Loading...
 

July - September 2007: 
Volume 20, Issue 3

Click on the image to download the Issue in PDF format.

ARCHIVE

The Prevalence of Metabolic Syndrome in patients with Sleep Apnoea Syndrome
Abstract
SUMMARY. Background: Obstructive sleep apnoea syndrome (OSAS) and metabolic syndrome share common pathogenetic mechanisms such as central obesity, insulin resistance, dyslipidaemia, inflammation, and cardiovascular disease. Objectives: The aim of this study was to investigate the prevalence of metabolic syndrome in patients with OSAS referred to the sleep laboratory of the Department of Pneumonology of the Medical School of the Democritus University of Thrace. Population and Method: Seventy-nine (79) subjects were studied, with medical history, clinical examination, laboratory biochemical tests and full polysomnography. Results: Twenty-one subjects (27%) did not suffer from OSAS and served as controls, while 58 subjects (73%) suffered from mild (n=17), moderate (n=8) or severe (n= 33) OSAS. In the control group 15/21 subjects (71.43%) met the diagnostic criteria for metabolic syndrome. In the OSAS group, 16/17 patients (94.18%) with mild disease, 7/8 patients (87.5%) with moderate disease and 25/33 patients (75.75%) with severe disease suffered from metabolic syndrome. No statistically significant difference in the prevalence of metabolic syndrome was detected between the groups. Conclusions: The prevalence of metabolic syndrome, although high in patients with OSAS, did not differ significantly from that in subjects without OSAS. Pneumon 2007; 20(3):240-244.
Full text
INTRODUCTION

Obstructive sleep apnoea syndrome (OSAS) is characterized by repeated episodes of partial or full cessation of breathing during sleep, usually accompanied by oxyhaemoglobin desaturation1. The diagnostic criteria are: 1) Sleepiness or insomnia; 2) Frequent episodes of obstructed breathing during sleep; 3) Snoring, morning headaches, mouth dryness on waking; 4) ≥5 episodes of apnoea per hour of sleep with a duration of at least 10 sec in the sleep study and one or more of the following: Repeated waking, Cardiac arrhythmia, Oxyhaemoglobin desaturation, MSLT with sleep latency less than 10 min; 5) Comorbidities e.g. tonsillar enlargement, and 6) Comorbidity with other sleep disorders e.g. narcolepsy. A recent study has suggested that OSAS affects approximately 5% of the adult population2. Patients with OSAS are reported to have a higher incidence of various cardiovascular diseases.

Metabolic syndrome is also related to cardiovascular disease. The main characteristics of the syndrome are insulin resistance, obesity of the central type, hypertension and dyslipidaemia3. A recent report has suggested that there is a significant relationship between OSAS and metabolic syndrome4.

To the knowledge of the authors, no data have been published on the relationship between OSAS and metabolic syndrome in the Greek population. This study investigated the prevalence of metabolic syndrome in patients with OSAS and subjects without OSAS referred to the sleep laboratory in the Department of Pneumonology of the Medical School of the Democritus University of Thrace.

MATERIALS AND METHODS


Study group

The study group consisted of 79 subjects, who were referred to the sleep laboratory for whole-night polysomnography because of suspected sleep disorders. Αll the patients signed an informed consent form.

Definitions

Apnoea was defined as complete cessation of airflow lasting more than 10 sec, and hypopnoea as a discernible fall in airflow, lasting 10 sec or more, accompanied by a decrease in oxygen saturation of at least 3%, or by an electroencephalographic (EEG) recorded arousal.

The Apnoea-Hypopnoea Index (AHI) was defined as a total number of episodes of apnoea and hypopnoea per hour of EEG sleep. OSAS was defined as AHI of ≥5/h.

The patients were divided into subgroups according to OSAS severity, as follows: mild OSAS, 5≤AHI<15; moderate OSAS, 15≤AHI<30; severe OSAS, AHI ≥306, 7. Patients with AHI<5 were considered as the control group. Patients with pure or mainly central apnoea were excluded from the study.

Patients were considered to have metabolic syndrome if they had three or more of the following risk factors, according to the diagnostic criteria of the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III)3:
1) fasting blood glucose above 110 mg/dl, or current use of antidiabetic medication
2) waist circumference above 88 cm for women or 102 cm for men
3) blood pressure of 130/85mmHg or greater, or current use of antihypertensive medication 4) fasting triglyceride level above 150 mg/dL
5) high density lipoprotein cholesterol (HDL-C) below 50 mg/dL for women or 40 mg/dL for men.

Methods

At baseline, the patients’ medical history was recorded and a physical examination was performed. Each participant completed a detailed questionnaire about his/her sleep, and sleepiness was evaluated by the Greek version of the Epworth Sleepiness Scale (ESS).

Weight and height were measured to the nearest kilogram and centimeter, respectively, and the body mass index (BMI) was calculated [BMI=weight/(height)²]. Neck circumference was measured at the cricothyroid level, waist circumference midway between the 12th rib and the iliac crest, and hip circumference at the level of great trochanter, using a measuring tape. Blood pressure was calculated based on the average of two seated blood pressure readings with a mercury sphygmomanometer adapted to arm circumference.

Polysomnography

All subjects underwent an attended overnight sleep study (from 22.00-06.00 h) with the use of a computerized polysomnogram system (Alice 4, Respironics, Murrysville, Pennsylvania, USA). The following signals were included: Four leads of EEG (C3-A2, C4-A1, O3-A2, O4-A1), two leads of electroocculogram (REOG, L-EOG), and one lead of submental electromyogram (subEMG). Additionally, one channel continuously recorded ECG signals and one channel recorded leg movements by anterior tibialis electromyogram (tibEMG). Breathing sounds and snoring were recorded by a microphone placed at the level of the jugular vein. Airflow was monitored by combined oronasal thermistors, and arterial oxyhaemoglobin saturation by a finger pulse oxymeter. Thoracic cage and abdominal motion were recorded by inductive plethysmography. EEG recordings were scored manually according to standard criteria5.

Blood assays

Blood was collected after polysomnography, at between 8 and 9 a.m. following an overnight fast, for biochemical analyses, which were performed in an ILAB 600 analyzer (Biochem, Japan) by the enzymatic method for glucose (mg/dl) and enzymatic colorimetric methods for total cholesterol, triglycerides and HDL-C (mg/dl).

Statistical analysis

The Statistical Package for the Social Sciences (SPSS- 15) was used for data handling and analysis (SPSS Inc, Chicago, Illinois). Continuous variables were expressed as the mean ±SD. Analysis of variance (ANOVA) was used for comparisons between groups. Probability (p) values of less than 0.05 were considered statistically significant.

RESULTS

The control group consisted of 21 subjects (Group 1 - 27% of the study population) who had an AHI of <5. Seventeen patients had mild OSAS (Group 2 - 22% of the study population), 8 had moderate OSAS (Group 3 - 10% of the study population), and 33 patients (Group 4 - 41% of the study population) had severe OSAS. The distribution of the study population is presented in Figure 1.


The demographic and biochemical characteristics of the patients in the four study groups are presented in Table 1. The subjects of the four groups did not differ significantly in waist and hip circumference and ΒΜΙ. The neck circumference was larger in the severe OSAS group than in the controls (45.09±0.92 cm vs. 41.18±0.68 cm, p=0.02). The patients with moderate OSAS were significantly older than the controls (62.2±2.12 years vs. 54.42±2.19 years, p=0.016).

The patients with moderate OSAS had significantly higher levels of total cholesterol (252.67±14.44 vs. 198.72±8.76, p=0.037) and triglycerides (215.67±43.97 vs. 136.83±12.12, p=0.032) and a trend toward lower levels of HDL-C.

The prevalence of metabolic syndrome in the controls and patients with mild, moderate and severe OSAS was 71.43%, 94.18%, 87.5% and 75.75% respectively (Figure 2). No statistically significant difference in the prevalence of metabolic syndrome was detected between the different groups.



In patients with OSAS, as a whole group, the prevalence of metabolic syndrome was 81,8% versus 68,4% in control group. No statistically significant difference was observed (p=ns). Furthermore, no statistically significant difference was observed in diseases included in the metabolic syndrome definition, like arterial hypertension (50% in OSAS group versus 42,1% in control group, p=ns), hyperlipidaimia (69,4% in OSAS group versus 50% in control group, p=ns) and diabetes mellitus (25% in OSAS group versus 5,3% in control group, p=ns). As expected, there was a male sex predominance in OSAS group compared to control group (84,1% and 52,6%, respectively, p=0,013).



DISCUSSION

In this study, the prevalence of metabolic syndrome in Greek patients with OSAS was investigated. It was found that patients with OSAS often suffered from metabolic syndrome, but its prevalence in sleep apnoeic patients was not statistically significant different from that in controls who presented at the sleep laboratory, but were not found to have OSAS.

The prevalence of metabolic syndrome in OSAS patients has been investigated in a few countries. A study performed in the UK (4) estimated that 87% of patients with OSAS had metabolic syndrome, a percentage similar to that observed in this Greek series. The respective percentage reported in the USA was 60%8, and in Italy 53%9. In China, 62.5% of OSAS patients also suffered from metabolic syndrome10, while in a study performed in Japan11 the prevalence of metabolic syndrome in OSAS patients was 49.5% for men and 32% for women. A difference in the mean BMI between Asians and Caucasians with OSAS, and possible different nutritional habits, may have contributed to the reported difference in the prevalence of metabolic syndrome. All studies observed a higher prevalence of metabolic syndrome in OSAS patients compared with controls.

According to the international literature, obesity of the central type is strongly associated with a high risk of OSAS in the general population12,13; 40% of obese subjects suffer from OSAS and 70% of patients with OSAS are obese14. A weight gain of 10% results in a 6-fold increase in the risk of OSAS15. Furthermore, OSAS results in deterioration of obesity, via an unknown pathophysiological mechanism. Patients with newly diagnosed OSAS usually report pronounced weight gain before the diagnosis14,16. Daytime sleepiness and reduced physical activity may contribute to this phenomenon.

The prevalence of OSAS is also high in disorders characterized by insulin resistance as a primary pathogenetic mechanism16. Women with polycystic ovary syndrome (PCOS) are 30 times more likely to suffer from sleep disordered breathing (SDB) than controls. The prevalence of sleep apnoea is quite low in pre-menopausal women and post-menopausal women on hormone replacement therapy (HT), and appears to be associated exclusively with obesity. Post-menopausal women without HT and men suffer almost equally from OSAS. In addition, patients with diabetes often suffer from OSAS14.

Both obesity of the central type and insulin resistance characterize the metabolic syndrome and potentiate the pathophysiology of the syndrome. Pathogenetic mechanisms common to OSAS, obesity and hypertension, such as activation of the sympathetic system, disorders in kidney function and activation of the renin – agiotensin system, hyperleptinaemia and leptin resistance, oxidotic stress, inflammation and endothelial deregulation, have led some physicians to propose a new syndrome, syndrome Z17, defined as metabolic syndrome (obesity of the central type, insulin resistance, inflammation, dyslipidaemia, cardiovascular disorders) along with OSAS17.

In this study, the patients with OSAS did not suffer from metabolic syndrome statistically significantly more often than controls. However, certain methodological issues and limitations of the study should be mentioned. The population was small and of mixed sex, which may have influenced the statistical power of the determination of an independent association between metabolic syndrome and OSAS. Furthermore, both patients with OSAS and the controls had been referred to the sleep laboratory for possible sleep disorders and not selected randomly from the general population. In addition, the population was extremely obese in all groups and as obesity is a proposed pathogenetic mechanism for both OSAS and metabolic syndrome, this may have influenced the statistical calculations.

In conclusion, although the prevalence of metabolic syndrome in OSAS patients was found to be high, it did not differ statistically significantly in comparison with normal controls. A large-scale study, using age- and BMI-matched controls is needed in order to clarify the relationship between OSAS and metabolic syndrome among Greeks.

REFERENCES

1. American Academy of Sleep Medicine, International Classification of Sleep Disorders, revised: Diagnostic and coding manual. Chicago, Illinois: American Academy of Sleep Medicine 2001.
2. Young T, Peppard PE, Gottlieb DJ: Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med 2002; 165: 1217–1239.
3. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, final report). Circulation 2002; 106: 3143–3421.
4. Coughlin SR, Mawdsley L, Mugarza JA, Calverley PM, Wilding JP: Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome. Eur Heart J 2004; 25: 735–741.
5. Rechtshaffen A, Kales A (eds): A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. Los Angeles, UCLA Brain Information Service/Brain Research Institute, 1968.
6. American Academy of Sleep Medicine Task Force: Sleep related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The report of an American Academy of Sleep Medicine Task Force. Sleep 1999; 22: 667–689.
7. Τρακαδά Γεωργία, Φυσιολογικός Ύπνος και μη Φυσιολογικός Ύπνος, 1η έκδοση, Πάτρα 2005, εκδόσεις ARTION.
8. Parish JM, Adam T, Facchiano L. Relationship of metabolic syndrome and obstructive sleep apnea. J Clin Sleep Med. 2007; 3(5): 467-72.
9. Ambrosetti M, Lucioni AM, Conti S, et al. Metabolic syndrome in obstructive sleep apnea and related cardiovascular risk. J Cardiovasc Med (Hagerstown). 2006; 7(11): 826-9.
10. Lam JC, Lam B, Lam CL, et al. Obstructive sleep apnea and the metabolic syndrome in community-based Chinese adults in Hong Kong. Respir Med. 2006;100(6): 980-7
11. R. Sasanabe, K. Banno, K. Otake, et al. Metabolic Syndrome in Japanese Patients with Obstructive Sleep Apnea Syndrome. Hypertens Res 2006; 29: 315–322.
12. Vgontzas AN, et al. Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Met 2000; 85: 1151-1158.
13. Young T, Preppard PE, Gottlied DJ. Epidemiology of obstructive sleep apnea. A population health prospective. Am J Respir Crit Care Med 2002; 165: 1217-1239.
14. Trakada G, Chrousos G, Pejovic S, et al. Sleep apnea and its association with the stress system, inflammation, insulin resistance and visceral obesity. Sleep Medicine Clinics, 2007; 2(2): 251-261.
15. Peppard PE, et al. Longitudinal study of moderate weight change and sleep-disordered breathing. JAMA 2000; 284: 3015-3021.
16. Vgontzas AN, Bixler EO, Chrousos GP. Sleep apnea is a manifestation of the metabolic syndrome. Sleep Med Rev 2005; 9: 211-224.
17. Wilcox I, et al. “Syndrome Z”: the interaction of sleep apnea, vascular risk factors and heart disease. Thorax 1998; 53: 25- 28.
References