Special Article 4, Issue 13.2

Toward a Multidimensional Burden-Based Definition of Sleep Disordered Breathing

http://dx.doi.org/10.15331/jdsm.7440

Michael Simmons, DMD, MScMed, MPH, MSc, FAASM, FAAOP

Disclaimer: The use, mention or depiction of any product, device, service or appliance shall not be interpreted as an endorsement, recommendation or preference by the AADSM. Any opinion expressed is solely the opinion of the individual, and not that of the AADSM.

As dentist health care providers in sleep medicine, it is important that we remain current with emerging research that expands how the impact of sleep disordered breathing (SDB) is measured and understood. Recent investigations have evaluated alternative “sleep burden” metrics and their dose/response relationships, to predict morbidity and mortality outcomes especially for obstructive sleep apnea (OSA). While hypoxic burden is frequently referenced, a literature search reflects additional but lesser published predictive burdens such as sustained airflow limitation, sleep fragmentation, autonomic reactivity, and treatment-residual wake-time impairment.

Below are summaries of selected publications examining some of these sleep burden metrics, as applied to OSA, along with a conceptual framework for multidimensional burdens, and clinical implications for dentists working in the field of sleep medicine.

 

Hypoxic Burden  (HB)

(Abstract)

Purpose: To determine whether cumulative hypoxic burden predicts cardiovascular mortality and whether it provides risk information beyond AHI.

Study Design and Population: Prospective analyses were performed in two large, community-based cohorts combined N≈8,000 adults where overnight polysomnography was used to derive hypoxic burden. Median follow-up ranged from approximately 8–11 years. Hypoxic burden (HB) metric included oximetry and timing to measure the cumulative area under event-related oxygen desaturation curves.

Cohort 1: Osteoporotic Fractures in Men Study (MrOS): N = 2,743 community-dwelling older men age ≥65, mean age 76. Population of whole MrOS was N = 5,994. 89.5% White, 4.1% African-American, 3.1% Asian, 2.1% Hispanic, Other/Unknown: 1.2%. Not all participants of MrOS met this study criteria.

Cohort 2: Sleep Heart Health Study (SHHS): N = 5,111 men and women age ≥40. Even distribution of male to female. Population of whole SHHS was N = 5,237. 86% White, 9% Black, 5% Hispanic/Mexican American. The vast majority but not all SHHS subjects met study criteria.

Main Conclusions:

• Participants in the highest HB categories had approximately 1.8 to 2.7 times higher risk of cardiovascular mortality compared with the lowest categories.
• Risk differences persisted after accounting for age, sex, BMI, smoking, hypertension, diabetes, and other cardiovascular risk factors.
• When HB and AHI were evaluated together, HB remained associated with cardiovascular mortality, whereas AHI did not consistently predict cardiovascular death.
• Higher hypoxic burden was strongly associated with increased CVD-related mortality, independent of AHI and traditional risk factors. Hypoxic burden provided superior mortality prediction compared with AHI, supporting a shift toward physiologic dose-based metrics of OSA severity. These associations were observed independently in both SHHS and MrOS large cohorts, underscoring the reproducibility of HB across mixed-sex and male-only populations.

Clinical Insights for Dentists in Sleep Medicine: HB has become one of the most widely cited alternatives to AHI and is often presented as a superior cardiovascular risk metric. It has emerged as influential largely because of its validation across two well-characterized longitudinal cohorts. However, HB remains a work in progress, particularly in populations with altered baseline oxygenation such as those living at altitude or with chronic pulmonary disease. Dental sleep medicine providers should recognize that while HB improves upon simple event counting, it is still fundamentally an oxygen-centric metric. HB represents meaningful progress beyond simple event counting, yet it is best understood as one component within a broader multidimensional sleep burden (MSB) framework rather than a definitive replacement for comprehensive physiologic assessment.

 

Ventilatory Burden (VB)

(Abstract)

Purpose: To develop and validate ventilatory burden (VB) and assess its association with mortality beyond AHI.

Study Design and Population: Multi-cohort analysis of N≈5,182 adults with airflow-based polysomnography data and longitudinal mortality outcome follow-up. The VB metric used nasal airflow waveform on a breath by breath basis, with an automated scoring to quantify the proportion of breaths with reduced airflow amplitude. Airflow signal quality is vulnerable to cannula displacement, mouth breathing, signal dropout and artifact and therefore may be considered a less robust measure than oximetry. In the SHHS cohort nasal cannula data was not available so airflow was derived using a digital differentiator applied to thoracic and abdominal belt (RIP) signals.

Multicohort observational analysis included epidemiologic cohorts 1,2 and retrospective clinical cohorts 3,4.:

Cohort 1: Sleep Heart Health Study (SHHS): N = 4,511 men and women ≥ 40 (different subset analytic sample to reference [1])

Cohort 2: EPISONO study N = 995 adult urban population from São Paulo, Brazil approximately 20–80 years age and 55% women.

Cohort 3: DAYFUN (daytime functioning) study N = 453 Clinic-referred sleep disordered breathing adults

Cohort 4: NYU Center for Brain Health study N = 223 community-dwelling adults primarily ≥60 years old

Main Conclusions:

• Higher VB categories were associated with approximately 1.4 to 2.0 times higher risk of cardiovascular and all-cause mortality.
• Associations remained after accounting for cardiovascular risk factors and hypoxic burden.
• When VB and AHI were analyzed together, VB remained predictive of mortality, whereas AHI was not consistently associated with cardiovascular mortality.

Clinical Insights for Dentists in Sleep Medicine: Ventilatory burden shifts emphasis from desaturation to airflow limitation as the primary physiological disturbance. For dentists who routinely treat partial airway obstruction with oral appliance therapy, this is particularly relevant. VB quantifies the mechanical “load” imposed on the airway independent of oxygen drops. This may better reflect the pathophysiology dentists using mandibular advancement devices are actually modifying. However, automated airflow analysis requires high-quality signals and standardized scoring algorithms. As with HB, this metric advances the field but still requires validation across diverse populations and treatment modalities.
 

Arousal (Fragmentation) Burden  (AB)

(Abstract)

Purpose: To evaluate whether arousal burden (AB) (cumulative duration of EEG arousals relative to total sleep time) predicts long-term all-cause and cardiovascular mortality.

Study Design and Population: Community-based cohorts including SHHS and MrOS with combined N≈8,000 adults undergoing overnight polysomnography used to quantify arousal burden with long-term mortality follow-up over approximately 10 years.

Cohort 1: Sleep Heart Health Study (SHHS): N = 5,111 (2221 males and 2574 females, mean age 64).

Cohort 2: Osteoporotic Fractures in Men Study (MrOS): N = 2,782 community-dwelling older men age ≥65, mean age 76.

Cohort 3: Study of Osteoporotic Fractures (SOF): N= 424 Females mean age 82.9, 40% overweight.

Main Conclusions:

• AB was associated with an approximate 1.2 to 1.6 times higher risk of all-cause and cardiovascular mortality independent of AHI.
• Associations were modest compared with HB but remained significant after adjustment for traditional risk factors.
• The findings support arousal burden as an independent physiologic severity metric with arousal burden associations stronger in women.

Clinical Insights for Dentists in Sleep Medicine: Arousal burden highlights that sleep disruption alone may carry independent cardiovascular consequences, even in the absence of severe oxygen desaturation. This has implications for patients with milder disease whose symptom burden may exceed their AHI classification. Repetitive cortical activation may represent a physiologic stressor distinct from hypoxia. Fragmentation metrics may help explain why some patients feel profoundly unwell despite “effective AHI treatment” and modest AHI scores.
 

Sympathetic (autonomic) Burden (SB) 

(Abstract)

• Among patients with OSA, those with low PWAD index had approximately 1.3 to 2.2 times higher risk of incident cardiovascular events. PWAD likely reflects impaired autonomic and vascular reactivity and represents a physiologic autonomic burden marker.
• Increased risk persisted after accounting for AHI and traditional cardiovascular risk factors.
• AHI alone did not consistently distinguish cardiovascular risk within OSA groups, whereas PWAD stratified risk more clearly.

Clinical Insights for Dentists in Sleep Medicine: Autonomic burden introduces dimensions of vascular reactivity and sympathetic activation. The PWAD index suggests that cardiovascular vulnerability may depend less on how many events occur and more on how the autonomic nervous system responds to them. This reframes OSA as a disorder of stress physiology, not airflow obstruction. For dental providers, this emphasizes the importance of understanding systemic cardiovascular implications of sleep-disordered breathing and may influence risk stratification before appliance therapy is initiated. Alternative measures of autonomic reactivity include HRV (heart rate variability) which measures general variability as opposed to PWAD which is more specific to sleep impact.
 

Residual (post-treatment) Wake-Time Burden (RB)

(Abstract)

Purpose: To determine whether residual physiologic burdens (residual hypoxic burden and residual sleep fragmentation) are independently associated with persistent subjective sleepiness and impaired objective alertness in CPAP compliant OSA patients despite acceptable residual AHI. (median daily CPAP use was 5.6 hours over previous month)

Study Design and Population: Observational cohort study of N = 122 CPAP-treated adults with OSA referred to a tertiary sleep center for Maintenance of Wakefulness Testing (MWT). Population was 91% male, 81% severe OSA (mean pretreatment AHI of 39). Participants were adherent to CPAP therapy and demonstrated generally acceptable residual AHI on treatment.
Residual physiologic burden was quantified during CPAP use, through (a) residual hypoxic burden, measured as the cumulative area under the oxygen desaturation curve associated with respiratory events and (b) residual arousal index, reflecting EEG-defined sleep fragmentation (with >25 events/hour examined as a clinically relevant threshold). Outcomes measured included objective alertness (mean sleep latency on MWT) and subjective sleepiness (Epworth Sleepiness Scale, ESS). Analysis evaluated independent associations between residual physiologic burdens and symptom domains.
 
Main Conclusions:

• Residual hypoxic burden was independently associated with impaired objective alertness (shortened MWT latency)
• Elevated EEG residual arousal index (>25/hour) was associated with persistent subjective sleepiness (higher ESS scores).
• Findings suggest different physiologic mechanisms underlying residual symptoms during CPAP therapy where persistent intermittent hypoxemia may preferentially affect objective vigilance capacity, whereas sleep fragmentation preferentially influences perceived sleepiness, highlighting the clinical relevance of residual domain-specific physiologic burdens.

Clinical Insights for Dentists in Sleep Medicine: This paper reinforces that improving AHI does not necessarily normalize patient well-being. Residual hypoxic burden and residual sleep fragmentation, together as component parts of RB appear more closely linked to persistent daytime impairment than remaining apnea and hypopnea event counts. This underscores for dentists the need to move beyond device efficacy measured solely by AHI reduction. Patient-centered outcomes such as alertness, cognitive clarity/executive functioning, mood, and functional capacity represent important dimensions of sleep burden. Another perspective is that even as CPAP therapy improves HB and VB it may concurrently contribute to SB and AB resulting in an aggravated RB. The net effect may be reflected by the patient’s choice in continued use of one or another therapy.
 

Conceptual Synthesis of Multidimensional Sleep Burden (MSB)

(Abstract)

The evolution from event counting to burden assessment represents a necessary recalibration in SDB. Viewed through the framework of allostatic load ("wear and tear" on the body from repeated stress-induced physiological responses) sleep related breathing disturbances represent cumulative biological stressors that contribute to progressive systemic wear (1). In this context, SDB is better understood as a chronic stress exposure, and burden metrics the dose/response biological challenge.

Current sleep burdens remain predominantly physiologic in orientation, but lived consequences extend beyond oxygen desaturation and airflow reduction. Relationship strain from snoring, sleeping apart from partners, impaired cognition and mood, reduced productivity, and downstream healthcare utilization reflect additional psychosocial burden dimensions of MSB. A MSB framework is the next evolutionary step in evaluating sleep health and interventions to improve sleep health as this expands assessment from respiratory events to whole-person impact.

For dentists working in sleep medicine, this reframing is consequential. Do oral appliances and positive airway pressure differ in their net reduction of hypoxic, autonomic, arousal, and psychosocial, etc burdens? Does combination therapy become the new gold standard to reduce multiple burdens concurrently? Might patients with upper airway resistance syndrome (UARS) or primary snoring, despite a “normal” AHI, carry significant MSB warranting intervention?

The future of sleep medicine may change its focus from reducing counts of apnea and hypopnea events, to reducing cumulative MSB. The underlying goal becomes lowering overall burden as this decreases allostatic load and favorably influences long-term health trajectory.
 

Abbreviations:

AB - arousal burden
HB - hypoxic burden
MSB – multidimensional sleep burden
PB- psychosocial burden
RB – residual burden with treatment
SB - sympathetic burden
VB – ventilatory burden
 
CITATION

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