Effects of the presence of hypertension on the relationship between obstructive sleep apnoea and sleepiness

Authors


Kazuo Chin, Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University, 54 Kawara-machi, Shogoin, Sakyo-ku, Kyoto-city, Kyoto, 606-8507, Japan. Tel.: +81-75-751-3852; fax: +81-75-751-3854; e-mail: chink@kuhp.kyoto-u.ac.jp

Summary

Obstructive sleep apnoea (OSA) plays a significant role in increasing blood pressure. Significant decreases were reported in blood pressure of hypertensive OSA patients with sleepiness who underwent continuous positive airway pressure (CPAP) treatment, but not in non-sleepy hypertensive OSA patients. More recently, however, significant decreases in blood pressure in non-sleepy hypertensive OSA patients following CPAP were shown. Effects of sleepiness on hypertension in OSA patients have been investigated, but not the effects of hypertension on sleepiness in OSA patients. We investigated the relationships between hypertension and sleepiness in patients with OSA. We analysed data on 275 middle-aged male subjects from a cross-sectional epidemiological health survey. We measured blood pressure and sleep duration objectively using an actigraph for 7 days and the respiratory disturbance index (RDI) with a type 3 portable device for 2 nights, and assessed sleepiness using the Epworth Sleepiness Scale (ESS). The RDI correlated significantly with ESS scores in the 88 hypertensive subjects (= 0.33, = 0.0024), but not in the 187 non-hypertensive subjects (= −0.01, = 0.91). Short sleep duration correlated significantly with ESS scores in both groups. Both the RDI and short sleep duration were related independently to sleepiness in only hypertensive subjects. Furthermore, the RDI was related negatively significantly to sleep duration in hypertensive subjects. Although short sleep duration was related significantly to sleepiness in both groups, hypertension may be important for the sleepiness in OSA patients. Detailed mechanisms of the difference in the relationship between sleepiness and the severity of OSA with or without hypertension should be studied further.

Introduction

A large body of work has shown that obstructive sleep apnoea (OSA) plays a significant role in increasing blood pressure (Garvey et al., 2009). Systemic hypertension in OSA, often underdiagnosed, is a large clinical problem, as it may increase the cardiovascular risk of OSA. Currently, continuous positive airway pressure (CPAP) treatment is the first-line treatment of OSA. However, there has been some conflict over whether CPAP can reduce systemic blood pressure in patients with OSA (Robinson et al., 2004). There may be subgroups of patients with OSA who benefit from CPAP treatment in terms of blood pressure control (Robinson et al., 2004). From this viewpoint, several studies suggested that OSA patients with prior daytime sleepiness were likely to experience a lowering of blood pressure after CPAP treatment (Barbéet al., 2001; Robinson et al., 2004, 2006, 2008), while Barbéet al. (2010) recently reported a decrease in blood pressure in non-sleepy hypertensive patients with OSA after CPAP treatment. Thus, the effects of sleepiness on hypertension in OSA patients have been investigated, but the effects of hypertension on sleepiness in these patients have not been studied.

We hypothesized that hypertension and sleepiness in OSA patients have a significant relationship. To investigate this relationship, using information from a cross-sectional epidemiological health survey in a group of middle-aged male employees in Japan (Chin et al., 2010; Nakayama-Ashida et al., 2008), we analysed the relationship between sleepiness and OSA in subjects with or without hypertension, taking into account objectively measured sleep duration by actigraph. Accurate measurements of sleep duration are important in investigating the effects of hypertension on sleepiness in OSA patients, as sleep duration has been shown to be an important factor for sleepiness in OSA patients (Vakulin et al., 2009). Although most epidemiological studies used subjective self-reported sleep duration, such self-reports may be inaccurate and cause misclassification of sleep duration (Lauderdale et al., 2008; Van Den Berg et al., 2008). Thus, actigraphic measurements used in this study will ensure greater accuracy in sleep duration data than in previous reports.

Methods

Subjects

Study subjects were male employees of an urban wholesale company in Japan, as reported previously elsewhere in detail (Chin et al., 2010; Nakayama-Ashida et al., 2008). Of the 322 male employees who were first entered into the study (Nakayama-Ashida et al., 2008), 275 were investigated further to examine the relationship between OSA and metabolic syndrome (Chin et al., 2010). In the present study, we analysed data on those 275 subjects regarding the relationship between sleepiness, sleep duration and OSA with or without hypertension. The study protocol was approved by the Kyoto University Graduate School and Faculty of Medicine Ethics Committee. Written informed consent was obtained from all subjects.

Measurements of weight, waist circumference and blood pressure

Trained research staff performed measurements of weight, waist circumference and blood pressure. Blood pressure was measured seven times using OMRON HEM-759P (Kyoto, Japan) after subjects were seated and rested for 1–2 min, with the average of the last three measurements used for the analyses. Individuals who had systolic blood pressure readings of more than 140 mmHg, diastolic readings of more than 90 mmHg, a history of a diagnosis of hypertension before the study measurements or were currently using anti-hypertensive medications were defined as having hypertension (Joint National Committee, 1993).

Home monitoring of sleep

We determined sleep duration by actigraphy (Littner et al., 2003), in conjunction with a sleep diary. Each subject was asked to wear an actigraph (Actiwatch AW-Light; Mini Mitter, Brend, OR, USA) (Littner et al., 2003) for 7 days to estimate sleep–wake time, and a type 3 portable monitor (PM) (Morpheus; Teijin, Tokyo, Japan, which is the same as Somté; Compumedics, Vic., Australia) (Chesson et al., 2003), an alternative for polysomnography in the diagnosis of OSA (Kushida et al., 2005), for 2 nights at home.

Actigraph and PM data analysis

The respiratory disturbance index (RDI: number of apnoea and hypopnoea episodes per hour of the analysed time) was calculated from both the actigraphy and PM. Records of the PM were inspected visually and scored by at least two medical doctors specialized in respiratory medicine. Apnoea is defined as the cessation of breathing for at least 10 s and hypopnoea as a more than 50% reduction in the amplitude of nasal pressure or respiratory effort associated with more than 3% reduction in oxyhaemoglobin saturation for at least 10 s. Apnoea and hypopnoea were scored while blinded to other information, except for sleep–wake time by actigraphy. Data without oxygen saturation values and illegible recordings were excluded from analysis. Data for <2 h were also excluded, because the Medicare guidelines require at least 2 h of documented sleep time. When data from both recorded nights were available, records from the second night were analysed further.

Assessment of sleepiness

The modified Japanese version of the Epworth Sleepiness Scale (ESS) was used to assess subjective sleepiness (Takegami et al., 2009). A separate sleep diary was also completed during the survey period (Nakayama-Ashida et al., 2008).

Statistical analysis

Results are expressed as mean ± standard deviation (SD). Unpaired t-tests were used to compare the backgrounds between the hypertensive and non-hypertensive subjects and between treated and untreated hypertensive subjects. Relationships between the two sets of data were analysed by Pearson’s correlation coefficient tests. Multiple regression analyses were performed to identify those variables that could best predict sleepiness by the ESS scores using the RDI and sleep duration as explanatory variables. P-values <0.05 were considered to be statistically significant. All analyses were performed using Statview 5.0 (SAS Institute, Inc. Cary, NC, USA).

Results

Characteristics of the subjects

Characteristics of the subjects are presented in Table 1. A total of 88 subjects (32.0%) had hypertension; among these, 25 (28.4%) were being treated with anti-hypertensive medicine. From our examination of the subjects, we could not identify any subject who took medicine during the daytime that could affect sleepiness. RDI, sleep duration and ESS scores of the hypertensive subjects treated with anti-hypertensive medicine and the untreated hypertensive subjects did not differ significantly (= 0.20, 0.061 and 0.87, respectively). A total of 161 subjects (58.5%) had OSA (5 ≤ RDI). The hypertensive subjects were older (< 0.001) and had a higher RDI than those without hypertension (12.2 ± 12.0 h−1 versus 9.3 ± 10.0 h−1, = 0.034), while the body mass index (BMI), waist circumference, sleep duration and ESS scores did not differ between the two groups.

Table 1.   Characteristics of the subjects
 All subjectsSubjects with hypertensionSubjects without hypertensionP-value
  1. Values are presented as mean ± standard deviation or n (%) unless stated otherwise. BMI, body mass index; ESS, Epworth Sleepiness Scale; RDI, respiratory disturbance index.

Number of subjects (%)27588 (32.0)187 (68.0) 
Age (years)44 ± 848 ± 742 ± 8<0.001
BMI (kg m−2)23.9 ± 3.124.2 ± 3.623.8 ± 2.90.42
Waist circumference (cm)83.6 ± 8.585.0 ± 9.383.0 ± 8.00.075
RDI (h−1)10.2 ± 10.712.2 ± 12.09.3 ± 10.00.034
Sleep duration (h)6.0 ± 0.86.0 ± 0.86.0 ± 0.80.51
ESS score8.2 ± 4.37.9 ± 4.38.3 ± 4.30.43
Systolic blood pressure (mmHg)129 ± 14143 ± 12122 ± 8<0.001
Diastolic blood pressure (mmHg)81 ± 1191 ± 976 ± 8<0.001

Among the 88 hypertensive subjects, 59 (67.0%) had OSA (5 ≤ RDI) and 23 (26.1%) had moderate-to-severe OSA (15 ≤ RDI). Among the 187 non-hypertensive subjects, 102 (54.5%) had OSA and 35 (18.7%) had moderate-to-severe OSA.

Relationships between sleepiness and OSA, and between sleepiness and sleep duration

Fig. 1 shows the relationships between sleepiness estimated by ESS scores and OSA in the hypertensive and non-hypertensive groups. The RDI was correlated significantly but weakly with ESS scores in the hypertensive subjects [correlation coefficient (r) = 0.33, = 0.0024] but not in the non-hypertensive subjects (= −0.01, = 0.91) (Table 2a). With regard to relationships between sleepiness and sleep duration in the hypertensive and non-hypertensive groups, as well as in all subjects taken together, although sleep duration was correlated significantly with ESS scores in the hypertensive subjects (= −0.30, = 0.0050) this relationship was also seen in the non-hypertensive subjects (= −0.18, = 0.014) (Table 2a) and in the entire subject population (= −0.22, < 0.001). Lastly, multiple regression analyses to predict sleepiness estimated by ESS scores were performed using the RDI and sleep duration as explanatory variables in the hypertensive and non-hypertensive groups. These analyses revealed that both the RDI and sleep duration explained ESS scores independently only in the hypertensive group [contribution rate (R2) = 8.6% and 6.9%, respectively] but, in contrast, sleep duration alone explained the ESS scores independently in the non-hypertensive group (R2 = 3.2%) (Table 2b,c).

Figure 1.

 Relationship between Epworth Sleepiness Scale scores and respiratory disturbance index in the subjects with hypertension (HT) (a) and in the subjects without hypertension (NHT) (b). ESS, Epworth Sleepiness Scale; RDI, respiratory disturbance index.

Table 2.   (a) Univariate analyses of correlation coefficient among sleepiness assessed by ESS scores, the severity of OSA assessed by RDI and sleep duration. Multiple regression analyses to predict sleepiness assessed by ESS scores in subjects (b) with hypertension (n = 88) and (c) without hypertension (= 187)
 Subjects with HTSubjects without HT
(a)
 ESS score and RDI0.33*−0.01
 ESS score and sleep duration−0.30*−0.18*
 RDI and sleep duration−0.29*−0.13
 βγR2(%)
  1. ESS, Epworth Sleepiness Scale; OSA, obstructive sleep apnoea; RDI, respiratory disturbance index; HT, hypertension; NA, not applicable. In (a), data are expressed as correlation coefficient and *< 0.05; in (b and c), β, standard regression coefficient, r, correlation coefficient and R2, contribution rate.

(b)
 RDI (h−1)0.260.338.6
 Sleep duration (h)−0.23−0.306.9
 Cumulative R2  15.5
(c)
 RDI (h−1)NANA NA
 Sleep duration (h)−0.18−0.183.2
 Cumulative R2  3.2

Relationship between RDI and sleep duration

We examined further the relationship between RDI and sleep duration. As a whole, RDI and sleep duration had a negative relationship (= −0.19, = 0.0017). As shown in Fig. 2, in the hypertensive group the RDI was related negatively significantly to sleep duration (= −0.29, = 0.0056), but there was no significant relationship in the non-hypertensive group (= −0.13, = 0.084) (Table 2a).

Figure 2.

 Relationship between respiratory disturbance index and sleep duration in the subjects with hypertension (HT) (a) and in the subjects without hypertension (NHT) (b). RDI, respiratory disturbance index.

Discussion

In the present cross-sectional epidemiological survey in an urban company in Japan, we compared the relationships between sleepiness and OSA in subjects with or without hypertension. We found that short sleep duration was related to sleepiness both in the hypertensive and non-hypertensive subjects, but that the RDI was also related significantly to sleepiness independently of sleep duration only in the hypertensive subjects. In addition, we observed an inverse relationship between the RDI and sleep duration in the hypertensive subjects.

In the present study, insufficient sleep was an important determinant of sleepiness regardless of the existence of hypertension. Pack et al. (2006) also reported that among commercial driver’s licence holders, chronic short sleep duration rather than sleep apnoea was a risk factor for sleepiness. In addition, a recent report showed that OSA patients were more vulnerable than healthy subjects to the effects of sleep restriction (Vakulin et al., 2009). Indeed, the patients with OSA made more mistakes in the driving simulation test following sleep restriction than the subjects without OSA (Vakulin et al., 2009). Thus, adequate sleep duration would be necessary for patients with OSA as well as for subjects without OSA. In this study, sleep duration was measured in home settings. Although, in many studies, sleep duration was assessed by overnight polysomnography in laboratory settings, in that situation subjects tended to sleep more poorly than at home (Kapur et al., 2005). In addition, sleep duration was measured by actigraph for a week in this study. Although most epidemiological studies use self-reported sleep duration, which may not be accurate, differences between actigraph-measured and subjective reported sleep durations were detected, and objectively measured sleep duration is recommended (Lauderdale et al., 2008; Van Den Berg et al., 2008). Thus, in our study, using both actigraphy and a sleep diary under usual circumstances for a week, we could examine sleep duration accurately to explore the importance of adequate sleep.

This study also showed that the significant but weak relationship between RDI and sleepiness was dependent on the existence of hypertension. Despite some conflicting results in interventional trials of treatment of OSA and hypertension, pre-treatment sleepiness is an important factor in determining a reduction in blood pressure after CPAP treatment (Robinson et al., 2004). Thus, it is suggested that there is some relationship between sleepiness in OSA and presence of hypertension. However, in this study there was a significant difference in age between subjects with and without hypertension. Therefore, including objective assessment of sleepiness, such as with the multiple sleep latency test (MSLT), further studies would be needed to investigate the difference in sleepiness in OSA subjects with and without hypertension.

We noticed an inverse relationship between the RDI and sleep duration. There has not been sufficient evidence to suggest that patients with OSA sleep more or less than average, although short sleep duration or sleep fragmentation is reported to be associated with obesity (Knutson et al., 2007; Van Den Berg et al., 2008), a main risk factor for OSA. Interestingly, this relationship was observed with actigraphically determined sleep duration, as in our study, and was undetectable with self-reported sleep duration (Van Den Berg et al., 2008) which indicated the advantage of our study, which included actigraph data.

The prevalence of males with moderate-to-severe OSA in this study was 21.1%, which is equivalent to the data from the Sleep Heart Health Study showing a prevalence of 25.0% (Baldwin et al., 2004). Among the hypertensive and non-hypertensive subjects, 26.1% and 18.7% had moderate-to-severe OSA, respectively, which is equivalent to findings of another study (Hla et al., 1994). In addition, the prevalence of hypertension among Japanese males in their 40s was 35.5% in 2006 (Ministry of Health, Labor and Welfare, 2006; updated 2008), which is similar to that in this study (32.0%). Therefore, our data are applicable to reflect the current background in Japan.

There are some limitations to this study. First, this was a cross-sectional study and it was difficult to exclude completely the influence of confounders such as age, obesity, and medication, etc., as mentioned above. Secondly, we did not perform polysomnography, partly because we wanted to perform the study under usual lifestyle conditions. However, the interscorer and night-to-night reliability of the RDI were excellent (interclass correlation coefficients of 0.98 and 0.95, respectively) (Nakayama-Ashida et al., 2008). In addition, it has been reported that the non-attached type 3 PM is reliable under the specified conditions in which our study was conducted (Collop et al., 2007). Thirdly, we did not assess sympathetic activity, nor did we administer the MSLT to estimate sleepiness objectively.

In conclusion, although this study had several limitations, we showed that sleepiness was related to the severity of OSA in the hypertensive subjects, but not in the non-hypertensive subjects. Also, we showed that sleepiness was related to short sleep duration in both groups. Furthermore, we observed a relationship between short sleep duration and the severity of OSA in the hypertensive subjects. Thus, in addition to sleep duration, OSA accompanied by hypertension may be important in sleepiness. Further study is needed to determine details of the mechanism of the difference in the relationship between sleepiness and the severity of OSA with or without hypertension.

Conflicts of Interest

No authors have indicated any financial conflicts of interest.

Acknowledgements

This work was supported in part by a grant from the Japanese Ministry of Education, Culture, Sports, Science and Technology (no.20590921), Respiratory Failure Research Group, a Health Science Research Grants, Comprehensive Research on Life-Style Related Diseases including Cardiovascular Diseases and Diabetes Mellitus, from the Japanese Ministry of Health, Labor and Welfare, the Japan Vascular Disease Research Foundation, and research grants from Presto JST, Suzuken Memorial Foundation, Takeda Science Foundation, Mitsui Life Social Welfare Foundation, Chiyoda Kenko Kaihatsu Jigyodan Foundation and Health Science Center Foundation. In addition, we would like to thank all the participants. This was not an industry-supported study.

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