Obstructive sleep apnea is becoming an increasinly common disease
Obstructive sleep apnea and epidemiology.
Obstructive sleep apnea (OSA) is a disease characterized by repetitive periods of apnea and hypoapnea during sleep. The term apnea refers to the suspension of the upper airway for a minimum period of 10 seconds while hyopapnea is defined as the partial collapse of the upper airway resulting in a 30% or greater reduction in airflow. OSA is increasingly becoming a wide spread disease and has developed as being the most common form of sleep-disordered breathing. Its ubiquitousness is compounded further if one takes into account the vast number of cases presently undiagnosed. An improved approached to the diagnosis of sleep apnea is likely to increase the incidence rates of the disease and so present data on sleep-apnea, is misleading in that respect. The estimated number of male patients diagnosed with sleep apnea is currently in the region of 15-25%; the estimate for women is 9-26%. Studies have concluded that the syndrome is at greater risk (of almost two to three times) of developing within men as opposed to women. In addition, it has also been established that the likelihood of developing the syndrome increases with advancing age; the data available suggests that patients over the age of 65 are three to four times more likely to develop OSA than middle-aged patients.
Clinical presentation of Obstructive Sleep Apnea
A typical OSA patient will exhibit a range of symptoms that can be divided according to the time of day they occur. Nocturnally, a patient is likely to experience symptoms typically including snoring, witnessed apneas and restlessness whereas diurnal symptoms include sleepiness, fatigue and impaired concentration. Other symptoms that may be exhibited include high blood pressure, obesity and hypertension.
Obstructive sleep apnea and hypertension
Recent studies indicate that OSA has continued to become an important public health issue in that it is clearly associated with the impairment of quality of life and the development of cardiovascular disease. More importantly, there is a substantial amount of evidence supporting the link between obstructive sleep apnea and systemic hypertension. The problem lies in the fact that there is a direct relationship between the two diseases that can be exacerbated by factors such as obesity. This study seeks to investigate whether sleep apnea is an independent variable for the development of hypertension or as a result of confounding variables.
It is estimated that 50- 60% of patients with known OSA are hypertensive; conversely 30-40% patients with diagnosed systemic hypertension show strong evidence of OSA. It is a worrying fact that about 40% of patients with systemic hypertension are unaware that they also have OSA. There is also a strong possibility that these figures are an underestimate, as OSA is not always diagnosed with high blood pressure patients.
There is, at present, a lack of clarity with regards to the process through which sleep apnea contributes to hypertension. Potential factors that may explain such a causal link include; an increase in sympathetic nerve activity increases in negative intrathoracic pressure and changes in chemo reflex mechanisms. The causal relationship between sleep apnea and hypertension is of critical importance and will be subject to further scrutiny and discussion later on in this study.
Another approach that may be adopted to assess the extent to which sleep apnea affects hypertension is by exploring whether treatment for sleep apnea has any effect on reducing hypertension. There are, however, certain considerations that have to be taken into account; we must assess whether the treatment was managed optimally and also how compliant patients were the treatment devices. The severity of sleep apnea is also an issue that requires consideration; Does treatment only benefit patients suffering from a more serious form of sleep apnea or is the converse true? Attempts by obese patients to lose weight by increasing levels of physical activity may influence the effectiveness of the treatment; how can one be sure that the decline in blood pressure is a result of effective sleep apnea treatment as opposed to the effect of reducing weight?
Obstructive sleep apnea is diagnosed through a selection of questions. The important question that must be asked at the outset is whether the patient snores and if so, how loudly. The frequency of their snoring patterns will also be questioned and if they are unable to give an accurate description their bed partner may be of use. Loud and frequent snoring is symptomatic of a patient with OSA. It is critical that the bed partner is present at the interview so they can cross-verify their partners sleep behaviour. The second question focuses on the diurnal symptoms of the patient; more specifically, whether they experience fatigue during the day. This may well include lapses of concentration during periods of work. A study has confirmed that the chances of being involved in a vehicular accident are far greater with OSA patients as opposed to non-sufferers. However, it is also important to find out if the daytime sleepiness is as a result of other factors such as depression, excessive alcohol consumption and side effects of regular medications. Lastly, it is important to question the bed partner as to whether they have witnessed episodes in which the patient stops breathing; such a question is of critical importance since a suspension in breathing is a frequent symptom of OSA.
During periods of screening, it is important to focus on the presence of hypertension since the number of patients suffering from systemic hypertension are often also OSA patients. This relationship strongly indicates that there exists a close relationship between OSA and hypertension. Another major indicator for OSA is obesity as 70% of patients who have OSA are also obese.
The ultimate diagnostic tool for OSA is “polysomnography”. It is an overnight process, which is supervised by a technician and conducted in a sleep laboratory. The procedure involves monitoring parameters such as oxygen saturation, heart rate, nasal flow etc. These measurements then allow the clinical to declare what type of sleep-disorder the patient has and also the severity of the disease. To quantify the severity of the disease the apnea-hypopnea index (AHI) is used which tells us the number of obstructive events per hour. Mild OSA is 5-15 events per hour, moderate 15-30 per hour and severe OSA 30 and above per hour. The severity of OSA and the prevalence of hypertension will be looked at in this study to establish if hypertension is more common in the group with highest AHI or the lowest AHI. It is more than likely that a dose-response relationship will be observed between the severity of the syndrome and the prevalence of high blood pressure.
A specific mechanism whereby sleep apnea causes hypertension is still not fully identified however there is a substantial amount of evidence to support numerous possibilities. The first possibility is the increase in sympathetic activity which leads to an increase in blood pressure. The second possibility is the excess production of vasoconstrictors which and the third being the confounding variable obesity which in the presence of sleep apnea can exacerbate blood pressure levels.
An average adult spends majority of their sleep in non-rapid eye movement sleep and under normal circumstances an adults blood pressure falls during their sleep. This is because as they fall asleep the parasympathetic nervous system tone increases and the sympathetic activity decreases. This in turn reduces the cardiac output and causes a dip in blood pressure. This situation is not the case with patients diagnosed with OSA. In an OSA event, the sensitivity peripheral and central chemoreceptor's are lowered. The upper airway becomes abnormally narrowed and collapses and as a result there is a decrease of gas exchange taking place at the lungs which makes breathing difficult. The hypoxemic-hypercaoneic state is activated which helps to force breathing. This causes repeated arousals and is linked to an increase in sympathetic activity which also causes high blood pressure. Since patients with OSA have this cycle repeated several times during their sleep it also means that the blood pressure rises after every apnoeic and hypnoaic event.
Endothelin-1 (ET-1) is an effective vasoconstrictor alongside having mitogenic properties. The production of ET-1 is initiated with hypoxia. Animal models have shown that irregular episodes of hypoxia had increased both the levels of ET-1 and blood pressure. After treating with an ET-1 blocker the blood pressure decreased in a dose-dependent manner. This indicates that the presence of ET-1 contributes to increasing blood pressure. This relationship was also seen in adults, patients who were not treated for sleep apnea for 4-5 hours had an average oxygen saturation level of 73% and a considerale increase of blood pressure and concentration of ET-1. However when treated with CPAP, oxygen saturation rose to an average of 91% and was accompanied by a reduction in both blood pressure and ET-1. The results shown above do not claim that there is a casual relationship between endothelins and hypertension but when over-expressed they may be implicated in the increased blood pressure in patients with sleep apnea.
It is already known that obesity and sleep apnea are both closely related to hypertension. They both play a role in being major risk factors for developing the disease and often co-exist and interact with each other. There is no specific mechanism explaining the relationship of obesity in 0SA related hypertension as was the case with OSA and hypertension alone, although there are proposed mechanisms such as SNS activation, baroflex dysfunction, high angiotensin II levels, oxidative and inflammatory stress and renal function.
mechanisms of obesity causing hypertension
The importance of the treatment of OSA is both beneifical for the short term and long term.
The treatment of patients who are also hypertensive is not such a simple task as one will need to consider modifying their risk factors for the disease as well as treating the hypertension. This may include motivating patients to lose weight, refrain from tobacco use and drinking less alcohol.
In obese patients, weight loss is strongly recommended, as obesity is major risk factor in developing OSA. Weight loss has been reported to decrease the numbers of apneas as well as increase the number of hours of undisturbed sleep. The relationship between weight loss and reduction in AHI is not linear, which means that a small reduction in weight can lead to a significant improvement in the number of apneas per hour. The number of apneas will reduce by approximately 50% with a 10% reduction in weight. A number of patients are non-compliant with this weight-loss strategy and an alternate way of losing weight quickly is through surgery, which has showed promising results in reducing the number of apnea and hyponea events.
In non-obese patients where losing weight is not an issue the most effective and widely used treatment is Continous Positive Airway Pressure (CPAP). It is used for patient with mild to severe OSA. This treatment works by splinting the upper airway with positive air pressure through a nasal mask and this counteracts the collapsing of the pharyngeal airway during OSA.
Effective use of nasal CPAP has shown a marked decrease in blood pressure asw ell as improved survival in patients suffering from OSA that compared to weight loss alone. Whilst CPAP is very effective treatment option it is hampered by two pitfalls. Firstly, CPAP does not provide a permanent cure it is only a symptomatic treatment. When the patient has ceased treatment, there is a reoccurrence of OSA and its symptoms. Secondly, patients find it extremely difficult to tolerate therapy therefore compliance rates are not good. In an earlier study it was revealed that compliance rates were as low as 45%, however in recent studies the figures have improved to a region between 65% and 90%. The low compliance rates are not surprising as one would find it rather annoying to sleep with a facemask every night. A high percentage of patients also report of side effects such as nasal congestion, nasal dryness, rhinorrhea, sinusitis, and skin reactions arising from the face mask. Nasal dryness is the most common symptom reported by patients, a study showed that after CPAP treatment 65% reported nasal dryness, 35% sneezing and 25% nasal congestion. These symptoms are although easily alleviated through administration of a heat humidifier and nasal steroids. Good education from health care providers will mean that the level of understanding of using CPAP will increase and overall this should increase compliance rates.
A surgical approach is indicated to patients who are not compliant with CPAP and is directed towards the site of obstruction. Initially, tracheomasty was the preferred option of surgery as it reduced both mortality and morbidity rates with people with OSA however was also associated with local bleeding around the area. In recent time uvulopalatopharyngoplasty (UPPP) has become increasingly common. It has shown to be effective in treating the upper airway but only 40-60% of patients have shown improvements in symptoms. Other surgical options may include tonsillectomy, adenoidectomy and somnoplasty, which have recently been discovered.
Till date there has been no successful pharmacological treatment for OSA. Some compounds have shown to be as effective as surgery but still not close to being effective as nasal CPAP. Other treatment options for OSA are positional therapy and oral devices to treat snoring.