Obstructive Sleep Apnea Variables Research Articles

Factors influencing severity variability in obstructive sleep apnea and the role of fluid shift

Objective:The variability of the apnea-hypopnea index（AHI） measured in the first and second halves of the night is significant in patients with obstructive sleep apnea hypopnea syndrome（OSAHS）. This variation may be related to fluid redistribution caused by the supine position during sleep. Methods:Eighty-nine adult subjects were enrolled. Circumferences（neck, chest, waist, and calf） were measured before sleep onset and upon awakening. Polysomnography（PSG） was performed, and the night was divided into two halves based on the midpoint of total sleep time to calculate AHI for each half. The correlation between changes in AHI and changes in circumferences was analyzed. Results:Twenty simple snorers and sixty-nine OSAHS patients were included, with a median AHI of 22.6（11.8, 47.3） events/hour. Compared to pre-sleep measurements, there was no significant change in neck circumference upon awakening in the control group（P=0.073）, while reductions were observed in the other three measurements（P=0.006, P=0.038, P<0.001）. In the OSAHS group, neck circumference increased（P<0.001）, and reductions were noted in the other three measurements（P<0.001 for all）, with the most significant change observed in calf circumference 40.0（37.1, 42.0） cm to 38.0（35.8, 40.5） cm. Compared to the first half of the night, total AHI, supine AHI, and NREM AHI significantly decreased in the second half（P=0.010, P=0.031, P=0.001）, while no significant changes were observed in lateral AHI and REM AHI（P=0.988, P=0.530）. Further analysis revealed a significant relationship between increased chest circumference and decreases in NREM AHI, supine AHI, and supine NREM AHI（P=0.036, P=0.072, P=0.034）, as well as between decreased lateral position AHI and increased waist circumference（P=0.048）. Additionally, this study found a negative correlation between changes in calf circumference and changes in AHI（R=-0.24, P=0.048）, while neck circumference changes positively correlated with changes in AHI（R=0.26, P=0.03）. Conclusion:In OSAHS patients during the second half of sleep compared to before sleeping, chest circumference, waist circumference, and calf circumference decrease while neck circumference increases; total AHI, supine position AHI, and NREM period AHI decrease; increases in chest circumference are associated with decreases in NREM period AHI, supine position AHI, supine position NREM period AHI. There is nocturnal variability in AHI among OSAHS patients that may be associated with fluid shifts during sleep.

Night to night variability in obstructive sleep apnea severity, the physiological endotypes and the frequency of flow limitation.

There is substantial night-to-night variability (NtNV) in obstructive sleep apnea (OSA) severity in some individuals, however predictors for this remain incompletely understood. This study aims to quantify the degree of NtNV in the apnea-hypopnea index (AHI), hypoxic burden, airflow limitation, and OSA endotypes; to determine if a relationship exists between the degree of NtNV in AHI and in endotype expression; to assess whether the degree of flow limited breathing is predictive of the degree of NtNV of the AHI. 71 patients with OSA underwent two polysomnograms (PSGs). OSA endotypes, hypoxic burden and flow limitation frequency were extracted from PSG data. Intra-individual agreement was assessed and associations with the NtNV of the AHI were calculated. Patients were grouped into High Variability vs Low Variability based on the degree of difference in AHI between each night. Despite wide limits of agreement, at the group level most PSG and endotype variables were not statistically different between first and second night. Flow limitation frequency was 7.7% (2.1 to 13, P<0.01) higher on the second night compared to baseline. There were weak linear associations between NtNV of endotypes and NtNV of the AHI. In sub-group analysis, there was greater difference between nights for Vactive (5%eupnea, P=0.01), Vpassive (3.1%eupnea, P=0.03), Vcomp (3.2%eupnea, P=0.01) and arousal threshold (4.1%eupnea, P=0.04) in the High Variability compared to the Low Variability group. There is high NtNV in AHI, OSA endotypes and flow limitation in some individuals, however no strong linear relationship exists between these changes.

Acute Effect of Positive Airway Pressure on Heart Rate Variability in Obstructive Sleep Apnea.

Autonomic dysregulation is associated with cardiovascular consequences in obstructive sleep apnea (OSA). This study aimed to investigate the effect of acute continuous positive airway pressure (CPAP) treatment on autonomic activity and to identify factors contributing to heart rate variability (HRV) changes in OSA. Frequency domain HRV parameters were calculated and compared between the baseline polysomnography and during the CPAP titration in 402 patients with moderate to severe OSA. There were significant reductions in total power, very low-frequency band power, low-frequency band power, and high-frequency band power during the CPAP titration as compared to the baseline polysomnography. This tendency was pronounced in male patients with severe OSA. Multivariate analysis found that changes in the apnea-hypopnea index and oxygen saturation were significantly associated with changes in sympathetic and parasympathetic activity, respectively. This study demonstrated that HRV parameters significantly changed during the CPAP titration, indicating a beneficial effect of CPAP in the restoration of sympathetic and parasympathetic hyperactivity in OSA. Prospective longitudinal studies should determine whether long-term CPAP treatment aids in maintaining the long-lasting improvement of the autonomic functions, thereby contributing to the prevention of cardiovascular and cerebrovascular diseases in patients with OSA.

A sleep stage estimation algorithm based on cardiorespiratory signals derived from a suprasternal pressure sensor.

Automatic estimation of sleep structure is an important aspect in moving sleep monitoring from clinical laboratories to people's homes. However, the transition to more portable systems should not happen at the expense of important physiological signals, such as respiration. Here, we propose the use of cardiorespiratory signals obtained by a suprasternal pressure (SSP) sensor to estimate sleep stages. The sensor is already used for diagnosis of sleep-disordered breathing (SDB) conditions, but besides respiratory effort it can detect cardiac vibrations transmitted through the trachea. We collected the SSP sensor signal in 100 adults (57 male) undergoing clinical polysomnography for suspected sleep disorders, including sleep apnea syndrome, insomnia, and movement disorders. Here, we separate respiratory effort and cardiac activity related signals, then input these into a neural network trained to estimate sleep stages. Using the original mixed signal the results show a moderate agreement with manual scoring, with a Cohen's kappa of 0.53 in Wake/N1-N2/N3/rapid eye movement sleep discrimination and 0.62 in Wake/Sleep. We demonstrate that decoupling the two signals and using the cardiac signal to estimate the instantaneous heart rate improves the process considerably, reaching an agreement of 0.63 and 0.71. Our proposed method achieves high accuracy, specificity, and sensitivity across different sleep staging tasks. We also compare the total sleep time calculated with our method against manual scoring, with an average error of -1.83 min but a relatively large confidence interval of ±55 min. Compact systems that employ the SSP sensor information-rich signal may enable new ways of clinical assessments, such as night-to-night variability in obstructive sleep apnea and other sleep disorders.

Breathing rate variability in obstructive sleep apnea during wakefulness.

Obstructive sleep apnea (OSA) is defined by pauses in breathing during sleep, but daytime breathing dysregulation may also be present. Sleep may unmask breathing instability in OSA that is usually masked by behavioral influences during wakefulness. A breath-hold (BH) challenge has been used to demonstrate breathing instability. One measure of breathing stability is breathing rate variability (BRV). We aimed to assess BRV during rest and in response to BH in OSA. We studied 62 participants (31 with untreated OSA: respiratory event index [mean ± SD] 20 ± 15 events/h, 12 females, age 51 ± 14 years, body mass index [BMI] 32 ± 8 kg/m2; 31 controls: 17 females, age 47 ± 13 years; BMI 26 ± 4 kg/m2). Breathing movements were collected using a chest belt for 5 minutes of rest and during a BH protocol (60 seconds baseline, 30 seconds BH, 90 seconds recovery, 3 repeats). From the breathing movements, we calculated median breathing rate (BR) and interquartile BRV at rest. We calculated change in BRV during BH recovery from baseline. Group comparisons of OSA vs control were conducted using analysis of covariance with age, sex, and BMI as covariates. We found 10% higher BRV in OSA vs controls (P < .05) during rest. In response to BH, BRV increased 7% in OSA vs 1% in controls (P < .001). Resting BR was not significantly different in OSA and controls, and sex and age did not have any significant interaction effects. BMI was associated with BR at rest (P < .05) and change in BRV with BH (P < .001), but no significant BMI-by-group interaction effect was observed. The findings suggest breathing instability as reflected by BRV is high in OSA during wakefulness, both at rest and in response to a stimulus. Breathing instability together with high blood pressure variability in OSA may reflect a compromised cardiorespiratory consequence in OSA during wakefulness. Pal A, Martinez F, Akey MA, etal. Breathing rate variability in obstructive sleep apnea during wakefulness. J Clin Sleep Med. 2022;18(3):825-833.

The Different Facets of Heart Rate Variability in Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA), a heterogeneous and multifactorial sleep related breathing disorder with high prevalence, is a recognized risk factor for cardiovascular morbidity and mortality. Autonomic dysfunction leads to adverse cardiovascular outcomes in diverse pathways. Heart rate is a complex physiological process involving neurovisceral networks and relative regulatory mechanisms such as thermoregulation, renin-angiotensin-aldosterone mechanisms, and metabolic mechanisms. Heart rate variability (HRV) is considered as a reliable and non-invasive measure of autonomic modulation response and adaptation to endogenous and exogenous stimuli. HRV measures may add a new dimension to help understand the interplay between cardiac and nervous system involvement in OSA. The aim of this review is to introduce the various applications of HRV in different aspects of OSA to examine the impaired neuro-cardiac modulation. More specifically, the topics covered include: HRV time windows, sleep staging, arousal, sleepiness, hypoxia, mental illness, and mortality and morbidity. All of these aspects show pathways in the clinical implementation of HRV to screen, diagnose, classify, and predict patients as a reasonable and more convenient alternative to current measures.

The novel approach of temporal dependency complexity analysis of heart rate variability in obstructive sleep apnea

Obstructive sleep apnea (OSA) is a serious sleep disorder, which leads to changes in autonomic nerve function and increases the risk of cardiovascular disease. Heart rate variability (HRV) has been widely used as a non-invasive method for assessing the autonomic nervous system (ANS). We proposed the two-dimensional sample entropy of the coarse-grained Gramian angular summation field image (CgSampEn2D) index. It is a new index for HRV analysis based on the temporal dependency complexity. In this study, we used 60 electrocardiogram (ECG) records from the Apnea-ECG database of PhysioNet (20 healthy records and 40 OSA records). These records were divided into 5-min segments. Compared with the classical indices low-to-high frequency power ratio (LF/HF) and sample entropy (SampEn), CgSampEn2D utilizes the correlation information between different time intervals in the RR sequences and preserves the temporal dependency of the RR sequences, which improves the OSA detection performance significantly. The OSA screening accuracy of CgSampEn2D (93.3%) is higher than that of LF/HF (80.0%) and SampEn (73.3%). Additionally, CgSampEn2D has a significant association with the apnea-hypopnea index (AHI) (R = −0.740, p = 0). CgSampEn2D reflects the complexity of the OSA autonomic nerve more comprehensively and provides a novel idea for the screening of OSA disease.

Night-to-night variability in obstructive sleep apnea using peripheral arterial tonometry: a case for multiple night testing.

Night-to-night variability of obstructive sleep apnea severity is considerable and may depend on the diagnostic modality used. We investigated the night-to-night variability using peripheral arterial tonometry (PAT). Home sleep apnea testing was performed in 51 patients during 3 consecutive nights using PAT. Patients referred to our sleep clinic were screened and prospectively recruited for this study. All recordings were automatically and manually scored according to the PAT scoring guidelines. No systematic differences in PAT-derived apnea-hypopnea index (pAHI) were found between the nights. The night-to-night variability was comparable between manually and automatically scored data. pAHI varied in 35% of patients more than 10 events/h between the nights. The obstructive sleep apnea severity of 24% of patients was misclassified when using 1 night compared to the average of all nights. On average, pAHI varied by 57% from night to night. The variability of pAHI could partially be explained by the variability of time spent in the supine position with more time supine leading to a higher pAHI. On measuring a subsequent night, 12-14% of patients spontaneously fulfilled the commonly accepted criteria for treatment success without any intervention. With repeated recordings of PAT, we found no first night effect. However, there is considerable night-to-night variability similar to values found for polysomnography, which can partially be explained by the variability of time spent in the supine position. Obstructive sleep apnea severity was frequently misclassified due to the night-to-night variability. Our findings make a strong case for multiple testing in the diagnostic work-up of obstructive sleep apnea patients. Tschopp S, Wimmer W, Caversaccio M, Borner U, Tschopp K. Night-to-night variability in obstructive sleep apnea using peripheral arterial tonometry: a case for multiple night testing. J Clin Sleep Med. 2021;17(9):1751-1758.

Repeated exposure to transient obstructive sleep apnea–related conditions causes an atrial fibrillation substrate in a chronic rat model

High night-to-night variability in obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF). Obstructive apneas are characterized by intermittent deoxygenation-reoxygenation and intrathoracic pressure swings during ineffective inspiration against occluded upper airways. We elucidated the effect of repeated exposure to transient OSA conditions simulated by intermittent negative upper airway pressure (INAP) on the development of an AF substrate. INAP (48 events/4 h; apnea-hypopnea index 12 events/h) was applied in sedated spontaneously breathing rats (2% isoflurane) to simulate mild-to-moderate OSA. Rats without INAP served as a control group (CTR). In an acute test series (ATS), rats were either killed immediately (n = 9 per group) or after 24 hours of recovery (ATS-REC: n = 5 per group). To simulate high night-to-night variability in OSA, INAP applications (n = 10; 24 events/4 h; apnea-hypopnea index 6/h) were repeated every second day for 3 weeks in a chronic test series (CTS). INAP increased atrial oxidative stress acutely, represented in decreases of reduced to oxidized glutathione ratio (ATS: INAP: 0.33 ± 0.05 vs CTR: 1 ± 0.26; P = .016), which was reversible after 24 hours (ATS-REC: INAP vs CTR; P = .274). Although atrial oxidative stress did not accumulate in the CTS, atrial histological analysis revealed increased cardiomyocyte diameters, reduced connexin 43 expression, and increased interstitial fibrosis formation (CTS: INAP 7.0% ± 0.5% vs CTR 5.1% ± 0.3%; P = .013), which were associated with longer inducible AF episodes (CTS: INAP: 11.65 ± 4.43 seconds vs CTR: 0.7 ± 0.33 seconds; P = .033). Acute simulation of OSA was associated with reversible atrial oxidative stress. Cumulative exposure to these transient OSA-related conditions resulted in AF substrates and was associated with increased AF susceptibility. Mild-to-moderate OSA with high night-to-night variability may deserve intensive management to prevent atrial substrate development.

Effect of CPAP on blood pressure variability in obstructive sleep apnea and cardiovascular disease

Effect of CPAP on blood pressure variability in obstructive sleep apnea and cardiovascular disease

Sliding Trend Fuzzy Approximate Entropy as a Novel Descriptor of Heart Rate Variability in Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a common sleep disorder that is often associated with reduced heart rate variability (HRV), thus reflecting modulation of the autonomic system. Sliding trend fuzzy approximate entropy (SlTr-fApEn), which is based on the empirical mode decomposition (EMD) method, has been proposed as a novel index for analyzing HRV with OSA. This study included 60 electrocardiogram recordings from the PhysioNet database (40 OSA recordings and 20 healthy recordings) with apnea or no apnea in 5-minute segments. HRV indices obtained by sliding trend analysis were compared to those obtained by time-frequency domain analysis. Among all indices, the ratio of low-frequency power and high-frequency power (LF/HF) and sliding trend indices could significantly differentiate OSA recordings from normal recordings (p < 0.05). The OSA screening accuracy of SlTr-fApEn (85%) was higher than that of LF/HF (80%). Disease state analysis showed significant differences in SlTr-fApEn among the control group, normal OSA group, and apnea OSA group (p < 0.05). Therefore, SlTr-fApEn can reflect the complexity of autonomic changes during a short time period.

Night-to-night variability of obstructive sleep apnea.

www.controlled-trials.com (ISRCTN 93153804, ISRCTN 73047833) and www.clinicaltrials.gov (NCT01332175 & NCT02050425).

Variability in obstructive sleep apnea: Analysis of pacemaker-detected respiratory disturbances

Obstructive sleep apnea (OSA) is associated with several cardiovascular conditions. Some pacemakers feature specific algorithms detecting respiratory cycles and deriving indices well correlated with the identification of polysomnography-confirmed severe OSA. The purposes of this study were to analyze respiratory disturbances measured by a validated algorithm in clinical practice and to describe their variability over time and their association with atrial fibrillation. Fifty-eight patients implanted with dual-chamber LivaNova REPLY 200 DR or KORA 100 DR pacemakers measuring a respiratory disturbance index (RDI) were included. An RDI >20 events per hour of sleep is well correlated with severe OSA as determined by polysomnography. Patients with >10% nights with invalid RDI measurements were excluded. The RDI could be measured during 98% of nights. During a mean follow-up of 187 ± 123 days, the individual mean RDI was 19.9 ± 12.7 and was superior to 20 in 24 patients (41%). An RDI >20 events/h in at least 1 night was observed in 52 patients (90%). The mean day-to-day RDI variability in individual patients was 19% ± 21%. Patients with the highest burden of severe OSA (as defined by ≥75% of nights with RDI >20 events/h) were older, had a higher prevalence of hypertension, and were more often implanted for atrioventricular block than patients with lower burden of severe OSA. No RDI burden or cutoff was a predictor of atrial fibrillation occurrence. OSA is frequent in patients with a pacemaker and is reliably detected by pacemakers. OSA is highly variable and could probably be best analyzed in terms of burden.

Linear and nonlinear analyses of heart rate variability in obstructive sleep apnea with or without white matter change

Linear and nonlinear analyses of heart rate variability in obstructive sleep apnea with or without white matter change

More on heart rate variability in obstructive sleep apnea: confusion on a higher level or first step to unravel the cardiovascular mystery of the sleep apnea patient?

More on heart rate variability in obstructive sleep apnea: confusion on a higher level or first step to unravel the cardiovascular mystery of the sleep apnea patient?

Heart Rate Variability in Obstructive Sleep Apnea.

Introduction: Obstructive Sleep Apnea (OSA) is characterized by repeated episodes of upper airway obstruction leading to increased airway resistance and respiratory effort, producing oxygen desaturation, hypercapnia and central nervous system arousal. The intermittent hypoxemia and carbon-dioxide retention is responsible for the changes in autonomic and hemodynamic responses to sleep. Heart rate variability (HRV) is a marker of autonomic activity and can be analyzed using time-domain and frequency-domain methods. This study was undertaken to compare the HRV in patients with Obstructive Sleep Apnea Syndrome (OSAS) and normal subjects. Methods: Heart rate variability in 30 controls (Group I) and 30 patients with Obstructive Sleep Apnea Syndrome (Group II) aged 35-45 yrs was studied by using electrocardiographic data obtained during Polysomnography. Low frequency (LF) power, High frequency (HF) power and Low frequency/ High frequency ratio (LF/HF) were analyzed using frequency-domain analysis. Results: There was a significant difference (p 0.001) in LF power and LF/HF ratio of patients with OSAS when compared to the controls, with the values of the OSAS patients being higher, indicating a strong sympathetic activity and a significant difference (p 0.001) in HF power, with the values of the OSAS patients being lower, suggesting parasympathetic blunting. Conclusion: In our study, there was evidence of increased Sympathetic activity and a Parasympathetic attenuation in patients with Obstructive Sleep Apnea. Further studies can evaluate the usefulness of HRV indices for the non-invasive screening of asymptomatic patients suspected to have OSAS.

P.1.b.002 Detrended fluctuation analysis of heart rate variability in obstructive sleep apnea

P.1.b.002 Detrended fluctuation analysis of heart rate variability in obstructive sleep apnea

Heart rate variability in obstructive sleep apnea: a prospective study and frequency domain analysis.

Cyclic variation of the heart rate is observed during apneic spells in obstructive sleep apnea (OSA). We hypothesized that autonomic changes would affect frequency-domain measures of heart rate variability (HRV). We studied 20 patients (15 men, 5 women, mean age 47.2 +/- 12.2 years) with suspected OSA undergoing overnight polysomnography, and five patients (4 men, 1 woman, mean age 49.2 +/- 8.6 years) with recently diagnosed sleep apnea undergoing polysomnography while wearing continuous positive airway pressure (CPAP). Holter monitors were applied during sleep studies and data were analyzed in 5-minute blocks over the course of the night. Using spectral analysis, low frequency (LF) and high frequency (HF) powers were calculated for each interval. Overall mean and standard deviation (SD) for LF power, HF power, and the LF:HF ratio were recorded for each patient. Comparisons were made between patients with severe OSA (apnea hypopnea index (AHI) > 30, n = 8), moderate OSA (AHI 1-30, n = 5), without OSA (AHI < 10, n = 7), and patients wearing CPAP (n = 5). Assessment of overnight LF or HF power revealed no significant difference between the four groups. The LF:HF ratio, which represents sympathovagal balance, was higher among those with moderate disease compared to normals and those with severe OSA (both P = 0.037). The standard deviation of the LF:HF ratio was higher among those with moderate disease compared to normals (P = 0.0064) and those with severe OSA (P = 0.0006). OSA patients receiving CPAP behaved like patients with moderate OSA, with increased SD of the LF:HF ratio. The observed changes in the LF:HF ratio and its SD suggest an increased sympathetic tone and discordance in sympathovagal activity in moderate OSA, which is blunted in severe OSA. CPAP may restore autonomic defects, characteristic of severe OSA, to moderate levels.

Effects of CPAP therapy on cardiovascular variability in obstructive sleep apnea: a closed-loop analysis

To determine the long-term effects of continuous positive airway pressure (CPAP) therapy on cardiovascular variability, we measured R-R interval (RR), systolic blood pressure (SBP) and respiration (DeltaV) in 13 awake, supine patients with moderate-to-severe obstructive sleep apnea (OSA), before and after ~6 mo of treatment. Using these data, we estimated the dynamics of the following components of a closed-loop circulatory control model: 1) the baroreflex component, 2) the neural coupling of DeltaV to RR or respiratory sinus arrhythmia (RSA), 3) the mechanical effects of respiration (MER) on SBP, and 4) the circulatory dynamics (CID) component, which is responsible for the feedforward effect of RR fluctuations on SBP. Baroreflex and RSA gains increased whereas MER and CID gains decreased in compliant subjects whose average CPAP use was >3 h/night. In contrast, baroreflex, RSA, and MER gains remained unchanged and CID gain increased in noncompliant subjects. Other summary measures were unchanged in both groups, except for mean RR, which increased in compliant patients. Closed-loop analysis provides a simple but sensitive means for quantitatively assessing cardiovascular control in OSA by using data collected from a single, nonintrusive test procedure.

Altered cardiovascular variability in obstructive sleep apnea.

Altered cardiovascular variability is a prognostic indicator for cardiovascular events. Patients with obstructive sleep apnea (OSA) are at an increased risk for cardiovascular disease. We tested the hypothesis that OSA is accompanied by alterations in cardiovascular variability, even in the absence of overt cardiovascular disease. Spectral analysis of variability of muscle sympathetic nerve activity, RR interval, and blood pressure were obtained during undisturbed supine rest in 15 patients with moderate-to-severe OSA, 18 patients with mild OSA, and 16 healthy control subjects in whom sleep disordered breathing was excluded by complete overnight polysomnography. Patients with OSA were newly diagnosed, never treated for OSA, and free of any other known diseases. Patients with moderate-to-severe OSA had shorter RR intervals (793+/-27 ms) and increased sympathetic burst frequency (49+/-4 bursts/min) compared with control subjects (947+/-42 ms; 24+/-3 bursts/min; P=0.008 and P<0.001, respectively). In these patients, total variance of RR was reduced (P=0.01) and spectral analysis of RR variability showed an increase in low frequency normalized units, a decrease in high frequency normalized units, and an increase in the ratio of low to high frequency (all P<0.05). Even though blood pressure was similar to that of the control subjects, blood pressure variance in patients with moderate-to-severe OSA was more than double the variance in control subjects (P=0.01). Patients with mild OSA also had a reduction in RR variance (P=0.02) in the absence of any significant difference in absolute RR interval. For all patients with OSA, linear regression showed a positive correlation (r=0.40; P=0.02) between sleep apnea severity and blood pressure variance. Cardiovascular variability is altered in patients with OSA. This alteration is evident even in the absence of hypertension, heart failure, or other disease states and may be linked to the severity of OSA. Abnormalities in cardiovascular variability may be implicated in the subsequent development of overt cardiovascular disease in patients with OSA.