December 2008 no white pages.indd SULTAN QABOOS UNIVERSITY MEDICAL JOURNAL NOVEMBER 2008, VOLUME 8, ISSUE 3, P. 266-274 SULTAN QABOOS UNIVERSITY© SUBMITTED - 6TH MAY 2008 ACCEPTED - 13TH SEPTEMBER 2008 Obstructive Sleep Apnoea/Hypopnoea Syndrome and Hypertension *Mohammed A Al-Abri, Khamis M Al-Hashmi ThE OBSTRUCTIVE SLEEP APNOEA/HYPOP-NOEA syndrome (OSAHS) is a disorder char-acterised by repetitive upper airway collapse during sleep in association with daytime sleepiness that has an estimated prevalence of 2% among middle- aged women and 4% among middle-aged men.1 It was recognised only quite recently, although it has been extensively researched in the last 30 years. 1Department of Clinical Physiology, Sultan Qaboos University Hospital, Muscat, Sultanate of Oman *To whom correspondence should be addressed. Email: malabri@squ.edu.om R E V I E W بارتفاع وعالقتها الكامل/اجلزئي النومي النفس انقطاع متالزمة الدم ضغط محمد الهاشمي خميس بن عبداهللا العبري، بن محمد النفس انقطاع متالزمة بني ثيقة و عالقة توجد البالغني. 2-%4 من يصيب شائع اضطراب الكامل/اجلزئي النومي النفس انقطاع متالزمة امللخص: التدخلية. الدراسات الكبيرة وكذلك الوبائية ــات والدراس احليوانات على اجريت التي ــات للدراس وفقا وذلك الدم ضغط وارتفاع النومي الكامل/اجلزئي تؤدي أن ميكن عديدة هناك أسباب مستقبال. الدم ضغط ارتفاع من واخلطر النومي معدل انقطاع النفس بني طردية عالقة الوبائية الدراسات اظهرت وفي النوم اثناء يزيد هؤالء عند الودي ــي العصب اجلهاز ــاط فنش الكامل/اجلزئي. النومي انقطاع النفس مبتالزمة املصابني عند الدم ضغط ــاع ارتف ــى ال الكيمائية واملستقبالت مستقبالت الضغط تنشيط ناجتة عن تكون األشخاص رمبا هؤالء الودي عند العصبي اجلهاز في نشاط الزيادة هذه . اليقظة ضغط الهواء أن جهاز ــني تب النوم. أثناء الكامل/اجلزئي النفس انقطاع ــن الناجت ع الدم ــجني أكس ونقص املتكرر التيقظ نتيجة الدموية ــة األوعي ــي ف ذلك باإلضافة إلى الدم. وضغط ــودي ال ــاط اجلهاز من نش النفس النومي الكامل/اجلزئي يخفض كال متالزمة انقطاع لعالج ــتعمل الذي يس ــب املوج الكامل/اجلزئي. النومي النفس انقطاع مبتالزمة عند املصابني الدم ضغط ارتفاع في الدموية لألوعية البطانية ــية األغش وظائف في ــاعد اخللل يس قد نقص نتيجة ــخاص األش هؤالء عند ــع األوعية الدقيقة توس عن اختالل ــؤوال مس اجلذور احلرة وزيادة انتاج ــيد النيتريك اكس غاز نقص انتاج ــون ــد يك ق فعال. بشكل البطانية األغشية وظائف اعادة يساعد على املوجب الهواء العالج بجهاز ضغط أن الدراسات أظهرت االكسجني. الدم, ضغط ارتفاع ــة, البطاني ــية االغش وظائف ــية ، االنعكاس الكيميائية االفعال ، ضغط الدم ــية، االنعكاس الضغط الكلمــات: أفعال مفتــاح ودي. نشاط الكامل/اجلزئي, النومي النفس انقطاع متالزمة ABSTRACT The obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is a common disorder, affecting around 2–4% of the middle-aged population. There is a strong association between OSAHS and hypertension, based on animal, large epidemiological and interventional studies. The epidemiological studies have shown a dose-response relationship between apnoea/hypopnoea index (AHI) and the risk of developing hypertension. Different mechanisms may have a role in the process of elevated blood pressure in OSAHS. Sympathetic activity is increased in OSAHS patients during sleep and wakefulness. This increase in sympathetic activity is probably due to activation of baroreflexes and chemoreflexes by frequent arousals and hypoxaemia a result of apnoea or hypopnoea events. Continuous positive airway pressure (CPAP) has been shown to reduce sympathetic stimulation and blood pressure in OSAHS patients. Altered endothelial function may also have a role in the pathogenesis of hypertension in OSAHS subjects. Reduction of nitric oxide (NO) production and increase in the formation of free radicals may be responsible for the impairment of the vasodilatation of micro-vasculature in these subjects as a result of hypoxaemia. It has been shown that effective CPAP therapy has a reversible effect on endothelial dysfunction. Keywords: Baroreflex; Blood pressure; Chemoreflexes; Endothelial function; Hypertension; OSAHS (Sleep apnoea/hypopnoea syn- drome); Sympathetic activity. O B S T R U C T I V E S L E E P A P N O E A / H Y P O P N O E A S Y N D R O M E A N D H Y P E R T E N S I O N 267 OSAHS-related features include excessive day- time sleepiness, 2, 3 neurocognitive impairment, 4 and increased motor vehicle accidents.5-7 It has also been associated with adverse cardiovascular consequences such as hypertension and impairment of cardiovas- cular variability. Treating OSAHS is very rewarding, for the benefit to the patient is enormous in improv- ing the quality of life as well as preventing long-term sequelae. There is strong evidence that patients with sleep apnoea might be at increased risk of cardiovascu- lar disease. Patients with sleep apnoea are often hypertensive8, 9 and up to one-third of hypertensive patients may have sleep apnoea.10 Several cross-sec- tional studies have shown that the prevalence of hy- pertension increases progressively with the severity of OSAHS.11-13 How hypertension is associated with OSAHS is not fully understood. However, repetitive episodes of airway occlusion during sleep, with con- sequent hypoxia, hypercapnia, dramatic changes in intrathoracic pressure and repeated arousals, may provoke a number of autonomic, haemodynamic, hu- moral and neuroendocrine responses. This review fo- cuses mainly on the epidemiological link between OS- AHS and hypertension and the autonomic responses that might occur in OSAHS patients. Other aspects of the possible vasculopathy in OSAHS will also be briefly reviewed. E P I D E M I O L O G Y OSAHS and hypertension have common risk factors, such as obesity, alcohol intake, age, gender and lack of exercise, which makes causation impossible to prove, using epidemiology alone. However, several epidemio- logical studies have revealed a strong association be- tween OSAHS and hypertension.11-17 O SA H S I N TH E GE N E R A L P O P UL ATI O N Early studies of the association between hypertension and snoring came from Norton et al. and Koskenvuo et al., who found that snoring was a risk factor for hypertension.14, 15 Subsequent studies found that sleep apnoea was an independent risk factor for the devel- opment of hypertension, similar to age and obesity.16 A large epidemiological study showed that sleep apnoea significantly contributed to hypertension, independ- ent of other risk factors.11 Each apnoeic event per hour of sleep added 1% to the risk of having hypertension. More evidence linking OSAHS with hypertension is provided by the Wisconsin Sleep Cohort study, which showed a dose-response association between OSAHS and de novo hypertension after 4 years of follow-up independent of confounding factors although the number of new hypertensive subjects was small.13 In the original report, patients with an apnea-hypopnea index (AHI) > 25 had a fivefold risk of hypertension.17 The increase in risk of hypertension was greater in thinner patients who had abnormal breathing. After correction for confounding factors, those with an AHI >15 had a 2.9-fold greater chance of developing hyper- tension in the following four years. A similar relation- ship between OSAHS and hypertension was found in the Sleep Heart Health Study.12 In this study of 6,000 middle-aged and older adults, the prevalence of hy- pertension (defined as a resting BP ≥ 140/90 mmHg or the use of anti-hypertensive drugs) increased progres- sively with the severity of OSAHS. After adjusting for the confounding factors, including obesity, the odds ratio in the group with severe OSAHS (AHI >30) was 1.37 (95% confidence interval (CI), 1.03-1.83; p = .005) compared with those with lowest AHI (< 1.5). A cross- sectional study in a normal population by Bixler et al. also indicated an association between hypertension and sleep apnoea independent of other risk factors. The association was strongest in young subjects, and decreased with age.18 O SA H S I N TH E H Y PE RTE N SI V E P O P UL ATI O N Epidemiological studies of hypertensive patients have also suggested an association between sleep ap- noea and hypertension. Hypertensive patients had a greater prevalence of sleep apnoea than normotensive subjects.19 Grote et al. found that OSAHS was a risk factor for poor blood pressure control in younger hy- pertensive patients.20 A greater prevalence of obstruc- tive sleep apnoea is found in adults with drug-resistant hypertension (BP > 140/90 who require a combination of three or more antihypertensive drugs) 21 supporting the idea of an etiological role of OSAHS in the cause of hypertension. H Y PE RTE N SI O N I N O SA H S SUB JE C TS Animal models In dogs, obstructive sleep apnoea leads to the devel- opment of sustained hypertension.22 Obstructive sleep apnoea (OSA) was produced in four dogs using an oc- clusion valve attached to an endotracheal tube through which the dog could breathe. Obstruction of the air- way by the valve was controlled by telemetry of elec- M O H A M M E D A A L - A B R I A N D K H A M I S M A L - H A S H M I 268 trocardiogram (ECG) and electromyography (EMG) signals from the dog during a one to three month pe- riod. In the same dogs, sleep fragmentation was also induced. Arterial blood pressure was monitored for 12 hours every night. Obstructive sleep apnoea (OSA) caused a progressive increase in night-time mean arte- rial BP in each of the four dogs. There was no differ- ence between the change in night-time BP caused by sleep fragmentation and that caused by OSA (p = 0.4). In contrast, the change in daytime BP caused by sleep fragmentation was significantly less than the change during OSA (p = 0.001). There were no changes in night-time or daytime heart rates during either OSA or sleep fragmentation. In another dog study of chron- ic OSA by Parker et al., acute airway occlusion during sleep increased left ventricular (LV) afterload and de- creased fractional shortening. Chronic OSA caused a sustained decrease in LV systolic performance, caused by systemic hypertension and/or transient increases in LV afterload during episodes of airway obstruction.23 Human studies A case-control study found that patients with OSA- HS had higher blood pressure than matched control subjects. Diastolic blood pressure in patients with OSAHS was significantly greater than controls during the daytime, night-time, and overall. OSAHS patients also had significantly greater night-time systolic BP (p = 0.01), although daytime and overall systolic blood pressure did not differ from control subjects.8 Direct evidence that OSAHS causes hypertension is provided by intervention studies, in which continuous positive airway pressure (CPAP) reduced BP.24, 25 Nevertheless, in order to understand the pathophysiology of hyper- tension in OSAHS, the mechanism of blood pressure elevation is discussed below. O S A H S A N D B L O O D P R E S S U R E In healthy subjects, blood pressure normally decreases by 10% to 15% from its daytime value during sleep. This circadian drop in BP has been called dipping. Howev- er, some patients with OSAHS do not show nocturnal dipping of BP and are thus called non-dippers.26 This may relate to apnoeas and hypopnoeas, which cause repeated nocturnal increases in BP, which consequent- ly increase the mean sleeping BP.27 The greatest pres- sure peaks occur after apnoea and may be 100 mmHg above the baseline value.28, 29 These acute nocturnal changes may lead to persistent daytime hypertension as a long-term consequence29 with an increased risk of target organ damage.30 In a case-control study, sleep apnoea patients had significantly increased mean di- astolic BP during both the daytime and night-time, and systolic BP was higher among OSAHS patients at night compared with controls. The nocturnal dip in BP was smaller in patients with OSAHS than in matched control subjects.8 Hypoxia may explain partly these variations in BP in sleep apnoea patients. In animals, repetitive episodic hypoxia causes diurnal elevation in BP in rats.31 Simi- larly rises in daytime blood pressure follow induced apnoeas in dogs and are probably related to hypoxae- mia rather than arousal, because noise-induced arous- al did not cause daytime hypertension in the same dogs.22 Increased sympathetic activation, perhaps in- duced by hypoxaemia, may be a key factor in causing long-term BP changes.32 However, other factors may be implicated in the development of hypertension in OSAHS patients, such as endothelial dysfunction, as discussed below. S Y M P A T H E T I C A C T I V I T Y I N O S A H S P A T I E N T S D UR I N G SL E E P Normal sleep is physiologically divided into rapid eye movement (REM) and non-rapid eye move- ments (NREM) sleep. NREM is further divided into 4 stages from Stage 1 to 4. In normal sleep, heart rate, blood pressure, and sympathetic nerve traffic usually decrease.33, 34 This reduction of sympathetic activ- ity appears to increase progressively from Stage 1 to Stage 4 sleep.28 However, during REM sleep, sympa- thetic activity increases, to as much as double that of wakefulness.34 Blood pressure and heart rate during REM are variable, but average about the same as dur- ing wakefulness.28 In contrast, sympathetic activity is increased dur- ing sleep in OSAHS patients and the sympathetic and the haemodynamic state during sleep is determined primarily by the duration and severity of apnoea rather than by the sleep stage itself.29 Repetitive episodes of obstructive apnoea, hypoxia and hypercapnia probably act through chemoreceptor reflexes and other mecha- nisms to increase sympathetic drive. 35 Furthermore, resumption of breathing results in increased venous return and increased cardiac output. This increased cardiac output is delivered into a severely constricted peripheral vasculature, with surges in BP.35 O B S T R U C T I V E S L E E P A P N O E A / H Y P O P N O E A S Y N D R O M E A N D H Y P E R T E N S I O N 269 E FFE C TS O F A R O USA L FR OM SL E E P O N BP Normal spontaneous arousals from sleep are associ- ated with transient increases in blood pressure, heart rate and ventilation.36 These increases are caused by changes in sympathetic activity caused by the arousal. In a study in dogs, 37 ventricular stroke volume (SV) remained constant when apnoea ended, if there was no arousal. However, with arousal from apnoeas, heart rate and cardiac output increased, although SV de- creased. Arousal increased the systemic, but not the pulmonary arterial pressure, in response to obstructive apnoea. The increase in systemic blood pressure was more marked during NREM sleep than in REM sleep.37 In a large population-based study, sleep fragmentation index (SFI), calculated as the total number of awaken- ings or shifts to Stage 1 divided by the total sleep time per hour, was significantly associated with systolic, but not diastolic blood pressure, during wakefulness in in- dividuals with AHI < 1. However, sleep fragmentation and blood pressure were not associated in those with AHI > 1 after controlling for the influence of the AHI. The authors concluded that sleep fragmentation was independently associated with a greater systolic blood pressure during wakefulness. 38 Noda et al.39 found that end-apnoeic arousal and hypoxic asphyxia and the subsequent sleep fragmentation might contribute to nocturnal and diurnal elevation of BP. The rise in blood pressure with arousal might be caused by an increase in sympathetic activity. Sympathetic outflow remained elevated for a substantial period even after a hypoxic stimulus was removed; 35 nevertheless, it is unwise to conclude that sleep arousal is the sole con- tributor to sustained hypertension in awake sleep ap- noea patients. However, in patients with higher AHI, sleep disruption may modulate the BP along with other effects such as hypoxaemia and changes in in- trathoracic pressure, which may overcome the effects of arousal. 38 D UR I N G WA K E F UL N E S S Greater sympathetic activity in OSAHS patients may be present even during daytime wakefulness, when subjects are breathing normally and both arterial oxygen and carbon dioxide levels are normal.29, 40 Cir- culating catecholamines41 and muscle sympathetic nerve activity42 were greater in patients with OSAHS compared with normal subjects, probably because of baroreflex dysfunction, chemoreflex excitation and endothelial dysfunction. Greater sympathetic drive in these patients may contribute, to a certain extent, to chronic elevation of resting BP. The mechanism un- derlying the sustained increase in sympathetic drive is not clear. Morgan et al. suggested that combined hy- poxia and hypercapnia evoke long-lasting sympathetic activation.35 This may explain in part the increased daytime sympathetic drive in OSAHS patients. How- ever, repeated BP increases, acting via the barorecep- tors, may reset the baroreflex, permitting a higher level of sympathetic activity and BP even during wakeful- ness. To understand the role of the chemoreflexes and baroreflexes in BP control in OSAHS patients, these two aspects are explained in detail below. C H E M O R E F L E X E S The chemoreflexes are important and powerful mod- ulators of sympathetic activation. Hypoxia, which acts primarily on the peripheral chemoreceptors lo- cated in the carotid bodies, 43 and hypercapnia, acting on the central chemoreceptors located in the brain stem, trigger reflex increases in minute ventilation as well as sympathetic activity. Patients with OSAHS have an enhanced vascular response to hypoxia.44 In a double-blind, randomised, controlled trial, it was found that muscle sympathetic nerve activity (MSNA) and mean arterial pressure were significantly re- duced in OSAHS patients compared with control subjects during chemoreflex deactivation by 100% oxygen;44, 45 however, the enhancement of peripheral chemoreflexes is selective to autonomic, haemody- namic and ventilatory responses in normotensive OSAHS.44 Furthermore, this enhancement of the re- flex response to hypoxia is not explained by obesity, since obese subjects who are otherwise healthy with no OSAHS have chemoreflex responses similar to those seen in control subjects.44, 46 Nevertheless, obese patients have a greater response to hypercapnia.46 - 48 Both hypoxia and hypercapnia have local vascular ef- fects, causing vasodilation, which lowers the blood pressure initially, which in turn increases sympathetic activity and catecholamine release.49 During apnoea, sympathetic activity rises gradually, reaching its peak at the end of the apnoea, when oxygen desaturation and carbon dioxide retention are most marked. 34, 45 On release of the airway obstruction and resumption of breathing, increased cardiac output, together with the constricted peripheral vasculature, result in a marked increase in blood pressure.34 There is also a carry-over effect to the tonic activation of the peripheral chem- M O H A M M E D A A L - A B R I A N D K H A M I S M A L - H A S H M I 270 oreceptors, even during normoxia, which may partly explain the increased sympathetic activity during the daytime (see above). However a double-blind study suggested that hyperoxia can suppress peripheral chemoreceptors in OSAHS patients, shown by a de- crease in blood pressure and slowing of heart rate.44 B A R O R E F L E X A N D H Y P E R T E N S I O N There is evidence that the cardiac baroreflex is im- paired if blood pressure is increased, in both humans 50, 51 and animals.52 Floras et al. found that the arterial baroreflex could buffer acute changes in blood pres- sure in subjects with WHO Stage 1 hypertension. However, this ability is weakened if the baroreflex sensitivity (BRS) is reduced. With the development of clinically evident cardiac adaptation to hyperten- sion (WHO Stage 2), the contribution of the arte- rial baroreflex to the regulation of blood pressure is no longer detectable and the influence of cardiac and somatic afferents to reflex circulatory adjustment to activity may predominate.50 Furthermore, Lantelme et al. found that hypertensive rats have impaired cardiac baroreflex responses, characterised by a range-inde- pendent decreased gain, which is not caused by car- diac hypertrophy.52 The impaired baroreflex may even precede the development of hypertension. Baroreflex inhibition of muscle sympathetic nerve activity is re- duced in adolescents with a family history of hyper- tension, even when they are normotensive, which may lead to the development of hypertension by increas- ing sympathetic vasomotor tone.53 This could also be a factor for hypertension in OSAHS patients, although there is no evidence for this so far. B A R O R E F L E X I N S L E E P A P N O E A Patients with OSAHS have baroreflex dysfunction. Narkiewicz et al. used phenylephrine to activate baroreceptors and nitroprusside to deactivate them. Normotensive patients with OSAHS had an impaired response to baroreceptor deactivation, but not to baroreceptor activation. They suggested that the re- duced baroreflex sympathetic modulation in patients with sleep apnoea was not accompanied by any im- pairment of baroreflex control of heart rate.42 In ad- dition, OSAH patients have impaired baroreflex re- sponses to a hypotensive stimulus.54 Using sequence method analysis, it has been noted that baroreflexes are impaired in OSAHS patients compared with healthy controls. 55, 56 E F F E C T O F T R E A T I N G S L E E P A P N O E A O N S Y M P A T H E T I C A C T I V I T Y A N D B P CPAP is the treatment of choice for majority of OSA- HS patients. In addition to improvement of symptoms, CPAP treatment may also reduce sympathetic activity. Nasal CPAP was found to reduce catecholamines. 57 Somers et al. found that CPAP treatment caused an acute and marked reduction in nocturnal sympathetic nerve traffic.29 However, CPAP does not reduce day- time blood pressure acutely, although it significantly reduces the large oscillations in blood pressure seen overnight in patients with untreated sleep apnoea.58 Nevertheless, a small fall in night-time systolic BP was seen in OSAH patients after 2 weeks of treatment, 59 with some improvement in daytime mean arterial blood pressure in non-dippers after 3 weeks of CPAP treatment compared with the placebo.60 However, when effective CPAP treatment was given for a longer period (8 weeks) in a before-and-after non-placebo controlled design, there was a significant fall in both systolic and diastolic BP, independent of changes in body weight.61 Thus, long-term treatment with CPAP may be needed to attenuate sympathetic activation and consequently reduce BP. This idea is supported by the findings that CPAP treatment reduced the mus- cle sympathetic nerve activity (MSNA) in otherwise healthy OSAHS patients, although the reduction was evident only after one and a half years of treatment.47 Furthermore, in a randomized placebo-controlled crossover study, Faccenda et al. found that CPAP ther- apy reduced 24-hour diastolic blood pressure in com- parison with the placebo, although the overall reduc- tion was small, averaging 1.5mmHg over the 24 hours. The decrease was greater during the early morning period that is at 2:00 a.m. As predicted a priori, the decrease was greater in those with more nocturnal hy- poxaemia (> 20% desaturations/hour).24 O S A H S A N D E N D O T H E L I A L D Y S F U N C T I O N The endothelium is the cell layer lining the blood ves- sels. It is one cell thick and senses changes in haemo- dynamic states.62 The endothelium responds to physi- cal and chemical stimuli by synthesis or release of substances such as nitric oxide (NO), prostacyclin, endothelins, endothelial cell growth factors, inter- O B S T R U C T I V E S L E E P A P N O E A / H Y P O P N O E A S Y N D R O M E A N D H Y P E R T E N S I O N 271 leukins, adhesion molecules, and fibrinolytic factors.63 Therefore, the endothelium can greatly influence vas- cular tone and structure by releasing NO. Impaired endothelium dependent function and endothelium in- dependent function in the forearm vascular bed is as- sociated with an increased risk of acute cardiovascular events, including cardiac death.64, 65 The endothelium is a major target of oxidative stress, and this stress may play a role in the pathophysiology of vascular disease. In OSAHS, recurrent episodes of hypoxaemia followed by re-oxygenation may trigger endothelial damage, via oxidative stress, superoxide radical formation.66 The combination of superoxide radical with nitric oxide and reducing nitric oxide bioavailability in the vessel wall leads to vasoconstriction. More recent studies have shown that oxidative stress and lipid preoxida- tion do not appear to be the key mediator for the car- diovascular diseases in OSAHS.67, 68 This finding con- tradicts the results of other studies which showed that OSAHS patients have an increased status of oxidative stress such as thiobarbituric reactive substances and peroxides 69 and decreased antioxidant capacity which could be reversed by CPAP treatment.70, 71 Only a few studies have shown increased expression of adhesion molecules72 and production of reactive oxygen spe- cies in leukocytes of sleep apnoea patients.73, 74 Pro- inflammatory factors such as interleukins, C-reac- tive protein and leukocyte adhesion molecules such as CD15 73 might also contribute to the pathogenesis of developing cardiovascular diseases and merit fur- ther evaluation. In addition, prothrombotic factors75 such as fibrinogen, plasminogen activator inhibitor, and reduced fibrinolytic activity with enhanced plate- let activity, may play a role in the process.76 In a ran- domized double-blind placebo controlled crossover trial, it was shown that OSHAS is associated with en- dothelial dysfunction using venous occlusion plethys- mography during intra-arterial infusion of endothe- lium-dependent (acetylcholine and substance P) and endothelium-independent (sodium nitroprusside) vasodilator. Vasodilatation was significantly impaired in subjects with oxygen desaturations (20 dips of 4% desaturations/hr) compared to non-desaturators (p <0.05) In the same study, treatment with CPAP for 6 weeks improved forearm blood flow to all vasodilators in comparison to results after sham CPAP (p <0.05 for all vasodilators).77 C O N C L U S I O N Obstructive sleep apnoea/hypopnoea syndrome is a common condition and its association with hy- pertension is very strong. Clinically, it is essential to understand the relationship between OSAHS and hypertension for the benefit of patients in order to prevent long-term sequelae and optimise treatment. The mechanisms behind the elevation of blood pres- sure in OSAHS are mainly due to autonomic changes that occur as a result of recurrent arousal and hypoxia. Impairment of baroreflex and chemoreflexes may lead to sustained activation of sympathetic activities. En- dothelial dysfunction may also have a role in the proc- ess of development of hypertension in sleep apnoea subjects. Effective CPAP therapy has been shown to reverse these changes and may prevent its occurrence. Further studies are required to explore the role of OS- AHS in the pathogenesis of atherosclerotic changes and subsequently developing arterial stiffness. Ran- domised control trials are also needed to assess the ef- fect of CPAP therapy in reversing or preventing these changes. R E F E R E N C E S 1. Young T, Finn L. 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