Journal of Sleep Disorders: Treatment and CareISSN: 2325-9639

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Research Article, J Sleep Disor Treat Care Vol: 5 Issue: 1

Masked Hypertension and Morning Blood Pressure Surge in Patients with Obstructive Sleep Apnea Syndrome

Miyata S1, Noda A2*, Otake H1 and Yasuda Y3
1Department of Sleep Medicine, Nagoya University Graduate School of Medicine, Japan
2Department of Biomedical Sciences, Chubu University Graduate School of Life and Health Sciences, Japan
3Department of CKD Initiatives, Nagoya University Graduate School of Medicine, Japan
Corresponding author : Noda A, PhD
Department of Biomedical Sciences, Chubu University Graduate School of Life and Health Sciences 1200, Matsumoto-cho, Kasugai-shi, Aichi 487-8501, Japan
Tel: +81-568-51-9607; Fax: +81-568-51-5370
E-mail: [email protected]
Received: December 25, 2015 Accepted: February 18, 2016 Published: February 18, 2016
Citation: Miyata S, Noda A, Otake H, Yasuda Y (2016) Masked Hypertension and Morning Blood Pressure Surge in Patients with Obstructive Sleep Apnea Syndrome. J Sleep Disor: Treat Care 5:1. doi:10.4172/2325-9639.1000168

Abstract

Objective: Frequent hypoxic episodes and arousal during sleep in obstructive sleep apnea syndrome (OSAS) result in increased nocturnal blood pressure, which in turn may lead to sustained hypertension. Patients with severe OSAS exhibit attenuated nocturnal blood pressure (BP) dipping, as well as marked and rapid BP elevation in the morning shortly after waking. We examined the prevalence of masked hypertension and morning BP surge in patients with OSAS, and the relationship between the severity of OSAS and abnormal circadian BP patterns.
Methods: We performed 24-hour ambulatory BP monitoring in the absence of antihypertensive medication on 26 patients with OSAS (49.3 ± 8.4 yrs) to investigate masked hypertension and morning BP surge.
Results: Results of the 26 patients, three (11.7%) were normotensive, six (23.0%) exhibited masked hypertension, and 17 (65.3%) were hypertensive. The apnea/hypopnea index was significantly correlated with 24-hour mean, daytime, and night time systolic and diastolic BP. 24-hour mean, daytime, and night time BPs in the severe OSAS group were significantly higher than in the mild to moderate OSAS group. We observed morning BP surge in 16 patients (61.5%). There were no significant differences in the prevalence of morning BP surge and masked hypertension between the mild to moderate and the severe OSAS groups.
Conclusion: Mild to moderate OSAS may play an important role in masked hypertension and morning BP surge.

Keywords: Obstructive sleep apnea; 24-hour ambulatory blood pressure monitoring; Hypertension; Masked hypertension; Morning blood pressure surge; Daytime blood pressure; Night time blood pressure

Keywords

Obstructive sleep apnea; 24-hour ambulatory blood pressure monitoring; Hypertension; Masked hypertension; Morning blood pressure surge; Daytime blood pressure; Night time blood pressure

Introduction

The frequent hypoxic episodes and arousal that occur during sleep in obstructive sleep apnea syndrome (OSAS) contribute to systemic inflammation, oxidative stress, production of endogenous vasoactive factors, endothelial dysfunction, increased sympathetic activation, and metabolic dysregulation [1]. These phenomena increase nocturnal blood pressure, which in turn may lead to sustained hypertension [2]. We previously reported that sympathetic activity and aortic pressure augmentation increased in patients with OSAS and continuous positive airway pressure (CPAP) improved these indices [3,4]. Prospective population-based epidemiology studies have shown that individuals with OSAS are 2 to 3 times more likely to develop essential hypertension than individuals who do not have OSAS [5,6].
Ambulatory blood pressure monitoring (ABPM) is more accurate than clinic measurements because multiple readings are taken, and ABPM correlates better with a range of cardiovascular outcomes and end organ damage [7]. Patients with severe OSAS exhibit attenuated nocturnal blood pressure (BP) dipping, as well as marked and rapid BP elevation in the morning shortly after waking (morning BP surge) [8,9]. We previously reported that episodes of arousal, hypoxia and sleep fragmentation resulting from apnea increased nocturnal BP, possibly leading to left ventricle hypertrophy [9], which is linked to poor prognosis in patients with OSAS [10]. Cohort studies have reported poor prognosis in patients with masked hypertension detected by ABPM compared with normotensive individuals [11-13]. Morning BP surge was associated with increased hypertensive target organ damage, and with increased cardiovascular morbidity and mortality [14-17].
In the present study, we examined the prevalence of masked hypertension and morning BP surge in patients with OSAS, and the relationship between the severity of OSAS and abnormal circadian BP patterns.

Methods

Patients
We studied 26 consecutive men who were suspected of having OSAS (Table 1). Those with chronic diseases in terminal stages, cardiac arrhythmia, history of cardiovascular events, chronic renal failure, heart failure, diabetes, or other diseases that could compromise the study, and those who underwent previous OSAS and hypertension treatments, were excluded. All patients were informed of the objectives and conditions of the study, and provided written informed consent prior to participation. The Nagoya University Ethics Committee approved all procedures associated with this study.
Table 1: Baseline Characteristics of patients.
Sleep study
All participants underwent standard polysomnography (PSG) with pulse oximetry (ALICE 3; Respironics, Murrysville, PA, USA). The electroencephalogram, electrooculogram, electromyogram, and electrocardiogram were recorded continuously, and respiration was monitored with an oronasal thermistor and thoracoabdominal piezo gauges. Sleep stages and arousal were defined according to published criteria [18]. Obstructive apnea and the presence of central sleep apnea were identified if airflow was absent or nearly absent for at least 10 s. Hypopnea was defined as a ≥ 50% reduction in airflow associated with arousal, awakening, or ≥ 3% desaturation, also for at least 10 s. AHI was calculated as the number of apnea/hypopnea episodes per hour, and the lowest oxygen saturation level (lowest SpO2) was determined. Patients with AHI ≥ 5/h and an Epworth sleepiness scale score ≥11 were diagnosed as having OSAS [18]. We classified patients into two groups; mild to moderate and severe OSAS groups according to the criterion of American Academy of Sleep Medicine [19].
Clinic blood pressure measurement
Clinic BP measurements were made using an automatic sphygmomanometer according to the method previously described [20]. BP was measured at least twice for each patient with a 2-minute interval between measurements. If the difference between measurements was greater than 5 mmHg, the mean was calculated using an additional measurement taken after 2 minutes.
24-hour ambulatory blood pressure monitoring
24-hour ambulatory BP was measured with the ABPM 630 (Omron Colin Co. Ltd., Tokyo, Japan) after attachment of a properlysized cuff on the patient’s non-dominant arm. BP was measured continuously over 30 minutes. During measurement, participants were allowed to carry out routine daily activities, and a diary was provided for them to record subjective symptoms and changes in physical or mental condition. Artifactual readings were identified by trained technologists and omitted from analyses. Established guidelines were used to define hypertension detected by 24-hour ambulatory BP as a mean daytime systolic BP (SBP) of at least 130 mmHg or mean daytime diastolic BP (DBP) of at least 80 mmHg [21].
Hypertension was defined independently by clinic BP and 24- hour ambulatory BP. The normotensive group included participants who were normotensive according to both methods, the hypertension group included participants who were hypertensive by both methods, and the masked hypertension group included participants who were normotensive by clinic BP but hypertensive by ambulatory BP.
For the analysis of morning BP surge, awake and asleep periods were determined from diary cards. The sleep-through morning surge was the difference between the morning SBP (average SBP during the 2 hours after waking) and the lowest nighttime SBP (average of the lowest SBP reading and the 2 readings immediately preceding and following it) [14]. An amplitude of morning SBP ≥ 20 mmHg was defined as morning BP surge [22].
Statistical analysis
All results are presented as mean ± standard deviation (SD). We confirmed that the distributions of age, height, weight, BMI, SBPs, DBPs and AHI or lowest SpO2 followed the normal distributions using the Shapiro-Wilk normality test. Pearson’s correlation analysis was used to examine the relationship between results of blood pressure and AHI or lowest SpO2. The non-paired t test was used to study differences on age, height, weight, BMI, SBPs, and DBPs between the mild to moderate OSAS group and the severe OSAS group. The prevalence of hypertension and morning BP surge between the mild to moderate OSAS group and the severe OSAS group was compared using a 2×2 χ2 test. P < 0.05 was considered statistically significant. Statistical analyses were performed using IBM SPSS Statistics ver. 20 (IBM, NY).

Results

Patient characteristics are summarized in Table 1. Of the 26 patients, three (11.7%) were normotensive, six (23.0%) exhibited masked hypertension, and 17 (65.3%) were hypertensive. Morning BP surge was observed in 16 patients (61.5%).
AHI was significantly correlated with 24-hour, daytime, and night time SBPs (24-hour SBP, r = 0.526, P = 0.007; daytime SBP, r = 0.472, P = 0.017; night time SBP, r = 0.544, P = 0.005). It was also significantly correlated with 24-hour, daytime, and night time DBPs (24-hour DBP, r = 0.519, P = 0.008; daytime DBP, r = 0.456, P = 0.022; night time DBP, r = 0.555, P = 0.004) (Figure 1 and Table 2). Lowest SpO2 did not significantly correlate with 24-hour, daytime, and night time BPs (Figure 2 and Table 2).
Figure 1: Correlation between AHI and blood pressure.
Table 2: Correlation between AHI, lowest SpO2 and 24-hour ambulatory BP monitoring results.
Figure 2: Correlation between lowest SpO2 and blood pressure.
24-hour, daytime, and night time SBPs in the severe OSAS group were significantly higher than in the mild to moderate OSAS group (24- hour SBP, 142.5 ± 13.8 vs 127.9 ± 14.9 mmHg, P = 0.021; daytime SBP, 146.6 ± 13.4 vs 134.7 ± 14.1 mmHg, P = 0.046; night time SBP, 135.2 ± 14.8 vs 117.8 ± 16.5 mmHg, P = 0.013, respectively). Similarly, DBPs measured using 24-hour ABPM were significantly higher in the severe OSAS group than in the mild to moderate OSAS group (24-hour DBP, 92.0 ± 13.4 vs 77.6 ± 9.6 mmHg, P = 0.007; daytime DBP, 95.6 ± 13.0 vs 82.6 ± 9.9 mmHg, P = 0.013; night time DBP, 85.3 ± 14.1 vs 70.2 ± 10.5 mmHg, P = 0.008, respectively). There were no significant differences in age, height, weight, and BMI between the OSAS groups.
The prevalence of hypertension between the severe OSAS group and the mild to moderate OSAS group did not show significant difference (80.0 vs 45.4%). There were no significant differences on the prevalence of masked hypertension and morning BP surge between the mild to moderate OSAS group and the severe OSAS group (masked hypertension; 36.3 vs 13.3%, mornig BP surge; 81.8 vs 46.6%).

Discussion

We observed masked hypertension in 23.0% of OSAS patients and BP surge in 61.5% of all participants. AHI was significantly correlated with BPs measured by 24-hour ABPM. Our findings suggest that OSAS patients who showed normal BP in a clinical office should be approached to evaluate abnormal BP circadian rhythms by 24-hour ABPM.
Patients with masked hypertension detected by ABPM have a poor prognosis compared to normotensive subjects [11-13]. OSAS patients with masked hypertension have a significantly higher carotidfemoral pulse wave velocity than those without masked hypertension [23]. Increased daytime SBP variability associated with masked hypertension is significantly correlated with common carotid intimamedia thickness and a decrease in baroreflex sensitivity [24]. Arterial baroreflex dysfunction promotes the development of atherosclerosis in a rat model [25]. Similar to obesity, dyslipidemia, and glucose intolerance, masked hypertension is related to a significantly greater long-term risk of stroke and cardiovascular mortality, even among patients with a low-cardiovascular risk profile [12]. The monitoring of 24-hour BP could be benefit in patients with OSAS without sustained hypertension to prevent cardiovascular disease related to BP elevation.
More than half of the patients with OSAS had morning BP surge in our study. OSAS is strongly associated with cardiovascular disease. A high morning BP surge is linked to organ damage, stroke, and other cardiovascular complications. A morning SBP surge ≥ 25 mmHg was associated with an increased risk of cerebral hemorrhage in 1430 individuals aged ≥ 40 years in Japan [16]. A 1 mmHg sleeping-towaking SBP rise was related to a 3.3% increase in risk of cardiovascular events [26]. In addition to the risk of morning BP surge, one study reported that the morning period elevated the risk of cardiovascular complications in 30–40% of patients, relative to other periods of the day [27]. Collectively, these results suggest that morning BP surge in OSAS patients should be considered even when clinic SBP and DBP are less than 140 and 90 mmHg, respectively.
We found that 23.0% and 61.5% of OSAS patients had masked hypertension and morning BP surge, respectively. In a previous study, 639 (21.9%) subjects had masked hypertension among 1374 community-dwelling Japanese aged ≥ 40 years [28], while the prevalence of masked hypertension was 8.1% in an untreated Finnish adult population (n = 1459, age 45-74 years) [29]. Moreover, in another Japanese study, 19% of participants had morning BP surge ≥ 25 mmHg in a community population aged ≥ 40 years (16). In a hospital-based population, 49% of patients exhibited morning BP surge (≥ 20/15 mmHg, SBP and DBP, respectively) [30]. An independent correlation between greater AHI and increasing BP, both at baseline and when measured over long-term follow-up, was observed in a prior population-based study [31]. Increased sympathetic activity, impaired renin–angiotensin–aldosterone system function, and endothelial dysfunction by OSAS all lead to an increase in peripheral vascular resistance [32]. Despite the differences in study design, OSAS likely results in a high prevalence of masked hypertension and morning BP surge.
This study has several limitations. First, we did not include female patients because of the protective effect of estrogens and low prevalence and risk of OSAS in women. Then, BMI, which is also well known as the risk factor of hypertension, did not show significant correlation to AHI in our study. Craniofacial morphology as well as body fat has a significant role in Japanese patients. Third, we did not include some indices such as Epworth sleepiness scale, oxygen desaturation index and time spent with oxygen saturations below 90%. Those indices might help to understand the relationship between BP circadian rhythm and OSAS. Further evaluation including female patients and large number of patients might give the general suggestions to be applicable to OSAS patients.
In conclusion, we found that mild to moderate OSAS patients were at high risk of masked hypertension and morning BP surge, and AHI was significantly correlated with BPs monitored by 24-hour ABPM. Even when daytime BP is normal, 24-hour ABPM could be useful for monitoring BP circadian rhythm in OSAS patients.

Acknowledgment

This work was partially supported by Japan Science and Technology Agency (JST) under Adaptable and Seamless Technology Transfer Program through Target-driven R&D.

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