Long-term All-Cause Mortality Risk in Obstructive Sleep Apnea Using Hypopneas Defined by a ≥3 Percent Oxygen Desaturation or Arousal

Rohit Budhiraja, MD¹

Stuart F. Quan, MD^1,2

¹Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA

²Arizona Asthma and Airways Research Center, University of Arizona College of Medicine, Tucson, AZ    

Abstract

Study Objectives: Some prior studies have demonstrated an increase in mortality associated with obstructive sleep apnea (OSA) utilizing a definition of OSA that requires a minimum 4% oxygen desaturation to identify a hypopnea. No large community-based studies have determined the risk of long-term mortality with OSA with hypopneas defined by a ≥3% O₂ desaturation or arousal (AHI3%A).

Methods: Data from 5591 Sleep Heart Health Study participants without prevalent cardiovascular disease at baseline who underwent polysomnography were analyzed regarding OSA diagnosed using the AHI3%A criteria and all-cause mortality over a mean follow up period of 10.9±3.2 years.

Results: There were 1050 deaths in this group during the follow-up period. A Kaplan-Meir plot of survival revealed a reduction in survival with increasing AHI severity. Cox proportional hazards regression models revealed significantly increased all-cause mortality risk with increasing AHI, hazard ratio (HR, 95% CI) 1.13 (1.04-1.23), after adjusting for age, sex, race, BMI, cholesterol, HDL, self-reported hypertension and/or diabetes and smoking status. In categorical models, the mortality risk was significantly higher with severe OSA [adjusted HR 1.38 (1.09-1.76)]. When stratified by gender or age, severe OSA was associated with increased risk of death in men [adjusted HR 1.14 (1.01-1.28)] and in those <70 years of age [adjusted HR 1.51 (1.02-2.26)]. In contrast, AHI severity was not associated with increased mortality in women or those ≥70 years of age in fully adjusted models.

Conclusion: Severe AHI3%A OSA is associated with significantly increased mortality risk, especially in men and those <70 years of age.

Introduction

Obstructive sleep apnea (OSA) is a prevalent disorder associated with diverse physiological changes. Intermittent hypoxia-reoxygenation, sympathetic nervous system activation and endothelial dysfunction have been demonstrated in OSA and likely contribute to adverse outcomes including daytime sleepiness, hypertension, coronary artery disease, and stroke (1,2). It is also associated with increased mortality, especially in those with more severe disease (3-7).

The severity of OSA is most frequently categorized using the apnea hypopnea index (AHI). However, the definition of the ‘hypopnea’ component of this index remains a matter of controversy. American Academy of Sleep Medicine (AASM) guidelines recommend that hypopnea be defined as a 30% or greater reduction in the airflow associated with either ≥3% decrease in oxyhemoglobin saturation, or an arousal from sleep (AHI3%A) (8). However, Centers for Medicare and Medicaid Services (CMS), along with several other payors in the United States, utilize an alternate hypopnea definition that requires at least a 4% desaturation and does not recognize arousals for defining hypopnea (AHI4%). The reimbursement for OSA therapy from these payors is reserved for the subset of patients that meets this more stringent definition of OSA. Unfortunately, this policy systematically deprives some patients, even those with clear symptoms attributable to sleep apnea such as increased sleepiness, of appropriate therapy, since they do not meet the higher diagnostic cutoff mandated by this definition.

Much of the current status quo may be related to a lack of substantial data evaluating the impact of hypopnea events associated with less severe desaturation or arousals on diverse OSA outcomes. In contrast, several large cohort studies have established a robust relationship between OSA defined using the AHI4% definition and cardiovascular outcomes (9-11). Two large community-based longitudinal studies demonstrating an association between OSA severity and all-cause mortality, that from Sleep Heart Health Study (SHHS) cohort (3) and that from Wisconsin Sleep Cohort (5), also utilized the AHI4% definition. However, no large community-based longitudinal studies have assessed the association between OSA diagnosed using the AHI3%A definition and mortality. The current study utilized data from SHHS to assess the relationship between OSA defined by the AHI3%A at baseline and all-cause mortality over an 11-year follow up period.

Methods

Participants

The Sleep Heart Health Study (SHHS) was a multicenter cohort study that investigated prospectively the relationship between OSA and cardiovascular diseases in the United States. Details of the rationale and study design have been described elsewhere (12). Recruitment began in 1995 with eventual enrollment of 6,441 participants, 40 years of age and older, from several ongoing “parent” cardiovascular and respiratory disease cohorts who were initially assembled between 1976 and 1995 (13). These “parent” cohorts consisted of the Offspring and the Omni Cohorts of the Framingham Heart Study in Massachusetts; the Hagerstown, MD, and Minneapolis, MN, sites of the Atherosclerosis Risk in Communities Study; the Hagerstown, MD, Pittsburgh, PA, and Sacramento, CA, sites of the Cardiovascular Health Study; 3 hypertension cohorts (Clinic, Worksite, and Menopause) in New York City; the Tucson Epidemiologic Study of Airways Obstructive Diseases and the Health and Environment Study; and the Strong Heart Study of American Indians in Oklahoma, Arizona, North Dakota, and South Dakota. Between 1995 and 1997, these participants underwent a home sleep evaluation that included full unattended polysomnography to determine whether they had OSA. Subsequently, they were followed for mortal events by their parent cohorts. Follow-up duration was 10.9±3.2 years (Mean±SD). As shown in Figure 1, consent was withdrawn by 134 participants from the Arizona cohort of the Strong Heart Study because of sovereignty issues after the end of the follow-up period.

Figure 1. Diagram of Sleep Heart Health Study (SHHS) analytic cohort.

Participants with self-reported prevalent cardiovascular disease (CVD: coronary heart disease, stroke or congestive heart failure) at enrollment also were excluded. Consequently, there were 5,591 participants in the analytic cohort. Parent cohort data were used for documentation of age, height, sex and ethnicity. Co-morbid self-reported diabetes, cardiovascular disease (CVD), concurrent treatment for OSA and smoking status were ascertained from parent cohort data or from responses on health interview and sleep habit questionnaires administered on the evening of the polysomnography home visit (vide infra). Hypertension status was derived as previously described from blood pressure measurements on the night of the home visit and hypertensive medication use (14). Body mass index (BMI) was calculated as weight (kg)/height (m²).

Institutional review boards for human subjects’ research of the respective parent cohorts approved the study. Informed written consent was obtained from all participants at the time of their recruitment.

Polysomnography and Home Visit

Participants underwent overnight in-home polysomnograms using the Compumedics Portable PS-2 System (Abbottsville, Victoria, Australia) administered by trained technicians (15). The home visits were performed by two-person, mixed-sex teams in visits that lasted 1.5 to 2 hours. At the time of the home visit, blood pressure was measured manually in triplicate in a seated position after 5 minutes of rest (16). The average of the second and third measurements was used. Body weight was measured using a digital scale.

The SHHS recording montage for both the initial and follow-up sleep evaluations consisted of electroencephalogram (C4/A1 and C3/A2), right and left electrooculogram, a bipolar submental electromyogram, thoracic and abdominal excursions (inductive plethysmography bands), airflow (detected by a nasal-oral thermocouple [Protec, Woodinville, WA]), oximetry (finger pulse oximetry [Nonin, Minneapolis, MN]), electrocardiogram and heart rate (using a bipolar electrocardiogram lead), body position (using a mercury gauge sensor), and ambient light (on/off, by a light sensor secured to the recording garment). Equipment and sensors were applied and calibrated during the evening home visit by a study certified technician. In the morning, the equipment and the data stored in real time on PCMCIA cards, were retrieved and downloaded to the computers of each respective clinical site. The data were locally reviewed, and then forwarded to a central reading center (Case Western Reserve University, Cleveland, OH). Comprehensive descriptions of polysomnography scoring and quality-assurance procedures have been previously published (15,17). In brief, sleep was scored according to guidelines developed by Rechtschaffen and Kales (18). Strict protocols were maintained to ensure comparability among centers and technicians. Intra-scorer and inter-scorer reliabilities were high (17).

The apnea hypopnea index (AHI) was calculated for each participant using the AASM recommended definition of hypopnea. Thus, hypopneas were identified if the amplitude of a measure of flow or volume (detected by the thermocouple or thorax or abdominal inductance band signals) was reduced discernibly (at least 25% lower than baseline breathing) for at least 10 seconds, did not meet the criteria for apnea and the event was associated with either a ≥3% oxygen desaturation from baseline or terminated with electroencephalographic evidence of an arousal. An apnea was defined as a complete or almost complete cessation of airflow, as measured by the amplitude of the thermocouple signal, lasting at least 10 seconds.

Statistical Analyses

Mean and standard deviation were used to provide an overall description of the data used in the analyses. For analyses using the AHI, each participant’s AHI was assigned to one of 4 OSA severity categories: No OSA (AHI <5 /hour), Mild (AHI ≥5 and <15 /hour), Moderate (AHI ≥15 and < 30/hour) and Severe (AHI ≥30). For some analyses, because values for AHI were extremely left skewed, a natural log transformation was performed to express AHI as a continuous factor in the form of lnAHI+0.1. To nullify the impact of 0 values of the AHI, 0.1 was added to the ln function. Mortality rates were computed by dividing the number of deaths by accumulated person-years at risk.

Analysis of variance was used to test for differences within continuous variables and ² was employed for categorial variables. A Kaplan-Meir plot was computed to assess the overall relationship between severity of OSA and mortality. Cox proportional hazards regression models were calculated to examine the association between AHI as a categorical and continuous factor and mortality. Covariates included in the models were sex, race, age, BMI, cholesterol, high density lipoprotein (HDL), hypertension and/or diabetes and smoking status. Consistent with a previous study assessing mortality in SHHS, age was dichotomized into those <70 and those ≥ 70 years (3). Race was stratified as non-Hispanic White or other. Smoking was recategorized into those who were current or former smokers and those who were never smokers. Prevalent hypertension or self-reported diabetes was expressed as present or absent. Three models were constructed: Model 1 adjusted for age, race and sex, Model 2 adjusted for covariates in Model 1 plus BMI and Model 3 adjusted for covariates in Models 1 and 2 plus cholesterol, HDL, hypertension/diabetes and smoking status.

Analyses were performed using IBM SPSS Statistics v27 (Armonk, NY). The survival package in R was used to obtain the Kaplan Meir plot. A p value of <0.05 was considered statistically significant.

Results

Demographic and clinical characteristics of the cohort stratified by AHI are shown in Table 1.

Table 1. Baseline Characteristics Stratified by Apnea Hypopnea Index^a,b

Age and BMI increased across AHI strata as well as the % of men, current/ex-smokers, diabetic/hypertensives and non-Hispanic Whites. In contrast, HDL decreased. No changes were observed for cholesterol or % receiving OSA treatment.

Figure 2 depicts the Kaplan-Meir plot of survival over ~11 years of follow-up stratified by AHI categories.

Figure 2. Kaplan Meir plot of survival stratified by apnea hypopnea (AHI) severity.

There was a clear reduction in survival with apparent differences related to AHI severity. However, because several covariates also impacted survival across AHI strata, multivariate proportional hazard modelling was employed as shown in for all participants as shown in Table 2.

Table 2. Hazard Ratios (95% confidence intervals) for All-Cause Mortality

There were 1,050 deaths with full covariate data available for analysis. For the categorical modelling, there was an increase in the hazard ratio as the AHI severity increased, but this was only statistically significant at an AHI ≥30 /h (HR: 1.36, 95% CI: 1.09-1.69). Increasing model complexity did not alter this finding. A model using AHI as a continuous factor also demonstrated a significant association between severity of AHI and increasing mortality in a fully adjusted model. A sensitivity analysis where concurrent OSA treatment was included also did not change this relationship.

Because previous analyses have demonstrated differences in mortality between men and women, sex stratified analyses were performed as shown in Table 3.

Table 3. Hazard Ratios (95% confidence intervals) for All-Cause Mortality Stratified by Sex

These findings confirmed that in men AHI severity in both categorical and continuous analyses was associated with increased mortality. As observed in the combined analyses, this was only statistically significant in the continuous analysis (HR: 1.14, 95% CI: 1.01-1.28) although strong trends were noted in the categorical analyses in all models. In women, however, the relationship between AHI severity and mortality was less robust. In demographic (Model 1) and demographic/anthropometric (Model 2) adjusted analyses, an AHI ≥30 /h was associated with increased mortality, but this observation was attenuated and lost statistical significance in the fully adjusted categorical and continuous models.

Table 4 shows age stratified analyses comparing those <70 years to those ≥70 years of age.

Table 4. Hazard Ratios (95% confidence intervals) for All-Cause Mortality Stratified by Age at 70 years

In those who were <70 years, AHI severity was strongly associated with increased mortality. Although this finding was statistically significant only at AHI ≥30 /h in the fully adjusted model, it was significant at AHI 15-29.9/h in less complex models (HR: 1.45, 95% CI: 1.03-2.04) and approached significance in the fully adjusted model (HR: 1.41, 95% CI: 0.98-2.00). In contrast, AHI severity was not found to be associated with increased mortality among those ≥70 years of age in either categorial or continuous models.

Of the 1,050 deaths used in the proportional hazard models, 258 (24.7%) were classified as related to CVD. In analyses restricted to CVD deaths, a Kaplan-Meir plot (not shown) indicated a reduction in survival with increasing OSA severity (Log Rank ² = 11.2-20.4 for comparisons vs. AHI <5 /h, p<.001). However, in fully adjusted proportional hazard models, no differences in survival attributable to OSA were observed.

Discussion

The current study demonstrated using the AHI3%A definition of hypopnea, a significant association between increasing severity of AHI and all-cause mortality in a model adjusted for relevant anthropometric and demographic factors and clinical co-morbidities. In stratified analyses, this association was more robust among men than in women, and those below 70 years of age compared to the older subjects.

Notably, some earlier studies have demonstrated an increase in mortality associated with OSA. An 18-year follow-up from Wisconsin cohort revealed a significantly increased hazard ratio for all-cause mortality and cardiovascular mortality in severe OSA (5). Punjabi et al. (3) used data from SHHS and demonstrated an increase in all-cause mortality with severe OSA, particularly in men aged 40–70, during an average follow-up period of 8.2 years. Both these studies utilized the AHI4% criteria for OSA diagnosis. Similarly, Martínez-García (19) utilized AHI4% criteria in a clinic population of 939 elderly (median follow-up, 69 months) and found HR of 2.25 for cardiovascular mortality in the untreated severe OSA group. A study from Denmark included 22,135 OSA patients found that male gender, age>40 years, diabetes (types 1 and 2), hypertension, and heart failure were associated with greater mortality (criteria for hypopnea not specified (6). Marin et al. (10) also noted increased fatal and non-fatal cardiovascular events in men with untreated severe OSA diagnosed using the AHI4% criteria during a mean 10.1 years follow-up period. A meta-analysis with 11,932 patients from 6 prospective observational studies found severe OSA to be a strong independent predictor for cardiovascular and all-cause mortality (4). Finally, a meta-analysis of 27 cohort studies included 3,162,083 participants showed higher all-cause mortality in severe OSA and lower mortality in CPAP-treated than in untreated patients (7). Virtually all of these aforementioned studies utilized a definition of OSA requiring a minimum 4% oxygen desaturation to identify a hypopnea.

To our knowledge, our study is the first large community-based study to assess the association between OSA diagnosed using the AHI3%A criteria and mortality. Severe OSA was associated with a higher mortality, especially in those <70 years of age, and in men. Consistent with our findings, an earlier study in a clinical population of over 10,000 adults observed OSA diagnosed utilizing AHI3%A criteria predicted incident sudden cardiac death (20). The higher mortality risk in men and in younger people is similar to that reported in other analyses from this database using AHI4% criteria (3,21). Our results provide evidence that the more liberal AHI3%A criteria is associated with increased all-cause mortality thus providing further justification for its use in identifying persons with OSA who may benefit from treatment.

We observed that approximately 25% of the deaths in our analytic cohort were attributable to CVD. Data from the Wisconsin Sleep Cohort indicate that excess mortality associated with OSA over a 18 year follow-up is partially related to CVD (5). Our unadjusted analyses are consistent with this observation. However, our study did not have sufficient power in adjusted models to replicate it.

There are several factors that could explain the association between OSA and increased mortality. OSA increases the risk for hypertension, cardiovascular disease, diabetes, and stroke and can, thus, increase mortality. Hypoxemic burden has been suggested to be a conspicuous factor conferring an increased mortality risk (22). Other factors, however, may also play a notable role. Analyses from 5,712 participants revealed that short respiratory event duration, a marker for low arousal threshold, was associated with higher mortality risk (21). The authors hypothesized that the shorter event duration reflected greater “arousability”, resulting in greater sleep fragmentation, shorter sleep, and excess sympathetic tone, and hence increased mortality. Arousals are associated with an increase in the sympathetic activity and a decrease in the parasympathetic activity and data support their role in the development of hypertension.

From a clinical perspective, utilizing the AHI4% criteria in lieu of AHI3%A to identify persons as having OSA impacts those who are classified as having OSA by the latter standard, but not the former. Using the SHHS database, we found that 36.1% of individuals fall into this category. Importantly, similar to persons who were classified as having OSA by both criteria, we observed that this group who were designated as having OSA by only AHI3%A criteria had increased rates of prevalent and incident hypertension (23,24). There also was a significant association with CVD (25). Combined with these previous studies, the current analyses demonstrating increased mortality associated with OSA defined by AHI3%A criteria provide evidence that use of this more liberal definition will benefit patients.

This study has several strengths. SHHS is large, ethnically diverse cohort, making the results more generalizable. The cohorts were community-based, obviating any referral bias. Polysomnography, the gold standard diagnostic test for OSA, was performed on all individuals. The substantive database allowed controlling for multiple confounders. Finally, the participants were followed for an ample time with the average follow-up period of 11 years.

The study also has some limitations. First, being a community derived cohort, the severity of OSA seen in SHHS was generally mild to moderate. The outcomes, including mortality, would be expected to be worse in a clinical cohort with higher severity of sleep apnea. Secondly, while the current study included a substantial number of potential covariates in the models, residual confounding from other factors may have occurred. Thirdly, the severity of OSA may have changed over the follow up period. Fourthly, while the follow-up period of the study was long, it is possible that an even longer follow-up period may have allowed a better estimate of the long-term impact of OSA on mortality. Finally, although the study demonstrated increased mortality risk, elucidation of the mechanisms thereof was beyond the scope of this study.

In conclusion, the current study demonstrated in a large community-based cohort that even OSA defined by a more liberal AHI3%A is associated with increased mortality. Considering the adverse outcomes associated with OSA, a restrictive definition that excludes these persons from warranted OSA therapy is potentially deleterious to overall health with significant individual and healthcare implications.

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Abbreviations

• AASM            American Academy of Sleep Medicine
• AHI               Apnea hypopnea index
• AHI3%A        Apnea hypopnea index defined using a hypopnea definition requiring a minimum 3% O2 desaturation or arousal
• AHI4%          Apnea hypopnea index defined using a hypopnea definition requiring a minimum 4% O2 desaturation
• BMI              Body mass index
• CMS             Centers for Medicare and Medicaid Services
• CVD             Cardiovascular disease
• HDL              High density lipoprotein
• HR               Hazard ratio
• OSA             Obstructive sleep apnea
• SHHS           Sleep Heart Health Study

Acknowledgements

The Sleep Heart Health Study was supported by National Heart, Lung and Blood Institute cooperative agreements U01HL53940 (University of Washington), U01HL53941 (Boston University), U01HL53938 (University of Arizona), U01HL53916 (University of California, Davis), U01HL53934 (University of Minnesota), U01HL53931 (New York University), U01HL53937 and U01HL64360 (Johns Hopkins University), U01HL63463 (Case Western Reserve University), and U01HL63429 (Missouri Breaks Research). A list of SHHS investigators, staff and their participating institutions is available on the SHHS website, http://jhuccs1.us/shhs/details/investigators.htm.

Cite as: Budhiraja R, Quan SF. Long-term all-cause mortality risk in obstructive sleep apnea using hypopneas defined by a ≥3 percent oxygen desaturation or arousal. Southwest J Pulm Crit Care. 2021;23(1):23-35. doi: https://doi.org/10.13175/swjpcc025-21 PDF

Role of Spousal Involvement in Continuous Positive Airway Pressure (CPAP) Adherence in Patients with Obstructive Sleep Apnea (OSA)

Salma Batool-Anwar, MD, MPH ²

Carol M. Baldwin, PhD, MSN ³

Shira Fass, PhD⁴

Stuart F. Quan, MD ^1,2

¹University of Arizona College of Medicine, Tucson, AZ USA

²Brigham and Women’s Hospital, Boston, MA USA

³Arizona State University College of Nursing and Health Innovation and College of Health Solutions, Phoenix, AZ USA

⁴Case Western Reserve University, Cleveland, Ohio USA

Abstract

Introduction: Little is known about the impact of spousal involvement on continuous positive airway pressure (CPAP) adherence. The aim of this study was to determine whether spouse involvement affects adherence with CPAP therapy, and how this association varies with gender.  

Methods: 194 subjects recruited from Apnea Positive Pressure Long Term Efficacy Study (APPLES) completed the Dyadic Adjustment Scale (DAS). The majority of participants were Caucasian (83%), and males (73%), with mean age of 56 years, mean BMI of 31 kg/m². & 62% had severe OSA. The DAS is a validated 32-item self-report instrument measuring dyadic consensus, satisfaction, cohesion, and affectional expression. A high score in the DAS is indicative of a person’s adjustment to the marriage. Additionally, questions related to spouse involvement with general health and CPAP use were asked. CPAP use was downloaded from the device and self-report, and compliance was defined as usage > 4 h per night.

Results: There were no significant differences in overall marital quality between the compliant and noncompliant subjects. However, level of spousal involvement was associated with increased CPAP adherence at 6 months (p=0.01). After stratifying for gender these results were significant only among males (p=0.03). Three years after completing APPLES, level of spousal involvement was not associated with CPAP compliance even after gender stratification.

Conclusion: Spousal involvement is important in determining CPAP compliance in males in the 1^st 6 months after initiation of therapy but is not predictive of longer-term adherence. Involvement of the spouse should be considered an integral part of CPAP initiation procedures.

Abbreviations List

AASM: American Academy of Sleep Medicine

AHI: Apnena Hyponea Index

APPLES: Apnea Positive Pressure Long Term Efficacy Study

BMI: Body Mass Index

CPAP: Continuous positive airway pressure

DAS: Dyadic Adjustment Scale

EEG: Electroencephalogram

EMG: Electromyograms

EOG: Electroocculogram

OSA: Obstructive Sleep Apnea

PSG: polysomnography

Introduction

Obstructive Sleep apnea (OSA) is characterized by repetitive episodes of upper airway closure during sleep resulting in oxygen desaturation and frequent arousals. In addition to cardiovascular comorbidities, OSA has been linked to poor quality of life, depression and motor vehicle accidents. Recent data suggest an increase in the prevalence of OSA for both men and women (34% and 17.4% respectively) (1).

Continuous positive airway pressure (CPAP) is the treatment of choice for OSA. Poor adherence, however, remains a widely recognized problem limiting overall effectiveness of CPAP therapy. Prior studies have identified various factors and strategies to promote CPAP adherence (2). In addition to disease, educational, and technology-specific considerations that can affect CPAP adherence, social and psychological dynamics are important components of adherence as well.

Several studies have suggested that partner/spousal dyadic support can play a positive role in the patient’s overall health and health behaviors (3,4) . For example, higher CPAP adherence was reported among patients with bed partners (5), as well as persons who were married versus single (6). Little is known about the influence of spousal involvement on CPAP adherence. One study indicated that perceived spousal support predicted greater CPAP adherence among men with high disease severity; however, pressure to adhere to treatment by the wife was not of benefit and predicted poorer CPAP adherence (7). Another study indicated reduced marital conflict by OSA patients following 3 months of CPAP, suggesting that marital conflict resolution might serve as an intervention for CPAP adherence (8). Despite these hints that dyadic support may play a role in CPAP adherence, participants in both studies by Baron et al. (7.8) consisted primarily of men, and the studies focusing on CPAP adherence by Lewis et al. (5) and Gagnadoux et al. (6) included only men. Thus, the aim of the current study was to determine whether spouse involvement affects CPAP adherence and how this association differs by gender using data from a large randomized trial of CPAP versus sham CPAP to treat OSA. 

Methods

Study Population and Protocol

The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month multicenter, randomized, double-blinded, 2-arm, sham-controlled, intention-to-treat study of CPAP efficacy on three domains of neurocognitive function in OSA. Three of the 5 APPLES Clinical Centers, the University of Arizona, Stanford University and St. Luke’s Hospital (Chesterfield, MO) participated in this ancillary study. A detailed description of the protocol has previously been published (9). Briefly, participants were either recruited through local advertisement, or from attending sleep clinics for evaluation of possible OSA. Symptoms indicative of OSA were used to prescreen potential participants. The initial clinical evaluation included administering informed consent, screening questionnaires, a history and physical examination, and a medical assessment by a study physician. Participants subsequently returned 2-4 weeks later for a 24-h sleep laboratory visit, during which polysomnography (PSG) was performed to confirm the diagnosis, followed by a day of neurocognitive, mood, sleepiness, and quality of life survey testing. Inclusion and exclusion criteria have been published previously and included age ≥ 18 years and a clinical diagnosis of OSA as defined by American Academy of Sleep Medicine (AASM) criteria. Only participants with an apnea hypopnea index (AHI) ≥ 10 by PSG were randomized to continue in the APPLES study. Exclusion criteria were previous treatment for OSA with CPAP or surgery, oxygen saturation on baseline PSG <75% for >10% of the recording time, history of motor vehicle accident-related to sleepiness within the past 12 months, presence of chronic medical conditions, use of various medications known to affect sleep or neurocognitive function, and various health and social factors that may impact standardized testing procedures (e.g., shift work).

Following the PSG, participants with an AHI ≥ 10 who met other enrollment criteria were randomized to CPAP or sham CPAP for continued participation in APPLES. After randomization, participants returned to the sleep laboratory for a CPAP or sham CPAP titration PSG. Subsequent assessments were made at 2, and 6 months post-randomization at which time a test battery was re-administered. At the conclusion of their 6-month post-randomization evaluations, each participant was informed of their treatment group assignment and offered CPAP treatment going forward. Approximately 36 months after the conclusion of APPLES, participants were sent the Dyadic Adjustment Scale (DAS) questionnaire with the addition of several additional questions related to health.

Assessment of Spouse involvement

Inclusion in the current analysis required that subjects were married during the APPLES study and remained married at the time of questionnaire administration. The DAS (10), a quality of marriage questionnaire, was utilized to assess marital relationship. It is a 32-item self-report instrument that incorporates four dimensions, including a 13 item dyadic consensus, 10 item dyadic satisfaction, 5 item dyadic cohesion, and 4 item affectional expression. A high DAS score is indicative of a person’s positive adjustment to the marriage. Additionally, questions related to spouse involvement with general health and CPAP use were asked (See Appendix for full questionnaire).

Polysomnography

The PSG montage included monitoring of the electroencephalogram (EEG, C₃-A₂ or C₄-A₁, O₂-A₁ or O₁-A₂), electro-oculogram (EOG, ROC-A₁, LOC-A₂), chin and anterior tibialis electromyograms (EMG), heart rate by 2-lead electrocardiogram, snoring intensity (anterior neck microphone), nasal pressure (nasal cannula), nasal/oral thermistor, thoracic and abdominal movement (inductance plethysmography bands), and oxygen saturation (pulse oximetry). All PSG records were electronically transmitted to a centralized data coordinating and PSG reading center. Sleep and wakefulness were scored using Rechtschaffen and Kales criteria (11). Apneas and hypopneas were scored using American Academy of Sleep Medicine Task Force (1999) diagnostic criteria (12, 13). Briefly, an apnea was defined by a clear decrease (> 90%) from baseline in the amplitude of the nasal pressure or thermistor signal lasting ≥ 10 sec. Hypopneas were identified if there was a clear decrease (> 50% but ≤ 90%) from baseline in the amplitude of the nasal pressure or thermistor signal, or if there was a clear amplitude reduction of the nasal pressure signal ≥ 10 sec that did not reach the above criterion, but was associated with either an oxygen desaturation > 3% or an arousal.

Obstructive events were scored if there was persistence of chest or abdominal respiratory effort. Central events were noted if no displacement occurred on either the chest or abdominal channels. Sleep apnea was classified as mild (AHI 10.0 to 15.0 events per hour), moderate (AHI 15.1 to 30.0 events per hour), and severe (AHI more than 30 events per hour) (12).

CPAP adherence

The primary dependent variable of interest was CPAP adherence and was assessed by nightly use of CPAP at the 6-months follow up visit. CPAP use was downloaded from the device and the participants were considered to be adherent if the mean CPAP use was > 4 hours per night at 6-months. Long-term CPAP adherence was measured as self-reported adherence (hours per night) at the time of the DAS administration.

Statistical Analysis 

Statistical analyses were performed using STATA (Version 11, StataCorp TX USA). Univariate and multivariate logistic regression models were used to estimate the degree to which variables correlated with CPAP adherence. We examined the association between CPAP adherence and following variables: OSA severity as measured by the AHI, age, baseline body mass index (BMI, kg/m²), spousal involvement and the DAS. For these models, dichotomous variables were created for OSA severity (AHI < 15 vs. ≥ 15), obesity (BMI <30 kg/m² vs. ≥30 kg/m²) and CPAP adherence (< 4 hours/night vs. ≥4 hours/night). Spousal involvement was ascertained using a 5 point Lickert scale and analyzed as a continuous variable.

To assess predictors of CPAP adherence we used multiple regression models. Unpaired t-tests were used to assess the effect of gender, age, OSA severity, BMI, and CPAP adherence in both the CPAP and Sham CPAP groups. Data for continuous and interval variables were expressed as mean ± SD, and as a percentage for categorical variables. Statistical significance was set at a P value <0.05, two-tailed. The variables that produced P value of < 0.05 were included in the final model.

Results

Baseline demographic data on participants (N=194) who completed the DAS are outlined in Table 1.

Table1. Baseline Characteristics of APPLES Participants Who Completed Dyadic Data.

The majority of the participants were Caucasian (83%) and males (73%), with mean age of 56 years and a mean BMI of 31 kg/m². Over half of the participants had severe OSA (62%). Table 2a demonstrates CPAP adherence at 6 months using multivariate analysis.

Table 2A. Multivariate Analysis of Adherence to CPAP or Sham CPAP at 6 Months.

The CPAP adherence was independently associated with advanced age (p < 0.01) and increasing spousal involvement (p < 0.01). After stratifying by treatment group, the association between CPAP adherence and spousal involvement was seen only amongst the CPAP group (Table 2b).

Table 2B. Multivariate Analysis of Adherence to CPAP at 6 Months.

Adjustment to marriage as reflected by items on the DAS questionnaire, however, was not associated with CPAP adherence.

Notably, after gender stratification, significant association between spousal involvement and CPAP adherence was limited to men alone (p=0.03). Three years after completing APPLES, 82 participants were still adherent by self-report (Table 3).

Table 3. Multivariate Analysis CPAP Adherence 3 years After Completing APPLES Study (based on subjective adherence).

At this time point, spousal involvement was not associated with CPAP adherence even after gender stratification.

Discussion

This multicenter double blind study demonstrates that spousal involvement is important in determining CPAP adherence during the initial treatment period, but has no effect on long-term adherence. Notably, the positive results for adherence were seen only among husbands using CPAP, but there was no effect on wives using CPAP. In line with previous research, we also found that increase in age was associated with greater CPAP adherence among both men and women.

Prior studies have indicated that married versus single, CPAP patients with bed partners, perceived spousal support, and quality of marital relationship all play a role in promoting CPAP adherence (5-8). Although these studies support the idea of social support as a conduit to CPAP adherence, the role of spousal involvement was not clear, sample sizes in the spousal role studies were small, and CPAP users were men, which reduces generalizability.

Baron et al. (3) used a spousal involvement measure, including positive and negative collaboration and one-sided items one week after beginning CPAP treatment (N=23 married men on CPAP), in addition to an interpersonal measure of supportive behaviors at 3 months to evaluate interpersonal qualities (n=16/23 responded). These investigators found that perceived collaborative involvement was related to greater CPAP adherence at 3 months (p=0.002). These findings are similar to our study in that spousal support, at least for husbands on CPAP, fostered greater adherence during the initial period of treatment.

Our observations and those of Baron et al. (14) fit well with the theories of motivation. The fundamental fact of motivation and adherence in healthcare is that individuals cannot be forced to change their behaviors. The behavior change, in this case the CPAP adherence, may be initiated by extrinsic motivation. External motivation may be rewards, punishments, or pressure from other people, such as family members or healthcare providers. However, extrinsic motivation, such as spousal pressure, is less effective in the long-term. In order to sustain long term behavioral change for CPAP adherence one needs to rely on intrinsic motivation which can be strengthened by examining the decisional balance of the ratio between a patient’s perceived pros and cons for engaging in a health behavior. The decisional balance has been found to be predictive of adherence to treatment in a variety of healthcare settings.

Our study also found increased age as an independent predictor of CPAP adherence at 6-months, yet the results were not significant for long-term adherence. Previous studies have also demonstrated conflicting results on the association between age and CPAP adherence. Sin et al. (15) found that a 10 year increment in age resulted in 0.24 ± 0.11-h increase in CPAP use. Alternatively, McArdle and colleagues (16) found that older patients were less likely to use their CPAP machines. Similarly, Janson et al. (17) found older age to be an independent risk factor for discontinuing CPAP treatment, and this finding was thought to be secondary to nasal, or pharyngeal problems. In another study, Russo-Magno et al. (18) found that adherent patients were younger in age compared to non-adherents, and increasing age made CPAP adherence difficult. Cognitive and physical impairments were thought to be contributing to difficulty with CPAP adherence. Mean age in this cohort was 73 years, which was higher than the mean age in our study. It is possible that these inconsistent associations of age on CPAP adherence may be related to the length of follow-up as well. With longer durations, the effect of time on comorbidities in the elderly may make adherence more difficult.

To our knowledge, this is the first study to demonstrate a gender bias in support for CPAP adherence. While men on CPAP were significantly more likely to adhere with support from their wives, there was no such effect for married women on CPAP, suggesting little to no support from their husbands. Although the effect of gender on CPAP adherence and spousal involvement has not been studied, previous research suggests that women are more likely to be the health caregivers in families, and thus exercise more social control (19). It is the social norm and expectation that women are often involved in their husbands’ health. As indicated in the literature regarding type 2 diabetes (20), male patients and their wives shared an expectation that the wives will be involved in their care while female patients and their husbands did not have similar expectations. We can support this finding in relationship to CPAP adherence.

Not surprisingly, spousal support for adherence did not apply to sham CPAP. This suggests that if an intervention is not having any perceived benefit, spousal involvement will have little impact on adherence. 

There are several limitations to this study. A major limitation is self-reported long term CPAP adherence. Additionally, our study was limited to husbands and wives on CPAP completing the DAS; their respective spouses were not asked about their degree of involvement. Moreover, it is unclear which components of spouse involvement played a role in CPAP adherence. We cannot assume that patients welcome all types of spouse involvement. Spouse involvement may be perceived by patients as control and nagging and may not be advantageous for all patients (21). In the context of chronic illness significant differences are demonstrated across couples in expectations for spouse involvement (20).

Despite these limitations, to our knowledge this is the first study of its type that examined spousal support for both men and women on CPAP supporting generalizability of our findings. Other strengths of this study include a large number of participants across multiple sites, randomized CPAP and Sham CPAP control groups, and objective documentation of CPAP adherence at 6 months.

Dyadic coping has been utilized in other health related interventions and can also be used to improve CPAP adherence. Ye et al. (4) has provided a comprehensive review of dyadic support in CPAP adherence, including methodological considerations, recommendations for future research, and implications for interventions. In tandem with the Ye et al. (4) review, our findings, particularly with respect to the need for spousal support of wives on CPAP, can provide a springboard for future clinical/intervention studies to promote CPAP adherence for men and women, to develop gender-relevant training needs to support their spouse on CPAP, and to determine spousal support activities that are the most efficient at promoting CPAP adherence.

Acknowledgments

APPLES was funded by contract 5UO1-HL-068060 from the National Heart, Lung and Blood Institute. The APPLES pilot studies were supported by grants from the American Academy of Sleep Medicine and the Sleep Medicine Education and Research Foundation to Stanford University and by the National Institute of Neurological Disorders and Stroke (N44-NS-002394) to SAM Technology. In addition, APPLES investigators gratefully recognize the vital input and support of Dr. Sylvan Green who died before the results of this trial were analyzed, but was instrumental in its design and conduct.

Administrative Core

Clete A. Kushida, MD, PhD; Deborah A. Nichols, MS; Eileen B. Leary, BA, RPSGT; Pamela R. Hyde, MA; Tyson H. Holmes, PhD; Daniel A. Bloch, PhD; William C. Dement, MD, PhD

Data Coordinating Center

Daniel A. Bloch, PhD; Tyson H. Holmes, PhD; Deborah A. Nichols, MS; Rik Jadrnicek, Microflow, Ric Miller, Microflow Usman Aijaz, MS; Aamir Farooq, PhD; Darryl Thomander, PhD; Chia-Yu Cardell, RPSGT; Emily Kees, Michael E. Sorel, MPH; Oscar Carrillo, RPSGT; Tami Crabtree, MS; Booil Jo, PhD; Ray Balise, PhD; Tracy Kuo, PhD

Clinical Coordinating Center

Clete A. Kushida, MD, PhD, William C. Dement, MD, PhD, Pamela R. Hyde, MA, Rhonda M. Wong, BA, Pete Silva, Max Hirshkowitz, PhD, Alan Gevins, DSc, Gary Kay, PhD, Linda K. McEvoy, PhD, Cynthia S. Chan, BS, Sylvan Green, MD

Clinical Centers

Stanford University 

Christian Guilleminault, MD; Eileen B. Leary, BA, RPSGT; David Claman, MD; Stephen Brooks, MD; Julianne Blythe, PA-C, RPSGT; Jennifer Blair, BA; Pam Simi, Ronelle Broussard, BA; Emily Greenberg, MPH; Bethany Franklin, MS; Amirah Khouzam, MA; Sanjana Behari Black, BS, RPSGT; Viola Arias, RPSGT; Romelyn Delos Santos, BS; Tara Tanaka, PhD

University of Arizona 

Stuart F. Quan, MD; James L. Goodwin, PhD; Wei Shen, MD; Phillip Eichling, MD; Rohit Budhiraja, MD; Charles Wynstra, MBA; Cathy Ward, Colleen Dunn, BS; Terry Smith, BS; Dane Holderman, Michael Robinson, BS; Osmara Molina, BS; Aaron Ostrovsky, Jesus Wences, Sean Priefert, Julia Rogers, BS; Megan Ruiter, BS; Leslie Crosby, BS, RN

St. Mary Medical Center

Richard D. Simon Jr., MD; Kevin Hurlburt, RPSGT; Michael Bernstein, MD; Timothy Davidson, MD; Jeannine Orock-Takele, RPSGT; Shelly Rubin, MA; Phillip Smith, RPSGT; Erica Roth, RPSGT; Julie Flaa, RPSGT; Jennifer Blair, BA; Jennifer Schwartz, BA; Anna Simon, BA; Amber Randall, BA

St. Luke’s Hospital

James K. Walsh, PhD, Paula K. Schweitzer, PhD, Anup Katyal, MD, Rhody Eisenstein, MD, Stephen Feren, MD, Nancy Cline, Dena Robertson, RN, Sheri Compton, RN, Susan Greene, Kara Griffin, MS, Janine Hall, PhD

Brigham and Women’s Hospital

Daniel J. Gottlieb, MD, MPH, David P. White, MD, Denise Clarke, BSc, RPSGT, Kevin Moore, BA, Grace Brown, BA, Paige Hardy, MS, Kerry Eudy, PhD, Lawrence Epstein, MD, Sanjay Patel, MD

*Sleep HealthCenters for the use of their clinical facilities to conduct this research

Consultant Teams

Methodology Team: Daniel A. Bloch, PhD, Sylvan Green, MD, Tyson H. Holmes, PhD, Maurice M. Ohayon, MD, DSc, David White, MD, Terry Young, PhD

Sleep-Disordered Breathing Protocol Team: Christian Guilleminault, MD, Stuart Quan, MD, David White, MD

EEG/Neurocognitive Function Team: Jed Black, MD, Alan Gevins, DSc, Max Hirshkowitz, PhD, Gary Kay, PhD, Tracy Kuo, PhD

Mood and Sleepiness Assessment Team: Ruth Benca, MD, PhD, William C. Dement, MD, PhD, Karl Doghramji, MD, Tracy Kuo, PhD, James K. Walsh, PhD

Quality of Life Assessment Team: W. Ward Flemons, MD, Robert M. Kaplan, PhD

APPLES Secondary Analysis-Neurocognitive (ASA-NC) Team: Dean Beebe, PhD, Robert Heaton, PhD, Joel Kramer, PsyD, Ronald Lazar, PhD, David Loewenstein, PhD, Frederick Schmitt, PhD

National Heart, Lung, and Blood Institute (NHLBI)

Michael J. Twery, PhD, Gail G. Weinmann, MD, Colin O. Wu, PhD

Data and Safety Monitoring Board (DSMB)

Seven year term: Richard J. Martin, MD (Chair), David F. Dinges, PhD, Charles F. Emery, PhD, Susan M. Harding MD, John M. Lachin, ScD, Phyllis C. Zee, MD, PhD

Other term: Xihong Lin, PhD (2 yrs), Thomas H. Murray, PhD (1 yr)

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Cite as: Batool-Anwar S, Baldwin CM, Fass S, Quan SP. Role of spousal involvement in continuous positive airway pressure (CPAP) adherence in patients with obstructive sleep apnea (OSA). Southwest J Pulm Crit Care. 2017;14(5):213-27. doi: https://doi.org/10.13175/swjpcc034-17 PDF