Understanding Hypoxic Burden: Decreasing Sleep Quality in Obstructive Sleep Apnea Patients
February 11, 2024
In the realm of sleep disorders, Obstructive Sleep Apnea (OSA) stands out as one of the most prevalent, affecting millions across the United States alone. Central to diagnosing OSA is the apnea/hypopnea index (AHI), a metric that quantifies the frequency of breathing interruptions during sleep. However, while AHI serves as a diagnostic cornerstone, it fails to provide a comprehensive picture of the disorder's impact on individuals. This limitation prompted the exploration of alternative metrics, leading to the development of the Hypoxic Burden (HB). Unlike AHI, HB delves deeper into the physiological consequences of OSA, considering factors such as the depth and duration of respiratory-related desaturations. This study dives into the implications of HB on sleep quality indices, shedding light on its significance in understanding OSA's symptomatic variations and potential for comorbidities.
The quest to unravel OSA's intricacies beyond AHI has led researchers to scrutinize the role of HB, recognizing its potential to elucidate why some individuals with seemingly mild OSA experience profound symptoms while others do not. Grounded in the understanding that OSA extends beyond mere breathing interruptions to encompass broader physiological disruptions, HB emerges as a promising avenue for comprehensive assessment. Through meticulous examination of sleep metrics and their correlation with HB, this study endeavors to untangle the complex interplay between hypoxia and sleep disturbances, offering valuable insights into OSA's multifaceted nature. By exploring the impact of HB across different severity levels of OSA and its combined effect with AHI, this research aims to refine our understanding of OSA pathology and enhance the precision of diagnostic and treatment strategies.
Abstract
The gold standard for diagnosing OSA is the apnea/hypopnea index (AHI). While AHI determines if a patient has OSA, it lacks vital information about how severely the patient is impacted. An alternative to AHI, called Hypoxic Burden (HB) accounts for the frequency of respiratory-related desaturation under a set SPO2 threshold, the depth of the desaturation, and the duration of the desaturation. A high HB has previously been correlated with an increased risk for comorbidities and mortality, regardless of AHI. This study aimed to evaluate the impact HB has on sleep quality indices in a population of patients who underwent OSA testing with a home sleep apnea test. The results indicate that patients with a high HB had a significant decrease in sleep efficiency, an increase in nocturnal awakenings, and an increase in wake time after sleep onset, regardless of AHI. A high HB was found in 27.5% of patients with a mild AHI, and filtering for mild AHI and high HB was found to have a more negative impact on nocturnal awakenings and wake after sleep onset than filtering for mild AHI alone. This study concluded that hypoxic burden plays a significant role in sleep deficit in OSA patients and may explain why some mild OSA patients are more symptomatic than others.
Introduction
Obstructive Sleep Apnea (OSA) is one of the most common sleep disorders, affecting 20% of men and 10% of women in the United States. The gold standard for diagnosis OSA is the apnea/hypopnea index (AHI), which calculates the average amount of apneas and hypopneas per hour of sleep time.
While AHI determines if a patient has OSA, it lacks vital information about how severely the patient is impacted. Specifically, AHI cannot explain why some patients are more symptomatic or at a higher risk for comorbid health conditions.
An alternative to AHI, called Hypoxic Burden (HB), aims to better understand how much a patient is impacted by their OSA, and predicts their risk for sleep disruption, comorbid health conditions, and mortality [1]. HB accounts for the frequency of respiratory-related desaturation under a set SPO2 threshold, the depth of the desaturation (how low they go), and the duration of the desaturation (how long they last).
HB is calculated as a percentage of minutes per hour of sleep time (%min/hr). Clinical studies have shown that comorbidities and mortality increase with HB percentage. For example, a 2019 study by Azarbarzin and colleagues [2] found that patients with a HB of >88 (%min/hr) had a 15-year survival probability of 65%, compared to an 82% survival probability for patients with an HB of <20 (%min/hr). Thus, similar HB scales may be used to assess how HB correlates to common sleep apnea symptoms, such as sleep disruption.
Methods
A total of 1,884 Wesper tests were evaluated ( )participants; mean age 49.73 years, SD 15.0; mean tests/participant 3.1, SD 4.5). HB was calculated for each test and recorded as %min/hour as per previous studies [1]. HB severity was grouped according to a previous study that demonstrated increased mortality in individuals with an HB >88 %min/hr [2].
Sleep metrics associated with sleep quality, including total sleep time (TST), sleep efficiency (SE), number of awakenings after sleep onset (W), and wake time after sleep onset (WASO) were assessed with a Kruskal-Wallis test for non-parametric data.
To better understand why some patients may be more symptomatic, we evaluated the percentage of tests with a high HB (>88 %min/hr) for subjects with normal (AHI <5), mild (AHI 5-14.99), moderate (AHI 15-29.99), and severe OSA (AHI ≥30).
Finally, to evaluate if AHI alone or AHI plus HB was a better predictor of sleep deficit in mild patients, we assessed sleep quality indices in patients filtered for mild OSA, and patients filtered by both mild old and HB >88 %min/hr.
Results
The mean hypoxic burden across all subjects was 188.80 %min/hr (Range: 0 - 3,175.85, SD 285.9) and mean AHI was 15.02 (Range: 0 - 180, SD 18.71).
There was no significant difference in total sleep time across all HB groups, however a significant decrease in sleep efficiency (2% - 4%) between all low HB groups (<88 %min/hr) and the high HB group (>88 %min/hr) was identified (Figure 1, Table 1).
Figure 1: Sleep efficiency is reduced in individuals with a HB >88 %min/hr.
Table 1: Statistical comparison between HB groups for SE.
|
Comparison HB (%min/hr) |
SE% Mean Difference |
P-Value |
|
<20 vs. >88 |
-2.12% |
0.0002 |
|
20-34 vs. >88 |
-2.36% |
0.0045 |
|
34-53 vs. >88 |
-4.01% |
<0.0001 |
|
53-88 vs. >88 |
-2.91% |
<0.0001 |
The high HB group had a significant increase in nocturnal awakenings compared to the lower HB groups, with 2.6 to 3.7 more awakenings on average (Figure 2, Table 2).
Figure 2: The number of nocturnal awakenings is increased in individuals with a HB >88 %min/hr.
Table 2: Statistical comparison between HB groups for SE.
|
Comparison HB (%min/hr) |
Awakenings Mean Difference |
P-Value |
|
<20 vs. >88 |
+3.68 |
<0.0001 |
|
20-34 vs. >88 |
+2.43 |
0.0052 |
|
34-53 vs. >88 |
+3.72 |
<0.0001 |
|
53-88 vs. >88 |
+2.26 |
0.0045 |
The high HB group had a significant increase in wake time after sleep onset compared to the lower HB groups, with 16.8 to 23.9 more minutes awake on average (Figure 3, Table 3).
Figure 3: Minutes of wake time after sleep onset increased in individuals with a HB >88 %min/hr.
Table 3: Statistical comparison between HB groups for SE.
|
Comparison HB (%min/hr) |
Wake Time Mean Difference |
P-Value |
|
<20 vs. >88 |
+23.9 min |
<0.0001 |
|
20-34 vs. >88 |
+16.8 min |
0.0002 |
|
34-53 vs. >88 |
+22.9 min |
<0.0001 |
|
53-88 vs. >88 |
+17.0 min |
<0.0001 |
Tests that fell within the high HB (>88 %min/hr) range (n = 1,019) were analyzed to compare AHI scores. The percentage of tests within normal range (AHI <5) was 0.68%, the mild range (AHI 5-14.99) was 27.5%, the moderate range (AHI 15-29.9) was 41.6%, and the severe range AHI: >30) was 30.1% (Figure 4).
Figure 4: Percent of tests that had an HB of >88 %min/hr in each AHI severity group
To determine if AHI alone or AHI and HB was a better predictor of sleep deficit in mild patients, tests with an AHI of 5-14.99 were filtered. An additional filter produced mild AHI tests that had an HB of >88 %min/hr.
Tests that filtered for both AHI (0-15) and HB >80 %min/hr had a significantly higher number of wakes (Figure 5) and higher WASO (Figure 6) than tests that were filtered for AHI alone.
Figure 5: The number of nocturnal awakenings is increased when filtering by both AHI and HB >88 %min/hr.
Figure 6: Wake time after sleep onset increased when filtering by both AHI and HB >88 %min/hr.
Table 3: Statistical comparison between AHI alone vs. AHI + HB >88 %min/hr
|
Comparison |
Mean Difference |
P-Value |
|
# Wakes |
+2.03 Wakes |
0.001 |
|
WASO |
+6.4 min |
0.032 |
Conclusion
This study demonstrates that an elevated HB negatively impacts sleep quality regardless of AHI. Interestingly, over a quarter of tests with an elevated HB fell within the mild range, which may explain why some mild OSA patients are highly symptomatic while others are not. Further, evaluating AHI and HB >88 %min/hr together yielded the worst sleep deficit, compared to assessing AHI alone.
This study reaffirms that HB is a useful metric for evaluating a patient’s risk for OSA symptoms and comorbidities. Providers should use HB in combination with AHI to evaluate OSA severity and treatment efficacy, especially treatments that require titration.
References
- Martinez-Garcia MA, Sánchez-de-la-Torre M, White DP, Azarbarzin A. Hypoxic Burden in Obstructive Sleep Apnea: Present and Future. Arch Bronconeumol. 2023 Jan;59(1):36-43. English, Spanish. doi: 10.1016/j.arbres.2022.08.005. Epub 2022 Sep 5. PMID: 36115739.
- Azarbarzin A, Sands SA, Stone KL, Taranto-Montemurro L, Messineo L, Terrill PI, Ancoli-Israel S, Ensrud K, Purcell S, White DP, Redline S, Wellman A. The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study. Eur Heart J. 2019 Apr 7;40(14):1149-1157. doi: 10.1093/eurheartj/ehy624. Erratum in: Eur Heart J. 2019 Apr 7;40(14):1157. PMID: 30376054; PMCID: PMC6451769.