Abstract
We investigated the relationship between ambulatory blood pressure (BP) and oxygen desaturation index (ODI), while accounting for pulse rate and age. ODI was assessed by overnight finger pulse oximetry in 2342 participants on the day of ambulatory BP monitoring, and calculated as the number of desaturation episodes per sleeping hour. Both BP and pulse rate increased significantly (P ≤ .006) from normal (< 5 events/h) to mildly (5‐14), moderately (15‐30), and severely (≥ 30 events/h) elevated ODI. The association for BP was substantially attenuated by accounting for pulse rate (partial r² from .003‐.012 to .002‐.006). In adjusted analysis, the associations of 24‐hour diastolic BP and 24‐hour pulse rate with ODI were dependent on age (P ≤ .0001) and only significant in younger subjects (< 60 years, P ≤ .0001). In conclusion, the association between ambulatory BP and ODI was partially mediated by pulse rate, a measure of sympathetic activity, and was more prominent in younger subjects.
Keywords: age, ambulatory blood pressure, hypertension, oxygen desaturation, pulse oximetry, pulse rate
1. INTRODUCTION
Obstructive sleep apnea and hypopnea syndrome (OSAHS) is a common comorbidity of hypertension. The prevalence of OSAHS was from 37%1 to 56%2 in hypertensive patients and 83% in patients with hypertension resistant to antihypertensive treatment.3 However, causal relationship between OSAHS and hypertension has not been well established. Some,4, 5 but not other,6 hypertension guidelines considered OSAHS as a secondary cause of hypertension. Previous studies often used apnea/hypopnea index (AHI), a direct measure of respiration, instead of oxygen desaturation index, a measure of hypoxemia.7, 8 The latter rather than the former may be a critical pathophysiological mechanism for hypertension. Previous studies also did not sufficiently account for the circadian profile of blood pressure, sympathetic over‐activation (i.e, as assessed by tachycardia), or aging. Indeed, sympathetic over‐activation may be the mediator between hypoxemia and high blood pressure, and its role may be attenuated with aging because heart rate increase induced by sympathetic activation is less prominent in the elderly.9, 10, 11
Our hypothesis was that oxygen desaturation might be closely associated with blood pressure, especially on ambulatory measurement, and that the association might be enhanced in younger subjects by accounting for heart rate as a rough measure of sympathetic activity. We recently performed overnight finger pulse oximetry in outpatients who had established or suspected diagnosis of hypertension and underwent 24‐hour ambulatory blood pressure monitoring. In the present study, we investigated association of oxygen desaturation with 24‐hour daytime and nighttime blood pressure and pulse rate, and possible interaction between oxygen desaturation and various factors, such as age, in relation to ambulatory blood pressure and pulse rate.
2. METHODS
2.1. Study population
Our study subjects were consecutive patients who were referred for ambulatory blood pressure monitoring in the specialized hypertension outpatient clinic, Ruijin Hospital, Shanghai, China; they were not aware of OSAHS nor on continuous positive airway pressure (CPAP) therapy or oral device treatment for OSHAS. They all underwent overnight oximetry on the same night of the 24‐hour ambulatory blood pressure recording. The study was conducted in compliance with the principles of the Declaration of Helsinki. The study protocol was approved by the Ethics Committee of Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. All subjects gave written informed consent.
Between August 2013 and December 2015, 2603 subjects were enrolled. We excluded 254 subjects from the present analysis because the ambulatory blood pressure recording was not valid (n = 202), the oximetry was less than 4 hours (n = 52), or because of other missing information (n = 7), leaving 2342 participants included in the analysis.
2.2. Overnight finger pulse oximetry
Pulse oximetry was performed overnight in the middle finger (no painting nail polish), irrespective of right or left hand, on the same night of the ambulatory blood pressure recording at home. The sampling rate of the oximetry was 100 Hz. After recording, the data was transmitted into a validated Matlab system for offline analysis. A recording duration of at least 4 hours was deemed to be valid for inclusion in the analysis. Oxygen desaturation event was defined as a decrease of at least 4% SpO2 from baseline, with a dropping speed less than 2% per second and an afterwards recovery. Oxygen desaturation index was calculated as the number of oxygen desaturation events per hour of the recording time.
2.3. Ambulatory blood pressure monitoring
We programmed validated oscillometric SpaceLabs 90 217 monitors to obtain ambulatory blood pressure readings on the non‐dominant arm at 20‐minute intervals from 06:00 to 22:00 and at 30‐minute intervals from 22:00 to 06:00. In the analysis, daytime was defined as the period from 08:00 to 18:00 hours and nighttime as the period from 23:00 to 05:00 hours.12 A recording was considered valid and included in the analysis, if it had at least 20 daytime and 7 nighttime blood pressure readings and included ≥ 70% of the programmed readings.13 Within individual subjects, we weighted the means of the ambulatory blood pressure level by the interval between successive readings. Ambulatory pulse rate was derived from the same ambulatory blood pressure recording. Reading‐to‐reading blood pressure variability was assessed by calculating the standard deviation and the coefficient of variation for 24‐hour daytime and nighttime systolic and diastolic blood pressure readings, respectively.
2.4. Other measurements
The Epworth Sleepiness Scale was used to assess daytime sleepiness. We collected information on demographics and the use of antihypertensive medication. Body mass index was the body weight in kilograms divided by the body height in meters squared.
2.5. Statistical analysis
For database management and statistical analysis, we used SAS software, version 9.2. Means and proportions were compared by the Student's t‐test and the χ2 test, respectively. In categorical analysis, we classified study participants according to oxygen desaturation index into four levels (< 5, 5‐14, 15‐29, ≥ 30 events/h).14 We performed analyses of covariance for the comparison of 24‐hour daytime and nighttime blood pressure according to oxygen desaturation levels while controlling for confounding factors. We investigated the possible involvement of nighttime pulse rate in linking nighttime blood pressure to oxygen desaturation using pathway analysis as implemented in the PROC CALIS procedure of the SAS package. In pathway analysis, we applied a logarithmic transformation to normalize the distribution of oxygen desaturation index. In analysis for interaction, interaction term was calculated by oxygen desaturation index times age as continuous variables. Sensitivity analysis was performed in untreated subjects. All tests were two‐sided and a P value < .05 was considered to be statistically significant.
3. RESULTS
3.1. Characteristics of the study participants
Table 1 shows the characteristics of the 2342 study participants according to gender. Men (n = 1165) and women (n = 1177) had similar proportions of antihypertensive treatment (43.6% vs 47.3%; P = .07) or an Epworth sleep scale > 10 (12.1% vs 9.9%; P = .15). However, men, compared with women, were a few years younger (45.1 ± 12.9 vs 52.0 ± 11.0 years; P < .0001), and had a greater body mass index (25.2 ± 3.3 vs 23.9 ± 3.3 kg/cm2; P < .0001).
Table 1.
Characteristics of the study participants by gender
| Characteristic | Men (n = 1165) | Women (n = 1177) | P |
|---|---|---|---|
| Age, y | 45.1 ± 12.9 | 52.0 ± 11.0 | <.0001 |
| Body mass index, kg/m² | 25.2 ± 3.3 | 23.9 ± 3.3 | <.0001 |
| Use of antihypertensive drugs, n (%) | 508 (43.6) | 557 (47.3) | .07 |
| 24‐h ambulatory normotension, n (%)a | 343 (29.4) | 589 (50.0) | <.0001 |
| ESS score > 10, n (%) | 141 (12.1) | 117 (9.9) | .15 |
| Oxygen desaturation index | |||
| Median (interquartile range), events/h | 3.7 (1.5‐8.8) | 3.0 (1.3‐6.6) | <.0001 |
| ≥15 events/h, n (%) | 150 (12.9) | 74 (6.3) | <.0001 |
| ≥5 events/h, n (%) | 485 (41.6) | 385 (32.7) | <.0001 |
| ≥5 events/h in ambulatory hypertension, n (%) | 377 (45.7) | 188 (31.9) | <.0001 |
| Ambulatory recording | |||
| 24‐h systolic, mm Hg | 128.9 ± 13.2 | 124.8 ± 13.6 | <.0001 |
| 24‐h diastolic, mm Hg | 84.3 ± 9.2 | 78.8 ± 9.6 | <.0001 |
| 24‐h pulse rate, beats/min | 73.0 ± 8.5 | 71.9 ± 7.8 | .0008 |
| Daytime systolic, mm Hg | 135.4 ± 13.6 | 130.6 ± 14.2 | <.0001 |
| Daytime diastolic, mm Hg | 88.7 ± 9.7 | 82.7 ± 10.2 | .0001 |
| Daytime pulse rate, beats/min | 79.2 ± 10.0 | 77.6 ± 9.1 | <.0001 |
| Nighttime systolic, mm Hg | 116.6 ± 15.1 | 113.2 ± 15.6 | <.0001 |
| Nighttime diastolic, mm Hg | 75.4 ± 10.5 | 70.7 ± 10.4 | <.0001 |
| Nighttime pulse rate, beats/min | 62.9 ± 8.2 | 62.8 ± 7.4 | .96 |
Values are mean ± standard deviation, median (interquartile range) or number of subjects (%). The P value is for the comparison between men and women subjects. ESS indicates Epworth Sleepiness Scale.
24‐h ambulatory normtension was defined as a 24‐h ambulatory systolic/diastolic blood pressure < 130/80 mm Hg.
Men, compared with women, had significantly (P < .0001) higher 24‐hour (mean 128.9/84.3 vs 124.8/78.8 mm Hg), daytime (135.4/88.7 vs 130.6/82.7 mm Hg) and nighttime systolic/diastolic blood pressure (116.6/75.4 vs 113.2/70.7 mm Hg), and higher ambulatory pulse rate over 24 hours (73.0 vs 71.9 beats/min), in the daytime (79.2 vs 77.6 beats/min), but not during nighttime (62.9 vs 62.8 beats/min, P = .96). Men, compared with women, also had a higher oxygen desaturation index (median 3.7 vs 3.0 events/h, P < .0001). The prevalence of oxygen desaturation index ≥ 15 events/h was higher in men than women (12.9% vs 6.3%, P < .0001) and with advancing age and greater body mass index (P ≤ .02 for trend, Figure 1).
Figure 1.
Prevalence of oxygen desaturation index ≥15 events/h according to gender, age (left panel) and body mass index groups (right panel). Symbols indicate the prevalence for each subgroup. The P values for trend are given for men (filled symbols with solid line) and women (open symbols with dashed line) separately. The number of patients is given alongside the symbols. For analysis according to body mass index, we excluded 18 subjects who did not have information on body height or body weight
3.2. Association between ambulatory blood pressure and oxygen desaturation index
In unadjusted analysis, 24‐hour daytime and nighttime systolic and diastolic blood pressure and pulse rate increased with greater oxygen desaturation index (P ≤ .006 for trend, Table 2). The association tended to be stronger for the nighttime than daytime (P ≤ .003 for the difference between nighttime and daytime regression coefficients). The night‐to‐day ratio therefore also increased with greater oxygen desaturation index (P < .0001 for trend). The blood pressure variability indices were significantly associated with oxygen desaturation index mainly for nighttime blood pressure (P ≤ .002 for trend, Table 3).
Table 2.
Ambulatory blood pressure and pulse rate according to oxygen desaturation index
| Ambulatory recording | Oxygen desaturation index | P (for trend) | |||
|---|---|---|---|---|---|
| 0‐4 (n = 1473) | 5‐14 (n = 645) | 15‐29 (n = 165) | ≥30 (n = 59) | ||
| 24‐h systolic, mm Hg | 126.2 ± 13.7 | 126.8 ± 12.8 | 130.4 ± 12.7a | 134.9 ± 16.5a | <.0001 |
| 24‐h diastolic, mm Hg | 81.2 ± 9.8 | 81.1 ± 9.6 | 84.0 ± 9.0a | 87.0 ± 10.7a | <.0001 |
| 24‐h pulse rate, beats/min | 72.0 ± 7.9 | 72.5 ± 8.3 | 74.1 ± 8.2a | 77.9 ± 10.4a | <.0001 |
| Daytime systolic, mm Hg | 132.6 ± 14.4 | 132.7 ± 13.4 | 136.3 ± 13.4a | 138.4 ± 16.2a | .0004 |
| Daytime diastolic, mm Hg | 85.6 ± 10.5 | 85.1 ± 10.3 | 87.9 ± 9.9a | 89.7 ± 10.9a | .006 |
| Daytime pulse rate, beats/min | 78.2 ± 9.4 | 78.2 ± 9.6 | 79.6 ± 9.6 | 82.7 ± 11.8a | .003 |
| Nighttime systolic, mm Hg | 113.9 ± 15.3 | 115.1 ± 14.7 | 118.9 ± 15.2a | 127.6 ± 18.4a | <.0001 |
| Nighttime diastolic, mm Hg | 72.4 ± 10.7 | 72.8 ± 10.3 | 76.2 ± 9.9a | 81.5 ± 11.6a | <.0001 |
| Nighttime pulse rate, beats/min | 62.2 ± 7.5 | 63.4 ± 8.0a | 64.9 ± 7.8a | 69.0 ± 10.7a | <.0001 |
| Night‐day ratio | |||||
| Systolic | 0.860 ± 0.082 | 0.869 ± 0.087a | 0.874 ± 0.091 | 0.923 ± 0.086a | <.0001 |
| Diastolic | 0.848 ± 0.084 | 0.858 ± 0.086a | 0.871 ± 0.095a | 0.910 ± 0.086a | <.0001 |
| Pulse rate | 0.799 ± 0.077 | 0.814 ± 0.080a | 0.819 ± 0.083a | 0.838 ± 0.102a | <.0001 |
Data are mean ± standard deviation.
P value < .05 compared with oxygen desaturation index of 0‐4 events/h group.
Table 3.
Ambulatory blood pressure variability according to oxygen desaturation index
| Ambulatory recording | Model | Oxygen desaturation index | P (for trend) | |||
|---|---|---|---|---|---|---|
| 0‐4 (n = 1473) | 5‐14 (n = 645) | 15‐29 (n = 165) | ≥30 (n = 59) | |||
| 24‐h systolic | SD | 14.4 ± 3.7 | 14.7 ± 3.7 | 14.9 ± 3.9 | 13.8 ± 4.0 | .35 |
| CV | 11.5 ± 2.9 | 11.6 ± 3.0 | 11.5 ± 3.1 | 10.3 ± 3.0 | .31 | |
| 24‐h diastolic | SD | 10.1 ± 2.3 | 10.2 ± 2.3 | 10.2 ± 2.4 | 9.8 ± 2.5 | .80 |
| CV | 12.6 ± 3.0 | 12.6 ± 2.9 | 12.3 ± 3.0 | 11.3 ± 3.0 | .02 | |
| Daytime systolic | SD | 11.4 ± 3.5 | 11.8 ± 3.7 | 11.9 ± 3.5 | 11.4 ± 4.0 | .04 |
| CV | 8.6 ± 2.7 | 9.0 ± 3.0a | 8.8 ± 2.7 | 8.3 ± 3.1 | .31 | |
| Daytime diastolic | SD | 7.6 ± 2.2 | 7.8 ± 2.2 | 7.7 ± 2.1 | 7.8 ± 2.3 | .13 |
| CV | 9.0 ± 2.8 | 9.3 ± 2.9a | 8.9 ± 2.7 | 8.8 ± 2.8 | .76 | |
| Nighttime systolic | SD | 8.9 ± 3.3 | 9.5 ± 3.7 | 10.0 ± 3.5a | 10.4 ± 4.6a | <.0001 |
| CV | 7.9 ± 2.8 | 8.3 ± 3.0a | 8.5 ± 2.8a | 8.2 ± 3.6 | .001 | |
| Nighttime diastolic | SD | 6.9 ± 2.4 | 7.4 ± 2.5a | 7.8 ± 2.8a | 8.2 ± 3.3a | <.0001 |
| CV | 9.7 ± 3.4 | 10.2 ± 3.6a | 10.4 ± 3.8a | 10.2 ± 4.2 | .002 | |
Data are mean ± standard deviation. SD indicates standard deviation; CV, coefficient of variation.
P value < .05 compared with oxygen desaturation index of 0‐4 events/h group.
After adjustment for age, sex, body mass index, the Epworth sleep scale score, and antihypertensive treatment, the associations of oxygen desaturation index with ambulatory blood pressure slightly shrank (partial r² from .002‐.017 to .003‐.012). However, further adjustment for pulse rate substantially attenuated the association between ambulatory blood pressure and oxygen desaturation index (partial r² from .003‐.012 to .002‐.006), and only nighttime and 24‐hour systolic and diastolic blood pressure remained significantly associated with increasing oxygen desaturation index (P ≤ .009 for trend; Figure 2). After adjustment for confounding factors, including the 24‐hour blood pressure level, the association between the night‐to‐day ratio and oxygen desaturation index remained statistically significant for both systolic and diastolic blood pressure (P < .001 for trend).
Figure 2.
Adjusted 24‐h, daytime and nighttime blood pressure according to oxygen desaturation index group. Symbols indicate mean values of 24‐h (dots with solid line), daytime (filled squares with dashed line) and nighttime blood pressure (open squares with dashed line), adjusted for age, gender, body mass index, antihypertensive treatment, Epworth Sleepiness Scale and pulse rate. The P values for trend and the number of subjects are given along the line and at the bottom, respectively
In further pathway analysis, we considered ambulatory blood pressure as outcome and oxygen desaturation index and ambulatory pulse rate as explanatory variables. For each 1‐SD (3.55‐fold) increment of log‐transformed oxygen desaturation index, the direct effect and the indirect effect mediated via nighttime pulse rate on nighttime systolic/diastolic blood pressure (±SE) were 3.01 ± 0.58/1.58 ± 0.40 mm Hg and 0.65 ± 0.12/0.61 ± 0.10 mm Hg (P < .0001), respectively. The corresponding effect values were 2.09 ± 0.53/0.72 ± 0.37 mm Hg (P ≤ .05) and 0.06 ± 0.08/0.09 ± 0.13 mm Hg (P ≥ .47) for daytime systolic/diastolic blood pressure as outcome, respectively; and 2.64 ± 0.51/0.96 ± 0.36 mm Hg (P ≤ .007) and 0.23 ± 0.08/0.36 ± 0.11 mm Hg (P ≤ .003) for 24‐hour systolic/diastolic blood pressure as outcome, respectively.
3.3. Interaction between oxygen desaturation with age or gender in relation to 24‐hour pulse rate and blood pressure
There was significant (P ≤ .002) interaction between oxygen desaturation index and age in relation to 24‐hour daytime and nighttime pulse rate and diastolic blood pressure (Figure 3), but not 24‐hour daytime or nighttime systolic blood pressure (P ≥ .17). Both ambulatory pulse rate and diastolic blood pressure were significantly associated with oxygen desaturation index in younger subjects (< 60 years, P < .0001 for trend), especially those younger than 40 years of age, but not older (≥ 60 years, P ≥ .051 for trend) subjects. Indeed, compared with subjects with an oxygen desaturation index < 5 events/h, subjects with an oxygen desaturation index of 15 events/h or greater had a higher 24‐hour daytime and nighttime diastolic blood pressure and pulse rate (±SE) by 6.1 ± 1.7, 5.2 ± 1.7, and 6.8 ± 1.9 mm Hg and 6.8 ± 1.3, 5.9 ± 1.5, and 6.9 ± 1.3 beats/min, respectively, in subjects younger than 40 years of age and by 3.3 ± 1.2, 2.5 ± 1.3, and 5.7 ± 1.4 mm Hg and 1.9 ± 1.2, 1.7 ± 1.4, and 2.2 ± 1.1 beats/min, respectively, in subjects older than 60 years of age (P ≤ .52 vs subjects younger than 40 years).
Figure 3.
Relationship between 24‐h pulse rate (left panel) and 24‐h diastolic blood pressure (right panel) with oxygen desaturation index according to age group. Symbols represent mean values of 24‐h ambulatory pulse rate and 24‐h diastolic blood pressure, for each subgroup according to age and oxygen desaturation index. The number of subjects for each subgroup is given alongside the symbols. The P values for interaction between age and oxygen desaturation index in relation to 24‐h ambulatory pulse rate and 24‐h diastolic blood pressure are given
There was also significant interaction (P ≤ .005) between oxygen desaturation index and gender in relation to 24‐hour daytime and nighttime pulse rate and diastolic blood pressure (Figure 4), but not systolic blood pressure (P ≥ .73). The associations were stronger in men than women for both ambulatory pulse rate and diastolic blood pressure.
Figure 4.
Relationship between 24‐h pulse rate (left panel) and 24‐h diastolic blood pressure (right panel) with oxygen desaturation index according to sex group. Symbols represent mean values of 24‐h ambulatory pulse rate and 24‐h diastolic blood pressure, for each subgroup according to sex and oxygen desaturation index. The number of subjects for each subgroup is given alongside the symbols. The P values for interaction between sex and oxygen desaturation index in relation to 24‐h ambulatory pulse rate and 24‐h diastolic blood pressure are given
3.4. Sensitivity analysis
We performed subgroup analysis in untreated subjects. The results were confirmatory in both unadjusted and adjusted analyses (Tables S1 and S2; Figure S1).
4. DISCUSSION
Our new finding was that 24‐hour daytime and nighttime blood pressures were positively associated with oxygen desaturation. This association might be mediated at least partially by heart rate, which is a rough measure of sympathetic activity, and was more prominent in younger male subjects.
Our study has sufficient power to investigate ambulatory blood pressure in relation to various stages of oxygen desaturation, while accounting for age. In two previous studies, ambulatory blood pressure was found to be associated with severe oxygen desaturation.14, 15 Compared with habitual snorers (0 to 5 events/h), those with severe oxygen desaturation (> 30 events/h), had significantly (P < .04) higher daytime (13/10 mm Hg) and nighttime systolic/diastolic blood pressure (21/15 mm Hg).14 Similar results were observed in a case‐control study in 55 patients with obstructive sleep apnea and 45 normal controls.15 Obstructive sleep apnea was defined as an oxygen desaturation > 4% of more than 10 episodes per hour. Patients with obstructive sleep apnea, compared to control subjects, had significantly (P ≤ .03) higher daytime (87.4 vs 82.8 mm Hg) and nighttime diastolic blood pressure (78.6 vs 71.4 mm Hg), and higher nighttime systolic blood pressure (119.4 vs 110.2 mm Hg). These early studies had insufficient power to perform age‐stratified analysis, but did include patients in the younger age range (average age 50.014 and 51.9 years,15 respectively).
The reading‐to‐reading blood pressure variability indices were associated with oxygen desaturation mainly for nighttime blood pressure. This observation is in keeping with the results of several previous studies,16, 17 and may have straightforward interpretations. Blood pressure and oxygen desaturation index were recorded on the same day. Intermittent hypoxia during sleeping hours probably directly induced variability in blood pressure by activating autonomic nervous system, while increasing the level of nighttime blood pressure.
Several studies investigated office blood pressure in relation to oxygen desaturation or apnea/hypopnea.18, 19, 20 In a study by Young et al. in 1060 participants, there was a dose‐response relationship between AHI and clinic blood pressure.18 Compared with normal subjects (AHI 0 to 2, n = 642), those with severe sleep‐disordered breathing (AHI ≥ 30, n = 37) had higher systolic and diastolic blood pressure (13.6 and 7.4 mm Hg, respectively). In a study of 1190 participants who did not have history of hypertension and were referred for sleep‐related breathing disorder, respiratory disturbance index was defined as the number of significant events of sleep‐disordered breathing (oxygen desaturation of > 4% from baseline) per estimated sleep time.19 Those with a respiratory disturbance index ≥ 40 events/h (n = 188) had higher systolic and diastolic blood pressure (8.8 and 6.7 mm Hg, respectively) than those with a respiratory disturbance index < 5 events/h (n = 166). In consistent with our study, this association was more prominent in younger (≤ 50 years, n = 557) than older subjects (> 50 years, n = 663, odds ratio for hypertension 7.14 vs 2.70, respectively). In a study of 1424 Japanese men in the community, oxygen desaturation of ≥ 3% was selected as the indicator of sleep‐disordered breathing.20 This study showed that a 5 events/h increment in the number of sleep‐disordered breathing was associated with 0.8 mm Hg (95% confidence interval [CI], 0.0‐1.6) and 0.7 mm Hg (95% CI, 0.3‐1.1) higher systolic and diastolic blood pressure, respectively, after adjustment for age, body mass index, alcohol intake, smoking category, and community. In our current study, we did not measure clinic blood pressure along with the ambulatory recording. We therefore cannot perform analysis on clinic blood pressure and directly compare these previous studies18, 19, 20 with ours in this regard. Nonetheless, with different blood pressure measuring techniques, these studies produced similar results.
Why the association between diastolic blood pressure and oxygen desaturation is stronger in younger subjects remained to be elucidated. There are several possible explanations. First, older subjects have less elastic arteries than younger people and have higher prevalence of hypertension.21, 22 Older subjects therefore are less likely to show effect of oxygen desaturation on blood pressure, if any. Second, as shown in the present study and numerous previous studies,11, 23, 24 heart rate and sympathetic over‐activation might be a pathogenic mechanism for hypertension associated with hypoxia and hypoxemia in obstructive sleep apnea. Both sympathetic nervous function and the heart rate response to sympathetic activation tend to be impairing with age advancing.11 In the absence of heart rate response to sympathetic activation, the effect of hypoxia or hypoxemia on blood pressure may be attenuated. Third, it is also possible that with age advancing, oxygen is simply less required, and in other words, tolerability to hypoxia or hypoxemia increases.25, 26, 27 The effect of hypoxia or hypoxemia is therefore attenuated.
Similar explanations might help in understanding why the association between systolic blood pressure and oxygen desaturation index was less dependent on age, and did not reach statistical significance. Systolic blood pressure increases with arterial stiffness. With elastic arteries in the young, systolic blood pressure is less likely to increase even in the presence of sympathetic activation.
In our study, men, compared with women, had significantly higher 24‐hour daytime and nighttime systolic and diastolic blood pressure, and higher ambulatory pulse rate over 24 hours. Men also had a higher oxygen desaturation index, and a higher prevalence of oxygen desaturation index ≥ 15 events/h. The possible reasons underpinning these sex‐related discrepancies could be that in our study, men, compared with women, had significantly greater body mass index (+1.3 kg/m²) and it is well known that Chinese men have a much higher proportion of alcohol intake than women.28 Both obesity29 and alcohol intake30 are well defined risk factors for OSAHS and hypertension.
Our study should be interpreted in the context of its limitations. First, our study is cross‐sectional and hence does not allow any causal inference. Second, our study was based on pulse oximetry. A full polysomnography was not performed. We cannot differentiate obstructive from central sleep apnea. In some patients, oxygen desaturation can be a consequence of central or combined central with obstructive apnea. Third, the information on the specific antihypertensive medication was incomplete. We cannot perform analysis according to the use of various antihypertensive medications. However, sensibility analysis in those people not on antihypertensive medication was confirmatory.
In conclusion, our study showed that nocturnal oxygen desaturation was positively associated with ambulatory blood pressure during nighttime sleep hours and in the daytime, especially in younger male subjects. This association might be mediated by pulse rate, a rough measure of sympathetic activity. An implication of our finding is that correction of hypoxemia by CPAP therapy or other therapeutic modalities may be particularly efficacious in younger subjects with sleep apnea and with faster heart rate. Future research should address the issue of therapeutic efficacy on intermediate or hard cardiovascular outcomes, especially after the failure of the Sleep Apnea Events Reduction (SAVE) trial in showing clinical outcome benefit of CPAP therapy in obstructive sleep apnea.31
DISCLOSURES
Dr. Wang reports receiving lecture and consulting fees from Bayer, Daiichi‐Sankyo, Novartis, Omron, Pfizer, Sanofi, and Servier.
Supporting information
ACKNOWLEDGMENTS
We gratefully acknowledge the voluntary participation of all study subjects and the technical assistance of Jun‐Wei Li, Xiao‐Ren Lin, Bei‐Wen Lv, Yu‐Zhong Shi, Yi Zhou, and Yi‐Ni Zhou (The Shanghai Institute of Hypertension, China).
Chen Q, Cheng Y‐B, Liu C‐Y, et al. Ambulatory blood pressure in relation to oxygen desaturation index as simultaneously assessed by nighttime finger pulse oximetry at home. J Clin Hypertens. 2018;20:648–655. 10.1111/jch.13254
Qi Chen and Yi‐Bang Cheng contributed equally to this work.
Funding information
The present study was financially supported by grants from the National Natural Science Foundation of China, grant numbers: 81270373, 81470533, and 91639203); the Ministry of Science and Technology, grant numbers: 2015AA020105‐06 and 2016YFC1300100; the Shanghai Commission of Science and Technology, grant number: 15XD1503200; and grants from Philips.
REFERENCES
- 1. Sjostrom C, Lindberg E, Elmasry A, Hagg A, Svardsudd K, Janson C. Prevalence of sleep apnoea and snoring in hypertensive men: a population based study. Thorax. 2002;57:602‐607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Drager LF, Genta PR, Pedrosa RP, et al. Characteristics and predictors of obstructive sleep apnea in patients with systemic hypertension. Am J Cardiol. 2010;105:1135‐1139. [DOI] [PubMed] [Google Scholar]
- 3. Logan AG, Perlikowski SM, Mente A, et al. High prevalence of unrecognized sleep apnoea in drug‐resistant hypertension. J Hypertens. 2001;19:2271‐2277. [DOI] [PubMed] [Google Scholar]
- 4. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA. 2003;289:2560‐2572. [DOI] [PubMed] [Google Scholar]
- 5. Leung AA, Nerenberg K, Daskalopoulou SS, et al. Hypertension Canada's 2016 Canadian hypertension education program guidelines for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol. 2016;32:569‐588. [DOI] [PubMed] [Google Scholar]
- 6. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31:1281‐1357. [DOI] [PubMed] [Google Scholar]
- 7. Nieto FJ, Young TB, Lind BK, et al. Association of sleep‐disordered breathing, sleep apnea, and hypertension in a large community‐based study. Sleep Heart Health Study. JAMA. 2000;283:1829‐1836. [DOI] [PubMed] [Google Scholar]
- 8. Nagata K, Osada N, Shimazaki M, et al. Diurnal blood pressure variation in patients with sleep apnea syndrome. Hypertens Res. 2008;31:185‐191. [DOI] [PubMed] [Google Scholar]
- 9. Fletcher EC. Sympathetic over activity in the etiology of hypertension of obstructive sleep apnea. Sleep. 2003;26:15‐19. [DOI] [PubMed] [Google Scholar]
- 10. Roche F, Pepin JL, Achour‐Crawford E, et al. At 68 years, unrecognised sleep apnoea is associated with elevated ambulatory blood pressure. Eur Respir J. 2012;40:649‐656. [DOI] [PubMed] [Google Scholar]
- 11. Sforza E, Chouchou F, Pichot V, Barthelemy JC, Roche F. Heart rate increment in the diagnosis of obstructive sleep apnoea in an older population. Sleep Med. 2012;13:21‐28. [DOI] [PubMed] [Google Scholar]
- 12. Zhang L, Li Y, Wei FF, et al. Strategies for classifying patients based on office, home, and ambulatory blood pressure measurement. Hypertension. 2015;65:1258‐1265. [DOI] [PubMed] [Google Scholar]
- 13. Parati G, Stergiou G, O'Brien E, et al. European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring. J Hypertens. 2014;32:1359‐1366. [DOI] [PubMed] [Google Scholar]
- 14. Pankow W, Nabe B, Lies A, et al. Influence of sleep apnea on 24‐hour blood pressure. Chest. 1997;112:1253‐1258. [DOI] [PubMed] [Google Scholar]
- 15. Davies CW, Crosby JH, Mullins RL, Barbour C, Davies RJ, Stradling JR. Case‐control study of 24 hour ambulatory blood pressure in patients with obstructive sleep apnoea and normal matched control subjects. Thorax. 2000;55:736‐740. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Martynowicz H, Porębska I, Poręba R, Mazur G, Brzecka A. Nocturnal blood pressure variability in patients with obstructive sleep apnea syndrome. Adv Exp Med Biol. 2016;952:9‐15. [DOI] [PubMed] [Google Scholar]
- 17. Lettau F, Schwarz EI, Stradling JR, Kohler M. Blood pressure variability in obstructive sleep apnoea: data from 4 randomised controlled CPAP withdrawal trials. Respiration. 2017;93:311‐318. [DOI] [PubMed] [Google Scholar]
- 18. Young T, Peppard P, Palta M, et al. Population‐based study of sleep‐disordered breathing as a risk factor for hypertension. Arch Intern Med. 1997;157:1746‐1752. [PubMed] [Google Scholar]
- 19. Grote L, Ploch T, Heitmann J, Knaack L, Penzel T, Peter JH. Sleep‐related breathing disorder is an independent risk factor for systemic hypertension. Am J Respir Criti Care Med. 1999;160:1875‐1882. [DOI] [PubMed] [Google Scholar]
- 20. Tanigawa T, Tachibana N, Yamagishi K, et al. Relationship between sleep‐disordered breathing and blood pressure levels in community‐based samples of Japanese men. Hypertens Res. 2004;27:479‐484. [DOI] [PubMed] [Google Scholar]
- 21. Avolio AP, Chen SG, Wang RP, Zhang CL, Li MF, O'Rourke MF. Effects of aging on changing arterial compliance and left ventricular load in a Northern Chinese urban community. Circulation. 1983;68:50‐58. [DOI] [PubMed] [Google Scholar]
- 22. Lloyd‐Jones DM, Evans JC, Levy D. Hypertension in adults across the age spectrum: current outcomes and control in the community. JAMA. 2005;294:466‐472. [DOI] [PubMed] [Google Scholar]
- 23. Imadojemu VA, Mawji Z, Kunselman A, Gray KS, Hogeman CS, Leuenberger UA. Sympathetic chemoreflex responses in obstructive sleep apnea and effects of continuous positive airway pressure therapy. Chest. 2007;131:1406‐1413. [DOI] [PubMed] [Google Scholar]
- 24. Mansukhani MP, Kara T, Caples SM, Somers VK. Chemoreflexes, sleep apnea, and sympathetic dysregulation. Curr Hypertens Rep. 2014;16:476. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Bianchi G, Di Giulio C, Rapino C, Rapino M, Antonucci A, Cataldi A. P53 and p66 proteins compete for hypoxia‐inducible factor 1 alpha stabilization in young and old rat hearts exposed to intermittent hypoxia. Gerontology. 2006;52:17‐23. [DOI] [PubMed] [Google Scholar]
- 26. Lavie P, Lavie L. Unexpected survival advantage in elderly people with moderate sleep apnoea. J Sleep Res. 2009;18:397‐403. [DOI] [PubMed] [Google Scholar]
- 27. Launois SH, Pepin JL, Levy P. Sleep apnea in the elderly: a specific entity? Sleep Med Rev. 2007;11:87‐97. [DOI] [PubMed] [Google Scholar]
- 28. Huang QF, Sheng CS, Liu M, Li FH, Li Y, Wang JG. Arterial stiffness and wave reflections in relation to plasma advanced glycation end products in a Chinese population. Am J Hypertens. 2013;26:754‐761. [DOI] [PubMed] [Google Scholar]
- 29. Goodfriend TL. Obesity, sleep apnea, aldosterone, and hypertension. Curr Hyperten Rep. 2008;10:222‐226. [DOI] [PubMed] [Google Scholar]
- 30. Choi SJ, Lee SI, Joo EY. Habitual alcohol consumption and metabolic syndrome in patients with sleep disordered breathing. PLoS One. 2016;11:e0161276. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. McEvoy RD, Antic NA, Heeley E, et al. CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med. 2016;375:919‐931. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials