Abstract
Study Objectives:
Observational studies have demonstrated the association between the single-point measurement of oxygen saturation (SpO2) level and mortality in the general population. This study aimed to evaluate whether nocturnal SpO2 level could predict all-cause mortality in a community-based population.
Methods:
The study samples were obtained from the Sleep Heart Health Study, which included 2,280 men and 2,606 women (mean age, 63.8 ± 11.1 years). A pulse oximeter based on overnight in-home polysomnography was used to monitor SpO2 levels during total sleep time (SpO2-TOTAL). Multivariable Cox proportional hazards analysis was performed to examine the association between nocturnal SpO2 and all-cause mortality.
Results:
During the follow-up period of 10.7 ± 3.0 years, 1,110 (22.7%) people died. After adjusting for confounding factors, multivariable Cox regression analysis showed that the average SpO2-TOTAL (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.90–0.96, P < .001) was associated with all-cause mortality. These findings remained stable in individuals with low and high apnea-hypopnea index levels. Additionally, maximum SpO2-TOTAL (HR, 0.91; 95% CI, 0.87–0.96; P = .001) and minimum SpO2-TOTAL (HR, 0.98; 95% CI, 0.97–0.99; P = .001) could predict all-cause mortality. A significant association between nocturnal hypoxemia and all-cause mortality was also observed.
Conclusions:
Our findings highlight the importance of monitoring nocturnal SpO2 level and improving hypoxemia in the general populations.
Citation:
Yan B, Gao Y, Zhang Z, Shi T, Chen Q. Nocturnal oxygen saturation is associated with all-cause mortality: a community-based study. J Clin Sleep Med. 2024;20(2):229–235.
Keywords: nocturnal oxygen saturation, nocturnal hypoxemia, all-cause mortality, apnea-hypopnea index, SHHS
BRIEF SUMMARY
Current Knowledge/Study Rationale: Oxygen saturation (SpO2) monitoring is widely used in clinical practice. The present study aimed to evaluate whether nocturnal SpO2 level could predict all-cause mortality in a community-based population.
Study Impact: In middle-aged and older adults, nocturnal SpO2 level in total sleep time, rapid eye movement sleep and non–rapid eye movement sleep was associated with all-cause mortality after adjusting for potential confounders. An inverse association between nocturnal hypoxemia and all-cause mortality was also observed. Our findings highlight the importance for monitoring nocturnal SpO2 level and improving hypoxemia in community populations.
INTRODUCTION
Oxygen saturation (SpO2), which refers to the ratio of oxyhemoglobin to total hemoglobin in the blood, is an essential measurement in critical care.1 It is estimated that more than 1.5 million adults with chronic lung disease in the United States use supplemental oxygen therapy to improve their quality of life.2 Various conditions, such as chronic obstructive pulmonary disease, asthma, coronavirus disease 2019, heart failure, anemia, and high altitudes, can affect SpO2. In addition, individuals with sleep-disordered breathing (SDB) usually experience abnormal respiration during sleep and may experience decreased SpO2.3,4
Pulse oximetry is the standard method for continuous and noninvasive monitoring of SpO2.5 Wearable devices, such as smartwatches, are also effective tools to track SpO2 levels.6,7 The normal range of SpO2 is usually between 95% and 100% in healthy adults, and low SpO2 suggests hypoxemia. Several observational studies have demonstrated the association between SpO2 level during sleep and cardiovascular risk.8–10 Decreased SpO2 level was also associated with in-hospital mortality.11,12 However, there is little evidence regarding the association between nocturnal SpO2 level and all-cause mortality in the general population.
This study aimed to determine whether nocturnal SpO2 in total sleep time (TST) could predict all-cause mortality based on the Sleep Heart Health Study (SHHS). Considering the potential effects of SDB on SpO2, we also investigated the association between nocturnal SpO2 level and all-cause mortality in participants with low and high apnea-hypopnea index (AHI) values.
METHODS
Study population
All participants included in the current study were selected from the SHHS. The SHHS is a community-based, prospective cohort study implemented by the National Heart, Lung, and Blood Institute to investigate the cardiovascular consequences of SDB (ClinicalTrials.gov identifier: NCT00005275). Between November 1995 and January 1998, a total of 6,441 middle-aged and older men and women were recruited from parent cohorts and completed baseline examinations, including overnight in-home polysomnography and sleep habit questionnaires. Participants who had been treated with SDB; who received home oxygen therapies, such as a pressure mask (continuous positive airway pressure) or mouthpiece; and who underwent tracheostomy were excluded from the SHHS. Details of the study design have been reported previously.13,14 All participants provided written informed consent, and the SHHS was approved by the institutional review board of each participating institution. Figure S1 (551.3KB, pdf) in the supplemental material shows the selection process for the study sample, from the initial participant to the final analysis subset.
Data collection
All participants underwent overnight in-home polysomnography at SHHS baseline (Compumedics Pty Ltd, Abbotsford, Australia). SpO2 levels in TST (SpO2-TOTAL), rapid eye movement (REM) sleep (SpO2-REM), and non-REM (NREM) sleep (SpO2-NREM) were monitored using a pulse oximeter (Nonin XPOD 3011, 8000 sensor; Nonin Medical, Inc. USA).15 Trained and certified technicians set up the Compumedics sleep monitor and conducted home visits. The percentage of sleep time SpO2 below 90% (T90) was defined as the ratio of the time spent with SpO2 under 90% to TST. Other nocturnal hypoxemia parameters, including percentage of sleep time SpO2 below 95% (T95), percentage of sleep time SpO2 below 85% (T85), and percentage of sleep time SpO2 below 80% (T80), were also included in this study. AHI was defined as all apnea and hypopnea episodes divided by TST, accompanied by at least a 4% drop in SpO2 level per hour of sleep. The severity of SDB was categorized using conventional clinical cutoff points: normal (AHI < 5.0 events/h), mild (AHI 5.0–14.9 events/h), moderate (AHI 15.0–29.9 events/h), and severe (AHI ≥ 30.0 events/h). The forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio (FEV1/FVC %) was calculated as FEV1 divided by FVC and multiplied by 100%.
Other covariates, including age, sex, race, smoking status, alcohol use, body mass index (BMI), history of diabetes mellitus and hypertension, history of major cardiovascular diseases (CVDs; including myocardial infarction, congestive heart failure, and stroke), history of chronic respiratory disease (including chronic obstructive pulmonary disease, chronic bronchitis, and asthma), and lipid-lowering medication use, were collected from the parent cohort study and SHHS baseline investigations.
All-cause mortality events were identified and confirmed in the parent cohorts using follow-up interviews, written annual questionnaires, telephone contacts with study participants or next of kin, surveillance of local hospital records and community obituaries, and linkage with the Social Security Administration Death Master File.16
Statistical analysis
The baseline characteristics are presented as mean ± standard deviation and number (percentage), as appropriate. Comparisons between participants alive and all-cause mortality were performed using the chi-square test for categorical variables and Student’s t test for continuous variables. Unadjusted Kaplan–Meier survival curves were constructed to evaluate the overall survival of different SpO2 categories, and the differences among groups were tested using the log-rank test.
Multivariable Cox proportional hazards regression models were used to assess the association between nocturnal SpO2 traits and all-cause mortality after adjusting for age, sex, race, smoking status, alcohol use, BMI, hypertension, diabetes mellitus, TST, AHI, lipid-lowering medication use, history of major CVD, history of chronic respiratory disease, and FEV1/FVC. The results are presented as hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. To assess the dose–response association of nocturnal SpO2 with all-cause mortality, restricted cubic spline analysis based on Cox proportional hazards models was used (5 knots at the 5.0th, 27.5th, 50.0th, 72.5th, and 95.0th percentiles of SpO2).
The association between nocturnal SpO2 traits and all-cause mortality was further investigated in participants with and without SDB (AHI ≥ 5 events/h vs AHI < 5 events/h). Additional subgroup analyses stratified by age (≥ 65 vs < 65 years), sex (men vs women), AHI levels (≥ 15 vs < 15 events/h), and FEV1/FVC (≥ 70% vs < 70%) were also performed. Interactions among subgroups were examined by adding multiplicative interaction terms to a multivariable Cox regression model.
All statistical analyses were performed using the Statistical Package for Social Sciences statistics software (version 24.0; SPSS, Inc, Chicago, IL, USA) and R software version 3.6.3 (R Foundation for Statistical Computing, Vienna, Austria). A 2-sided P value < .05 was considered statistically significant.
RESULTS
Participants’ characteristics
A total of 4,886 participants (2,280 men and 2,606 women [mean age, 63.8 ± 11.1 years]) met the selection criteria and were available for all-cause mortality analysis. During the 10.7 ± 3.0 years of follow-up, 1,110 (22.7%) patients died. Significant differences in nocturnal SpO2 levels were observed between people alive and all-cause mortality. The baseline characteristics of the study samples of people alive and with all-cause death are shown in Table 1.
Table 1.
Baseline characteristics of study samples in people alive and all-cause death.
| Characteristics | Total | All-Cause Death | Alive | P |
|---|---|---|---|---|
| (n = 4,886) | (n = 1,110) | (n = 3,776) | ||
| Age, y | 63.8 ± 11.1 | 73.3 ± 8.9 | 61.0 ± 10.1 | <.001 |
| Sex, n (%) | <.001 | |||
| Men | 2,280 (46.7) | 594 (53.5) | 1,686 (44.7) | |
| Women | 2,606 (53.3) | 516 (46.5) | 2,090 (55.3) | |
| Race, n (%) | .149 | |||
| White | 4,265 (87.3) | 983 (88.6) | 3,282 (86.9) | |
| Non-White | 621 (12.7) | 127 (11.4) | 494 (13.1) | |
| Body weight, n (%) | .001 | |||
| Obese | 1,495 (30.7) | 302 (27.3) | 1,193 (31.7) | |
| Overweight | 2,064 (42.4) | 461 (41.6) | 1,603 (42.6) | |
| Normal | 1,311 (26.9) | 344 (31.1) | 967 (25.7) | |
| Smoking status, n (%) | <.001 | |||
| Current | 469 (9.6) | 107 (9.7) | 362 (9.6) | |
| Former | 2,136 (43.9) | 541 (48.9) | 1,595 (42.4) | |
| Never | 2,267 (46.5) | 459 (41.4) | 1,808 (48.0) | |
| Alcohol use, n (%) | <.001 | |||
| At least 1 drink per day | 1,966 (43.0) | 384 (35.7) | 1,582 (45.2) | |
| None | 2,607 (57.0) | 691 (64.3) | 1,916 (54.8) | |
| Diabetes mellitus | 349 (7.1) | 168 (15.1) | 181 (4.8) | <.001 |
| Hypertension | 1,954 (40.0) | 671 (60.5) | 1,283 (34.0) | <.001 |
| History of major CVD, n (%) | 504 (10.3) | 253 (22.8) | 251 (6.6) | <.001 |
| History of chronic respiratory disease | 613 (12.5) | 151 (13.6) | 462 (12.2) | .226 |
| Lipid-lowering medication use, n (%) | 620 (12.7) | 160 (14.4) | 460 (12.2) | .050 |
| SpO2 traits, % | ||||
| Average SpO2-TOTAL | 94.5 ± 2.0 | 93.8 ± 2.3 | 94.7 ± 1.9 | <.001 |
| Average SpO2-REM | 94.3 ± 2.5 | 93.3 ± 2.9 | 94.5 ± 2.3 | <.001 |
| Average SpO2-NREM | 94.5 ± 1.9 | 93.9 ± 2.2 | 94.7 ± 1.8 | <.001 |
| Maximum SpO2-TOTAL | 98.3 ± 1.1 | 98.0 ± 1.3 | 98.4 ± 0.9 | <.001 |
| Maximum SpO2-REM | 97.9 ± 1.3 | 97.4 ± 1.7 | 98.0 ± 1.2 | <.001 |
| Maximum SpO2-NREM | 98.2 ± 1.1 | 97.8 ± 1.4 | 98.2 ± 1.0 | <.001 |
| Minimum SpO2-TOTAL | 85.6 ± 6.0 | 84.5 ± 6.2 | 86.0 ± 5.9 | <.001 |
| Minimum SpO2-REM | 86.9 ± 5.9 | 85.8 ± 6.2 | 87.2 ± 5.8 | <.001 |
| Minimum SpO2-NREM | 87.2 ± 5.1 | 86.2 ± 5.3 | 87.5 ± 5.1 | <.001 |
| Nocturnal hypoxemia, % | ||||
| T95 | 45.0 ± 35.0 | 54.8 ± 35.1 | 42.2 ± 34.5 | <.001 |
| T90 | 3.5 ± 10.3 | 6.3 ± 14.9 | 2.7 ± 8.4 | <.001 |
| T85 | 0.5 ± 3.4 | 1.0 ± 5.2 | 0.4 ± 2.5 | .001 |
| T80 | 0.1 ± 1.6 | 0.3 ± 2.4 | 0.1 ± 1.3 | .040 |
| FEV1/FVC (%) | 75.4 ± 7.7 | 73.6 ± 9.4 | 75.9 ± 7.0 | <.001 |
| AHI, events/h | 10.1 ± 13.2 | 12.3 ± 14.5 | 9.4 ± 12.8 | <.001 |
| TST, h | 6.1 ± 1.0 | 5.8 ± 1.1 | 6.2 ± 1.0 | <.001 |
| Follow-up time, y | 10.7 ± 3.0 | 6.9 ± 3.2 | 11.9 ± 1.7 | <.001 |
History of major CVD included myocardial infarction, congestive heart failure, and stroke. History of chronic respiratory disease included chronic obstructive pulmonary disease, chronic bronchitis, and asthma. Results are presented as mean ± standard deviation or n (%). P values represent the difference between people alive and all-cause death. AHI = apnea-hypopnea index, CVD = cardiovascular disease, FEV1 = forced expiratory volume in 1 second, FVC = forced vital capacity, NREM = non–rapid eye movement, REM = rapid eye movement, SpO2 = oxygen saturation, T95 = percent of sleep time SpO2 < 95%, T90 = percent of sleep time SpO2 < 90%, T85 = percent of sleep time SpO2 < 85%, T80 = percent of sleep time SpO2 < 80%, TST, total sleep time.
Nocturnal SpO2 and all-cause mortality
The unadjusted Kaplan–Meier survival curves are shown in Figure 1 (log-rank test, P < .001). After adjusting for age, sex, race, smoking status, alcohol use, BMI, hypertension, diabetes mellitus, TST, AHI, lipid-lowering medication use, history of major CVD, history of chronic respiratory disease, and FEV1/FVC, multivariable Cox proportional hazards regression analysis demonstrated that increased levels (per 1% increase) of average SpO2-TOTAL (HR, 0.93; 95% CI, 0.90–0.96; P < .001) was significantly associated with a 7% decreased risk of all-cause mortality (Table 2). Moreover, there was a linear association between average SpO2-TOTAL and all-cause mortality in the restricted cubic spline analysis (Figure 2). The maximum SpO2-TOTAL (HR, 0.91; 95% CI, 0.87–0.96; P = .001) and minimum SpO2-TOTAL (HR, 0.98; 95% CI, 0.97–0.99; P = .001) were also predictors for all-cause mortality (Table 2). Furthermore, the similar associations between SpO2 and all-cause mortality were observed in REM sleep and NREM sleep (Figure S2 (551.3KB, pdf) , Figure S3 (551.3KB, pdf) , and Table S1 (551.3KB, pdf) ).
Figure 1. Kaplan–Meier plots of overall survival for all-cause mortality by quartiles of average SpO2-TOTAL.
Q = quartile, SpO2 = oxygen saturation.
Table 2.
HRs and 95% CIs for SpO2-TOTAL associated with all-cause mortality.
| SpO2 Traits* | Univariable Model | Age and Sex Adjusted | Multivariable Adjusted† | Multivariable Adjusted‡ | ||||
|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | |
| Average SpO2-TOTAL | 0.86 (0.84–0.88) | <.001 | 0.91 (0.87–0.94) | <.001 | 0.92 (0.89–0.95) | <.001 | 0.93 (0.90–0.96) | <.001 |
| Maximum SpO2-TOTAL | 0.77 (0.74–0.81) | <.001 | 0.87 (0.83–0.91) | <.001 | 0.90 (0.85–0.94) | <.001 | 0.91 (0.87–0.96) | .001 |
| Minimum SpO2-TOTAL | 0.97 (0.96–0.98) | <.001 | 0.98 (0.97–0.99) | <.001 | 0.98 (0.97–0.99) | .001 | 0.98 (0.97–0.99) | .001 |
*Per 1% increment. †Each individual SpO2 parameter was adjusted by age, sex, race, smoking status, alcohol use, BMI, hypertension, diabetes mellitus, TST, AHI, lipid-lowering medication use, history of major CVD, and history of chronic respiratory disease. ‡Adjusted for “†” + FEV1/FVC. AHI = apnea-hypopnea index, BMI = body mass index, CI = confidence interval, CVD = cardiovascular disease, FEV1 = forced expiratory volume in 1 second, FVC = forced vital capacity, HR = hazard ratio, SpO2 = oxygen saturation, TST = total sleep time.
Figure 2. Multivariable Cox proportional HR for all-cause mortality based on restricted cubic spline analysis with 5 knots at the 5.0th, 27.5th, 50.0th, 72.5th, and 95.0th percentiles of average SpO2-TOTAL (reference was 90%).
The model was adjusted for age, sex, race, smoking status, alcohol use, body mass index, hypertension, diabetes mellitus, total sleep time, apnea-hypopnea index, lipid-lowering medication use, history of major cardiovascular disease, history of chronic respiratory disease, and FEV1/FVC. CI = confidence interval, FEV1/FVC = forced expiratory volume in 1 second/forced vital capacity ratio, HR = hazard ratio, SpO2 = oxygen saturation.
Nocturnal hypoxemia and all-cause mortality
The effect of nocturnal hypoxemia traits (including T95, T90, T85, and T80) on all-cause mortality was also explored. In the final multivariable Cox–adjusted model, T90 (per 5% increase) was significantly associated with increased all-cause mortality (HR, 1.05; 95% CI, 1.02–1.07; P < .001). In addition, every 5% increase in T95 (HR, 1.01; 95% CI, 1.00–1.02; P = .005), T85 (HR, 1.13; 95% CI, 1.06–1.19; P < .001), and T80 (HR, 1.20; 95% CI, 1.07–1.35; P = .002) could also predict all-cause mortality, respectively (Table 3).
Table 3.
HRs and 95% CIs for nocturnal hypoxemia traits associated with all-cause mortality.
| Nocturnal Hypoxemia* | Univariable Model | Age and Sex Adjusted | Multivariable Adjusted† | Multivariable Adjusted‡ | ||||
|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | |
| T95 | 1.05 (1.04–1.06) | <.001 | 1.02 (1.01–1.03) | <.001 | 1.02 (1.01–1.03) | <.001 | 1.01 (1.00–1.02) | .005 |
| T90 | 1.10 (1.09–1.13) | <.001 | 1.07 (1.05–1.09) | <.001 | 1.05 (1.03–1.07) | <.001 | 1.05 (1.02–1.07) | <.001 |
| T85 | 1.14 (1.08–1.19) | <.001 | 1.13 (1.08–1.20) | <.001 | 1.13 (1.06–1.19) | <.001 | 1.13 (1.06–1.19) | <.001 |
| T80 | 1.14 (1.04–1.26) | .008 | 1.20 (1.07–1.34) | .002 | 1.19 (1.06–1.34) | .004 | 1.20 (1.07–1.35) | .002 |
*Per 5% increment. †Each individual SpO2 parameter was adjusted by age, sex, race, smoking status, alcohol use, BMI, hypertension, diabetes mellitus, TST, AHI, lipid-lowering medication use, history of major CVD, and history of chronic respiratory disease. ‡Adjusted for “†” + FEV1/FVC. AHI = apnea-hypopnea index, BMI = body mass index, CI = confidence interval, CVD = cardiovascular disease, FEV1 = forced expiratory volume in 1 second, FVC = forced vital capacity, HR = hazard ratio, SpO2 = oxygen saturation, T95 = percent of sleep time SpO2 < 95%, T90 = percent of sleep time SpO2 < 90%, T85 = percent of sleep time SpO2 < 85%, T80 = percent of sleep time SpO2 < 80%, TST = total sleep time.
Subgroup analysis
The relationships between SpO2-TOTAL and all-cause mortality were stable in subgroup analyses (Table 4 and Table S2 (551.3KB, pdf) ). Average SpO2-TOTAL could predict all-cause mortality in participants with (HR, 0.94; 95% CI, 0.90–0.98; P = .001) and without (HR, 0.91; 95% CI, 0.86–0.97; P < .001) SDB. In addition, the average SpO2-TOTAL was significantly associated with all-cause mortality when stratified by moderate-and-severe SDB (HR, 0.93; 95% CI, 0.88–0.98; P = .005) and non-or-mild SDB (HR, 0.93; 95% CI, 0.89–0.97; P = .001). Similar results were also found for SpO2-REM and SpO2-NREM (Table S3 (551.3KB, pdf) ). Furthermore, the associations of nocturnal SpO2 level and hypoxemia traits with all-cause mortality stratified by age (≥ 65 years vs < 65 years), sex (men vs women), and FEV1/FVC (≥ 70% vs < 70%) were assessed (Table S2 (551.3KB, pdf) and Table S3 (551.3KB, pdf) and Table S4 (551.3KB, pdf) ).
Table 4.
The association between average SpO2-TOTAL and all-cause mortality in subgroup analysis.
| Subgroup | Persons, n | Event, n (%) | HR (95% CI)* | P |
|---|---|---|---|---|
| Age | ||||
| ≥65 y | 2,348 | 943 (40.2) | 0.94 (0.91–0.97) | .001 |
| <65 y | 2,538 | 167 (6.6) | 0.86 (0.80–0.91) | <.001 |
| Sex | ||||
| Men | 2,280 | 594 (26.1) | 0.94 (0.90–0.98) | .003 |
| Women | 2,606 | 516 (19.8) | 0.92 (0.87–0.96) | <.001 |
| AHI | ||||
| ≥5 events/h | 2,511 | 660 (26.3) | 0.94 (0.90–0.98) | .001 |
| <5 events/h | 2,375 | 450 (18.9) | 0.91 (0.86–0.97) | <.001 |
| AHI | ||||
| ≥15 events/h | 1,026 | 306 (29.8) | 0.93 (0.88–0.98) | .005 |
| <15 events/h | 3,860 | 804 (20.8) | 0.93 (0.89–0.97) | .001 |
| FEV1/FVC | ||||
| ≥70% | 3,705 | 800 (21.6) | 0.94 (0.91–0.98) | .003 |
| <70% | 893 | 310 (34.7) | 0.90 (0.86–0.96) | <.001 |
All models were adjusted by age, sex, race, smoking status, alcohol use, BMI, hypertension, diabetes mellitus, TST, AHI, lipid-lowering medication use, history of major CVD, history of chronic respiratory disease, and FEV1/FVC. *Per 1% increment. AHI = apnea-hypopnea index, BMI = body mass index, CI = confidence interval, CVD = cardiovascular disease, FEV1 = forced expiratory volume in 1 second, FVC = forced vital capacity, HR = hazard ratio, SpO2 = oxygen saturation, TST = total sleep time.
DISCUSSION
In this large community-based study, we found that average SpO2-TOTAL was significantly associated with all-cause mortality after adjusting for potential confounders, such as AHI and FEV1/FVC. These associations remained stable in the subgroup analysis. Maximum SpO2-TOTAL and minimum SpO2-TOTAL could also predict all-cause mortality. Furthermore, we examined the effect of nocturnal hypoxemia on all-cause mortality. Our findings indicate that T95, T90, T85, and T80 are risk factors for all-cause mortality.
SpO2 is an essential element of vital signs and is commonly used in emergency and intensive care medicine. Several studies have found a close relationship between SpO2 and human health. A previous study showed that average SpO2-TOTAL was related to cardiovascular health.17 Baguet et al8 suggested that an average SpO2-TOTAL of < 92% was associated with carotid plaque formation. Yu et al12 showed that admission SpO2 was associated with in-hospital mortality in patients with acute myocardial infarction. In the general population, low SpO2 level measured using a single-point measurement was associated with increased mortality.18 However, there is little evidence regarding the association between nocturnal SpO2 level and all-cause mortality. In our study, nocturnal SpO2 levels were monitored using a pulse oximeter based on the Compumedics P-Series Sleep Monitoring System. The average SpO2-TOTAL represents the mean level of SpO2 during TST. We found a significant reduction in all-cause mortality in participants with higher average SpO2-TOTAL. In addition, the maximum and minimum SpO2 levels could reflect fluctuations in SpO2 level to a certain extent. Observational studies have demonstrated that minimum SpO2-TOTAL was a predictor for carotid atherosclerosis.8,9 Our results showed that maximum and minimum SpO2-TOTAL values were associated with all-cause mortality. These findings indicate that average SpO2-TOTAL, maximum SpO2-TOTAL, and minimum SpO2-TOTAL may be useful predictors of all-cause mortality.
REM sleep and NREM sleep are 2 components of TST and have distinct physiological characteristics.19 Different from NREM sleep, REM sleep is characterized by eye movement, vivid dreams, increased heart rate, elevated blood pressure, irregular breathing, muscle atony, low voltage, and fast frequency in the electroencephalogram.20 Hypoxemia worsens during sleep and is most pronounced during REM sleep in patients with chronic obstructive pulmonary disease.21 Moreover, the percentage of REM sleep is associated with all-cause mortality.22,23 In the present study, we did not find differences between REM sleep and NREM sleep in the association of SpO2 with all-cause mortality.
SDB is a common condition characterized by abnormal respiration patterns during sleep and is often accompanied by a drop in SpO2 level.24 AHI is a universal diagnostic tool for evaluating people with and without SDB. Previous studies have suggested that decreased SpO2 level may play a mediating role in the association between cardiovascular risk and SDB.25–28 Individuals with an AHI of ≥ 15 events/h are also an important cutoff point for the severity of SDB. Moreover, FEV1/FVC (≥ 70% vs < 70%) is usually used to determine lung function and diagnose obstructive and restrictive pulmonary diseases, such as chronic obstructive pulmonary disease and asthma. In these subgroup analysis, the association between average SpO2-TOTAL and all-cause mortality was still significant.
We also found a significant association between nocturnal hypoxemia and high risk of mortality. Nocturnal hypoxemia is common in patients with pulmonary diseases, CVD, and SDB and is characterized by a drop in SpO2 level during sleep time. T90 is the most commonly used metric for nocturnal hypoxemia and can predict increased mortality in patients with stable heart failure.29 Several observational studies suggested that nocturnal hypoxemia strongly predicted CVD better than AHI.30,31 In this community-based study, we observed a significant association between T90 and all-cause mortality. Other nocturnal hypoxemia traits, including T95, T85, and T80, could also predict all-cause mortality. Oxygen therapy is a common supportive treatment for chronic pulmonary diseases and nocturnal hypoxemia, which provides people with supplemental oxygen that can be used at home.21,24 Our findings underline the importance of maintaining nocturnal SpO2 levels in reducing all-cause mortality in the general population.
The present study has several strengths. Our findings are based on a large community-based population and may be applicable to the general population. Nocturnal SpO2 level and hypoxemia were objectively monitored using a pulse oximeter during sleep. Notably, SpO2 is relatively easy to monitor in daily life. For example, some smartwatches are equipped with oxygen sensors to measure SpO2 levels in real time and can monitor nocturnal SpO2. With the popularization of smart wearable devices and technological updates, SpO2 monitoring will become more convenient and reliable.
However, this study has some limitations. The study population was selected from the SHHS datasets, and most of them were middle-aged and elderly White individuals. Therefore, our findings do not represent those of other ethnic groups or young individuals. Moreover, single-night monitoring of SpO2 level may not fully reflect the level and fluctuation of nocturnal SpO2 level. The association between SpO2 level and mortality in high-altitude populations warrants further investigation.
CONCLUSIONS
This study provides evidence that nocturnal SpO2 levels can predict all-cause mortality in middle-aged and older adults, which persisted after adjusting for AHI, FEV1/FVC, and multiple confounding factors. High levels of average SpO2-TOTAL were associated with a low risk of all-cause mortality, even in subgroup analysis stratified by age, sex, AHI level, and FEV1/FVC. Nocturnal hypoxemia traits, including T95, T90, T85, and T80, were also important predictors of all-cause mortality. These findings suggest the necessity for monitoring nocturnal SpO2 level and improving hypoxemia, not only in hospitalized patients but also in general middle-aged and elderly people.
DISCLOSURE STATEMENT
All authors have approved this manuscript. Work for this study was performed at the First Affiliated Hospital of Xi’an Jiaotong University. This study was funded by the Natural Science Basic Research Program of Shaanxi (no. 2021JQ-395). The authors report no conflicts of interest.
ACKNOWLEDGMENTS
The authors thank the Brigham and Women’s Hospital for sharing the Datasets of Sleep Heart Health Study (SHHS). The SHHS was supported by National Heart, Lung, and Blood Institute cooperative agreements U01HL53916 (University of California, Davis), U01HL53931 (New York University), U01HL53934 (University of Minnesota), U01HL53937 and U01HL64360 (Johns Hopkins University), U01HL53938 (University of Arizona), U01HL53940 (University of Washington), U01HL53941 (Boston University), and U01HL63463 (Case Western Reserve University). The National Sleep Research Resource was supported by the National Heart, Lung, and Blood Institute (R24 HL114473, 75N92019R002). The SHHS is particularly grateful to the members of these cohorts who agreed to participate in SHHS as well. The SHHS further recognizes all the investigators and staff who have contributed to its success.
Author contributions: B.Y. and Q.C. conceived the idea for the study. Q.C., Y.G., Z.Z., T.S., and B.Y. contributed to the study design, writing, and review of the report. B.Y. performed the data analysis. Q.C. handled supervision in our study.
Data sharing statement: The data using in this study was based on SHHS datasets (https://doi.org/10.25822/ghy8-ks59).
ABBREVIATIONS
- AHI
apnea-hypopnea index
- BMI
body mass index
- CI
confidence interval
- CVD
cardiovascular disease
- FEV1
forced expiratory volume in 1 second
- FVC
forced vital capacity
- HR
hazard ratio
- NREM
non–rapid eye movement
- REM
rapid eye movement
- SDB
sleep-disordered breathing
- SHHS
Sleep Heart Health Study
- SpO2
oxygen saturation
- T95
percent of sleep time SpO2 < 95%
- T90
percent of sleep time SpO2 < 90%
- T85
percent of sleep time SpO2 < 85%
- T80
percent of sleep time SpO2 < 80%
- TST
total sleep time
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