Hypoxic burden to guide CPAP treatment allocation in patients with obstructive sleep apnoea: a post hoc study of the ISAACC trial.

BACKGROUND: Hypoxic burden (HB) has emerged as a strong predictor of cardiovascular risk in obstructive sleep apnoea (OSA). We aimed to assess the potential of HB to predict the cardiovascular benefit of treating OSA with continuous positive airway pressure (CPAP). METHODS: This was a post hoc analysis of the ISAACC trial (ClinicalTrials.gov: NCT01335087) including non-sleepy patients with acute coronary syndrome (ACS) diagnosed with OSA (apnoea-hypopnoea index ≥15 events·h-1) by respiratory polygraphy. Patients were randomised to CPAP or usual care and followed for a minimum of 1 year. HB was calculated as the total area under all automatically identified desaturations divided by total sleep time. Patients were categorised as having high or low baseline HB according to the median value (73.1%min·h-1). Multivariable Cox regression models were used to assess whether the effect of CPAP on the incidence of cardiovascular outcomes was dependent on the baseline HB level. RESULTS: The population (362 patients assigned to CPAP and 365 patients assigned to usual care) was middle-aged (mean age 59.7 years), overweight/obese and mostly male (84.5%). A significant interaction was found between the treatment arm and the HB categories. In the high HB group, CPAP treatment was associated with a significant reduction in the incidence of cardiovascular events (HR 0.57, 95% CI 0.34-0.96). In the low HB group, CPAP-treated patients exhibited a trend toward a higher risk of cardiovascular outcomes than those receiving usual care (HR 1.33, 95% CI 0.79-2.25). The differential effect of the treatment depending on the baseline HB level followed a dose-response relationship. CONCLUSION: In non-sleepy ACS patients with OSA, high HB levels were associated with a long-term protective effect of CPAP on cardiovascular prognosis.

A new tool to screen patients with severe obstructive sleep apnea in the primary care setting: a prospective multicenter study.

BACKGROUND: The coordination between different levels of care is essential for the management of obstructive sleep apnea (OSA). The objective of this multicenter project was to develop a screening model for OSA in the primary care setting. METHODS: Anthropometric data, clinical history, and symptoms of OSA were recorded in randomly selected primary care patients, who also underwent a home sleep apnea test (HSAT). Respiratory polygraphy or polysomnography were performed at the sleep unit to establish definite indication for continuous positive airway pressure (CPAP). By means of cross-validation, a logistic regression model (CPAP yes/no) was designed, and with the clinical variables included in the model, a scoring system was established using the ß coefficients (PASHOS Test). In a second stage, results of HSAT were added, and the final accuracy of the model was assessed. RESULTS: 194 patients completed the study. The clinical test included the body mass index, neck circumference and observed apneas during sleep (AUC 0.824, 95% CI 0.763-0.886, P < 0.001). In a second stage, the oxygen desaturation index (ODI) of 3% (ODI3% ≥ 15%) from the HSAT was added (AUC 0.911, 95% CI 0.863-0.960, P < 0.001), with a sensitivity of 85.5% (95% CI 74.7-92.1) and specificity of 67.8% (95% CI 55.1-78.3). CONCLUSIONS: The use of this model would prevent referral to the sleep unit for 55.1% of the patients. The two-stage PASHOS model is a useful and practical screening tool for OSA in primary care for detecting candidates for CPAP treatment. Clinical Trial Registration Registry: ClinicalTrials.gov; Name: PASHOS Project: Advanced Platform for Sleep Apnea Syndrome Assessment; URL: https://clinicaltrials.gov/ct2/show/NCT02591979 ; Identifier: NCT02591979. Date of registration: October 30, 2015.

The Effect of Sleep Apnea on Cardiovascular Events in Different Acute Coronary Syndrome Phenotypes.

Rationale: Obstructive sleep apnea (OSA) is associated with increased cardiovascular disease (CVD) risk. Conversely, OSA has not been shown to increase recurrent cardiovascular events in patients with acute coronary syndrome (ACS). This lack of homogeneity could suggest that the deleterious effect of OSA and its contribution to CVD could depend on specific patient profiles.Objectives: To evaluate the effect of OSA on cardiovascular risk for patients with different ACS phenotypes.Methods:Post hoc analysis of the ISAACC (Continuous Positive Airway Pressure in Patients with ACS and OSA) study, including 1,701 patients admitted for ACS (NCT01335087). To evaluate the presence of OSA (apnea-hypopnea index ≥ 15 events · h-1), all patients underwent polygraphy. Patients were followed up for a minimum period of 1 year. We performed nonsupervised clustering using latent class analysis to identify subgroups of patients on the basis of 12 clinical factors associated with cardiovascular risk. The effect of OSA on recurrent cardiovascular event risk was evaluated for each phenotype identified.Measurements and Main Results: Two phenotypes were identified: patients without previous heart disease and without previous ACS ("no-previous-CVD" phenotype; 81%) and patients with previous heart disease and previous ACS ("previous-CVD" phenotype; 19%). The median (interquartile range) at follow-up was 2.67 (3.8) years. For the no-previous-CVD phenotype, the effect of OSA showed an adjusted hazard ratio (95% confidence interval) of 1.54 (1.06-2.24; P value = 0.02), whereas for the previous-CVD phenotype, the effect of OSA showed an adjusted hazard ratio of 0.69 (0.46-1.04; P value = 0.08).Conclusions: For patients with ACS and a specific phenotype, OSA is associated with an increased risk of recurrent cardiovascular events. These patients are mainly characterized by no previous heart disease and admission for a first ACS occurrence.

Effects of Ethnicity on the Prevalence of Obstructive Sleep Apnoea in Patients with Acute Coronary Syndrome: A Pooled Analysis of the ISAACC Trial and Sleep and Stent Study.

BACKGROUND: Obstructive sleep apnoea (OSA) is an emerging risk factor for acute coronary syndrome (ACS). We sought to determine the effects of ethnicity on the prevalence of OSA in patients presenting with ACS who participated in an overnight sleep study. METHODS: A pooled analysis using patient-level data from the ISAACC Trial and Sleep and Stent Study was performed. Using the same portable diagnostic device, OSA was defined as an apnoea-hypopnoea index of ≥15 events per hour. RESULTS: A total of 1961 patients were analysed, including Spanish (53.6%, n=1050), Chinese (25.5%, n=500), Indian (12.0%, n=235), Malay (6.1%, n=119), Brazilian (1.7%, n=34) and Burmese (1.2%, n=23) populations. Significant differences in body mass index (BMI) were found among the various ethnic groups, averaging from 25.3kg/m2 for Indians and 25.4kg/m2 for Chinese to 28.6kg/m2 for Spaniards. The prevalence of OSA was highest in the Spanish (63.1%), followed by the Chinese (50.2%), Malay (47.9%), Burmese (43.5%), Brazilian (41.2%), and Indian (36.1%) patients. The estimated odds ratio of BMI on OSA was highest in the Chinese population (1.17; 95% confidence interval: 1.10-1.24), but was not significant in the Spanish, Burmese or Brazilian populations. The area under the curve (AUC) for the Asian patients (ranging from 0.6365 to 0.6692) was higher than that for the Spanish patients (0.5161). CONCLUSION: There was significant ethnic variation in the prevalence of OSA in patients with ACS. The magnitude of the effect of BMI on OSA was greater in the Chinese population than in the Spanish patients.

Unraveling the Molecular Mechanisms of OSA-Related Cardiovascular Event Recurrence: A Post Hoc Analysis From the ISAACC Study.

RATIONALE: Although obstructive sleep apnea (OSA) is a prevalent condition among patients with acute coronary syndrome (ACS), the impact of OSA on cardiovascular event (CVE) recurrence is not homogeneous. We previously defined a specific phenotype of first-ACS patients without previous cardiovascular disease who are at increased risk of OSA-related CVE recurrence. However, the pathobiological mechanisms whereby OSA leads to adverse cardiovascular outcomes in this singular ACS phenotype remain to be investigated. OBJECTIVE: To characterize the molecular pathways that relate OSA with CVE recurrence. METHODS: This post hoc analysis of the ISAACC study (NCT01335087) included subjects without previous cardiovascular disease who were hospitalized for a first ACS and developed a recurrent CVE during the follow-up. Patients underwent respiratory polygraphy and fasting blood extraction during hospitalization. Two study groups were established on the basis of the apnea-hypopnea index (AHI): untreated severe OSA (AHI≥30events/h) and non-OSA (AHI<15events/h) groups. Proteomic profiling analysis included 276 cardiovascular and inflammatory-related plasma proteins via Olink® technology. RESULTS: Proteomics was performed in 58 patients (77.6% male, median [p25;p75] age 58.0 [51.2;65.8] years, and median BMI 28.6 [25.8;31.2]kg/m2). Thirty patients had severe OSA, and 28 subjects were considered non-OSA controls. A total of 24 plasma proteins were differentially expressed between the groups. Among these proteins, 18 were significantly associated with OSA severity parameters derived from respiratory polygraphy. Further bioinformatic analyses of OSA-related proteins revealed their involvement in several molecular pathways, mostly related to immune function, cell signaling, and inflammatory processes. CONCLUSION: A specific proteomic profile related to OSA presence and severity was identified in the plasma of ACS patients who developed recurrent CVEs. This analysis suggests the activation of key OSA-mediated molecular pathways with potential implications for cardiovascular prognosis.

Proteomic profiling for prediction of recurrent cardiovascular event in patients with acute coronary syndrome and obstructive sleep apnea: A post-hoc analysis from the ISAACC study.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with a recurrent cardiovascular event (CVE) risk in patients with a first acute coronary syndrome (ACS). However, the pathological pathways by which OSA promotes this deleterious role are unknown. We aim to explore the proteomic profile associated with OSA that promote the recurrent CVE risk in severe OSA patients with ACS without previous cardiovascular diseases. METHODS: This post-hoc analysis from the ISAACC study (NCT01335087) included 86 patients admitted for ACS. Patients underwent respiratory polygraphy for the first 24-72 h to OSA diagnosis. We analyzed of 276 cardiovascular and inflammatory related proteins in baseline fasting plasma samples using proximity expression assay technology (Olink®, Sweden). Protein levels were compared between severe OSA patients with/without recurrent CVEs during follow-up. Random forest was conducted to select relevant proteins and generate a predictive model of recurrent CVE. RESULTS: We included 86 patients (median age: 61 years, median BMI: 29.4 kg/m2 and 86 % males) admitted for ACS with severe OSA (56 without recurrent CVE/30 with recurrent CVE). The plasma levels of 38 proteins were differentially expressed between groups. Additionally, 12 proteins had a significant association with respiratory polygraphy parameters. Three proteins discriminate with an AUC of 0.81 (95 % CI of 0.71-0.9) between severe OSA patients with and without recurrent CVE. These proteins were implicated in cell proliferation, communication and apoptosis, and regulation/response to the inflammatory and immune systems. CONCLUSION: In ACS patients with severe OSA, a proteomic profile was associated with recurrent CVEs. This proteomic profile was correlated with specific OSA parameters from respiratory polygraphy. Proteomic profiling may provide an new direction for patient risk stratification and clinical management.

Respiratory Polygraphy Patterns and Risk of Recurrent Cardiovascular Events in Patients With Acute Coronary Syndrome.

Introduction: Obstructive sleep apnea (OSA) severity is based on the apnea-hypopnea index (AHI). The AHI is a simplistic measure that is inadequate for capturing disease severity and its consequences in cardiovascular diseases (CVDs). Deleterious effects of OSA have been suggested to influence the prognosis of specific endotypes of patients with acute coronary syndrome (ACS). We aim to identify respiratory polygraphy (RP) patterns that contribute to identifying the risk of recurrent cardiovascular events in patients with ACS. Methods: Post hoc analysis of the ISAACC study, including 723 patients admitted for a first ACS (NCT01335087) in which RP was performed. To identify specific RP patterns, a principal component analysis (PCA) was performed using six RP parameters: AHI, oxygen desaturation index, mean and minimum oxygen saturation (SaO2), average duration of events and percentage of time with SaO2 < 90%. An independent HypnoLaus population-based cohort was used to validate the RP components. Results: From the ISAACC study, PCA showed that two RP components accounted for 70% of the variance in the RP data. These components were validated in the HypnoLaus cohort, with two similar RP components that explained 71.3% of the variance in the RP data. The first component (component 1) was mainly characterized by low mean SaO2 and obstructive respiratory events with severe desaturation, and the second component (component 2) was characterized by high mean SaO2 and long-duration obstructive respiratory events without severe desaturation. In the ISAACC cohort, component 2 was associated with an increased risk of recurrent cardiovascular events in the third tertile with an adjusted hazard ratio (95% CI) of 2.44 (1.07 to 5.56; p-value = 0.03) compared to first tertile. For component 1, no significant association was found for the risk of recurrent cardiovascular events. Conclusion: A RP component, mainly characterized by intermittent hypoxemia, is associated with a high risk of recurrent cardiovascular events in patients without previous CVD who have suffered a first ACS.

Long-Term Effect of Obstructive Sleep Apnea and Continuous Positive Airway Pressure Treatment on Blood Pressure in Patients with Acute Coronary Syndrome: A Clinical Trial.

Rationale: Obstructive sleep apnea (OSA) is prevalent in patients with acute coronary syndrome (ACS) and is a cause of secondary hypertension. Objectives: To explore the long-term effects of OSA and continuous positive airway pressure (CPAP) treatment on blood pressure (BP) in patients with ACS. Methods: Post hoc analysis of the ISAACC study (Continuous Positive Airway Pressure in Patients with Acute Coronary Syndrome and Obstructive Sleep Apnea; NCT01335087) included 1,803 patients admitted for ACS. Patients with OSA (apnea-hypopnea index [AHI], ⩾15 events/h) were randomly assigned to receive either CPAP or usual care and were seen in follow-up for 1-5 years. Office BP was determined at each visit. Results: We included 596 patients without OSA, 978 patients in the usual care or poor CPAP adherence group, and 229 patients in the good CPAP adherence group. At baseline, 52% of the patients were diagnosed with hypertension. Median (25th to 75th percentile) age and body mass index were 59 (52.0 to 67.0) years and 28.2 (25.6 to 31.2) kg/m2, respectively. After a median (25th to 75th percentile) follow-up of 41.2 (18.3 to 59.6) months, BP changes were similar in the OSA and non-OSA groups. However, we observed an increase in BP in the third tertile of the AHI (AHI, >40 events/h), with a maximum difference in mean BP of +3.3 mm Hg at 30 months. Patients with OSA with good CPAP adherence (⩾4 h/night) reduced mean BP after 18 months compared with patients with usual care/poor CPAP adherence, with a maximum mean difference (95% confidence interval) of -4.7 (-6.7 to -2.7) mm Hg. In patients with severe OSA, we observed a maximum mean difference of -7.1 (-10.3 to -3.8) mm Hg. Conclusions: In patients with ACS, severe OSA is associated with a long-term increase in BP, which is reduced by good CPAP adherence. Clinical trial registered with www.clinicaltrials.gov (NCT01335087).

Primary care and sleep unit agreement in management decisions for sleep apnea: a prospective study in Spain.

STUDY OBJECTIVES: Involvement of primary care teams in the care of patients with OSA is a focus of interest. The study objective was to compare diagnostic and therapeutic agreement between decisions taken by primary care professionals and sleep unit specialists. METHODS: This was a prospective multicenter study conducted at primary care and specialized care centers in the urban area of Barcelona, Spain. Men and women aged 18-75 years who visited the participating primary care centers for any reason were recruited. Both primary care physicians and sleep specialists made a diagnostic and therapeutic decision with clinical data and results of a home sleep apnea test. All patients were finally assessed with respiratory polygraphy or polysomnography as a gold-standard test. RESULTS: A total of 229 patients underwent a home sleep apnea test and were evaluated at the primary care centers and the sleep units. Diagnostic agreement using the same tools and excluding indeterminate decisions was 69.8% (Cohen's kappa = 0.64; 95% confidence interval, 0.56-0.72). Agreement for therapeutic decisions (PAP vs conservative treatment) was obtained in 82.5% of patients (Cohen's kappa = 0.62; 95% confidence interval, 0.51-0.73), increasing to 92.5% (Cohen's kappa = 0.49, 95% confidence interval, 0.40-0.58) when indeterminate options were excluded. As compared with the final therapeutic decisions made at the sleep unit with respiratory polygraphy/polysomnography, primary care physicians agreed regarding 83.3% (Cohen's kappa = 0.62; 95% confidence interval, 0.49-0.74) of patients. CONCLUSIONS: Primary care professionals may assume an important role in the management of OSA in coordination with sleep centers, identifying patients who require specific treatment and should be referred to specialized care. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: PASHOS Project: Advanced Platform for Sleep Apnea Syndrome Assessment; URL: https://clinicaltrials.gov/ct2/show/NCT02591979; Identifier: NCT02591979.

Intra- and Inter-Physician Agreement in Therapeutic Decision for Sleep Apnea Syndrome.

BACKGROUND: Large variation in diagnostic procedures and treatment recommendations may hinder the management of obstructive sleep apnea (OSA) and also compromise correct interpretation of the results of multicenter clinical trials, especially in subjects with non-severe OSA. The aim of this study was to analyze the therapeutic decision-making between different sleep physicians in patients with AHI<40events/h. METHODS: Six experienced senior sleep specialists from different sleep centers of Spain were asked to make a therapeutic decision (CPAP treatment) based on anonymized recordings of patients with suspected OSA that has previously performed a sleep study. The clinical data was shown in an online database and included anthropometric features, clinical questionnaires, comorbidities, physical examination and sleep study results. Intra- and inter-observer decision-making were analyzed by the Fleiss' Kappa statistics (Kappa). RESULTS: A total of 720 medical decisions were taken to analyze the agreement between sleep professionals. Overall intra-observer evaluation reliability was almost perfect (Kappa=0.83, 95% CI, 0.75-0.90, p<0.001). However, overall inter-observer concordance decreased to moderate agreement (Kappa=0.46, 95% CI, 0.42-0.51, p<0.001). Nevertheless, it was especially low when considering AHI<15events/h. CONCLUSIONS: This study demonstrates a good intra-observer concordance in the therapeutic decision-making of different sleep physicians treating patients with low/moderate OSA. However, when analyzing inter-observer agreement the results were considerably worse. These findings underline the importance of developing improved consensus management protocols.

Effect of obstructive sleep apnoea and its treatment with continuous positive airway pressure on the prevalence of cardiovascular events in patients with acute coronary syndrome (ISAACC study): a randomised controlled trial.

BACKGROUND: Despite the improvement in the prognosis of acute coronary syndrome (ACS), substantial morbidity and mortality remain. We aimed to evaluate the effect of obstructive sleep apnoea (OSA) and its treatment with continuous positive airway pressure (CPAP) on the clinical evolution of patients with ACS. METHODS: We designed a multicentre, open-label, parallel-group, randomised controlled trial of patients with ACS at 15 hospitals in Spain. Eligible non-sleepy patients were men and women aged 18 years and older, admitted to hospital for documented symptoms of ACS. All patients underwent respiratory polygraphy during the first 24-72 h after admission. OSA patients were randomly assigned (1:1) to CPAP treatment plus usual care (CPAP group) or usual care alone (UC group) by a computerised system available 24 h a day. A group of patients with ACS but without OSA was also included as a reference group. Because of the nature of the intervention, the trial intervention could not be masked to either investigators or patients. Patients were monitored and followed for a minimum of 1 year. Patients were examined at the time of inclusion; after 1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, and 36 months; and every 12 months thereafter, if applicable, during the follow-up period. The primary endpoint was the prevalence of a composite of cardiovascular events (cardiovascular death or non-fatal events [Acute myocardial infarction, non-fatal stroke, hospital admission for heart failure, and new hospitalisations for unstable angina or transient ischaemic attack]) in patients followed up for a minimum of 1 year. The primary analysis was done according to the intention-to-treat principle. This study is registered with Clinicaltrials.gov, NCT01335087 and is now closed. FINDINGS: Between April 25, 2011, and Feb 2, 2018, a total of 2834 patients with ACS had respiratory polygraphy, of whom 2551 (90·01%) were recruited. 1264 (49·55%) patients had OSA and were randomly assigned to the CPAP group (n=633) or the UC group (n=631). 1287 (50·45%) patients did not have OSA, of whom 603 (46·85%) were randomly assigned to the reference group. Patients were followed up for a median of 3·35 years (IQR 1·50-5·31). The prevalence of cardiovascular events was similar in the CPAP and UC groups (98 events [16%] vs 108 events [17%]; hazard ratio [HR] 0·89 [95% CI 0·68-1·17]; p=0·40) during follow-up. Mean time of adherence to CPAP treatment was 2·78 h/night (SD 2·73). The prevalence of cardiovascular events was similar between patients in the reference group (90 [15%] events) and those in the UC group (102 (17%) events) during follow-up (1·01 [0·76-1·35]; p=0·93). The prevalence of cardiovascular events seem not to be related to CPAP compliance or OSA severity. 464 (74%) of 629 patients in the CPAP group had 1538 serious adverse events and 406 (65%) of 626 patients in the UC group had 1764 serious adverse events. INTERPRETATION: Among non-sleepy patients with ACS, the presence of OSA was not associated with an increased prevalence of cardiovascular events and treatment with CPAP did not significantly reduce this prevalence. FUNDING: ResMed (Australia), Fondo de Investigación Sanitaria (Fondo Europeo de Desarrollo Regional), the Spanish Respiratory Society, the Catalonian Cardiology Society, Esteve-Teijin, Oxigen Salud, and ALLER.

Coordinated program between primary care and sleep unit for the management of obstructive sleep apnea.

The purpose of this study is to develop and validate a work model in the primary health-care setting for identifying patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) based on clinical variables and an ambulatory sleep monitoring study. After screening, patients with mild-moderate OSAHS could be managed by primary care physicians, whereas those identified with severe OSAHS would be referred to specialists from sleep units for starting specific treatment. The proposed model does not move the entire health-care process to a generally overburdened primary care level and favors the coordinated work and the necessary flexibility to adapt the model to challenges and perspectives of OSAHS.

Muscle MRI Findings in Childhood/Adult Onset Pompe Disease Correlate with Muscle Function.

OBJECTIVES: Enzyme replacement therapy has shown to be effective for childhood/adult onset Pompe disease (AOPD). The discovery of biomarkers useful for monitoring disease progression is one of the priority research topics in Pompe disease. Muscle MRI could be one possible test but the correlation between muscle MRI and muscle strength and function has been only partially addressed so far. METHODS: We studied 34 AOPD patients using functional scales (Manual Research Council scale, hand held myometry, 6 minutes walking test, timed to up and go test, time to climb up and down 4 steps, time to walk 10 meters and Motor Function Measure 20 Scale), respiratory tests (Forced Vital Capacity seated and lying, Maximun Inspiratory Pressure and Maximum Expiratory Pressure), daily live activities scales (Activlim) and quality of life scales (Short Form-36 and Individualized Neuromuscular Quality of Life questionnaire). We performed a whole body muscle MRI using T1w and 3-point Dixon imaging centered on thighs and lower trunk region. RESULTS: T1w whole body muscle MRI showed a homogeneous pattern of muscle involvement that could also be found in pre-symptomatic individuals. We found a strong correlation between muscle strength, muscle functional scales and the degree of muscle fatty replacement in muscle MRI analyzed using T1w and 3-point Dixon imaging studies. Moreover, muscle MRI detected mild degree of fatty replacement in paraspinal muscles in pre-symptomatic patients. CONCLUSION: Based on our findings, we consider that muscle MRI correlates with muscle function in patients with AOPD and could be useful for diagnosis and follow-up in pre-symptomatic and symptomatic patients under treatment. TAKE HOME MESSAGE: Muscle MRI correlates with muscle function in patients with AOPD and could be useful to follow-up patients in daily clinic.

Impact of Obstructive Sleep Apnea on the Levels of Placental Growth Factor (PlGF) and Their Value for Predicting Short-Term Adverse Outcomes in Patients with Acute Coronary Syndrome.

BACKGROUND: Placental growth factor (PlGF) induces angiogenesis and promotes tissue repair, and plasma PlGF levels change markedly during acute myocardial infarction (AMI). Currently, the impact of obstructive sleep apnea (OSA) in patients with AMI is a subject of debate. Our objective was to evaluate the relationships between PlGF levels and both the severity of acute coronary syndrome (ACS) and short-term outcomes after ACS in patients with and without OSA. METHODS: A total of 538 consecutive patients (312 OSA patients and 226 controls) admitted for ACS were included in this study. All patients underwent polygraphy in the first 72 hours after hospital admission. The severity of disease and short-term prognoses were evaluated during the hospitalization period. Plasma PlGF levels were measured using an electrochemiluminescence immunoassay. RESULTS: Patients with OSA were significantly older and more frequently hypertensive and had higher BMIs than those without OSA. After adjusting for age, smoking status, BMI and hypertension, PlGF levels were significantly elevated in patients with OSA compared with patients without OSA (19.9 pg/mL, interquartile range: 16.6-24.5 pg/mL; 18.5 pg/mL, interquartile range: 14.7-22.7 pg/mL; p<0.001), and a higher apnea-hypopnea index (AHI) was associated with higher PlGF concentrations (p<0.003). Patients with higher levels of PlGF had also an increased odds ratio for the presence of 3 or more diseased vessels and for a Killip score>1, even after adjustment. CONCLUSIONS: The results of this study show that in patients with ACS, elevated plasma levels of PlGF are associated with the presence of OSA and with adverse outcomes during short-term follow-up. TRIAL REGISTRATION: ClinicalTrials.gov NCT01335087.

Are daytime arterial blood gases a good reflection of nighttime gas exchange in patients on long-term oxygen therapy?

OBJECTIVE: Compare nighttime and daytime arterial blood gas values in patients undergoing long-term oxygen therapy (LTOT). METHODS: We studied 39 LTOT patients with chronic airflow limitation. Oxygen from an oxygen concentrator was administered via nasal prongs until daytime blood oxygen saturation (measured via pulse oximetry [S(pO2)]) was > or = 90%. Arterial blood samples were drawn at 6:00 PM, while the subject breathed room air, and also during oxygen administration at night (3:00 AM), early in the morning (7:00 AM), and at noon. S(pO2) was measured throughout the night. RESULTS: Mean patient age was 70 +/- 7 yr. All patients suffered severe chronic airflow limitation (mean forced expiratory volume in the first second 28 +/- 9% of predicted). The mean oxygen flow administered was 1.41 +/- 0.6 L/min. Mean overnight S(pO2) was 92 +/- 2.5%, with 21.5 +/- 28% of recording time under 90%. There were statistically significant differences between P(aO2), P(aCO2), and pH obtained at 3:00 AM and noon and between 7:00 AM and noon, while the patients breathed the same oxygen concentration. The differences between the 3:00 and 7:00 AM values were not significant. In 23 patients (59%) we observed a P(aCO2) increase > 10 mm Hg and/or a pH decrease to < 7.33 during that period, indicating poor response to LTOT. CONCLUSIONS: Daytime arterial blood gas measurements do not reflect nighttime gas exchange. However, samples taken early in the morning (7:00 AM) do seem to reflect arterial blood gases during the night and can therefore be used for setting and monitoring nighttime oxygen flow.

Intra- and Inter-Physician Agreement in Therapeutic Decision for Sleep Apnea Syndrome / Concordancia intra e inter-médico en la decisión terapéutica para el síndrome de apnea del sueño

Background: Large variation in diagnostic procedures and treatment recommendations may hinder the management of obstructive sleep apnea (OSA) and also compromise correct interpretation of the results of multicenter clinical trials, especially in subjects with non-severe OSA. The aim of this study was to analyze the therapeutic decision-making between different sleep physicians in patients with AHÍ < 40 events/h. Methods: Six experienced senior sleep specialists from different sleep centers of Spain were asked to make a therapeutic decision (CPAP treatment) based on anonymized recordings of patients with suspected OSA that has previously performed a sleep study. The clinical data was shown in an online database and included anthropometric features, clinical questionnaires, comorbidities, physical examination and sleep study results. Intra- and inter-observer decision-making were analyzed by the Fleiss’ Kappa statistics (Kappa). Results: A total of 720 medical decisions were taken to analyze the agreement between sleep professionals. Overall intra-observer evaluation reliability was almost perfect (Kappa = 0.83, 95% CI, 0.75-0.90, p < 0.001). However, overall inter-observer concordance decreased to moderate agreement (Kappa = 0.46, 95% CI, 0.42-0.51, p < 0.001). Nevertheless, it was especially low when considering AHÍ < 15 events/h. Conclusions: This study demonstrates a good intra-observer concordance in the therapeutic decision-making of different sleep physicians treating patients with low/moderate OSA. However, when analyzing inter-observer agreement the results were considerably worse. These findings underline the importance of developing improved consensus management protocols

Introducción: La gran variedad de procedimientos diagnósticos y recomendaciones de tratamiento puede dificultar el manejo del síndrome de apnea obstructiva del sueño (SAHS), y del mismo modo comprometer la correcta interpretación de los resultados de ensayos clínicos multicéntricos, especialmente en pacientes con SAHS no grave. El objetivo de este estudio fue analizar la decisión terapéutica de distintos médicos expertos en sueño en pacientes con el índice de apnea hipopnea < 40 eventos/h. Métodos: Se pidió a seis especialistas con amplia experiencia en sueño de diferentes centros de España que tomaran una decisión terapéutica (terapia de presión positiva continua en las vías respiratorias o CPAP) basada en datos anónimos de los pacientes con sospecha de SAHS en los que previamente se había llevado a cabo un estudio del sueño. Los datos clínicos procedían de una base de datos online e incluían características antropométricas, cuestionarios clínicos, comorbilidades, examen físico y resultados del estudio del sueño. La concordancia intra- e interobservador de la toma de decisiones se analizó mediante el estadístico Fleiss' Kappa (Kappa). Resultados: Se analizaron un total de 720 decisiones médicas para evaluar el consenso entre profesionales del sueño. De manera global, la fiabilidad de la evaluación intraobservador fue casi perfecta (Kappa = 0,83; 95% CI; 0,75 a 0,90, p < 0,001). Sin embargo, la concordancia global interobservador disminuyó hasta alcanzar un grado moderado de consenso (Kappa = 0,46; 95% CI; 0,42 a 0,51, p < 0,001), que fue especialmente bajo cuando se tuvo en cuenta un índice de apnea hipopnea < 15 eventos/h. Conclusiones: Este estudio demuestra una buena concordancia intraobservador en la toma de decisiones terapéuticas de distintos médicos expertos en sueño que tratan a pacientes con SAHS leve o moderado. Sin embargo, los resultados relativos al acuerdo interobservador fueron notablemente peores. Estos hallazgos señalan la importancia de desarrollar mejores protocolos consensuados de manejo

[Sleep apnoea in patients of elderly: care activity in Spain (2002-2008)]. / Apnea del sueño en individuos de edad avanzada. Actividad asistencial (2002-2008) en España.

INTRODUCTION AND OBJECTIVE: There is a significant lack of scientific evidence on the role of SAHS in the elderly despite the increasing ageing of the population. The objective of the present study is to analyse the current healthcare situation in Spain on the diagnosis and treatment of sleep apnea in the population ≥65 years and its progress over the last few years. MATERIAL AND METHOD: Cross-sectional study. Healthcare information was collected on the diagnosis and treatment of patients of both sexes and ≥65 years suspected with having SAHS and referred to sleep units (SU) between 2002 and 2008. RESULTS: There were 51,229 sleep studies performed in 16 SU. Of these, 24.3% were performed on subjects ≥ 65 years (64.9% males), of which 71.5% had an AHI (apnoea-hypopnoea index) >10 (68.6% treated with CPAP). There were no differences over time as regards mean age, mean AHI or percentage of studies done. A significant decrease was observed in the number of CPAP prescribed to males ≥65 years from 2002 to 2005 (p=0.01) which subsequently increased up to 2008 (p=0.01). This phenomenon was not observed in women ≥65 years. CONCLUSION: Despite the lack of evidence on the subject, healthcare activity due to suspected SAHS in the elderly population is intense, therefore it should be a priority to start clinical studies that may be able to answer key questions on the diagnosis and treatment of SAHS in this age group.

Apnea del sueño en individuos de edad avanzada. Actividad asistencial (2002–2008) en España / Sleep Apnoea in Patients of Elderly: Care Activity in Spain (2002–2008)

Introducción y objetivoExiste una importante falta de evidencia científica sobre el papel del SAHS en edades avanzadas a pesar del envejecimiento progresivo de la población. El objetivo del presente estudio es analizar el panorama asistencial actual en nuestro país sobre el diagnóstico y tratamiento del SAHS en individuos ≥65 años y su evolución a lo largo de los últimos años.Material y métodoEstudio de corte trasversal. Fue recogida información asistencial sobre el diagnóstico y tratamiento de pacientes con sospecha de SAHS de ambos sexos con ≥65 años remitidos a las unidades de sueño (US) entre 2002 y 2008.ResultadosFueron incluidos 51.229 estudios de sueño de 16 US. El 24,3% de los estudios fue realizado en individuos ≥65 años (64,9% varones), de los que el 71,5% mostró un IAH≥10 (68,6% tratados con CPAP). No hubo cambios significativos a lo largo del tiempo en la edad media, IAH medio o porcentaje de estudios realizados. Se observo una disminución significativa en el número de CPAP prescritas en varones ≥65 años desde 2002 al 2005 (p=0,01) que aumentó posteriormente hasta 2008 (p=0,01). Este fenómeno no fue observado en mujeres ≥65 años.ConclusiónA pesar de la escasa evidencia científica sobre el tema, la actividad asistencial por sospecha de SAHS en individuos de edades avanzadas es intensa por lo que se hace prioritaria la puesta en marcha de estudios clínicos que den respuesta a preguntas clave sobre el diagnóstico y el tratamiento del SAHS en esta franja de edad(AU)

Introduction and objectiveThere is a significant lack of scientific evidence on the role of SAHS in the elderly despite the increasing ageing of the population. The objective of the present study is to analyse the current healthcare situation in Spain on the diagnosis and treatment of sleep apnea in the population ≥65 years and its progress over the last few years.Material and methodCross-sectional study. Healthcare information was collected on the diagnosis and treatment of patients of both sexes and ≥65 years suspected with having SAHS and referred to sleep units (SU) between 2002 and 2008.ResultsThere were 51,229 sleep studies performed in 16 SU. Of these, 24.3% were performed on subjects ≥ 65 years (64.9% males), of which 71.5% had an AHI (apnoea-hypopnoea index) >10 (68.6% treated with CPAP). There were no differences over time as regards mean age, mean AHI or percentage of studies done. A significant decrease was observed in the number of CPAP prescribed to males ≥65 years from 2002 to 2005 (p=0.01) which subsequently increased up to 2008 (p=0.01). This phenomenon was not observed in women ≥65 years.ConclusionDespite the lack of evidence on the subject, healthcare activity due to suspected SAHS in the elderly population is intense, therefore it should be a priority to start clinical studies that may be able to answer key questions on the diagnosis and treatment of SAHS in this age group(AU)