Obstructive sleep apnea syndrome: literature review

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introduction
Obstructive sleep apnea (OSA) is defined as periodic respiratory arrest or as events of a significant decrease in air intake through the upper respiratory tract (VDP) while maintaining the work of the muscles of the chest and abdomen, which is accompanied by a decrease in saturation and is manifested by sleep disturbance, snoring and daytime drowsiness. [1]
There are three types of SAS: obstructive (OSA), central (CAC), mixed. OSA is a disease manifested by recurrent partial (hypopnea) or complete (apnea) declines (collapses) of the upper respiratory tract during sleep while maintaining central control over breathing and muscle activity of the chest and abdominal wall. [2]
Data on the prevalence of obstructive sleep apnea in various authors are contradictory due to difficulties in diagnosing this condition. According to the results of various studies, about 10% of the population suffers from this disease, who are more at risk of arterial hypertension, including resistant to drug therapy. [3]. Central sleep apnea is usually diagnosed in a third of patients with stable CHF.[4].
According to Russian researchers, apnea in men is three times more common than in women, due to the peculiarities of the anatomy of the upper respiratory tract [1]. In the Russian recommendations of 2020, OSA is considered as the most common cause of secondary hypertension [5].
The United States Joint National Committee for the Prevention, Diagnosis, Evaluation and Treatment of High Blood Pressure reports that OSA ranks first among all causes of secondary arterial hypertension (AH). 40-50% of patients with OSA suffer from AH. [5]. According to the American Heart Association, 34% of men and 17% of women are susceptible to nocturnal respiratory disorders. Among patients with diabetes mellitus and pathologies of the cardiovascular system, the incidence of apnea is much higher - 40-80%. Despite the prevalence of this condition in patients with arterial hypertension, angina pectoris, atrial fibrillation and heart failure, its routine diagnosis is not carried out due to the unavailability of methods and insufficient awareness of clinicians. [6].
A meta-analysis carried out by the authors from England and combining 7 population studies clearly showed the relationship between sleep deprivation and the frequency of hypertension. However, it is not always possible to trace causal relationships between cardiovascular risk factors and OSA [7]
In patients with primary arterial hypertension, the prevalence of sleep apnea is about 35%, among patients with resistant arterial hypertension - from 60 to 80%. Resistance to drug therapy in patients with sleep apnea is due to sodium retention in the body due to sympathetic effects on the renin-angiotensin-aldosterone system. [8] The presence of moderate or severe OSA increases the risk of arterial hypertension resistance to medications by more than 2 times. [9]

THE AIM OF THE STUDY is to analyze and summarize the available data on obstructive sleep apnea syndrome as a risk factor for diseases of the cardiovascular system, and to assess their place in the modern concept of prevention of cardiovascular diseases.

MATERIALS AND METHODS OF RESEARCH
The review presents data from domestic and foreign authors on the risk factors of the cardiovascular system. To write the article, 42 sources of literature published in the international citation databases Pubmed, Scopus, as well as published in the RSCI, fundamental research, monographs, abstracts of dissertations were used. Data selection was carried out by keywords: cardiovascular diseases, risk factors, apnea, arterial hypertension, diabetes mellitus. Materials whose authorship has not been established, textbooks, and near-scientific Internet resources were excluded from the analysis.

The importance of sleep for physical and mental well-being is generally recognized by both healthcare professionals and the general public. Initial physiological studies demonstrating acute effects on the physiology of the cardiovascular system during sleep were followed by prospective epidemiological studies that confirmed a long-term association with CVD.
Obstructive sleep apnea syndrome (OSA) is defined by recurring episodes of upper respiratory tract obstruction during sleep. In addition to the peculiarities of the anatomy of the upper respiratory tract, a violation of the neuromodulating control of the muscles of the upper respiratory tract during sleep plays an important role in the pathogenesis of OSA. [10] Repeated strong breaths in the closed airways cause fluctuations in intra-thoracic pressure, which, in turn, can increase left ventricular pressure, transmural pressure [11, 12]. As a result, jumps in sympathetic tone increase arterial stiffness and blood pressure. [13]. Maintaining a high sympathetic tone carried over to the waking hours may be an important mechanism of hypertension associated with OSA. Cessation of breathing leads to gas exchange disorders characterized by intermittent hypoxemia and hypercapnia - another important cause of increased sympathetic tone. Chronic intermittent hypoxemia is probably crucial to explain many cardiovascular and metabolic consequences of OSA [14]. Moreover, obstructive phenomena often culminate in awakening, thereby disrupting the continuity of sleep and contributing to the occurrence of some symptoms of OSA, such as non-restorative daytime sleep, drowsiness.
Metabolic disorders detected in OSA include an increase in the level of endothelin-1, angiotensin 2 and aldosterone, a decrease in the amount of nitric oxide, which leads to fluid retention in the body and peripheral vasoconstriction, causing a persistent increase in blood pressure [15].
Patients suffering from OSA can be conditionally divided into three groups: middle-aged men, overweight and risk factors for cardiovascular diseases; older men with severe forms of sleep apnea, cardiovascular risk factors or already existing coronary heart disease, atrial fibrillation; women with moderate sleep apnea, cardiovascular risk factors, high prevalence of depression with concomitant use of antidepressants, anxiolytics, sleeping pills, nonsteroidal anti-inflammatory drugs and light opioids.[16]
Sleep apnea and arterial hypertension. Given the high prevalence of OSA and the adverse effects of day and night hypertension on cardiovascular diseases, the detection and treatment of OSA in patients is of high importance for public health. [17-18] OSA is recognized as an independent risk factor for hypertension. Obstructive respiratory phenomena leading to sympathetic jumps are accompanied by a sharp increase in blood pressure of varying degrees. In fact, apnea is considered an important reason for the absence of a physiological decrease in blood pressure at night. In addition to this nocturnal (more precisely, "sleepy") hypertension, OSA is also associated with daytime hypertension. A significant proportion of patients with resistant has concomitant OSA. [19] The Wisconsin cohort Study and the Sleep Heart Health Study (SHHS) demonstrated a similar dose-response relationship between OSA and AH, although it was significantly weakened after adjusting for body mass index. Treatment of OSA with constant positive airway pressure improves long-term blood pressure control based on 24-hour outpatient blood pressure monitoring, especially in patients with resistant arterial hypertension (RAH). [20-22]
There is a dose-dependent effect of the relationship between OSA and AH: with an increase in the severity of respiratory disorders during sleep, the risk of having RAH increases. Volume overload is considered as the leading mechanisms of the formation of the vicious circle of the connection between RAH and OSA, which is mainly due to hyperactivation of the renin-angiotensin-aldosterone system, hyperactivation of the sympathetic nervous system. Other mechanisms, such as oxidative stress, inflammation and endothelial dysfunction, also contribute to maintaining high blood pressure levels [23].
During a prospective study in Spain, in which 1,889 patients participated, it was determined that those who did not receive CPAP therapy had a higher incidence of hypertension compared to those who received such treatment. [24].
OSA and AF have common risk factors-obesity, old age and hypertension. In 50-80% of patients with AF, OSA is diagnosed, and AF is 3 times more common in people suffering from OSA. [25]
Numerous studies have documented a higher prevalence of AF in individuals with sleep apnea compared to those without sleep apnea, and sleep apnea has been associated with a higher incidence of AF recurrence after cardioversion and ablation. According to observations, CAC is more often the cause of AF than obstructive apnea.[26]
In the study of L. Chen et al. (2022), which used the tools of Mendelian genetic analysis, also confirms the cause-and-effect relationships of genetically predictable OAS with a higher risk of AF [27].
The risk of atrial fibrillation increases due to changes in the electrophysiological activity of the atria during fluctuations in intra-thoracic pressure and the change of short periods of deoxygenation and reoxygenation. Prolonged exposure to these factors can cause structural remodeling of the atria. AF paroxysms that occur after isolated episodes of apnea may be the result of transient tachycardia induced by LV dysfunction and diastolic dysfunction due to a decrease in cardiac output and increased pressure in the pulmonary vessels.[28] OSA is considered by a number of researchers as a factor that reduces the effectiveness of catheter and pharmacological antiarrhythmic therapy, therefore, treatment of apnea before these interventions may increase the likelihood of rhythm restoration. [29]

CHF and OSA CSA are present in 25-40% of patients with chronic heart failure. LV diastolic dysfunction underlying CHF with preserved ejection fraction may be caused by a drop in cardiac output and an increase in pressure in the pulmonary vessels during episodes of apnea.[30]OSA is widespread among patients with asymptomatic systolic and diastolic dysfunction of the left ventricle and congestive heart failure. (CH)[31]. OSA is associated with poor quality of life, excessive readmission and premature mortality in patients with HF, while treatment of OSA is associated with a decrease in readmissions and mortality. [32].Heart failure can complicate the diagnosis of sleep apnea due to similar symptoms - feelings of lack of air at night, paroxysmal night dyspnea, nocturia, drowsiness and fatigue during the daytime. There is evidence of the benefits of routine screening for OSA in all patients with heart failure using polysomnography.It is widely known that CPAP can be difficult to tolerate, especially in patients with HF. Alternative treatments include oral adaptations, hypoglossal nerve stimulation, and positional therapy in patients with recumbent OAS. Custom-made oral devices and hypoglossal nerve stimulation are recommended for people with CPAP intolerance, although there are limited studies on HF[31].Diagnosis of OSA.According to numerous studies, patients with CCC diseases rarely report to their doctor about symptoms associated with OSA, including snoring, frequent night awakening, sometimes with lack of air, and excessive daytime drowsiness, morning headache. Often these symptoms are mistaken for a complication of the underlying disease and remain without proper attention of the doctor. Identification of the risk group should include - anamnesis collection, physical examination and questionnaire.The question of which medications the patient takes requires clarification. It should be noted that there are drugs that aggravate the course of OAS: benzodiazepines, opioids, muscle relaxants, as well as male hormones, various sleeping pills. [34]The collection of anamnesis in a patient with obstructive sleep apnea includes the following questions: 1. the presence of daytime drowsiness, fatigue, lack of a sense of recovery after sleep. 2. waking up with a feeling of holding your breath, lack of air, suffocation. 3. stopping breathing in a dream and loud snoring from the words of those around the patient. [35]The severity of sleep apnea does not always correlate with the number of complaints and the subjective well-being of the patient. One of the questionnaires for collecting a patient's medical history is the BANG STOP Questionnaire, which is widely used to assess the risk of OSA. [36].The Epworth Sleepiness Scale and the BANG STOP Questionnaire have reduced sensitivity and specificity in patients with atrial fibrillation and heart failure due to similar symptoms.[33].Currently, the gold standard of diagnosis is polysomnography. This method allows continuous recording of thoracoabdominal effort, oxygenation, brain waves, rhinoceros air flow and snoring. The use of this method is often limited by its availability, especially in middle- and low-income countries. [37]. Polysomnography allows us to obtain two clinically significant indicators-the apnea-hypopnea index (IAG), i.e. the average number of episodes of apnea and hypopnea per hour of sleep) and the oxygen desaturation index (ODI, that is, the average number of oxygen desaturations is at least 3-4% lower than the baseline level per hour of sleep). According to the so-called Chicago criteria, severity is assessed by the value of IAG as follows: absent (< 5), mild (5-14), moderate (15-29) and severe (≥ 30).[38]Prevention and treatment of sleep apnea syndrome is largely associated with lifestyle modification. RV Buzunov described a "vicious circle" when sleep disturbance leads to the development of obesity, and in turn obesity contributes to the progression of OAS and aggravation of metabolic processes. [39] There is a positive relationship between weight loss and the risk of sleep apnea - weight loss by 10% leads to a decrease in the hypopnea-apnea index by 26%. In addition, weight loss itself is a factor in reducing the risk of cardiovascular diseases. [40]Some authors claim that smoking can aggravate the course of OSA due to inflammation of the upper respiratory tract, but there is no data on improving the course of OSA in patients who quit smoking.The most effective method of treating OSA is CPAP therapy - a regime of artificial lung ventilation with constant positive pressure.Indications for CPAP therapy are the absence of effects from other treatment, the presence of severe concomitant diseases of the cardiovascular system, the apnea index is higher than 30. Contraindications are a history of pneumothorax, frequent sinusitis, infectious eye diseases, hypotension, frequent nosebleeds, surgical interventions on the brain.Oral devices are used to treat OSA, the two most common designs are tongue retention devices and orthodontic or mandibular devices for promotion.  They improve the work of the upper respiratory tract by changing the position of the tongue and the associated structures of the upper respiratory tract.  The outcomes of such treatment are generally favorable in patients with certain craniofacial structures, such as narrow minimal retroglossal airways, mandibular retrusion and short anterior facial height. [41]Therapeutic tactics should include such stages as lifestyle changes (weight loss, alcohol restriction, anti-smoking, and aerobic exercise), drug treatment including antihypertensive therapy, and therapy including restoration of patency of the upper respiratory tract (positional treatment, surgical aids, intraoral applicators, CPAP-therapy).One of the varieties of sleep apnea is positional apnea, in which the symptoms of obstruction increase dramatically in the supine position. Young patients with the absence of obesity are more susceptible to this type of disease. The effect of sleep posture on apnea is found in about half of patients. Randomized studies have noted a decrease in the degree of obstruction during sleep of patients on their side or in a semi-sitting position, although the clinical effect of these poses is still less than from treatment with CPAP therapy.A simple and well-known technique of positional therapy is the tennis ball method - a pocket is made on the patient's pajamas in the back area, into which a small ball is placed, preventing him from turning on his back during sleep. [42].Currently, there is no drug therapy with a proven clinical effect to reduce the severity of OSA. SGLT-2 inhibitors are considered promising for the treatment of OSA, but their appointment requires additional research. [38] Theophylline showed a moderate improvement in periodic respiration and IAG. However, its narrow therapeutic window combined with an increased risk of arrhythmia limits its use in patients with HF.ACE inhibitors have also shown an improvement in the course of central sleep apnea in heart failure, possibly due to their ability to reduce ventricular afterload.Beta blockers help reduce nocturnal sympathetic activation of the heart caused by repetitive arousal and desaturation. Of the beta blockers recommended in the HF guidelines, carvedilol is preferable for patients with HF with central sleep apnea because it improves sleep quality due to the lack of melatonin inhibition. Acetazolamide acts as a diuretic and improves IAG and oxygen saturation during HF and CSA, thereby improving functional ability and quality of sleep. Although it reduces the central apnea index, potential side effects, including drowsiness, paresthesia and tinnitus, limit its use in patients with heart failure. [33] Conclusion Thus, sleep apnea is a widespread, but not often detected disease among patients with cardiovascular pathologies. Further study of methods of diagnosis and treatment of sleep apnea is a promising direction from the point of view of work on risk factors and the effectiveness of treatment of cardiovascular diseases.

About the authors

Nina A. Surikova

Orenburg State Medical University, Orenburg

Email: nina70494@mail.ru
ORCID iD: 0000-0001-8833-7043
SPIN-code: 7891-0830

Graduate Student 

Russian Federation, 6/45/7 Sovetskaya Str. / M. Gorky Str. / Dmitrievsky Ln, Orenburg, 460000

Anna S. Glykhova

Pokrovskaya City Hospital, St. Petersburg

Author for correspondence.
Email: ichi_08@mail.ru
ORCID iD: 0000-0001-8220-6739
SPIN-code: 6092-6140

cardiologist

Russian Federation, 85, Bolshoy Ave. of Vasilievsky Island, St.Petersburg, 199106

References