal continuous positive airway pressure (CPAP) therapy attenuates oxidative stress and nitrate deficiency. Methods: A prospective, randomised, placebo controlled, double-blind, crossover study was performed in 31 consecutive middle-aged men with newly diagnosed OSAS and 15 healthy control subjects. Patients with OSAS were randomised to receive sham CPAP or effective CPAP for 12 weeks. Blood pressure, urinary catecholamine levels and plasma 8-isoprostane and NOx concentrations were obtained before and after both treatment modalities. Results: Patients with OSAS had significantly higher 8-isoprostane levels (median (IQR) 42.5 (29.2–78.2) vs 20.0 (12.5–52.5) pg/ml, pu200a=u200a0.041, Mann-Whitney test) and lower NOx levels (264 (165–650) vs 590 (251–1465) μmol/l, pu200a=u200a0.022) than healthy subjects. Body mass index, blood pressure and urinary catecholamines were unchanged by CPAP therapy, but 8-isoprostane concentrations decreased (38.5 (24.2–58.7) pg/ml at baseline vs 22.5 (16.2–35.3) pg/ml on CPAP, pu200a=u200a0.0001) and NOx levels increased (280 (177–707) vs 1373 (981–1517) μmol/l, pu200a=u200a0.0001) after CPAP. Conclusions: OSAS is associated with an increase in oxidative stress and a decrease in NOx that is normalised by CPAP therapy.

CPAP effect on recurrent episodes in patients with sleep apnea and myocardial infarction

BACKGROUNDnObstructive sleep apnea (OSA) is linked to increased cardiovascular risk, but the association between OSA and myocardial infarction (MI) remains controversial. Our objectives were to compare the frequency of OSA in patients with acute MI and in a population-based sample of control subjects, and to evaluate the impact of CPAP on recurrent MI and coronary revascularization.nnnMETHODSnCase-control study with a 6-year follow-up of the case cohort. 192 acute MI patients and 96 matched control subjects without coronary artery disease (CAD) (ratio 2:1). After overnight polysomnography, CPAP was recommended if apnea-hypopnea index (AHI) ≥ 5, and a mean daily use >3.5h/day was considered necessary to maintain the treatment. Lipids, fasting glucose, blood pressure, spirometry, comorbidity and current treatment were also registered. End-points were recurrent MI or need of revascularization.nnnRESULTSnOSA was an independent predictor of MI, with odds ratio 4.9 (95% confidence interval [CI] 2.9-8.3, p=0.017). 63 MI patients without OSA, 52 untreated patients with OSA and 71 OSA patients treated with CPAP were included in the follow-up study. After adjustment for confounding factors, treated OSA patients had a lower risk of recurrent MI (adjusted hazard ratio 0.16 [95%CI 0.03-0.76, p=0.021]) and revascularization (adjusted hazard ratio 0.15 [95%CI 0.03-0.79, p=0.025]) than untreated OSA patients, and similar to non-OSA patients.nnnCONCLUSIONnMild-severe OSA is an independent risk factor for MI. Risk of recurrent MI and revascularization was lower in OSA patients who tolerated CPAP.

Effect of Continuous Positive Airway Pressure on Glycemic Control in Patients with Obstructive Sleep Apnea and Type 2 Diabetes. A Randomized Clinical Trial

RATIONALEnObstructive sleep apnea (OSA) is a risk factor for type 2 diabetes that adversely impacts glycemic control. However, there is little evidence about the effect of continuous positive airway pressure (CPAP) on glycemic control in patients with diabetes.nnnOBJECTIVESnTo assess the effect of CPAP on glycated hemoglobin (HbA1c) levels in patients with suboptimally controlled type 2 diabetes and OSA, and to identify its determinants.nnnMETHODSnIn a 6-month, open-label, parallel, and randomized clinical trial, 50 patients with OSA and type 2 diabetes and two HbA1c levels equal to or exceeding 6.5% were randomized to CPAP (nu2009=u200926) or no CPAP (control; nu2009=u200924), while their usual medication for diabetes remained unchanged.nnnMEASUREMENTS AND MAIN RESULTSnHbA1c levels, Homeostasis Model Assessment and Qualitative Insulin Sensitivity Check Index scores, systemic biomarkers, and health-related quality of life were measured at 3 and 6 months. After 6 months, the CPAP group achieved a greater decrease in HbA1c levels compared with the control group. Insulin resistance and sensitivity measurements (in noninsulin users) and serum levels of IL-1β, IL-6, and adiponectin also improved in the CPAP group compared with the control group after 6 months. In patients treated with CPAP, mean nocturnal oxygen saturation and baseline IL-1β were independently related to the 6-month change in HbA1c levels (r(2)u2009=u20090.510, Pu2009=u20090.002).nnnCONCLUSIONSnAmong patients with suboptimally controlled type 2 diabetes and OSA, CPAP treatment for 6 months resulted in improved glycemic control and insulin resistance compared with results for a control group. Clinical trial registered with www.clinicaltrials.gov (NCT01801150).

Telomere shortening in sleep apnea syndrome

BACKGROUNDnTelomere length (TL) in circulating leukocytes relates to the chronological age of the individual but it is believed to reflect also the cumulative burden of oxidative stress and inflammation over the life-time. Shortening of TL has been reported in several chronic conditions characterized by oxidative stress and inflammation, such as diabetes and atherosclerosis. Because these conditions also occur in patients with Obstructive Sleep Apnea Syndrome (OSAS), we hypothesized that TL would be reduced in patients with OSAS.nnnMETHODSnWe compared TL in 256 patients with OSAS and 148 controls without OSAS. We also investigated if TL was related to the severity of OSAS, the presence of metabolic disorders and/or cardiovascular risk factors in these patients.nnnRESULTSnTL was significantly shorter in patients with OSAS than in controls (p<0.001). This difference persisted after adjustment for age, body mass index, cholesterol, triglycerides, glucose, and uric acid levels, smoking status and the presence of arterial hypertension (p=0.018). TL was not related to the severity of OSAS as assessed by the apnea-hypopnea index, nocturnal oxygen saturation and daytime sleepiness.nnnCONCLUSIONSnTL in circulating leukocytes is shorter in patients with OSAS than subjects without OSAS. The mechanism of this observation is unresolved since it appears independent of chronological age, the severity of OSAS and/or the presence of cardiovascular or metabolic alterations but the potential utility of TL as a biomarker of increased cardiovascular risk in these patients justifies further studies.

Free fatty acids and the metabolic syndrome in patients with obstructive sleep apnoea

Obesity and metabolic syndrome (MS) occur frequently in patients with obstructive sleep apnoea syndrome (OSAS). We hypothesised that circulating free fatty acids (FFAs) are elevated in OSAS patients independently of obesity. This elevation may contribute to the development of MS in these patients. We studied 119 OSAS patients and 119 controls. Participants were recruited and studied at sleep unit of our institution (Hospital Universitari Son Dureta, Palma de Mallorca, Spain) and were matched for sex, age and body mass index (BMI). The occurrence of MS was analysed by clinical criteria. Serum levels of FFAs, glucose, triglycerides, cholesterol, high-density lipoprotein–cholesterol, aspartate aminotransferase, alanine aminotransferase, &ggr;-glutamyltransferase, C-reactive protein and 8-isoprostanes were determined. Prevalence of MS was higher in OSAS than in the control group (38 versus 21%; p = 0.006). OSAS patients had higher FFAs levels than controls (mean±sd 12.2±4.9 versus 10.5±5.0 mg·dL−1; p = 0.015). Among subjects without MS, OSAS patients (OSAS+ MS-) showed higher levels of FFAs than controls (OSAS- MS-) (11.6±4.7 versus 10.0±4.4 mg·dL−1; p = 0.04). In a multiple regression model, after adjustment for age, sex, BMI and the presence of MS, FFAs were significantly associated with apnoea/hypopnoea index (p = 0.04). This study shows that FFAs are elevated in OSAS and could be one of the mechanisms involved in the metabolic complications of OSAS.

Relationship between aldosterone and the metabolic syndrome in patients with obstructive sleep apnea hypopnea syndrome: effect of continuous positive airway pressure treatment

Background Metabolic syndrome (MS) occurs frequently in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). We hypothesized that aldosterone levels are elevated in OSAHS and associated with the presence of MS. Methods We studied 66 patients with OSAHS (33 with MS and 33 without MS) and 35 controls. The occurrence of the MS was analyzed according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) clinical criteria. Measurements of plasma renin activity (PRA), aldosterone, aldosterone:PRA ratio, creatinine, glucose, triglycerides, cholesterol and HDL cholesterol were obtained at baseline and after CPAP treatment. Results Aldosterone levels were associated with the severity of OSAHS and higher than controls (pu200a=u200a0.046). Significant differences in aldosterone levels were detected between OSAHS patients with and without MS (pu200a=u200a0.041). A significant reduction was observed in the aldosterone levels in patients under CPAP treatment (pu200a=u200a0.012). Conclusion This study shows that aldosterone levels are elevated in OSAHS in comparison to controls, and that CPAP therapy reduces aldosterone levels. It also shows that aldosterone levels are associated with the presence of metabolic syndrome, suggesting that aldosterone excess might predispose or aggravate the metabolic and cardiovascular complications of OSAHS. Trial registration The study is not a randomized controlled trial and was not registered.

Effectiveness of sequential automatic-manual home respiratory polygraphy scoring

Automatic home respiratory polygraphy (HRP) scoring functions can potentially confirm the diagnosis of sleep apnoea-hypopnoea syndrome (SAHS) (obviating technician scoring) in a substantial number of patients. The result would have important management and cost implications. The aim of this study was to determine the diagnostic cost-effectiveness of a sequential HRP scoring protocol (automatic and then manual for residual cases) compared with manual HRP scoring, and with in-hospital polysomnography. We included suspected SAHS patients in a multicentre study and assigned them to home and hospital protocols at random. We constructed receiver operating characteristic (ROC) curves for manual and automatic scoring. Diagnostic agreement for several cut-off points was explored and costs for two equally effective alternatives were calculated. Of 366 randomised patients, 348 completed the protocol. Manual scoring produced better ROC curves than automatic scoring. There was no sensitive automatic or subsequent manual HRP apnoea–hypopnoea index (AHI) cut-off point. The specific cut-off points for automatic and subsequent manual HRP scorings (AHI >25 and >20, respectively) had a specificity of 93% for automatic and 94% for manual scorings. The costs of manual protocol were 9% higher than sequential HRP protocol; these were 69% and 64%, respectively, of the cost of the polysomnography. A sequential HRP scoring protocol is a cost-effective alternative to polysomnography, although with limited cost savings compared to HRP manual scoring.

Association Between Obstructive Sleep Apnea and Pulmonary Embolism

OBJECTIVESnTo compare the prevalence of obstructive sleep apnea (OSA) in patients with pulmonary embolism (PE) with a sex-, age-, and body mass index (BMI)-matched, population-based control group and to assess the association between OSA and PE.nnnMETHODSnWe performed a case-control study from October 1, 2006, through November 30, 2009. We included 107 patients with PE and a control group (n=102) without PE in University Hospitals Son Espases and La Paz in Spain. Variables included in the analysis were medical history, anthropometric variables (weight, height, BMI, and neck circumference), Epworth Sleepiness Scale score, home respiratory polygraphy, basic biochemical profile and hemogram, spirometry, and physical activity.nnnRESULTSnThe mean ± SD apnea-hypopnea index (AHI) was significantly higher in patients with PE than population controls (21.2±20.6 vs 11.5±15.9 h(-1); P<.001). The presence of an AHI greater than 5 h(-1) and hypersomnolence (Epworth Sleepiness Scale score ≥11) was more frequent in PE patients than in controls (14.0% vs 4.9%; P=.0002). A crude model analysis by several cutoffs revealed that the AHI was significantly associated with PE. After adjustment for age, sex, smoking, BMI, lung function, and all known PE risk factors, the odds ratio for PE was 3.7 (95% CI, 1.3-10.5; P=.01).nnnCONCLUSIONnA higher prevalence of OSA was detected in patients diagnosed as having acute PE than controls. This study identified a significant and independent association between OSA and PE.

Impaired circadian variation of platelet activity in patients with sleep apnea

BackgroundCardiovascular diseases are frequent in patients with obstructive sleep apnea (OSAS). There is evidence that the day–night pattern of myocardial infarction and sudden cardiac death observed in the general population is altered in patients with OSAS. This study investigates potential abnormalities in the circadian profiles of platelet activity in OSAS.MethodsWe studied 37 patients with OSAS [7 of whom were also studied after 3xa0months on continuous positive airway pressure (CPAP) treatment] and 11 controls. In each subject, we obtained six different blood samples during 24-h period (2200, 0200, 0600, 1000, 1400, and 1800 hours). Platelet activity was determined by flow cytometry immediately after sampling.ResultsWe found that nocturnal platelet activity was significantly increased in patients with OSAS (pu2009=u20090.043) and that effective treatment with CPAP decreased platelet activity in these patients but differences just failed to reach statistical significance (pu2009=u20090.063).ConclusionsOSAS is associated with increased platelet activity during the night, and that this appears to be improved by chronic use of CPAP. These results may contribute to explain the high prevalence of cardiovascular events during sleep in OSAS.

Síndromes de apneas-hipopneas durante el sueño e insuficiencia cardiaca

La insuficiencia cardiaca (IC) y los trastornos respiratorios durante el sueno son entidades que presentan una elevada prevalencia en la poblacion general y es frecuente la presencia de ambas en un mismo paciente. Diversos estudios epidemiologicos y fisiopatologicos indican que puede haber una relacion causal entre dichos trastornos y el desarrollo del sindrome de IC, tanto asociada con la presencia de disfuncion sistolica ventricular izquierda como en casos con funcion sistolica conservada. La presencia de trastornos respiratorios durante el sueno en enfermos con IC expone al sistema cardiovascular a hipoxemia intermitente, activacion simpatica y aumento de la precarga y poscarga ventricular que, a su vez, ponen en marcha una serie de mecanismos inflamatorios, oxidativos y neurohumorales que pueden favorecer la progresion de la enfermedad. Aunque aun no disponemos de datos que demuestren que el tratamiento de los trastornos respiratorios durante el sueno en enfermos con IC disminuye la mortalidad de esta poblacion, diversos trabajos demuestran una mejoria significativa en distintos parametros de estructura y funcion cardiovascular. En este trabajo se revisan las bases clinicas y los datos epidemiologicos, las relaciones fisiopatologicas y las implicaciones terapeuticas entre el sindrome de IC y los sindromes de apneas-hipopneas durante el sueno.