Obstructive Sleep Apnea in Cardiovascular Disease: A Review of the Literature and Proposed Multidisciplinary Clinical Management Strategy
2018; Wiley; Volume: 8; Issue: 1 Linguagem: Inglês
10.1161/jaha.118.010440
ISSN2047-9980
AutoresJeremy Tietjens, David M. Claman, Eric J. Kezirian, Teresa De Marco, Armen Mirzayan, Bijan Sadroonri, Andrew N. Goldberg, Carlin S. Long, Edward P. Gerstenfeld, Yerem Yeghiazarians,
Tópico(s)Gastroesophageal reflux and treatments
ResumoHomeJournal of the American Heart AssociationVol. 8, No. 1Obstructive Sleep Apnea in Cardiovascular Disease: A Review of the Literature and Proposed Multidisciplinary Clinical Management Strategy Open AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessReview ArticlePDF/EPUBObstructive Sleep Apnea in Cardiovascular Disease: A Review of the Literature and Proposed Multidisciplinary Clinical Management Strategy Jeremy R. Tietjens, MD, David Claman, MD, Eric J. Kezirian, MD, MPH, Teresa De Marco, MD, Armen Mirzayan, DDS, Bijan Sadroonri, MD, Andrew N. Goldberg, MD, Carlin Long, MD, Edward P. Gerstenfeld, MD and Yerem Yeghiazarians, MD Jeremy R. TietjensJeremy R. Tietjens Department of Medicine, University of California, San Francisco, CA , David ClamanDavid Claman Department of Medicine, University of California, San Francisco, CA , Eric J. KezirianEric J. Kezirian USC Caruso Department of Otolaryngology – Head & Neck Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA , Teresa De MarcoTeresa De Marco Department of Medicine, University of California, San Francisco, CA , Armen MirzayanArmen Mirzayan Apnea Today LLC, Los Angeles, CA , Bijan SadroonriBijan Sadroonri Division of Pulmonary Diseases and Sleep Medicine, Holy Family Hospital, Methuen, MA , Andrew N. GoldbergAndrew N. Goldberg Department of Otolaryngology – Head & Neck Surgery, University of California, San Francisco, CA , Carlin LongCarlin Long Department of Medicine, University of California, San Francisco, CA , Edward P. GerstenfeldEdward P. Gerstenfeld Department of Medicine, University of California, San Francisco, CA and Yerem YeghiazariansYerem Yeghiazarians Department of Medicine, University of California, San Francisco, CA Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA Cardiovascular Research Institute, University of California, San Francisco, CA Originally published28 Dec 2018https://doi.org/10.1161/JAHA.118.010440Journal of the American Heart Association. 2019;8:e010440IntroductionCardiovascular disease (CVD) remains a highly prevalent cause of morbidity and mortality, both in the United States and worldwide. In parallel with the development of new and improved therapies for established CVD such as coronary artery disease or heart failure (HF), there has been an increased focus on modification of cardiovascular risk factors for both primary and secondary prevention, reflecting an evolving understanding of CVD as a systemic process with numerous determinants.Obstructive sleep apnea (OSA) has been associated with many different forms of CVD including hypertension, stroke, HF, coronary artery disease, and atrial fibrillation (AF).1 Adults with OSA not only have an increased risk of developing comorbid CVD but also have worse outcomes related to CVD. OSA is highly prevalent, estimated to affect 34% of men and 17% of women in the general population2 and 40% to 60% of patients with CVD.3 Furthermore, the prevalence is increasing, with these figures representing a 30% increase over the previous 2 decades,2 likely related to the obesity epidemic as well as an aging population.Despite the clear association between CVD and OSA, randomized trials have failed to demonstrate that treatment of sleep apnea improves hard cardiovascular outcomes in patients with established CVD.5 Nevertheless, this area remains controversial, as randomized trials performed to date remain limited in number as well as design, highlighting the need for further study.6 Furthermore, the current literature suggests that the impact of diagnosing and treating OSA varies between specific CVD processes, implying the need for a more sophisticated understanding and nuanced clinical approach to this issue. In this article we review the literature pertaining to OSA in patients with CVD. Additionally, we offer a practical clinical approach to the evaluation and management of known or suspected OSA in patients with CVD consisting of recommendations integrated from several separate societal practice guidelines combined with several of our own suggestions on issues not addressed by current guidelines, based on our own clinical experience and best available literature.Overview of Sleep ApneaDefinitionSleep apnea is characterized by repetitive episodes of apnea occurring during sleep. An apnea is defined as a cessation of inspiratory airflow lasting 10 seconds or more, while the term hypopnea refers to a reduction in inspiratory airflow (by at least 30%) lasting 10 seconds or more with an associated drop in oxygen saturation or arousal from sleep.7 The steps required for a successful inspiratory cycle include activation of a signal from the regulatory brainstem center, transmission of the signal via peripheral nerves, activation of respiratory muscles to produce negative intrathoracic pressure, and a patent airway. The mechanism for apneas or hypopneas can be either obstructive, in which airflow cessation results despite inspiratory effort because of blockage within the upper airways, or central, in which both airflow and inspiratory efforts are absent. The term sleep‐disordered breathing (SDB) encompasses OSA, central (CSA), and mixed apnea, the latter of which shows absent respiratory effort initially and clear effort with obstruction and the end of mixed apnea.Important risk factors for OSA include obesity, craniofacial or oropharyngeal anatomic abnormalities, male sex, and smoking.8 During sleep, there is a reduction in tone of the dilator muscles involved in maintaining airway patency. In particular, relaxation of the genioglossus muscle allows the tongue to fall posteriorly within the pharynx, facilitating obstruction in susceptible individuals.9 Anatomic factors including obesity that result in relative narrowing of the airway lumen increase the likelihood of obstruction. The observation that OSA also affects nonobese patients without identifiable anatomic abnormalities indicates that nonanatomic mechanisms are important as well. Examples of these include ventilatory control instability10 and reduced sleep arousal threshold.11 The relative contribution from these processes varies between individual patients, with potential therapeutic implications. A better understanding of the mechanisms underlying OSA could facilitate more personalized therapeutic strategies in the future.CSA results from transient failure of respiratory control centers in the medulla to trigger inspiration. The primary mechanism is thought to be abnormal regulation of the apneic threshold, the partial pressure of CO2 below which respiration is suppressed, although depending on the underlying cause CSA patients can be either hypercapnic, eucapnic, or hypocapnic.9 HF is one of the leading causes of CSA, associated in particular with Cheyne‐Stokes breathing, which is characterized by cyclic crescendo‐decrescendo respiratory efforts and hypocapnia.12Evaluation and DiagnosisThe evaluation for sleep apnea begins with a comprehensive sleep assessment, which includes a thorough clinical history documenting signs or symptoms, such as excessive daytime sleepiness, morning headaches, snoring, witnessed apnea, or difficulty concentrating, a physical examination, and a review of the medical history for relevant comorbidities and other risk factors13 (Table 1). Patients with suspected sleep apnea following this assessment should undergo diagnostic testing, the criterion standard of which is polysomnography. Treatment of OSA is generally reserved for those individuals with an apnea–hypopnea index (AHI; the number of apneas and hypopneas observed per hour) ≥5 measured during sleep study in patients with either signs/symptoms of sleep apnea or associated medical conditions (including hypertension, HF, coronary artery disease, significant arrhythmias, and other forms of CVD). Alternatively, an AHI ≥15 is often treated as OSA even in the absence of signs, symptoms, or associated medical conditions.14 Severity is also determined using the AHI, with 5 to 14 considered mild, 15 to 30 moderate, and >30 severe disease. Significant night‐to‐night variability of AHI has been observed in studies of consecutive night polysomnography, with 7% to 25% of patients meeting diagnostic criteria for moderate‐to‐severe OSA the second night despite a negative result the previous evening.15 Current guidelines therefore recommend repeating polysomnography in patients with a negative initial study when clinical suspicion of OSA remains high.16Table 1 Signs and Symptoms of Obstructive Sleep ApneaSnoringWitnessed apneas by sleep partnerEpisodes of gasping or choking during sleepInsomnia with repeated awakeningsExcessive daytime sleepinessNonrefreshing sleepMorning headachesDifficulty concentratingMemory impairmentIrritability and/or mood changesNocturiaDecreased libido and/or erectile dysfunctionHome sleep apnea testing (HSAT) using a portable monitoring device is a reasonable alternative testing strategy. Several HSAT devices exist, all of which measure heart rate and oximetry with some also measuring nasal pressure, chest and abdominal plethysmography, and/or peripheral arterial tonometry. Compared with polysomnography, the diagnostic accuracy of HSAT is lower and, importantly, varies depending on the population studied and diagnostic criteria used.17 Despite these caveats, HSAT represents a viable alternative to polysomnography in select circumstances and is recommended for diagnosis of OSA in uncomplicated patients with an increased risk of moderate‐to‐severe OSA.7 Given its limited sensitivity and the potential consequences of false‐negative results, negative or nondiagnostic studies should be followed up with polysomnography. Furthermore, patients at risk for central or mixed sleep apnea (significant cardiopulmonary disease, chronic opioid use, history of stroke, or neuromuscular disorders with potential respiratory muscle involvement) or other nonrespiratory sleep disorders requiring evaluation should undergo polysomnography rather than HSAT,16 because the diagnostic accuracy of the latter for central apneas has not been validated.Because a single night of HSAT is less resource intensive than a single full night of polysomnography, reduced cost has been cited as a potential benefit of increasing HSAT use in diagnosing OSA. Several economic analyses comparing the cost effectiveness of HSAT with full‐ or split‐night polysomnography in adults with suspected moderate to severe OSA instead found full‐night polysomnography to be the preferred testing modality.20 Increased costs related to repeat testing and false‐negative HSAT results account for these findings. A major caveat of these analyses is the potential for error related to imprecisions of modeling a clinical diagnostic pathway and limitations in the quality of real‐world data available to calibrate their models. Only 1 study published to date has analyzed relative cost effectiveness of various diagnostic modalities using measurement of real‐world resource utilization in the context of a randomized controlled trial (RCT). Using data from the HomePAP trial, Kim et al found that in 373 patients at risk for moderate‐to‐severe OSA, a home‐based testing pathway resulted in significantly lower costs to the payer than a laboratory‐based polysomnography pathway ($1575 versus $1840, P=0.02).22 Therefore, use of HSAT in appropriately selected patients with suspected OSA may have the potential to reduce costs; however, providers must recognize that extending HSAT use to other populations, in particular low‐risk patients, may actually increase overall costs because of more frequent follow‐up testing.Several clinical questionnaires and prediction tools have been developed to aid in the evaluation of OSA, such as the STOP‐BANG questionnaire, the Epworth Sleepiness Scale, and the Berlin Questionnaire (Table 2). These clinical tools were designed to provide a standardized assessment approach that can be performed relatively quickly in the outpatient setting, either in sleep centers or in primary care clinics. While offering the advantage of being quick, convenient, and inexpensive, studies evaluating the diagnostic accuracy of such clinical tools in comparison with polysomnography or HSAT have demonstrated inadequate sensitivity and specificity.7 Accordingly, clinical assessment prediction tools are not currently recommended for the diagnosis of OSA in the absence of polysomnography or HSAT. They can, however, play a useful role as adjunctive tools in the screening process or aid in assessment of treatment efficacy during long‐term follow‐up of patients with OSA.Table 2 Summary of Clinical Obstructive Sleep Apnea QuestionnairesQuestionnaireSummary of Questionnaire ContentsDiagnostic Accuracy Compared With AHI (>15 events/h)16Berlin Questionnaire10 questions pertaining to the following 3 symptoms/signs:SnoringDaytime sleepinessHypertensionPatients classified by score as having low risk or high risk of OSASensitivity: 0.77 (0.73–0.81)Specificity: 0.44 (0.38–0.51)STOP Questionnaire4 questions regarding the following signs/symptoms:SnoringSleepinessObserved apneas or chokingHypertensionSensitivity: 0.89 (0.81–0.94)Specificity: 0.32 (0.19–0.48)STOP‐BANG Questionnaire4 questions regarding signs/symptoms plus 4 clinical attributes:SnoringSleepinessObserved apneas or chokingHypertensionObesity (BMI >35 kg/m2)Age (>50 y)Neck sizeSexPatients classified as low, intermediate, or high risk for OSASensitivity: 0.90 (0.86–0.93)Specificity: 0.36 (0.29–0.44)Epworth Sleepiness Scale8 questions asking patients to rate the likelihood of falling asleep in various daytime contextsPatients classified as having normal sleep, average sleepiness, or severe and possibly pathologic sleepinessSensitivity: 0.47 (0.35–0.59)Specificity: 0.62 (0.56–0.68)AHI indicates apnea–hypopnea index; BMI, body mass index; OSA, obstructive sleep apnea.TreatmentEffective management of OSA requires a comprehensive assessment of each individual patient's phenotype as well as long‐term follow‐up and monitoring. Behavioral, medical, dental, and surgical options exist for treatment of sleep apnea.Positive airway pressure (PAP) therapy is a first‐line therapy for all patients diagnosed with obstructive sleep apnea and has been shown to both reduce the AHI23 and improve self‐reported sleepiness and quality of life.24 It is cost effective, with an estimated incremental cost‐effectiveness ratio of $15 915 per quality‐adjusted life year gained.20 The therapeutic mechanism of PAP is pneumatic splinting of the upper airway, thereby reducing airflow obstruction and apneic events. The 2 major PAP delivery modes are continuous positive airway pressure (CPAP) and bi‐level positive airway pressure. CPAP is the preferred first‐line modality in most patients with OSA, while bi‐level positive airway pressure is generally reserved for patients with OSA accompanied by hypoventilation syndromes, although it can also be used in patients with OSA alone who fail to tolerate CPAP and in some cases of CSA. The optimal settings are ideally determined via manual titration of PAP during full‐night polysomnography to a pressure that eliminates upper airway obstruction and remains tolerable to the patient. Alternatively, some patients undergo a split‐night study in which PAP titration is performed following the diagnostic portion of polysomnography. A split‐night study requires that a conclusive diagnosis of moderate‐to‐severe OSA be made with at least 3 hours remaining in the test to conduct PAP titration.Auto‐titrating CPAP (APAP) is another option that offers the advantage of performing titration at home rather than in a sleep laboratory. In APAP, the clinician programs a pressure range, and the level of administered PAP is automatically adjusted throughout the night to the lowest pressure required to maintain upper airway patency using proprietary event‐detection software. Several randomized trials comparing fixed CPAP with APAP showed either no difference or, in some cases, a small advantage of APAP with respect to adherence rate, reduction in AHI, and improvement in sleepiness in cohorts with uncomplicated OSA.25 Notably, patients with HF, chronic obstructive pulmonary disease or other form of significant lung disease, obesity hypoventilation syndrome, and SDB related to neuromuscular disease were excluded from these studies, and current guidelines recommend against use of APAP for either pressure titration or therapy in these patients.27PAP therapy is an efficacious treatment of OSA; however, effectiveness can be limited by patient nonadherence, which is not uncommon and can be caused by a variety of factors.28 Strategies that may be effective for some patients in improving adherence with therapy include changing the mask interface (superior tolerability of the nasal interface has been suggested), adding humidification to the PAP circuit (effectiveness may be limited to those with nasal congestion), adding a chinstrap to the mask interface (which also appears to reduce air leak and residual AHI),29 and utilizing an APAP mode.24 Cognitive behavioral therapy aimed at improving patients' self‐efficacy with respect to their health has been shown to increase adherence in several studies.28 Early assessment and prompt troubleshooting of any problems is extremely important following treatment initiation, because use during the first 2 weeks predicts long‐term adherence to therapy.23Behavioral therapies for sleep apnea include weight loss, positional therapy, and avoidance of alcohol or other sedating agents (Table 3). Weight loss reduces the severity of OSA in most overweight patients, with a significant correlation between the magnitude of weight loss and the reduction in AHI.30 Weight loss can be either medical or surgical.33 Intensive lifestyle modifications and weight loss may reduce the risk of future cardiovascular events including mortality in overweight/obese patients via mechanisms unrelated to OSA34 and therefore should be recommended to all such patients with OSA in addition to other therapies.36 Bariatric surgery is efficacious in terms of both weight loss and reduction in AHI and therefore should be considered in select obese patients with OSA.37 Although weight loss can reduce AHI, most patients will require some form of additional OSA therapy, because only 10% to 30% of patients have achieved an AHI 50% of all patients with an AHI >5 events/h have a positional component to their sleep apnea.40Oral appliances, such as a mandibular advancement device and tongue‐retaining devices, work by mechanically enlarging the upper airway by displacing the tongue forward and reducing its collapsibility during sleep,41 mimicking the Jaw‐Thrust technique used by anesthesiologists to open the airway in sedated patients. Both the mandibular advancement device and tongue‐retaining devices increase cross‐sectional area of the airway at the level of the velopharynx and oropharynx, although the change in diameter is greater with tongue‐retaining devices than with the mandibular advancement device.42 Oral appliances are effective in reducing AHI in patients with OSA43 but are less efficacious than PAP therapy.41 Baseline AHI ≥30 and maximum therapeutic CPAP pressure >12 mm Hg are predictive of oral appliance treatment failure (success defined by achieving either AHI <5, or 5≤ AHI 50% reduction from baseline), and thus these clinical features should be considered when selecting patients for oral appliance therapy.44 Oral appliances are recommended for treatment of primary snoring without OSA, and in mild‐to‐moderate OSA in cases where the patient strongly prefers to try an appliance over PAP therapy. They are also preferable compared with no therapy for primary snoring without OSA, or OSA of any severity in patients who are intolerant to or unwilling to try PAP therapy.43Upper airway surgery is designed to address anatomic airway obstruction in the upper airway and consists of a variety of different techniques. Individual surgical procedures may be classified as nasal, upper pharyngeal, lower pharyngeal, or global upper airway depending on the anatomic level at which obstruction is targeted. Many patients have obstructive anatomy at multiple sites and require multilevel surgical correction, in which several procedures are performed either simultaneously or in a staged manner. Surgery can be considered as primary therapy for patients with primary snoring with OSA, in patients with mild‐to‐moderate OSA where they may supersede oral appliances, and in cases of obstructive anatomy where surgery would be considered highly effective, and as secondary therapy for patients with OSA who experience inadequate response to or cannot tolerate PAP therapy.39Surgery is an effective management option for the treatment of OSA, with reported polysomnographic success rates (generally defined as a ≥50% reduction in AHI to an AHI value ≤20) of 35% to 83% in the literature.45 Limitations of the reported efficacy in the literature include significant heterogeneity of surgical technique as well as patient selection based on individual anatomic characteristics and surgeon preference. An overview of the different types of surgical procedures used to treat OSA along with reported efficacy of each technique is presented in Table 4.50 One particular form of surgery, hypoglossal nerve stimulation, has a growing body of literature supporting its efficacy. The STAR (Stimulation Treatment for Apnea Reduction) trial enrolled 126 patients with moderate‐to‐severe OSA who had difficulty adhering to CPAP and surgically implanted hypoglossal simulators.51 After 18 months, there was a 68% reduction in median AHI as well as improved scores on the Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire with only 2 serious adverse events reported throughout the trial.52Table 4 Overview of Surgical Procedures for Obstructive Sleep ApneaAnatomic RegionSpecific ProceduresOutcomesNasalTurbinate reductionSeptoplastyNasal valve surgeryRhinoplastyNasal polypectomyAdenoidectomySignificant 2.66 cm H2O reduction in required CPAP pressure (95% CI 1.67–3.65; P<0.00001) reported in meta‐analysis following nasal surgeries45Average nightly CPAP use increased from 3.0±3.1 h preoperatively to 5.5±2.0 h following surgeryUpper pharyngealUvulopalatopharyngoplastyUvulopalatal flapSeveral other variants of UPPP are usedTonsillectomyPooled polysomnographic success rate 50%a for UPPP in meta‐analyses; however, results from individual studies vary significantly, with success rates up to 83% in more selective cohorts50Lower pharyngealTongue reduction proceduresTongue advancement/stabilization proceduresEpiglottis proceduresPolysomnographic success rate ranges from 35% to 62% across studies of various hypopharyngeal procedures48Global upper airway proceduresMaxillomandibular advancementTracheotomyUpper airway stimulationPooled efficacy results from meta‐analyses of each procedure type:MMA: 86% success ratea and 43% cure rateb49Tracheotomy: significant reduction in AHI by mean 79.82 events/h (95% CI 63.7–95.9, P<0.00001)46Hypoglossal stimulation: significant reduction in AHI by mean 17.51 events/h (95% CI 20.7–14.3)47AHI indicates apnea–hypopnea index; CPAP, continuous positive airway pressure; MMA, maxillomandibular advancement; OSA, obstructive sleep apnea; UPPP, uvulopalatopharyngoplasty.aPolysomnographic success defined as ≥50% reduction from baseline AHI and postsurgical AHI <20 events/h.bCure rate defined as postsurgical AHI <5 events/h.Risks of upper airway surgery include those inherent to any surgical procedure such as bleeding, infection, and complications related to anesthesia. The latter category as well as perioperative cardiovascular complications are known to be higher in patients with OSA as compared with the general surgical population.53 Additional risks vary according to the specific procedural technique utilized and include, but are not limited to, airway compromise, dysphagia, local anesthesia or paresis, vocal changes, globus sensation, and taste changes.55Cardiovascular Conditions Associated With OSAResistant HypertensionOf all the cardiovascular disease processes associated with OSA, the relationship with hypertension is the best established. Multiple observational studies have demonstrated this association,56 and an influential study by Peppard et al, which followed 709 patients in the Wisconsin Sleep Cohort, found a linear, dose‐dependent relationship between the severity of OSA at baseline and the relative risk of developing hypertension during follow‐up.58 The relationship is particularly strong between OSA and resistant hypertension, commonly defined as inability to adequately control blood pressure despite use of 3 antihypertensive agents including a diuretic or adequate blood pressure control requiring ≥4 agents. For example, 1 study found the prevalence of OSA to be 71% in patients with resistant hypertension versus 38% in those with essential hypertension.59Several randomized controlled trials have demonstrated a reduction in systemic blood pressure in patients treated with CPAP. A recent meta‐analysis of 5 randomized trials enrolling 457 total patients found a significant reduction in 24‐hour ambulatory blood pressure (4.78 mm Hg [95% CI, 1.61–7.95] systolic and 2.95 mm Hg [95% CI, 0.53–5.37] diastolic) as well as a mean nocturnal diastolic blood pressure (1.53 mm Hg [95% CI, 0–3.07]) in patients treated with CPAP.60 While the magnitude of this reduction was relatively modest, it has been shown that even small reductions in blood pressure confer reduced risk of adverse cardiovascular events.61 Based on these data, we believe that diagnostic testing is reasonable in all patients with resistant hypertension, including those without clear signs or symptoms of OSA.Pulmonary HypertensionOSA is strongly associated with pulmonary hypertension (PH) and may play a causative role in its pathophysiology. Whereas ≈10% to 20% of patients with moderate‐to‐severe OSA have coexisting PH,62 the prevalence of OSA in patients with PH diagnosed by right heart catheterization has been estimated to be 70% to 80%.63 Both hypercapnia and nocturnal episodes of hypoxia can trigger pulmonary arteriolar constriction leading to acute, reversible elevation in pulmonary artery pressures. Signaling pathways implicated in hypoxic vasoconstriction in PH include nitric oxide, endothelin, angiopoietin‐1, serotonin, and NADPH‐oxidase.64 Chronic hypoxia activates additional inflammatory pathways resulting in pulmonary vascular remodeling and, eventually, irreversible increases in pulmonary vascular resistance.65 Additional postulated mechanisms contributing to PH include increased right‐sided preload resulting from negative transthoracic pressure during periods of airway obstruction, generation of reactive oxygen species as well as endothelial dysfunction within the pulmonary vasculature.66 Echocardiographic evidence of right ventricular remodeling and dysfunction has been observed in association with OSA as well.67 In addition to direct mechanisms involving the pulmonary vasculature, OSA can lead to PH indirectly via contributing to left HF with associated postcapillary PH such as in patients with refractory hypertension.Pulmonary hypertension resulting solely from OSA is generally mild; however, OSA can further exacerbate elevations in pulmonary artery pressures and pulmonary vascular resistance when superimposed on PH associated with other underlying causes. Importantly, the presence of OSA in patients found to have severe PH has been associated with increased mortality.68 Regarding the effects of OSA treatment in patients with PH, the current literature, while limited by small sample size and paucity of randomized trials, does suggest a benefit. Observational studies have demonstrated reduction in pulmonary vascular resistance in patients treated with CPAP.69 In the 1 randomized trial to date, treatment of OSA with CPAP was associated with a significant reduction in pulmonary artery systolic pressure (28.9 mm Hg versus 24 mm Hg) when compared with a sham device.70 Given the detrimental effects of sleep apnea in patients with PH and limited evidence suggesting a beneficial effect of CPAP, we recommend clinical screening of all PH patients for sleep apnea with a comprehensive sleep assessment. In addition, we believe tha
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