Carlos Egea

Obstructive Sleep Apnea and Systemic Hypertension

RATIONALE Obstructive sleep apnea and systemic hypertension (SH) are highly prevalent. Although their association has been suggested in cross-sectional studies, conflicting evidence has emerged from longitudinal studies. OBJECTIVES To assess the association between obstructive sleep apnea and SH in the middle-aged general population. METHODS A total of 2,148 subjects were included in a longitudinal study of the Vitoria Sleep Cohort, a general population sample aged 30-70 years. We analyzed data on office blood pressure, anthropometric measures, health history, and home polygraphy. Out of 1,557 subjects who completed the 7.5-year follow-up, 377 were excluded for having SH at baseline. The odds ratios for the incidence of SH, according to the respiratory disturbance index (RDI) at baseline, were estimated in 1,180 subjects (526 men and 654 women) after adjustment for age; sex; body mass index; neck circumference; fitness level; and alcohol, tobacco, and coffee consumption. The RDI was divided into quartiles (0-2.9, 3-6.9, 7-13.9, and ≥ 14), using the first quartile as reference. MEASUREMENTS AND MAIN RESULTS The crude odds ratio for incident hypertension increased with higher RDI category with a dose-response effect (P < 0.001), but was not statistically significant after adjustment for age (P = 0.051). Adjustments for sex (P = 0.342), body mass index (P = 0.803), neck circumference (P = 0.885), and fitness level and alcohol, tobacco, and coffee consumption (P = 0.708) further reduced the strength of the association between RDI and SH. No differences were observed between men and women. CONCLUSIONS Our findings do not suggest an association between obstructive sleep apnea and the incidence of SH in the middle-aged general population. Long-term follow-up longitudinal studies are needed to better ascertain this association.

Efficacy of Different Treatment Alternatives for Obesity Hypoventilation Syndrome. Pickwick Study

RATIONALE The incidence of obesity hypoventilation syndrome (OHS) may be increasing in parallel with the present obesity epidemic. Despite extensive noninvasive ventilation (NIV) and continuous positive airway pressure (CPAP) use in patients with OHS, information regarding efficacy is limited. OBJECTIVES We performed a large, multicenter randomized controlled study to determine the comparative efficacy of NIV, CPAP, and lifestyle modification (control group) using daytime PaCO2 as the main outcome measure. METHODS Sequentially screened patients with OHS with severe sleep apnea were randomized into the above-mentioned groups for a 2-month follow up. Arterial blood gas parameters, clinical symptoms, health-related quality-of-life assessments, polysomnography, spirometry, 6-minute-walk distance, dropouts, compliance, and side effects were evaluated. Statistical analysis was performed using intention-to-treat analysis, although adjustments for CPAP and NIV compliance were also analyzed. MEASUREMENTS AND MAIN RESULTS In total, 351 patients were selected, and 221 were randomized. NIV yielded the greatest improvement in PaCO2 and bicarbonate, with significant differences relative to the control group but not relative to the CPAP group. In the CPAP group, PaCO2 improvement was significantly different than in the control group only after CPAP compliance adjustment. Additionally, clinical symptoms and polysomnographic parameters improved similarly with NIV and CPAP relative to the control. However, some health-related quality-of-life assessments, the spirometry, and 6-minute-walk distance results improved more with NIV than with CPAP. Dropouts were similar between groups, and compliance and secondary effects were similar between NIV and CPAP. CONCLUSIONS NIV and CPAP were more effective than lifestyle modification in improving clinical symptoms and polysomnographic parameters, although NIV yielded better respiratory functional improvements than did CPAP. Long-term studies must demonstrate whether this functional improvement has relevant implications. Clinical trial registered with www.clinicaltrials.gov (NCT01405976).

A Bayesian cost-effectiveness analysis of a telemedicine-based strategy for the management of sleep apnoea: a multicentre randomised controlled trial

Background Compliance with continuous positive airway pressure (CPAP) therapy is essential in patients with obstructive sleep apnoea (OSA), but adequate control is not always possible. This is clinically important because CPAP can reverse the morbidity and mortality associated with OSA. Telemedicine, with support provided via a web platform and video conferences, could represent a cost-effective alternative to standard care management. Aim To assess the telemedicine impact on treatment compliance, cost-effectiveness and improvement in quality of life (QoL) when compared with traditional face-to-face follow-up. Methods A randomised controlled trial was performed to compare a telemedicine-based CPAP follow-up strategy with standard face-to-face management. Consecutive OSA patients requiring CPAP treatment, with sufficient internet skills and who agreed to participate, were enrolled. They were followed-up at 1, 3 and 6 months and answered surveys about sleep, CPAP side effects and lifestyle. We compared CPAP compliance, cost-effectiveness and QoL between the beginning and the end of the study. A Bayesian cost-effectiveness analysis with non-informative priors was performed. Results We randomised 139 patients. At 6 months, we found similar levels of CPAP compliance, and improved daytime sleepiness, QoL, side effects and degree of satisfaction in both groups. Despite requiring more visits, the telemedicine group was more cost-effective: costs were lower and differences in effectiveness were not relevant. Conclusions A telemedicine-based strategy for the follow-up of CPAP treatment in patients with OSA was as effective as standard hospital-based care in terms of CPAP compliance and symptom improvement, with comparable side effects and satisfaction rates. The telemedicine-based strategy had lower total costs due to savings on transport and less lost productivity (indirect costs). Trial register number NCT01716676.

Conventional Polysomnography Is Not Necessary for the Management of Most Patients with Suspected Obstructive Sleep Apnea. Noninferiority, Randomized Controlled Trial

Rationale: Home respiratory polygraphy may be a simpler alternative to in‐laboratory polysomnography for the management of more symptomatic patients with obstructive sleep apnea, but its effectiveness has not been evaluated across a broad clinical spectrum. Objectives: To compare the long‐term effectiveness (6 mo) of home respiratory polygraphy and polysomnography management protocols in patients with intermediate‐to‐high sleep apnea suspicion (most patients requiring a sleep study). Methods: A multicentric, noninferiority, randomized controlled trial with two open parallel arms and a cost‐effectiveness analysis was performed in 12 tertiary hospitals in Spain. Sequentially screened patients with sleep apnea suspicion were randomized to respiratory polygraphy or polysomnography protocols. Moreover, both arms received standardized therapeutic decision‐making, continuous positive airway pressure (CPAP) treatment or a healthy habit assessment, auto‐CPAP titration (for CPAP indication), health‐related quality‐of‐life questionnaires, 24‐hour blood pressure monitoring, and polysomnography at the end of follow‐up. The main outcome was the Epworth Sleepiness Scale measurement. The noninferiority criterion was −2 points on the Epworth scale. Measurements and Main Results: In total, 430 patients were randomized. The respiratory polygraphy protocol was noninferior to the polysomnography protocol based on the Epworth scale. Quality of life, blood pressure, and polysomnography were similar between protocols. Respiratory polygraphy was the most cost‐effective protocol, with a lower per‐patient cost of 416.7&U20AC;. Conclusions: Home respiratory polygraphy management is similarly effective to polysomnography, with a substantially lower cost. Therefore, polysomnography is not necessary for most patients with suspected sleep apnea. This finding could change established clinical practice, with a clear economic benefit. Clinical trial registered with www.clinicaltrials.gov (NCT 01752556).

Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea

Background Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. Methods Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. Results A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of −6 (95% CI −7.7 to −4.2) mm Hg versus −2.8 (95% CI −4.3 to −1.3) mm Hg, (p<0.001) and serum bicarbonate of −3.4 (95% CI −4.5 to −2.3) versus −1 (95% CI −1.7 to −0.2 95% CI)  mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. Conclusions NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality. Trial registration number NCT01405976; results.

Protective Cardiovascular Effect of Sleep Apnea Severity in Obesity Hypoventilation Syndrome

BACKGROUND Obesity hypoventilation syndrome (OHS) is associated with a high burden of cardiovascular morbidity (CVM) and mortality. The majority of patients with OHS have concomitant OSA, but there is a paucity of data on the association between CVM and OSA severity in patients with OHS. The objective of our study was to assess the association between CVM and OSA severity in a large cohort of patients with OHS. METHODS In a cross-sectional analysis, we examined the association between OSA severity based on tertiles of oxygen desaturation index (ODI) and CVM in 302 patients with OHS. Logistic regression models were constructed to quantify the independent association between OSA severity and prevalent CVM after adjusting for various important confounders. RESULTS The prevalence of CVM decreased significantly with increasing severity of OSA based on ODI as a continuous variable or ODI tertiles. This inverse relationship between OSA severity and prevalence of CVM was seen in the highest ODI tertile and it persisted despite adjustment for multiple confounders. Chronic heart failure had the strongest negative association with the highest ODI tertile. No significant CVM risk change was observed between the first and second ODI tertiles. Patients in the highest ODI tertile were younger, predominantly male, more obese, more hypersomnolent, had worse nocturnal and daytime gas exchange, lower prevalence of hypertension, better exercise tolerance, and fewer days hospitalized than patients in the lowest ODI tertile. CONCLUSIONS In patients with OHS, the highest OSA severity phenotype was associated with reduced risk of CVM. This finding should guide the design of future clinical trials assessing the impact of interventions aimed at decreasing cardiovascular morbidity and mortality in patients with OHS. TRIAL REGISTRY Clinicaltrial.gov; No.: NCT01405976; URL: www.clinicaltrials.gov.

Sleep Apnea and Hypertension: Are There Sex Differences? The Vitoria Sleep Cohort

BACKGROUND: Evidence from longitudinal studies has reported contradictory results regarding the association between OSA and hypertension. In a previous analysis of the Vitoria Sleep Cohort, the relationship between OSA and the risk of developing hypertension was evaluated and no independent association after adjustment for confounding factors was found. In the present study, a post hoc analysis to assess the association between OSA and incident stage 2 hypertension (systolic BP ≥ 160 mm Hg and/or diastolic BP ≥ 100 mm Hg) was made on the basis of sex differences. METHODS: A prospective study was performed over 7.5 ± 0.8 years on a middle‐aged general population, which included 1,155 normotensive subjects (43.7% men) who completed the follow‐up. BP measurements (at baseline and follow‐up) and polygraphy at baseline were performed. Logistic regression models were used to determine the association between the respiratory disturbance index (RDI) and stage 2 hypertension and a recursive partitioning method was used to determine the variables related to the incidence of stage 2 hypertension. The RDI was divided into subgroups (0–2.9, 3–6.9, 7–13.9, and ≥ 14), using the first subgroup as reference. RESULTS: For men, an RDI ≥ 14 was associated with a significantly increased OR for stage 2 hypertension (OR, 2.54 [95% CI, 1.09–5.95], P = .032). This association was not statistically significant among women (P = .371). CONCLUSIONS: The results suggest an association between moderate and severe OSA, and the incidence of more severe forms of hypertension occurring in men but not in women. However, because this is a community‐based study, the womens population characteristics may differ from women usually seen in sleep‐disorders clinics.

Blood pressure response to CPAP treatment in subjects with obstructive sleep apnoea: the predictive value of 24-h ambulatory blood pressure monitoring

The reduction in blood pressure (BP) with continuous positive airway pressure (CPAP) is modest and highly variable. In this study, we identified the variables that predict BP response to CPAP. 24-h ambulatory BP monitoring (ABPM), C-reactive protein (CRP), leptin, adiponectin and 24-h urinary catecholamine were measured before and after 6 months of CPAP in obstructive sleep apnoea (OSA) patients. Overall, 88 middle-aged, obese male patients with severe OSA (median apnoea–hypopnoea index 42 events·h−1) were included; 28.4% had hypertension. 62 patients finished the study, and 60 were analysed. The daytime diastolic BP (−2 mmHg) and norepinephrine (−109.5 nmol·day-1) were reduced after CPAP, but no changes in the 24-h BP, night-time BP, dopamine, epinephrine, CRP, leptin or adiponectin were detected. The nocturnal normotension was associated with an increased night-time-BP (+4 mmHg) after CPAP, whereas nocturnal hypertension was associated with a reduction of 24-h BP (−3 mmHg). A multivariate linear regression model showed differential night-time BP changes after CPAP. Specifically, low night-time heart rate (<68 bpm) and BP dipper profile were associated with increased night-time BP and new diagnosis of nocturnal hypertension. Our results suggest that nocturnal hypertension, circadian BP pattern and night-time heart rate could be clinical predictors of BP response to CPAP and support the usefulness of 24-h ABPM for OSA patients before treatment initiation. These results need to be confirmed in further studies. 24-h ambulatory blood pressure monitoring showed predictive value for the blood pressure response to CPAP treatment http://ow.ly/Wuf230dqP4T

Primary Care Physicians Can Comprehensively Manage Patients with Sleep Apnea. A Noninferiority Randomized Controlled Trial

Rationale: General practitioners play a passive role in obstructive sleep apnea (OSA) management. Simplification of the diagnosis and use of a semiautomatic algorithm for treatment can facilitate the integration of general practitioners, which has cost advantages. Objectives: To determine differences in effectiveness between primary health care area (PHA) and in‐laboratory specialized management protocols during 6 months of follow‐up. Methods: A multicenter, noninferiority, randomized, controlled trial with two open parallel arms and a cost‐effectiveness analysis was performed in six tertiary hospitals in Spain. Sequentially screened patients with an intermediate to high OSA probability were randomized to PHA or in‐laboratory management. The PHA arm involved a portable monitor with automatic scoring and semiautomatic therapeutic decision‐making. The in‐laboratory arm included polysomnography and specialized therapeutic decision‐making. Patients in both arms received continuous positive airway pressure treatment or sleep hygiene and dietary treatment alone. The primary outcome measure was the Epworth Sleepiness Scale. Secondary outcomes were health‐related quality of life, blood pressure, incidence of cardiovascular events, hospital resource utilization, continuous positive airway pressure adherence, and within‐trial costs. Measurements and Main Results: In total, 307 patients were randomized and 303 were included in the intention‐to‐treat analysis. Based on the Epworth Sleepiness Scale, the PHA protocol was noninferior to the in‐laboratory protocol. Secondary outcome variables were similar between the protocols. The cost‐effectiveness relationship favored the PHA arm, with a cost difference of &U20AC;537.8 per patient. Conclusions: PHA management may be an alternative to in‐laboratory management for patients with an intermediate to high OSA probability. Given the clear economic advantage of outpatient management, this finding could change established clinical practice. Clinical trial registered with www.clinicaltrials.gov (NCT 02141165).

Cardiac Troponin Values in Patients With Acute Coronary Syndrome and Sleep Apnea: A Pilot Study

Background An analysis of cardiac injury markers in patients with OSA who sustain an episode of acute coronary syndrome (ACS) may contribute to a better understanding of the interactions and impact of OSA in subjects with ACS. We compared peak cardiac troponin I (cTnI) levels in patients with OSA and patients without OSA who were admitted for ACS. Methods Blood samples were collected every 6 hours from the time of admission until two consecutive assays showed a downward trend in the cTnI assay. The highest value obtained defined the peak cTnI value, which provides an estimate of infarct size. Results We included 89 patients with OSA and 38 patients without OSA with an apnea‐hypopnea index of a median of 32 (interquartile range [IQR], 20.8‐46.6/h and 4.8 [IQR, 1.6‐9.6]/h, respectively. The peak cTnI value was significantly higher in patients without OSA than in patients with OSA (median, 10.7 ng/mL [IQR, 1.78‐40.1 ng/mL] vs 3.79 ng/mL [IQR, 0.37‐24.3 ng/mL]; P = .04). The multivariable linear regression analysis of the relationship between peak cTnI value and patient group, age, sex, and type of ACS showed that the presence or absence of OSA significantly contributed to the peak cTnI level, which was 54% lower in patients with OSA than in those without OSA. Conclusions The results of this study suggest that OSA has a protective effect in the context of myocardial infarction and that patients with OSA may experience less severe myocardial injury. The possible role of OSA in cardioprotection should be explored in future studies.