Effect of mandibular advancement splint therapy on cardiac autonomic function in obstructive sleep apnoea.

PURPOSE: This study aimed to evaluate the effect of mandibular advancement splint (MAS) therapy on cardiac autonomic function in patients with obstructive sleep apnoea (OSA) using heart rate variability (HRV) analysis. METHODS: Electrocardiograms (ECG) derived from polysomnograms (PSG) of three prospective studies were used to study HRV of patients with OSA before and after MAS treatment. HRV parameters were averaged across the entire ECG signal during N2 sleep using 2-min epochs shifted by 30 s. Paired t-tests were used to compare PSG and HRV measures before and after treatment, and the percent change in HRV measures was regressed on the percent change in apnoea-hypopnea index (AHI). RESULTS: In 101 patients with OSA, 72% were Caucasian, 54% men, the mean age was 56 ± 11 years, BMI 29.8 ± 5.3 kg/m2, and treatment duration was 4.0 ± 3.2 months. After MAS therapy, there was a significant reduction in OSA severity (AHI, - 18 ± 16 events per hour, p < 0.001) and trends towards increased low-frequency to high-frequency ratio, low-frequency power, and reduced high-frequency power (LF:HF, - 0.4 ± 1.5, p = 0.01; LF, - 3 ± 16 nu, p = 0.02, HF, 3.5 ± 13.7 nu, p = 0.01). Change in NN intervals correlated with the change in AHI (ß(SE) = - 2.21 (0.01), t = - 2.85, p = 0.005). No significant changes were observed in the time-domain HRV markers with MAS treatment. CONCLUSION: The study findings suggest that successful MAS treatment correlates with changes in HRV, specifically the lengthening of NN intervals, a marker for improved cardiac autonomic adaptability.

Cardiac autonomic function in REM-related obstructive sleep apnoea: insights from nocturnal heart rate variability profiles.

PURPOSE: In light of the reported association between REM-related obstructive sleep apnoea (OSA) and heightened cardiovascular risk, this study aims to compare cardiac autonomic function in patients with REM-OSA and OSA independent of sleep stage. We hypothesized that REM-OSA patients would exhibit higher sympathetic cardiac modulation based on heart rate variability (HRV) profiles. METHODS: HRV was compared between the OSA group (AHI ≥ 5 events/h, n = 252) and the REM-OSA group (AHI ≥ 5 events/h, AHIREM:AHINREM ≥ 2, n = 137). Time- and frequency-domain measures of HRV were analysed during N2 and REM sleep. RESULTS: Clinical characteristics between the two test groups differed significantly, 45% of REM-OSA patients were female, with mild OSA (median, interquartile range (IQR)) AHI of 10 (7) events/h. Only 26% of the OSA cohort were female with moderate OSA (AHI = 17 (20) events/h, p < 0.001). Compared with the OSA group, the low frequency to high frequency ratio (LF:HF) and LF power were lower and HF power was higher in the REM-OSA group during N2 (LF:HF, p = 0.012; LF; p = 0.013; HF, p = 0.007) and in REM sleep (LF:HF, p = 0.002; LF, p = 0.004; HF, p < 0.001). Patient sex and OSA severity had a significant combined effect on average N to N interval, LF power, and LF:HF ratio during N2 and REM sleep (all p < 0.001). CONCLUSION: Contrary to our hypothesis, REM-OSA patients demonstrated consistently higher cardiac vagal modulation, reflecting better cardiac autonomic adaptation. These results were attributed to differences in OSA severity and sex in these two groups, both independently affecting HRV. This study emphasises the need for future research into the underlying pathophysiology of REM-OSA and the potential implications of sex and OSA severity on cardiovascular risk.

Phenotypic Characterisation of Obstructive Sleep Apnoea in Acute Coronary Syndrome.

BACKGROUND: Recent neutral randomised clinical trials have created clinical equipoise for treating obstructive sleep apnoea (OSA) for managing cardiovascular risk. The importance of defining the links between OSA and cardiovascular disease is needed with the aim of advancing the robustness of future clinical trials. We aimed to define the clinical correlates and characterise surrogate cardiovascular markers in patients with acute coronary syndrome (ACS) and OSA. METHOD: Overall, 66 patients diagnosed with ACS were studied. Patients underwent an unattended polysomnogram after hospital discharge (median [interquartile range] 62 [37-132] days). The Epworth Sleepiness Scale, Berlin, and STOP-BANG questionnaires were administered. Surrogate measures of vascular structure and function, and cardiovascular autonomic function were conducted. Pulse wave amplitude drop was derived from the pulse oximetry signals of the overnight polysomnogram. RESULTS: OSA (apnoea-hypopnea index [AHI] ≥5) was diagnosed in 94% of patients. Moderate-to-severe OSA (AHI≥15) was observed in 68% of patients. Daytime sleepiness (Epworth Sleepiness Scale ≥10) was reported in 17% of patients. OSA screening questionnaires were inadequate to identify moderate-to-severe OSA, with an area under the receiver operating characteristic curve of approximately 0.64. Arterial stiffness (carotid-femoral pulse wave velocity, 6.1 [5.2-6.8] vs 7.4 [6.6-8.6] m/s, p=0.002) and carotid intima-media thickness (0.8 [0.7-1.0] vs 0.9 [0.8-1.0] mm, p=0.027) was elevated in patients with moderate-to-severe OSA. After adjusting for age, sex and body mass index, these relationships were not statistically significant. No relationships were observed in other surrogate cardiovascular markers. CONCLUSIONS: A high prevalence of OSA in a mostly non-sleepy population with ACS was identified, highlighting a gross underdiagnosis of OSA among cardiovascular patients. The limitations of OSA screening questionnaires highlight the need for new models of OSA screening as part of cardiovascular risk management. A range of inconsistent abnormalities were observed in measures of vascular structure and function, and these appear to be largely explained by confounding factors. Further research is required to elucidate biomarkers for the presence and impact of OSA in ACS patients.

Heart rate variability and obstructive sleep apnea: Current perspectives and novel technologies.

Obstructive sleep apnea (OSA) is a highly prevalent condition, resulting in recurrent hypoxic events, sleep arousal, and daytime sleepiness. Patients with OSA are at an increased risk of cardiovascular morbidity and mortality. The mechanisms underlying the development of cardiovascular disease in OSA are multifactorial and cause a cascade of events. The primary contributing factor is sympathetic overactivity. Heart rate variability (HRV) can be used to evaluate shifts in the autonomic nervous system, during sleep and in response to treatment in patients with OSA. Newer technologies are aimed at improving HRV analysis to accelerate processing time, improve the diagnosis of OSA, and detection of cardiovascular risk. The present review will present contemporary understandings and uses for HRV, specifically in the realms of physiology, technology, and clinical management.

Monitoring the sleep health of adults: a scoping review of routine national surveillance systems.

Study Objectives: The aims of this review were to identify existing national surveillance systems monitoring one or more domains of sleep health in adults, and to describe the specific sleep health indicators used. Methods: We systematically searched the gray and peer-reviewed literature for routinely conducted cross-sectional and longitudinal nationally representative health surveys that included the assessment of at least one domain of sleep health. The methodology involved: (1) targeted searches of the websites of national and international health agencies and statistics departments for 199 countries, (2) country-specific customized internet searches, and (3) country-specific electronic database searches of PubMed. Results: A total of 19 762 records were identified from both the gray and peer-reviewed literature. Sleep health surveillance at the national level was conducted by 51 countries (25.6%) across 69 national health surveys. Sleep quality (96.1% of countries that surveilled sleep) was the most frequently assessed followed by sleep duration (27.5%), sleep medication use (25.5%), sleep disorders (17.6%), daytime alertness (15.7%), sleep satisfaction (15.7%), and sleep timing (7.8%). Additionally, 34.8% of the surveys utilized multiple sleep health indicators. Conclusions: This study identified three significant gaps in the coverage of sleep health within national surveillance systems. Limited population sleep data in low- and middle-income countries, inconsistent use of sleep-related items in surveys and questionnaires, and substantial variability in the definitions of sleep health indicators. Advocacy for the inclusion of sleep health within national surveillance systems may be warranted given the important role sleep plays in public health.

Heart rate variability analysis in obstructive sleep apnea patients with daytime sleepiness.

STUDY OBJECTIVES: Recent studies suggest that sleepy patients with obstructive sleep apnea (OSA) are at higher risk for incident cardiovascular disease. This study assessed cardiac autonomic function in sleepy versus non-sleepy patients with OSA using heart rate variability (HRV) analysis. We hypothesized that HRV profiles of sleepy patients would indicate higher cardiovascular risk. METHODS: Electrocardiograms (ECG) derived from polysomnograms (PSG) collected by the Sydney Sleep Biobank were used to study HRV in groups of sleepy (ESS ≥ 10) and non-sleepy OSA patients (ESS < 10). HRV parameters were averaged across available ECG signals during N2 sleep. RESULTS: A total of 421 patients were evaluated, with a mean age of 54 (14) years, body mass index of 33 (9) kg/m2, apnea-hypopnea index of 21 (28) events/h, and 66% male. The sleepy group consisted of 119 patients and the non-sleepy group 302 patients. Sleepy patients exhibited lower HRV values for: root mean square successive difference (RMSSD, p = 0.028), total power (TP, p = 0.031), absolute low frequency (LF, p = 0.045), and high-frequency (HF, p = 0.010) power compared to non-sleepy patients. Sleepy patients with moderate-to-severe OSA exhibited lower HRV values for: (RMSSD, p = 0.045; TP, p = 0.052), absolute LF (p = 0.051), and HF power (p = 0.025). There were no differences in other time and frequency domain HRV markers. CONCLUSIONS: This study shows a trend toward parasympathetic withdrawal in sleepy OSA patients, particularly in moderate-to-severe cases, lending mechanistic support to the link between the sleepy phenotype and CVD risk in OSA.

Does obstructive sleep apnoea modulate cardiac autonomic function in paroxysmal atrial fibrillation?

PURPOSE: The autonomic nervous system may mediate acute apnoea-induced atrial fibrillation (AF). We compared cardiac autonomic function in paroxysmal atrial fibrillation (PAF) patients with and without obstructive sleep apnoea (OSA). METHODS: Case control study of 101 patients with PAF recruited at two tertiary centres. All patients underwent in-laboratory polysomnography. ECG signal demonstrating "steady state" sinus rhythm (i.e. with arrhythmic beats and respiratory events excluded) was included in the analysis. Cardiac autonomic function was assessed via measures of heart rate variability (HRV) and reported by sleep stage (REM vs Non-REM) for patients with and without OSA. RESULTS: Sixty-five (66.3%) of patients were male, mean age 61.5 ± 11.6 years, mean BMI 27.1 ± 4.3 kg/m2. Global measures of HRV (triangular index, total power) did not differ between PAF patients with and without OSA in either REM or non-REM sleep. Frequency-domain analysis during non-REM sleep in PAF patients with OSA showed increased cardiac parasympathetic modulation (HF-nu: 39.1 ± 15.7 vs 48.0 ± 14.6, p = 0.008) and reduced cardiac sympathetic modulation (LF-nu 54.1 ± 19.7 vs 43.7 ± 18.0, p = 0.012, LF/HF ratio: 2.1 ± 2.0 vs 1.2 ± 1.0, p = 0.007). Results remained significant after adjusting for age, sex, and BMI (adjusted p values 0.024, 0.045 and 0.018 respectively). There were no differences in HRV parameters during REM sleep. CONCLUSIONS: This is the first study of HRV in PAF patients with and without OSA. Our results indicate limited differences in HRV between groups. However, this work suggests a chronic increase in parasympathetic nervous modulation and relative reduction in sympathetic modulation in PAF patients with OSA during steady-state non-REM sleep.

The effect of obstructive sleep apnea therapy on cardiovascular autonomic function: a systematic review and meta-analysis.

STUDY OBJECTIVES: Autonomic function is impaired in obstructive sleep apnea (OSA) and may mediate the association between OSA and cardiovascular risk. We investigated the effect of OSA therapy on autonomic function through a systematic review and meta-analysis of intervention studies. METHODS: A systematic search using three databases (Medline, Embase, and Scopus) was performed up to December 9, 2020. Studies of OSA patients ≥ 18 years with autonomic function assessed before and after treatment with positive airway pressure, oral appliance, positional therapy, weight loss, or surgical intervention were included for review. Random effects meta-analysis was carried out for five groups of autonomic function indices. Risk of bias was assessed using the Cochrane Collaboration tool. RESULTS: Forty-three eligible studies were reviewed with 39 included in the meta-analysis. OSA treatment led to large decreases in muscle sympathetic nerve activity (Hedges' g = -1.08; 95% CI -1.50, -0.65, n = 8) and moderate decreases in catecholamines (-0.60; -0.94, -0.27, n = 3) and radio nucleotide imaging (-0.61; -0.99, -0.24, n = 2). OSA therapy had no significant effect on baroreflex function (Hedges' g = 0.15; 95% CI -0.09, 0.39, n = 6) or heart rate variability (0.02; -0.32, 0.36, n = 14). There was a significant risk of bias due to studies being primarily non-randomized trials. CONCLUSIONS: OSA therapy selectively improves autonomic function measures. The strongest evidence for the effect of OSA therapy on autonomic function was seen in reduced sympathetic activity as assessed by microneurography, but without increased improvement in parasympathetic function. OSA therapy may reduce the risk of cardiovascular disease in OSA through reduced sympathetic activity.

Association between autonomic function and obstructive sleep apnea: A systematic review.

Obstructive sleep apnea (OSA) is an independent risk factor for hypertension and cardiovascular disease. Effects of OSA on the autonomic nervous system may mediate this association. We performed a systematic literature review to determine the profile of autonomic function associated with OSA. Three electronic databases were searched for studies of OSA patients aged ≥18 years in which autonomic function was assessed. Studies comparing patients with and without OSA, or examining the association of OSA severity with changes in autonomic function were included. Seventy-one studies met the inclusion criteria and autonomic function has been assessed using a range of techniques. The profile of autonomic function found in OSA include increased sympathetic activity, reduced parasympathetic activity and less consistently found low heart rate variability. Altered autonomic function in OSA may explain the pathophysiology of increased cardiovascular risk. Evidence from intervention studies is required to determine if treatment improves autonomic function associated with OSA.