Juan F. Masa

Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial.

CONTEXT Continuous positive airway pressure (CPAP) is the first-line treatment for patients with symptomatic obstructive sleep apnea (OSA). However, its indication for all patients with sleep-disordered breathing, regardless of daytime symptoms, is unclear. OBJECTIVE To evaluate the effect of CPAP treatment on the incidence of hypertension or cardiovascular events in a cohort of nonsleepy patients with OSA. DESIGN, SETTING, AND PATIENTS Multicenter, parallel-group, randomized controlled trial in 14 teaching hospitals in Spain. Between May 2004 and May 2006, 725 consecutive patients were enrolled who had an apnea-hypopnea index of 20 h(-1) or greater and an Epworth Sleepiness Scale score of 10 or less (scores range from 0-24, with values <10 suggesting no daytime sleepiness). Exclusion criteria were previous cardiovascular event, physical or psychological incapacity, chronic disease, or drug or alcohol addiction. Follow-up ended in May 2009. INTERVENTION Patients were allocated to receive CPAP treatment or no active intervention. All participants received dietary counseling and sleep hygiene advice. MAIN OUTCOME MEASURES Incidence of either systemic hypertension (taking antihypertensive medication or blood pressure greater than 140/90 mm Hg) or cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, hospitalization for unstable angina or arrhythmia, heart failure, or cardiovascular death). RESULTS Seven hundred twenty-three patients underwent follow-up for a median of 4 (interquartile range, 2.7-4.4) years (1 patient from each group did not receive allocated treatment); 357 in the CPAP group and 366 in the control group were included in the analysis. In the CPAP group there were 68 patients with new hypertension and 28 cardiovascular events (17 unstable angina or arrhythmia, 3 nonfatal stroke, 3 heart failure, 2 nonfatal myocardial infarction, 2 transient ischemic attack, 1 cardiovascular death). In the control group there were 79 patients with new hypertension and 31 cardiovascular events (11 unstable angina or arrhythmia, 8 nonfatal myocardial infarction, 5 transient ischemic attack, 5 heart failure, 2 nonfatal stroke). The hypertension or cardiovascular event incidence density rate was 9.20 per 100 person-years (95% CI, 7.36-11.04) in the CPAP group and 11.02 per 100 person-years (95% CI, 8.96-13.08) in the control group. The incidence density ratio was 0.83 (95% CI, 0.63-1.1; P = .20). CONCLUSIONS In patients with OSA without daytime sleepiness, the prescription of CPAP compared with usual care did not result in a statistically significant reduction in the incidence of hypertension or cardiovascular events. However, the study may have had limited power to detect a significant difference. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00127348.

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).

Effect of CPAP on Blood Pressure in Patients With Obstructive Sleep Apnea and Resistant Hypertension The HIPARCO Randomized Clinical Trial

IMPORTANCE More than 70% of patients with resistant hypertension have obstructive sleep apnea (OSA). However, there is little evidence about the effect of continuous positive airway pressure (CPAP) treatment on blood pressure in patients with resistant hypertension. OBJECTIVE To assess the effect of CPAP treatment on blood pressure values and nocturnal blood pressure patterns in patients with resistant hypertension and OSA. DESIGN, SETTING, AND PARTICIPANTS Open-label, randomized, multicenter clinical trial of parallel groups with blinded end point design conducted in 24 teaching hospitals in Spain involving 194 patients with resistant hypertension and an apnea-hypopnea index (AHI) of 15 or higher. Data were collected from June 2009 to October 2011. INTERVENTIONS CPAP or no therapy while maintaining usual blood pressure control medication. MAIN OUTCOMES AND MEASURES The primary end point was the change in 24-hour mean blood pressure after 12 weeks. Secondary end points included changes in other blood pressure values and changes in nocturnal blood pressure patterns. Both intention-to-treat (ITT) and per-protocol analyses were performed. RESULTS A total of 194 patients were randomly assigned to receive CPAP (n = 98) or no CPAP (control; n = 96). The mean AHI was 40.4 (SD, 18.9) and an average of 3.8 antihypertensive drugs were taken per patient. Baseline 24-hour mean blood pressure was 103.4 mm Hg; systolic blood pressure (SBP), 144.2 mm Hg; and diastolic blood pressure (DBP), 83 mm Hg. At baseline, 25.8% of patients displayed a dipper pattern (a decrease of at least 10% in the average nighttime blood pressure compared with the average daytime blood pressure). The percentage of patients using CPAP for 4 or more hours per day was 72.4%. When the changes in blood pressure over the study period were compared between groups by ITT, the CPAP group achieved a greater decrease in 24-hour mean blood pressure (3.1 mm Hg [95% CI, 0.6 to 5.6]; P = .02) and 24-hour DBP (3.2 mm Hg [95% CI, 1.0 to 5.4]; P = .005), but not in 24-hour SBP (3.1 mm Hg [95% CI, -0.6 to 6.7]; P = .10) compared with the control group. Moreover, the percentage of patients displaying a nocturnal blood pressure dipper pattern at the 12-week follow-up was greater in the CPAP group than in the control group (35.9% vs 21.6%; adjusted odds ratio [OR], 2.4 [95% CI, 1.2 to 5.1]; P = .02). There was a significant positive correlation between hours of CPAP use and the decrease in 24-hour mean blood pressure (r = 0.29, P = .006), SBP (r = 0.25; P = .02), and DBP (r = 0.30, P = .005). CONCLUSIONS AND RELEVANCE Among patients with OSA and resistant hypertension, CPAP treatment for 12 weeks compared with control resulted in a decrease in 24-hour mean and diastolic blood pressure and an improvement in the nocturnal blood pressure pattern. Further research is warranted to assess longer-term health outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00616265.

Estudio IBERPOC en España: prevalencia de síntomas respiratorios habituales y de limitación crónica al flujo aéreo

Se ha estudiado la prevalencia de los sintomas respiratorios habituales y de la limitacion cronica al flujo aereo mediante un estudio epidemiologico multicentrico realizado en 7 zonas geograficas diferentes de Espana. A partir de una poblacion diana de 236.412 personas, se ha seleccionado aleatoriamente una muestra censal de 4.035 individuos de entre 40 y 69 anos. Se les pasaron varios cuestionarios y se realizo una espirometria seguida de una prueba broncodilatadora cuando existia una obstruccion bronquial. El 48% de la poblacion referia algun sintoma respiratorio (IC del 95% = 46,4-49,5%), con mayor frecuencia entre los varones que entre las mujeres (el 55,2 frente al 41%; p

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.

Interpretation of quality of life scores from the St George's Respiratory Questionnaire

The aim of the study was to obtain the general population norms for the St. Georges Respiratory Questionnaire (SGRQ), a specific questionnaire for respiratory diseases. The IBERPOC project was a cross-sectional study of representative samples of the general population aged between 40–69 yrs. The study sample was composed of 862 individuals. All participants considered as “probable cases” of chronic obstructive pulmonary disease (COPD) (n=460) were eligible to complete the SGRQ and among the rest of the nonprobable COPD participants (n=3,571), 10 individuals from each defined age and sex group were eligible (n=402). Weights were applied to restore general population representativity of the sample. Mean forced expiratory volume in one second (FEV1) predicted was 89.4% (sd=16.5%; range: 16–131%). Chronbachs alpha coefficients were >0.7 in the symptoms, activity and impact scales, and >0.9 in the overall scale. Symptom scale score was significantly higher among males (11.6 versus 7.8; p<0.01) and activity scale score was significantly higher among females (12.2 versus 14.6; p=0.04). In a multiple linear regression model, respiratory diseases (asthma and COPD) and FEV1 % over pred showed the strongest association with the SGRQ total score. Smoking, sex, age and education were independently associated with the total SGRQ score. These results indicate that individuals from the general population presented some of the problems that are important when measuring health-related quality of life in respiratory patients, and provide St Georges Respiratory Questionnaire norms, a useful method for interpreting the St Georges Respiratory Questionnaire score in a given patient or study samples.

Daytime sleepiness and polysomnography in obstructive sleep apnea patients

BACKGROUND Excessive daytime sleepiness (EDS) is the major complaint in subjects with obstructive sleep apnea syndrome (OSAS). However, EDS is not universally present in all patients with OSAS. The mechanisms explaining why some patients with OSAS complain of EDS whereas others do not are unknown. OBJECTIVE To investigate polysomnographic determinants of excessive daytime sleepiness (EDS) in a large multicenter cohort of patients with obstructive sleep apnea (OSAS). METHODS All consecutive patients with an apnea-hypopnea index greater than 5h(-1) who were evaluated between 2003 and 2005. EDS was assessed using the Epworth Sleepiness Scale (ESS), and patients were considered to have EDS if the ESS was >10. RESULTS A total of 1649 patients with EDS ((mean [+/-SD] Epworth 15+/-3) and 1233 without EDS (Epworth 7+/-3) were studied. Patients with EDS were slightly younger than patients without EDS (51+/-12 vs 54+/-13 years, p<0.0001), had longer total sleep time (p<0.007), shorter sleep latency (p<0001), greater sleep efficiency (p<0.0001) and less NREM sleep in stages 1 and 2 (p<0.007) than those without EDS. Furthermore, patients with EDS had slightly higher AHI (p<0.005) and arousal index (p<0.001) and lower nadir oxygen saturation (p<0.01). CONCLUSIONS Patients with OSAS and EDS are characterized by longer sleep duration and increased slow wave sleep compared to those without EDS. Although patients with EDS showed a mild worsening of respiratory disturbance and sleep fragmentation, these results suggest that sleep apnea and sleep disruption are not the primary determinants of EDS in all of these patients.

Recent trends in COPD prevalence in Spain: a repeated cross-sectional survey 1997–2007

We aimed to describe changes in the prevalence of chronic obstructive pulmonary disease (COPD) in Spain by means of a repeated cross-sectional design comparing two population-based studies conducted 10 yrs apart. We compared participants from IBERPOC (Estudio epidemiológico de EPOC en España) (n = 4,030), conducted in 1997, with those of EPI-SCAN (Epidemiologic Study of COPD in Spain) (n = 3,802), conducted in 2007. Poorly reversible airflow obstruction compatible with COPD was defined according to the old European Respiratory Society definitions. COPD prevalence in the population between 40 to 69 yrs of age dropped from 9.1% (95% CI 8.1–10.2%) in 1997 to 4.5% (95% CI 2.4–6.6%), a 50.4% decline. The distribution of COPD prevalence by severity also changed from 38.3% mild, 39.7% moderate and 22.0% severe in 1997, to 85.6% mild, 13.0% moderate and 1.4% severe in 2007, and in the 40–69 yr EPI-SCAN sub-sample to 84.3% mild, 15.0% moderate and 0.7% severe. Overall, underdiagnosis was reduced from 78% to 73% (not a significant difference) and undertreatment from 81% to 54% (p<0.05) within this 10-yr frame. The finding of a substantial reduction in the prevalence of COPD in Spain is unexpected, as were the observed changes in the severity distribution, and highlights the difficulties in comparisons between repeated cross-sectional surveys of spirometry in the population.

Costes de la EPOC en España. Estimación a partir de un estudio epidemiológico poblacional

Objetivo En los estudios realizados hasta ahora, el coste de la enfermedad pulmonar obstructiva cronica (EPOC) puede estar sobrestimado porque han incluido a pacientes previamente diagnosticados que consultaron por sus sinto-mas, por lo que la gravedad puede ser superior a la que re-almente tendria una poblacion no seleccionada obtenida de la poblacion general. El proposito del presente estudio fue estimar el coste directo de la EPOC basandose en una mues-tra representativa del conjunto de la poblacion espanola de entre 40 y 69 anos (estudio IBERPOC). Metodo El coste se evaluo retrospectivamente a traves de un cuestionario referido al ultimo ano en los 363 pacien-tes con EPOC del estudio IBERPOC. Un neumologo realizo a todos ellos una espirometria estandarizada en cada una de las 7 areas geograficas en las que se llevo a cabo el estudio. Resultados La asistencia hospitalaria fue el coste mas elevado (41% del coste total), seguido del tratamiento farma-cologico (37%). El coste por paciente fue de 98,39 €, y por paciente previamente diagnosticado, de 909,5 €. El coste de la EPOC grave por persona fue mas de tres veces el coste de la EPOC moderada y mas de 7 veces el coste de la EPOC leve. El coste anual estimado de la EPOC en Espana fue de 238,82 millones de euros (informacion referida a 1997). Conclusiones Este es el primer estudio que estima el coste de la EPOC en una muestra representativa de la poblacion general, que es inferior al calculado por los estudios que han analizado una muestra seleccionada con diagnostico previo de EPOC. La distribucion del gasto no se ajusta a las practi-cas asistenciales recomendables, por lo que son necesarias actuaciones que optimicen los recursos empleados en el se-guimiento y en el tratamiento de la enfermedad, prestando especial atencion a su diagnostico temprano.

Diabetes Mellitus Prevalence and Control in Sleep-Disordered Breathing: The European Sleep Apnea Cohort (ESADA) Study

BACKGROUND OSA is associated with an increased risk of cardiovascular morbidity. A driver of this is metabolic dysfunction and in particular type 2 diabetes mellitus (T2DM). Prior studies identifying a link between OSA and T2DM have excluded subjects with undiagnosed T2DM, and there is a lack of population-level data on the interaction between OSA and glycemic control among patients with diabetes. We assessed the relationship between OSA severity and T2DM prevalence and control in a large multinational population. METHODS We performed a cross-sectional analysis of 6,616 participants in the European Sleep Apnea Cohort (ESADA) study, using multivariate regression analysis to assess T2DM prevalence according to OSA severity, as measured by the oxyhemoglobin desaturation index. Patients with diabetes were identified by previous history and medication prescription, and by screening for undiagnosed diabetes with glycosylated hemoglobin (HbA1c) measurement. The relationship of OSA severity with glycemic control was assessed in diabetic subjects. RESULTS T2DM prevalence increased with OSA severity, from 6.6% in subjects without OSA to 28.9% in those with severe OSA. Despite adjustment for obesity and other confounding factors, in comparison with subjects free of OSA, patients with mild, moderate, or severe disease had an OR (95% CI) of 1.33 (1.04-1.72), 1.73 (1.33-2.25), and 1.87 (1.45-2.42) (P < .001), respectively, for prevalent T2DM. Diabetic subjects with more severe OSA had worse glycemic control, with adjusted mean HbA1c levels 0.72% higher in patients with severe OSA than in those without sleep-disordered breathing (analysis of covariance, P < .001). CONCLUSIONS Increasing OSA severity is associated with increased likelihood of concomitant T2DM and worse diabetic control in patients with T2DM.