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Abstract

Objective

To investigate the prevalence of hypertension and circadian blood pressure (BP) variations in patients with obstructive sleep apnoea–hypopnoea syndrome (OSAHS).

Methods

Patients referred to a sleep clinic underwent polysomnography with measurement of BP at four time points. They were classified into four groups (control, and mild, moderate or severe sleep apnoea) using the apnoea–hypopnoea index (AHI). Circadian variation was assessed using night-time to daytime mean BP (R_N/D) and morning to evening mean BP (R_M/E) ratios.

Results

Hypertension was significantly more common in patients with OSAHS (50.5%) than in controls (30.4%). AHI was positively correlated with hypertension after controlling for related confounders. Mean BP values at all four time points rose with increasing AHI. The increase in night-time and morning values was more pronounced than the increase in daytime and evening values in patients with OSAHS, resulting in loss of the normal BP diurnal rhythm. The R_N/D and R_M/E ratios increased with increasing AHI. Daytime BP was significantly correlated with AHI and the lowest oxygen saturation value.

Conclusion

OSAHS was shown to be an independent risk factor for hypertension. It was also associated with loss of the normal BP diurnal rhythm.

Keywords

Obstructive sleep apnoea–hypopnoea syndrome hypertension apnoea–hypopnoea index lowest oxygen saturation circadian variation blood pressure

Introduction

Obstructive sleep apnoea–hypopnoea syndrome (OSAHS) is a common breathing disorder characterized by frequent upper airway collapse and obstruction during sleep.¹ Observational and longitudinal population studies have shown a clear independent association between OSAHS and hypertension.² Both OSAHS and hypertension are chronic conditions that, if untreated, are associated with impairment of quality of life and considerable morbidity and mortality resulting from chronic cardiopulmonary conditions and acute cardiovascular events such as stroke, myocardial infarction and nocturnal sudden death.³ A large multicentre study by He et al.⁴ reported variations in the BP profile in Chinese patients with OSAHS. However, further investigation of the prevalence and pattern of hypertension in these patients is required. The present study, therefore, investigated the prevalence of hypertension and circadian blood pressure (BP) variations in Chinese patients with OSAHS.

Patients and methods

Patients

Consecutive patients aged ≥18 years referred to the Sleep Clinic of Tianjin Medical University General Hospital, Tianjin, China, between April 2010 and December 2012 were recruited to the study. Patient information, including name, sex, age, body mass index (calculated as the weight in kilograms divided by the square of the height in metres), family medical history, smoking and drinking history, snoring history, Epworth sleepiness score (ESS),⁵ hypertension history and antihypertensive drug use, was collected and recorded by the same staff member. The effectiveness of antihypertensive treatment was scored from 3 to 0 as follows: 3 (effective), BP steadily controlled <140/90 mmHg with use of medications; 2 (partly effective), BP remains fluctuating with use of medications; 1 (ineffective), BP unable to be controlled with use of medications; 0 (resistant hypertension), BP remains above goal in spite of the concurrent use of three antihypertensive agents of different classes.

Verbal informed consent was obtained from all study participants and the study protocol was approved by Tianjin Medical University General Hospital Ethics Committee.

Blood pressure measurements

Blood pressure was measured in all study participants under standardized conditions at four time points: daytime (in clinic, 09:00 to 11:00 hours); evening (just before lights out on the night of the sleep polysomnography study, 21:30 to 23:30 hours); night-time (during sleep, 02:00 to 04:00 hours); and morning (just after waking following the polysomnography study, 05:30 to 07:30 hours). At each time point, three consecutive readings were taken from the right arm in a supine position at 15 s intervals following a 5 min rest; the mean of the three values was used for the subsequent analyses. Hypertension was defined according to the 2013 European Society of Hypertension/European Society of Cardiology guidelines⁶ as a systolic BP ≥ 140 mmHg and/or a daytime diastolic BP ≥90 mmHg, or a history of hypertension. The mean BP (MBP) was calculated as follows: (systolic BP − diastolic BP)/3 + diastolic BP.⁷ Circadian BP variation was assessed using the ratio of night-time to daytime MBP (R_N/D) and the ratio of morning to evening MBP (R_M/E).

Polysomnography

Nocturnal polysomnography (PSG) was performed in all study participants in the sleep centre of Tianjin Medical University General Hospital, Tianjin, China, and included the measurement of oral and nasal airflow, respiratory effort, snoring, heart rate and oxygen saturation ( S _ao₂). The presence and severity of OSAHS was assessed using the apnoea–hypopnoea index (AHI),⁸ which is based on the number of apnoic/hypopnoic episodes per h of sleep. Study participants were classified into four severity groups: control (AHI < 5 episodes/h); mild sleep apnoea (5 episodes/h ≤ AHI < 15 episodes/h); moderate sleep apnoea (15 episodes/h ≤ AHI < 30 episodes/h); and severe sleep apnoea (AHI ≥ 30 episodes/h).

Statistical analyses

Unless stated otherwise, values were reported as the mean ± SD. One-way analysis of variance with Tamhane’s T2 post hoc multiple comparisons were used to analyse differences between groups. Analysis of cross-tabulation tables using the χ²-test was used to compare the prevalence of hypertension in the different severity groups. The χ²-test was also used to compare the ESS, smoking history, drinking history and drug effectiveness score between the groups. To eliminate the effects of related confounders, partial correlations were performed between target variables; bivariate correlation was performed between AHI or the lowest S _ao₂ (L S _ao₂) and BP. Stepwise linear regression was performed for influential power estimating. A P-value < 0.05 was considered to be statistically significant. All statistical analyses were performed using SPSS software version 17.0 (SPSS Inc., Chicago, IL, USA).

Results

A total of 3131 patients aged 18–81 years (2669 male and 462 female) were included in the study. When divided according to severity of OSAHS on the basis of the AHI, 326 were classified as controls, 505 had mild sleep apnoea, 580 had moderate sleep apnoea and 1720 had severe sleep apnoea.

Patient characteristics and the prevalence of hypertension in the four different groups are summarized in Table 1. Patients with severe sleep apnoea had a significantly higher prevalence of hypertension than controls (58.4% compared with 30.4%; P < 0.001). In addition, the prevalence of hypertension in all patients with OSAHS (mild, moderate and severe) was significantly higher than in controls (50.5% compared with 30.4%; P < 0.001). AHI was positively correlated with the prevalence of hypertension after controlling for the related confounders of age, sex, body mass index, smoking history and drinking history (r = 0.176, P < 0.001).

Table 1.

Patient characteristics and prevalence of hypertension in controls and patients with obstructive sleep apnoea–hypopnoea syndrome (OSAHS).

	Controls n = 326	Patients with OSAHS
	Controls n = 326	Mild n = 505	Moderate n = 580	Severe n = 1720
Sex
Male	246 (75.5)	414 (82.0)	502 (86.6)	1507 (87.6)
Female	80 (24.5)	91 (18.0)	78 (13.5)	213 (12.4)
History of smoking	140 (42.9)	231 (45.7)	280 (48.3)	981 (57.0)
History of drinking	120 (36.8)	195 (38.6)	230 (39.7)	821 (47.7)
Age, years	43.2 ± 12.8	44.6 ± 13.7	45.5 ± 12.7	47.7 ± 11.0^a
Body mass index, kg/m²	26.5 ± 4.1	26.6 ± 3.8	26.9 ± 3.8	28.9 ± 4.0^a
AHI, episodes/h	2.0 ± 1.3^a	9.3 ± 2.9^a	21.6 ± 4.1^a	57.5 ± 17.7^a
L S _ao₂, %	87.3 ± 8.5^a	82.4 ± 9.9^a	79.0 ± 9.3^a	66.8 ± 13.2^a
Epworth sleepiness score	7.4 ± 5.2	7.8 ± 4.1	8.4 ± 4.3	11.7 ± 5.6
History of snoring	176 (54.0)	356 (70.5)	491 (84.7)	1633 (94.9)
History of hypertension	68 (20.9)	143 (28.3)	172 (29.7)	669 (38.9)
Regular medication	40 (12.3)	97 (19.2)	118 (20.3)	442 (25.7)
Drug effectiveness score
3	38 (55.9)	86 (60.1)	90 (52.3)	318 (47.5)
2	22 (32.4)	49 (34.3)	70 (40.7)	280 (41.9)
1	4 (5.9)	5 (3.5)	10 (5.8)	60 (9.0)
0	4 (5.9)	3 (2.1)	2 (1.2)	11 (1.6)
Hypertension	99 (30.4)	188 (37.2)	223 (38.5)	1004 (58.4^a)

Data presented as number (%) of patients or mean ± SD.

AHI, apnoea–hypopnoea index; L S _ao₂, lowest oxygen saturation.

^aP ≤ 0.001 compared with other groups using one-way analysis of variance with Tamhane’s T2 post hoc multiple comparisons or χ²-test analysis of cross-tabulation tables.

For Epworth sleepiness score: χ²= 370.64, v = 3, P ≤ 0.001 between groups. For smoking history: χ²= 40.39, v = 3, P ≤ 0.001 between groups. For drinking history: χ²= 26.42, v = 3, P ≤ 0.001 between groups. For drug effectiveness score: χ²= 9.31, v = 3, P = 0.025 between groups. For history of snoring: χ²= 458.27, v = 3, P ≤ 0.001 between groups. For prevalence of hypertension: χ²= 159.18, v = 3, P < 0.001 between groups.

Table 2 shows MBP, R_N/D and R_M/E values in the four different groups. MBP values at all the different time points rose as AHI increased, and were significantly higher in the severe group than in the other three groups after post hoc analysis. After controlling for the related confounders of age, sex, body mass index, smoking history and drinking history, partial correlations showed that all the daytime, night-time, evening and morning MBP values were positively correlated with AHI (r = 0.097, 0.073, 0.097 and 0.123, respectively; P < 0.001 for all) and were negatively correlated with L S _ao₂ (r = −0.098, −0.119, −0.162 and −0.124, respectively; P < 0.001 for all).

Table 2.

Mean blood pressure (MBP) values at different time points, and night-time to daytime (R_N/D) and morning to evening (R_M/E) MBP ratios in controls and patients with obstructive sleep apnoea–hypopnoea syndrome (OSAHS).

	Controls n = 326	Patients with OSAHS			F
	Controls n = 326	Mild n = 505	Moderate n = 580	Severe n = 1720	F
Daytime MBP, mmHg	92.4 ± 11.4	95.2 ± 11.2^a	96.2 ± 11.4^a	100.4 ± 12.1^a,b,c	63.07
Evening MBP, mmHg	93.1 ± 11.3	95.4 ± 11.3^a	96.1 ± 11.1^a	99.9 ± 11.7^a,b,c	49.23
Night-time MBP, mmHg	90.8 ± 10.7	94.6 ± 12.0^a	96.3 ± 11.8^a	101.3 ± 12.5^a,b,c	96.21
Morning MBP, mmHg	93.0 ± 12.4	96.0 ± 13.0^a	98.1 ± 12.5^a	103.9 ± 13.5^a,b,c	100.79
R _N/D	0.99 ± 0.10	1.00 ± 0.09	1.00 ± 0.10	1.01 ± 0.11^a	7.71
R _M/E	1.00 ± 0.11	1.01 ± 0.10	1.02 ± 0.09^a	1.04 ± 0.10^a	25.60

Data presented as mean ± SD.

^aP < 0.05 compared with control group; ^bP < 0.05 compared with mild group; ^cP < 0.05 compared with moderate group using one-way analysis of variance with Tamhane’s T2 post hoc multiple comparisons.

Patients with OSAHS appeared to lose the normal BP diurnal rhythm, with the pattern of hypertension showing non-dipping (defined as a nocturnal BP drop < 10%).⁴ The increase in night-time and morning MBP values was more pronounced than the increase in daytime and evening MBP values, resulting in an increase in the R_N/D and R_M/E values (Table 2).

Systolic and diastolic daytime BPs were positively correlated with AHI (r = 0.192 and 0.270, respectively; P < 0.01 for both) and negatively correlated with L S _ao₂ (r = −0.203 and −0.253, respectively; P < 0.01 for both). When plotted against AHI, daytime MBP increased gradually with small fluctuations (Figure 1), reaching a plateau or even dropping slightly at an AHI value of approximately 61–65 episodes/h.

Figure 1.

Daytime mean blood pressure and apnoea–hypopnoea index (AHI) in controls and patients with mild, moderate or severe obstructive sleep apnoea–hypopnoea syndrome.

Discussion

Several studies have reported an association between OSAHS and hypertension;^2,4,9 these conditions share similar risk factors and both play an important role in the development of cardiovascular disease.^10,11 In the present study, the prevalence of hypertension in all patients with OSAHS (50.5%) was significantly higher than that in controls (30.4%) and increased with the severity of OSAHS, which is consistent with previous reports.² In addition, AHI and L S _ao₂ were closely related to BP values, with daytime, evening, night-time and morning MBP values rising with increasing AHI and decreasing L S _ao₂ after controlling for related confounders. This association between AHI and hypertension is likely to be related to high levels of sympathetic nerve activity in patients with OSAHS. Recurrent episodes of airway obstruction result in hypoxia and hypercapnia, increasing sympathetic neural tone through chemoreceptor reflexes and other mechanisms, which in turn causes vasoconstriction and marked increases in BP.⁹ High levels of endothelin and angiotensin II¹² as well as endothelial dysfunction¹³ induced by systemic inflammation and oxidative stress may also contribute to the increase in BP.

The BP response to OSAHS may be important in understanding the absence of a nocturnal decrease in BP in the subgroup of hypertensive patients with ‘non-dipping’ hypertension. Non-dipping is a common pattern of arterial hypertension that is associated with increased cardiovascular risk.¹⁴ In the present study, the increase in night-time and morning MBP values was more pronounced than the increase in daytime and evening MBP values. Possible mechanisms include disruption of normal sleep and circadian rhythms.⁹ Deeper, less-fragmented sleep has been reported to be associated with more pronounced BP dipping in normal subjects.¹⁵ However, the percentage of slow wave sleep and the arousal index each independently predicted only a small percentage (approximately 10%) of the variance seen with nocturnal diastolic BP dipping.¹⁶ The renin–angiotensin–aldosterone system (RAAS), plasma noradrenaline level and plasma adrenaline level are characterized by a circadian rhythm whose acrophase is seen in the morning, with minimum levels at night during sleep.¹⁷ Prorenin and angiotensin-converting enzyme also show a circadian rhythm.¹⁷ It has been reported that OSAHS may disturb the RAAS due to the chronic recurrent hypoxia and hypercapnia that frequently occur at night, resulting in increased serum angiotensin II and endothelin levels in patients with essential hypertension.^12,18 These patients are more likely to develop a non-dipping BP pattern and consequently are at higher risk of cardiovascular events, end-organ damage and mortality, independent of the BP load.¹⁹ Similar to the results of the present study, Stergiou et al.¹⁹ reported that an increase in AHI at night was associated with an absence of nocturnal dipping and a significant increase in urinary catecholamine levels. In addition, continuous positive airway pressure (CPAP) therapy was effective in preventing the transitory increase in BP.¹⁹ CPAP has also been shown to result in significant improvements in 24-h urinary noradrenaline level and BP in patients with severe OSAHS.²⁰

In the present study, OSAHS was not only associated with an increased BP during sleep, but also affected morning and daytime BP. Daytime BP values increased as the AHI increased, with both systolic and diastolic BP values being significantly correlated with AHI. Several neural and humoral mechanisms sharing a common pathogenetic pathway may contribute to the maintenance of higher sympathetic activity and persistent daytime hypertension in OSAHS patients. These include chemoreflex and baroreflex dysfunction, RAAS dysfunction and altered cardiovascular variability caused by increased sympathetic activity. High sympathetic drive has been shown to be present even during daytime wakefulness when patients with OSAHS were breathing normally with no evidence of hypoxia or chemoreflex activation.²¹ A study in rats has shown that intermittent hypoxia can cause sympathetic activity and increased BP.²² High levels of vasoconstrictors in the plasma, endothelial dysfunction caused by systemic inflammation and oxidative stress, metabolic dysregulation and atherosclerosis may contribute to the increase in morning and daytime BP in OSAHS.²³ Effective CPAP has been reported to result in a significant decrease in both night-time and daytime BP.^24,25

In the present study, after the AHI reached approximately 61 episodes/h, the increasing trend in daytime BP reached a plateau. One possible explanation for this is that the inflammatory status of endothelial cells increases to peak levels and then falls to a minimum, with the frequency of intermittent hypoxia/reoxygenation continuously increasing.²⁶ In vitro experiments have shown that intermittent hypoxia significantly damages endothelial cells in a dose-dependent manner, especially when combined with hypercapnia.²⁷ However, further studies are needed to elucidate the mechanisms involved.

There are a number of limitations to the present study. Most of subjects referred to the sleep centre were suffering from snoring, and Nakano et al.²⁸ reported that snoring per se could increase BP; this is consistent with the prevalence of hypertension in the control group being a little higher than that in other studies.^2,25 Moreover, the present study did not consider first-night effects and insomnia,²⁷ which may have influenced the results.

The present study showed that OSAHS is not only associated with an increase in BP but also with changes in the BP circadian rhythm. A recent study has demonstrated that normotensive persons with a non-dipping BP profile had increased target organ damage.²⁹ The present study provides a new view on the appropriate management of hypertension: treatment for OSAHS, if present, may decrease BP and improve the BP circadian rhythm, which will contribute to reducing hypertension-related target organ damage and decreasing morbidity and mortality. The results of the present study also highlight the importance of circadian BP variations in patients with OSAHS, especially in those with undiagnosed hypertension who have a normal daytime BP but an abnormal night-time BP.³⁰ Use of ambulatory BP monitoring, as suggested in the 2013 European Society of Hypertension/European Society of Cardiology guidelines,⁶ could further increase the detection of hypertension among patients with OSAHS.

Footnotes

Declaration of conflicting interest

The authors declare that there are no conflict of interests.

Funding

This study was supported by grants from the National Natural Science Foundation of China (nos 81270144, 30800507 and 81170071).

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Prevalence of hypertension and circadian blood pressure variations in patients with obstructive sleep apnoea–hypopnoea syndrome

Abstract

Objective

Methods

Results

Conclusion

Keywords

Introduction

Patients and methods

Patients

Blood pressure measurements

Polysomnography

Statistical analyses

Results

Discussion

Footnotes

Declaration of conflicting interest

Funding

References