|Year : 2015 | Volume
| Issue : 4 | Page : 232-237
Sleep-related breathing disorders in stage II essential hypertension
Amira Labib1, Lamia Afifi MD 1, Reham Shamlool2, Mona M Nada1, Hanan A Amer2, Saly H ElKholy1
1 Clinical Neurophysiology Unit, Cairo University, Cairo, Egypt
2 Department of Neurology, Cairo University, Cairo, Egypt
|Date of Submission||15-Jan-2015|
|Date of Acceptance||01-Mar-2015|
|Date of Web Publication||27-Nov-2015|
Clinical Neurophysiology Unit, Cairo University, Kasr Al Ainy St., Cairo, 11562
Source of Support: None, Conflict of Interest: None
Sleep-related breathing disorders (SRBDs) are reported to be common among patients with hypertension (HTN).
Our aim was to use polysomnography (PSG) to objectively study the frequency and types of SRBDs in essential stage II HTN.
Patients and methods
We used an attended full PSG recording in a group of 20 patients suffering from stage II HTN and in a group of 20 age-matched and sex-matched controls. The Berlin Questionnaire was also administered to the patients. The patients were assessed for a history of smoking, fasting blood sugar, and BMI.
We found that 70% of HTN patients had SRBDs: 15% had mild, 30% had moderate, and 25% had severe SRBDs. As for the controls, we found that 40% of controls had SRBDs: 20% had mild, 15% had moderate, and 5% had severe SRBDs. The overweight patients with HTN had a significantly higher hypopnea index compared with normal weight patients. The diabetic hypertensive group showed a lower sleep efficiency. In addition, all the high-risk patients identified by the Berlin Questionnaire showed evidence of SRBDs, but not all SRBD patients were identified as high-risk patients by the Berlin Questionnaire.
SRBD is very common in stage II HTN. Clinicians should be aware of this high prevalence and make use of the Berlin Questionnaire and PSG, as treatment for SRBDs can have a profound impact on these patients.
Keywords: apnea-hypopnea index, Berlin questionnaire, hypertension, polysomnography, sleep-related breathing disorder
|How to cite this article:|
Labib A, Afifi L, Shamlool R, Nada MM, Amer HA, ElKholy SH. Sleep-related breathing disorders in stage II essential hypertension. Egypt J Neurol Psychiatry Neurosurg 2015;52:232-7
|How to cite this URL:|
Labib A, Afifi L, Shamlool R, Nada MM, Amer HA, ElKholy SH. Sleep-related breathing disorders in stage II essential hypertension. Egypt J Neurol Psychiatry Neurosurg [serial online] 2015 [cited 2018 Oct 16];52:232-7. Available from: http://www.ejnpn.eg.net/text.asp?2015/52/4/232/170653
| Introduction|| |
Hypertension (HTN) is a major risk factor for heart disease and stroke. Its prevalence ranges from 26 to 30% in the adult population , . HTN can be divided into two stages: stage I HTN and stage II HTN. Stage I HTN is defined as systolic pressure ranging from 140 to 159 mmHg or diastolic pressure ranging from 90 to 99 mmHg, whereas stage II HTN is defined as a systolic pressure of 160 mmHg or higher or a diastolic pressure of 100 mmHg or higher  . The prevalence of stage II HTN is ~5% in the general adult population, and this prevalence increases with age and may reach 30% among adults over 80 years of age  .
Sleep-related breathing disorders (SRBDs) might be a commonly undetected cause of uncontrolled HT, may share the same underlying factors, or might be an incidental condition  . Previous studies have shown that obstructive sleep apnea (OSA) is a risk factor for systemic HTN, independent of the effects of obesity, sex, and age  . The Wisconsin Sleep Cohort study showed that SRBD was associated with an increased prevalence of HTN in employed middle-aged adults  . Another cross-sectional study showed that even an increase by 1 in the apnea-hypopnea index (AHI) was associated with a 1% risk of having HTN  . However, there is a deficiency of studies evaluating the prevalence of SRBDs in stage II HTN patients, specifically those on antihypertensive therapy. Stage II HTN patients represent a challenge to the treating physicians; thus, identifying a treatable underlying risk factor for stage II HTN is an attractive step in the management of these patients.
| Aim of work|| |
We performed this study to analyze the frequency and characteristics of SRBDs in patients with stage II essential HTN who were on antihypertensive polytherapy and were not seeking medical attention for sleep complaints. Furthermore, we aimed to assess the utility of the Berlin questionnaire in detecting the HTN patients who are at high risk for SRBD.
| Patients and methods|| |
This case-control study was carried out on 20 adult patients suffering from uncontrolled stage II essential HTN who were on polytherapy. Twenty matched health volunteers participated as controls. The HTN patients underwent thorough history taking, with special attention to smoking history, cardiac condition, presence of diabetes mellitus and previous chest problems, and medications administered. Fasting blood sugar (FBS) was measured for both groups. Cardiac assessment using ECG was carried out to assess the presence of myocardial infarction or ischemia. Echocardiography was performed to exclude patients with heart failure. Chest radiography was carried out to exclude cases with chest diseases. Patients diagnosed with secondary HTN were also excluded from the study. BMI was measured for all participants. Participants who had a BMI greater than 25 kg/m 2 were considered overweight, in accordance with the WHO definition  . The experimental procedures used were approved by the Ethics Committee of the Faculty of Medicine, Cairo University. Written informed consent was obtained from all participants.
Sleep-apnea history was assessed by means of the Arabic version of the Berlin Questionnaire , . This is a validated questionnaire used to determine the occurrence of risk factors for OSA  . The questionnaire includes 10 items: five items on snoring (category I), three items on daytime somnolence (category II), and two items on the history of HTN and/or BMI greater than 30 kg/m 2 (category III). The study patients were classified as being at high risk of having sleep apnea (SA) if scores were positive on at least two of the three categories. Patients were identified as being at low risk of having SA if they scored positively on less than two categories.
All participants underwent one night of laboratory-based polysomnography (PSG). PSG was performed using a Shwarzer Epos 32 GmpH amplifier (Medical Diagnostic Equipment, Shwarzer, Germany) and Somnologica software. The following electrophysiological data were recorded: electroencephalography (EEG) (C3/A2, C4/A1, O2/C3 and O1/C4), left and right electro-oculography referenced to the opposite mastoid surface, mentalis and tibial electromyography, ECG, an airflow cannula to measure respiratory airflow, piezoelectric sensor belts to measure respiratory effort, finger pulse oximetry, snoring neck microphone, and body position sensors. The PSG was scored manually by an experienced sleep disorder physician according to the American Academy of Sleep Medicine guidelines  . This physician was blinded to the patients being scored. Sleep measures obtained for each participant included sleep-onset latency, number of awakenings, sleep efficiency, AHI, the average and lowest oxygen saturations, and the oxygen desaturation index. The AHI was used as a marker of SRBD severity, which was graded as 'mild' (5-15/h), 'moderate' (15-30/h), or 'severe' (>30/h) according to American Academy of Sleep Medicine guidelines  .
All statistical calculations were performed using Microsoft Excel 2003 and SPSS version 15 for Microsoft Windows (SPSS Inc., Chicago, Illinois, USA). Comparison of quantitative variables between the study groups was made using the paired t-test. For comparing categorical data, the χ2 -test was used. Fisher's exact test was used when the expected frequency was less than 5. Data are presented as range, mean ± SD, and median and percentages, where appropriate. A P-value less than 0.05 was used to define statistical significance.
| Results|| |
The study included 20 patients [10 men and 10 women aged between 43 and 70 years (53.7 ± 7.45)] and 20 controls [eight men and 12 women aged between 40 and 70 years (50.9 ± 4.38)]. The patients and controls were age and sex matched, with no significant demographic difference between them. [Table 1] presents the results of the clinical and laboratory findings in both groups. A highly significant difference was found in FBS levels and the percentage of smokers, whereas no difference was found in BMI between the two groups. We found that 30% of HTN patients had abnormal ECG readings: 20% showed signs of ischemia in the ECG and 10% showed signs of infarction.
|Table 1 Clinical and laboratory data in the hypertensive and control groups |
Click here to view
According to the Berlin Questionnaire, 20% of our HTN patients were at high risk of developing SRBD, whereas 80% of HTN patients were at low risk of developing SRBD.
The PSG showed that HTN patients had shorter sleep latency (P = 0.02) compared with the control group; yet, the number of awakening episodes and sleep efficiency were not different between the two groups (P = 0.07 and 0.4, respectively; [Table 2]). Seventy percent of HTN patients showed abnormally high AHI compared with 40% of controls (P = 0.002). A total of 14 HTN patients (70%) suffered from SA of different grades: three patients (15%) had mild SA, six patients (30%) had moderate SA, and five patients (25%) had severe SA. As for the controls, 40% suffered from SA: four controls (20%) had mild SA, three (15%) had moderate SA, and one control (5%) had severe SA. The difference in AHI between the two groups was highly significant, with the HTN group showing a higher AHI (P = 0.0046). We found that the majority of events contributing to the AHI were hypopneas, followed by obstructive apneas. The percentage of central, obstructive, and mixed apneas, or hypopneas to the total AHI showed no significant difference between the two groups. The hypopnea index was significantly higher in the HTN patients (P = 0.023); however, the apnea index was not different between the two groups (P = 0.51).
With regard to the oxygen saturation levels, three different parameters were studied. These were the average O 2 saturation, the lowest O 2 saturation, and the O 2 desaturation index. The average O 2 saturation was significantly lower in patients compared with controls (P = 0.04), whereas the lowest oxygen concentration and the oxygen desaturation index were similar between the two groups (P = 0.85 and 0.2, respectively; [Table 2]).
Comparison of the PSG parameters between smoker and nonsmoker HTN patients revealed no significant difference in the apnea index, the hypopnea index, the AHI, or sleep efficiency, as shown in [Table 3].Comparison of the PSG parameters between normal weight and overweight HTN patients revealed that the hypopnea index was significantly higher in overweight patients (P = 0.04), whereas apnea index, AHI, and sleep efficiency differences were nonsignificant ([Table 3]). The apnea and hypopnea indices, AHI, and sleep efficiency in patients with normal FBS levels compared with diabetic (elevated FBS) patients showed that diabetic patients had lower sleep efficiency ([Table 3]).
|Table 3 Effect of different risk factors on the AHI of hypertensive patients |
Click here to view
We compared the PSG parameters in patients who were classified as 'high risk' by the Berlin Questionnaire with those who were classified as 'low risk'. The high-risk group showed a higher apnea index, hypopnea index, and AHI compared with the low-risk group (P = 0.03, 0.001, and 0.014, respectively),whereas sleep efficiency was similar in both groups (P = 0.34; [Table 3]).
| Discussion|| |
Disentangling the inter-relations between SRBD and HTN remains a rather interesting challenge. Many individuals have both conditions, as previous studies have found that ~50% of HTN patients have SRBD and ~30% of SRBD patients have HTN , . Our study aimed to study the prevalence of SRBDs in stage II essential HTN patients and explore the possible risk factors that can increase the possibility of a hypertensive patient having SRBDs. The PSG data showed that hypertensive patients had shorter sleep-onset latencies and a tendency toward more frequent awakenings during sleep. These findings can be caused by any sleep disorder, including SRBD, that fragments sleep, causing frequent awakening and consequently causing sleep deprivation that manifests itself by shorter latency to sleep onset in HTN patients.
According to the literature, ~30% of hypertensive patients suffer from SRBDs , . In this study, we report a higher incidence of 70% in HTN patients. This difference in prevalence can be due to our selected sample of stage II HTN rather than all HTN patients. In accordance with our results, Logan et al.  observed that the prevalence of OSA was 83% in patients with drug-resistant HTN, defined as a clinical BP of at least 140/90 mmHg, while taking a combination of at least three antihypertensive drugs at maximal doses. Another possible explanation is the presence of additional risk factors for SRBD in our patients. For instance, the age of our patients ranged from 43 to 70 years, and hence young adults were not studied. Higher age is known to be associated with a higher risk for SRBD, which might have increased the prevalence in our study  . Another possible factor is the different methodologies between different studies. For example, some studies only defined SRBDs as having an apnea index of more than 10 per hour, and thus they reported a lower percentage of SRBDs in HTN patients  . We defined mild SRBD as having an AHI of more than 5 per hour, and thus more individuals were considered to have SRBD compared with other published studies. When we assessed the degree of SRBD in our patients we found that 15% had mild SRBD, 30% had moderate SRBD, and 25% had severe SRBD. Obstructive events were more frequent than central events. Hypopneas were more frequent than both, but as hypopneas are not classified as obstructive or central we can assume by the number of obstructive apneas that the hypopneas were due to airway obstruction too. These findings are in accordance with those of previous studies that report that OSA is more frequent than central SA in HTN patients  . According to the Berlin questionnaire 20% of our hypertensive patients were at high risk of developing SRBD. All of these high-risk patients had a high AHI in PSG. In fact, high-risk patients had a significantly higher AHI, apnea index, and hypopnea index compared with low-risk patients, determined by the Berlin Questionnaire. However, those defined as high risk were only 20% of HTN patients, whereas SRBD was found in 70% of patients. We can thus conclude that the Berlin Questionnaire can be a highly specific tool but is not highly sensitive. This highlights the importance of using a sleep questionnaire for screening patients with HTN and performing PSG in high-risk patients detected by the screening questionnaire.
We studied the impact of smoking, BMI, and FBS on the apnea index, the hypopnea index, AHI, and sleep efficiency. We found that the overweight patients suffering from HTN had significantly higher hypopnea indices than normal weight hypertensive patients. This is likely because obesity results in an anatomically small pharyngeal airway, thus increasing the predisposition to pharyngeal collapse in those individuals. The percentage of sleep efficiency was significantly higher in hypertensive patients having normal FBS than in diabetic hypertensive patients. A likely explanation is that the fragmented sleep pattern in diabetes mellitus patients is caused by other sleep disorders such as nocturia, restless leg syndrome, or paresthesias, which are known to be more common in diabetic patients  .We found no difference in PSG data between smoker and nonsmoker patients.
In the current study, there was a highly significant difference between the mean AHI of hypertensive patients (9.89 ± 8.72) and that of controls (3.28 ± 4.21). The relationship between OSA and HTN is complex. Population-based studies have reported a linear relationship between 24-h BP and AHI that was independent of other confounding factors such as sex, age, and BMI , . Patients with the most severe SA have the highest initial blood pressure levels and are more refractory to treatment  . Furthermore, SA was found to be an independent predictor of uncontrolled HTN in patients younger than 50 years of age  . Therefore, this cannot be simply attributed to causes common between the two conditions, such as male sex, old age, overweight, smoking, or lack of exercise. Indeed, the presence of shared risk factors for OSA and vascular disorders might explain some, but not all, of the correlations between the two conditions.
There are several mechanisms that act to promote the development of HTN in patients with OSA. These include sympathetic overactivation, endothelial dysfunction, systemic inflammation, and oxidative stress , . The recurrent hypoxemia caused by SA increases the release of several vasoactive and trophic substances, such as renin, noradrenaline, thromboxane A2, and endothelin, in addition to decreasing the production of nitric oxide and increasing vasoconstriction reactivity. These abnormalities affect the stiffness of the arterial wall  . OSA causes nocturnal oxygen desaturation, sleep fragmentation, and increased sympathetic activity, which lead to impaired daytime baroreflex sensitivity and nitric oxide production  . Increased aldosterone has also been suggested as a possible contributor to resistant HTN in SA  . Treatment of OSA with continuous positive airway pressure (CPAP) in HTN patients elicited contradicting data on the effect on BP, as some studies reported lowering of daytime and night-time BP after CPAP, some reported lowering of night-time BP only, and others found no effect on BP ,, .
| Conclusion|| |
We report a high prevalence of SRBDs in patients with stage II HTN. Clinicians should be aware of the sleep disorders that can be present in hypertensive patients, particularly in patients with refractory HTN, because SRBD is found in a significant number of these cases. A SA questionnaire, possibly the Berlin Questionnaire, can be a useful tool in screening HTN patients for SRBD. Thereafter, PSG becomes mandatory for the high-risk group determined by the Berlin questionnaire. As SRBD is a treatable condition that, if left untreated, is associated with poor quality of life and increased morbidity and mortality, the prompt diagnosis and treatment of this condition cannot be overemphasized.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gillespie CD, Hurvitz KA. Centers for Disease Control and Prevention (CDC). Prevalence of hypertension and controlled hypertension. United States, 2007-2010. MMWR Surveill Summ 2013; 62
Ibrahim MM, Rizk H, Appel LJ, el Aroussy W, Helmy S, Sharaf Y, et al.
Hypertension prevalence, awareness, treatment, and control in Egypt. Results from the Egyptian National Hypertension Project (NHP). NHP Investigative Team. Hypertension 1995; 26
(6 Pt 1): 886-890.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JLJr, et al.
The seventh report of the joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. JAMA 2003; 289
Qureshi AI, Suri MF, Kirmani JF, Divani AA. Prevalence and trends of prehypertension and hypertension in United States: National Health and Nutrition Examination Surveys 1976 to 2000. Med Sci Monit 2005; 11
Koyanagi A, Garin N, Olaya B, Ayuso-Mateos JL, Chatterji S, Leonardi M, et al.
Chronic conditions and sleep problems among adults aged 50 years or over in nine countries: a multi-country study. PLoS One 2014; 9
Nieto FJ, Young TB, Lind BK, Shahar E, Samet JM, Redline S, et al.
Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA 2000; 283
Young T, Peppard P, Palta M, Hla KM, Finn L Morgan B, Skatrud J. Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med 1997; 157
Lavie P, Herer P, Hoffstein V. Obstructive sleep apnoea syndrome as a risk factor for hypertension: population study. BMJ 2000; 320
World Health Organization. Report of a WHO consultation on obesity. Obesity: preventing and managing the global epidemic. Geneva: World Health Organization; 1998.
Saleh AB, Ahmad MA, Awadalla NJ. Development of Arabic version of Berlin questionnaire to identify obstructive sleep apnea at risk patients. Ann Thorac Med 2011; 6
ElKholy SH, Amer HA, Nada MM, Nada MA, Labib A. Sleep-related breathing disorders in cerebrovascular stroke and transient ischemic attacks: a comparative study. J Clin Neurophysiol 2012; 29
Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP. Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med 1999; 131
American Academy of Sleep Medicine. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications
. Westchester: American Academy of Sleep Medicine; 2007.
American Academy of Sleep Medicine. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measure techniques in clinical research. Sleep 1999; 22
Silverberg DS, Oksenberg A, Iaina A. Sleep-related breathing disorders as a major cause of essential hypertension: fact or fiction? Curr Opin Nephrol Hypertens 1998; 7
Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, et al
. American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology; American Heart Association Stroke Council; American Heart Association Council on Cardiovascular Nursing; American College of Cardiology Foundation. Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). Circulation 2008; 118
Kales A, Bixler EO, Cadieux RJ, Schneck DW, Shaw LC3rd, Locke TW, et al.
Sleep apnoea in a hypertensive population. Lancet 1984; 2
Lavie P, Ben-Yosef R, Rubin AE. Prevalence of sleep apnea syndrome among patients with essential hypertension. Am Heart J 1984; 108
Logan AG, Perlikowski SM, Mente A, Tisler A, Tkacova R, Niroumand M, et al.
High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens 2001; 19
Edwards BA, O′Driscoll DM, Ali A, Jordan AS, Trinder J, Malhotra A. Aging and sleep: physiology and pathophysiology. Semin Respir Crit Care Med 2010; 31
Taub LF, Redeker NS. Sleep disorders, glucose regulation, and type 2 diabetes. Biol Res Nurs 2008; 9
Hla KM, Young TB, Bidwell T, Palta M, Skatrud JB, Dempsey J. Sleep apnea and hypertension. A population-based study. Ann Intern Med 1994; 120
Grote L, Hedner J, Peter JH. Sleep-related breathing disorder is an independent risk factor for uncontrolled hypertension. J Hypertens 2000; 18
Lesske J, Fletcher EC, Bao G, Unger T. Hypertension caused by chronic intermittent hypoxia - influence of chemoreceptors and sympathetic nervous system.
J Hypertens 1997; 15
(12 Pt 2): 1593-
Narkiewicz K, Wolf J, Lopez-Jimenez F, Somers VK. Obstructive sleep apnea and hypertension. Current Cardiol Rep 2005; 7
Noda A, Nakata S, Koike Y, Miyata S, Kitaichi K, Nishizawa T, et al.
Continuous positive airway pressure improves daytime baroreflex sensitivity and nitric oxide production in patients with moderate to severe obstructive sleep apnea syndrome. Hypertens Res 2007; 30
Goodfriend TL, Calhoun DA. Resistant hypertension, obesity, sleep apnea, and aldosterone: theory and therapy. Hypertension 2004; 43
Becker HF, Jerrentrup A, Ploch T, Grote L, Penzel T, Sullivan CE, Peter JH. Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation 2003; 107
Campos-Rodriguez F, Grilo-Reina A, Perez-Ronchel J, Merino-Sanchez M, Gonzalez-Benitez MA, Beltran-Robles M, Almeida-Gonzalez C. Effect of continuous positive airway pressure on ambulatory BP in patients with sleep apnea and hypertension: a placebo-controlled trial. Chest 2006; 129
Hla KM, Skatrud JB, Finn L, Palta M, Young T. The effect of correction of sleep-disordered breathing on BP in untreated hypertension. Chest 2002; 122
[Table 1], [Table 2], [Table 3]