Mandibular Advancement vs CPAP for Blood Pressure Reduction in Patients With Obstructive Sleep Apnea.

BACKGROUND: Hypertension guidelines recommend diagnosis and treatment of obstructive sleep apnea (OSA) in patients with hypertension. The mandibular advancement device (MAD) is an oral appliance therapy for patients who decline or cannot tolerate continuous positive airway pressure (CPAP). OBJECTIVES: We compared the relative effectiveness of MAD vs CPAP in reducing 24-hour ambulatory blood pressure (BP). METHODS: In an investigator-initiated, randomized, noninferiority trial (prespecified margin 1.5 mm Hg), 321 participants aged ≥40 years with hypertension and increased cardiovascular risk were recruited at 3 public hospitals for polysomnography. Of these, 220 participants with moderate-to-severe OSA (apnea-hypopnea index ≥15 events per hour) were randomized to either MAD or CPAP (1:1). The primary outcome was the difference between the 24-hour mean arterial BP at baseline and 6 months. RESULTS: Compared with baseline, the 24-hour mean arterial BP decreased by 2.5 mm Hg (P = 0.003) at 6 months in the MAD group, whereas no change was observed in the CPAP group (P = 0.374). The between-group difference was -1.6 mm Hg (95% CI: -3.51 to 0.24, noninferiority P < 0.001). The MAD group demonstrated a larger between-group reduction in all secondary ambulatory BP parameters compared with the CPAP group, with the most pronounced effects observed in the asleep BP parameters. Both the MAD and CPAP improved daytime sleepiness, with the between-group difference similar (P = 0.384). There were no between-group differences in cardiovascular biomarkers. CONCLUSIONS: MAD is noninferior to CPAP for reducing 24-hour mean arterial BP in participants with hypertension and increased cardiovascular risk. (Cardiosleep Research Program on Obstructive Sleep Apnea, Blood Pressure Control and Maladaptive Myocardial Remodeling-Non-inferiority Trial [CRESCENT]; NCT04119999).

Obstructive sleep apnea and temporal changes in cardiac repolarization in patients undergoing coronary artery bypass grafting.

STUDY OBJECTIVES: In coronary artery bypass grafting (CABG), abnormal cardiac repolarization is associated with adverse cardiovascular events that can be measured via the QTc interval. We investigated the impact of obstructive sleep apnea on the change in repolarization after CABG and the association of change in repolarization with the occurrence of major adverse cardiac and cerebrovascular events. METHODS: A total of 1,007 patients from 4 hospitals underwent an overnight sleep study prior to a nonemergent CABG. Electrocardiograms of 954 patients (median age: 62 years; male: 86%; mean follow-up: 2.1 years) were acquired prospectively within 48 hours before CABG (T1) and within 24 hours after CABG (T2). QTc intervals were measured using the BRAVO algorithm by Analyzing Medical Parameters for Solutions LLC. The change in T2 from T1 for QTc (ΔQTc) was derived, and Cox regression was performed. RESULTS: Compared with those without, patients who developed major adverse cardiac and cerebrovascular events (n = 115) were older and had (1) a higher prevalence of smoking, hypertension, diabetes mellitus, and chronic kidney disease; (2) a higher apnea-hypopnea index and oxygen desaturation index; and (3) a smaller ΔQTc. Cox regression analysis demonstrated a smaller ΔQTc to be an independent risk factor for major adverse cardiac and cerebrovascular events (hazard ratio: 0.997; P = .032). In the multivariable regression model, a higher oxygen desaturation index was independently associated with a smaller ΔQTc (correlation coefficient: -0.58; P < .001). CONCLUSIONS: A higher preoperative oxygen desaturation index was an independent predictor of a smaller ΔQTc. ΔQTc within 24 hours after CABG could be a novel predictor of occurrence of major adverse cardiac and cerebrovascular events at medium-term follow-up. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Undiagnosed Sleep Apnea and Bypass OperaTion (SABOT); URL: https://classic.clinicaltrials.gov/ct2/show/NCT02701504; Identifier: NCT02701504. CITATION: Teo YH, Yong CL, Ou YH, et al. Obstructive sleep apnea and temporal changes in cardiac repolarization in patients undergoing coronary artery bypass grafting. J Clin Sleep Med. 2024;20(1):49-55.

Mandibular advancement device versus CPAP in lowering 24-hour blood pressure in patients with obstructive sleep apnoea and hypertension: the CRESCENT trial protocol.

INTRODUCTION: Although treatment of obstructive sleep apnoea (OSA) using continuous positive airway pressure (CPAP) reduces blood pressure (BP), adherence to CPAP is often suboptimal. A mandibular advancement device (MAD) is a guideline-endorsed alternative therapy for OSA. Still, there is limited evidence on the relative efficacy between MAD and CPAP on BP reduction. We evaluate whether treatment of moderate-to-severe OSA using MAD can improve BP and other health-related outcomes compared with CPAP. METHODS AND ANALYSIS: This is a randomised, controlled, non-inferiority trial conducted. We will recruit 220 Asians with a history of hypertension and high cardiovascular risk for an overnight polysomnography screening. Those with moderate-to-severe OSA (apnoea-hypopnoea index ≥15 events/hour) will be randomised to treatment with either MAD or CPAP in a 1:1 ratio. Stratified by age (60 vs <60 years old), body mass index (25 vs <25 kg/m2) and apnoea-hypopnoea index (30 vs <30 events/hour), an adaptive randomisation scheme with permuted blocks constructed in real-time is implemented to restrict imbalance. The overall study duration is 12 months. The primary endpoint is the 24-hour mean arterial BP difference between baseline and 6-month follow-up. The secondary endpoints include other measures of ambulatory BP monitoring, arrhythmia based on a 4-day electrocardiographic monitoring, biomarker and proteomic analysis, cardiovascular magnetic resonance-derived myocardial fibrosis and remodelling and quality-of-life questionnaires. Recruitment began in October 2019 and ended in December 2022. Comparison between MAD and CPAP will be performed using covariance (ANCOVA) analysis of the changes in 24-hour mean arterial BP while adjusting for the baseline 24-hour mean arterial BP. We will compare the 95% CIs around the treatment difference point estimate with the prespecified non-inferiority margin (1.5 mm Hg). If the upper limit of the 95% CI is <1.5 mm Hg and crosses 0, non-inferiority of the MAD relative to CPAP will be established. ETHICS AND DISSEMINATION: The Domain Specific Review Board-C, National Healthcare Group under approved the study protocol (NHG DSRB Ref: 2019/00359, approved on 28 August 2019). Study findings will be disseminated to various local, national, and international audiences through abstract presentations and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04119999.

The Belun sleep platform to diagnose obstructive sleep apnea in patients with hypertension and high cardiovascular risk.

STUDY OBJECTIVE: Current hypertension guidelines recommend that at-risk individuals be screened for obstructive sleep apnea (OSA). The Belun Ring is a wearable OSA diagnostic device worn on the palmar side of the proximal phalanx of the index finger. METHODS: We recruited 129 participants (age: 60 ±â€Š8 years, male sex: 88%, BMI: 27 ±â€Š4 kg/m 2 ) with hypertension and high cardiovascular risk for a simultaneous polysomnography and Belun Ring monitoring for one night. Epworth Sleepiness Scale score more than 10 was detected in 27 (21.0%) participants. RESULTS: In the 127 participants who completed the study, the apnea-hypopnea index (AHI) derived from polysomnography was 18.1 (interquartile range: 33.0) events/h and that derived from the Belun Ring was 19.5 (interquartile range: 23.3) events/h [intraclass correlation coefficient: 0.882, 95% confidence interval (95% CI): 0.837-0.916]. A Bland-Altman plot showed the difference between the Belun Ring and polysomnography AHIs to be -1.3 ±â€Š10.4 events/h. Area under the receiver operating characteristic for the Belun Ring AHI was 0.961 (95% CI: 0.932-0.990, P  < 0.001). When the Belun Ring AHI of at least 15 events/h was used to diagnose OSA, the sensitivity, specificity, positive predictive value, and negative predictive value were 95.7, 77.6, 85.3, and 93.8%, respectively. The overall accuracy was 87.4%. The Cohen's kappa agreement was 0.74 ±â€Š0.09 ( P  < 0.001). Similar results were obtained when the oxygen desaturation index was used to diagnose OSA. CONCLUSION: A high prevalence of OSA was detected in patients with hypertension and high cardiovascular risk. The Belun Ring is a reliable device for OSA diagnosis similar to polysomnography.

Management of hypertension in obstructive sleep apnea.

Obstructive sleep apnea (OSA) plays an important role in the development of hypertension. Thus, this review summarizes pharmacological and non-pharmacological approaches to blood pressure (BP) control in patients with OSA. Current treatments for OSA, such as continuous positive airway pressure, are effective at lowering BP. However, they only provide a modest BP reduction, and pharmacological treatment remains important for achieving optimal BP control. Furthermore, current guidelines for the treatment of hypertension do not make specific recommendations on pharmacological treatment protocols for controlling BP in patients with OSA. Moreover, the BP-lowering effects of various classes of antihypertensives may be different in hypertensive patients with OSA than in those without OSA due to the underlying mechanisms that promote hypertension in OSA. The acute and chronic increase in sympathetic nerve activity in patients with OSA explain the effectiveness of beta blockers in controlling BP in these patients. As activation of the renin-angiotensin-aldosterone system may also promote hypertension in OSA, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have generally been found effective for lowering BP in hypertensive patients with OSA. The aldosterone antagonist spironolactone also produces a good antihypertensive response in patients with OSA and resistant hypertension. However, there are limited data available that compare the effects of various classes of antihypertensive medication on BP control in those with OSA, and most data have been obtained from small-scale studies. This demonstrates the need for large-scale randomized controlled trials to evaluate a range of BP-lowering regimens in patients with OSA and hypertension.

Hour-to-hour variability of respiratory sleep indices and ambulatory blood pressure.

STUDY OBJECTIVES: Respiratory sleep indices are traditionally reported on the basis of the average total sleep time. The relationship between the hour-to-hour variability of these parameters and blood pressure (BP) has not been reported. METHODS: We evaluated the associations of the hour-to-hour variability of the apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and lowest oxygen saturation with the 24-h ambulatory BP in patients with hypertension and newly diagnosed obstructive sleep apnea. A total of 147 patients underwent polysomnography, based on which obstructive sleep apnea was diagnosed in 106 patients; these patients underwent 24-h ambulatory BP monitoring within the next 30 days. Each polysomnogram was divided into hourly reports to calculate the variability of the respiratory sleep indices. Variability independent of the mean was considered the primary measure of variability. RESULTS: The median number of hourly polysomnogram reports was 7 (range, 4-8). The hour-to-hour variability of both AHI and ODI, but not of the lowest oxygen saturation, was correlated with the 24-h pulse pressure, 24-h systolic BP, and awake systolic BP (p < 0.05 for all). The fully adjusted linear regression analysis indicated that the hour-to-hour variability of AHI and ODI remained associated with the 24-h pulse pressure (AHI: ß coefficient, 0.264 [95% CI = 0.033-0.495], p = 0.026; ODI: ß coefficient, 0.450 [95% CI = 0.174-0.726], p = 0.002). CONCLUSIONS: The hour-to-hour variability of AHI and ODI is independently associated with the 24-h pulse pressure. Further investigations are warranted to evaluate the clinical relevance of this new-found association.

Sudden deterioration of CPAP adherence after myocardial infarction in a Chinese patient: potential effect of ACEI-induced airway hyperresponsiveness.

A patient with obstructive sleep apnea was admitted to the hospital with non-ST segment elevation myocardial infarction. An angiotensin-converting enzyme inhibitor was prescribed upon discharge. She later became intolerant to continuous positive airway pressure therapy, and her adherence to the related device decreased precipitously. The intolerance subsided gradually after a switch in medication to an angiotensin receptor blocker, and her adherence to continuous positive airway pressure device usage returned to baseline after 4 weeks. CITATION: Ou Y-H, Thant AT, Lee C-H. Sudden deterioration of CPAP adherence after myocardial infarction in a Chinese patient: potential effect of ACEI-induced airway hyperresponsiveness. J Clin Sleep Med. 2022;18(5):1463-1465.

Obstructive sleep apnea therapy for cardiovascular risk reduction-Time for a rethink?

Obstructive sleep apnea (OSA) is a highly prevalent and underdiagnosed medical condition, which is associated with various cardiovascular and metabolic diseases. The current mainstay of therapy is continuous positive airway pressure (CPAP); however, CPAP is known to be poorly accepted and tolerated by patients. In randomized controlled trials evaluating CPAP in cardiovascular outcomes, the average usage was less than 3.5 hours, which is below the 4 hours per night recommended to achieve a clinical benefit. This low adherence may have resulted in poor effectiveness and failure to show cardiovascular risk reduction. The mandibular advancement device (MAD) is an intraoral device designed to advance the mandible during sleep. It functions primarily through alteration of the jaw and/or tongue position, which results in improved upper airway patency and reduced upper airway collapsibility. The MAD is an approved alternative therapy that has been consistently shown to be the preferred option by patients who are affected by OSA. Although the MAD is less efficacious than CPAP in abolishing apnea and hypopnea events in some patients, its greater usage results in comparable improvements in quality-of-life and cardiovascular measures, including blood pressure reduction. This review summarizes the impact of OSA on cardiovascular health, the limitations of CPAP, and the potential of OSA treatment using MADs in cardiovascular risk reduction.

Personalized anesthetic patches for dental applications.

Topical anesthetics are widely used in dental procedures. However, most commercially available medications are in the form of liquid or semisolid, which cannot provide prolonged effect intraorally. To address this issue, we proposed the use of three-dimensional printing (3DP) to fabricate a customizable dental anesthetic patch loaded with lidocaine that can be fitted perfectly onto the affected tooth. It has been shown that that patch can adhere on the tooth for more than 1 h, while releasing lidocaine from the patch made of hydrogels. In addition, the results illustrated the possibility of controlling the drug release profile by altering the shape of the patch, as well the use of a 3DP tooth model as the drug testing platform. Taken together, these data further reinforce the vast potential of the application of 3DP technology in personalized medicine.