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 Table of Contents  
REVIEW ARTICLE
Year : 2014  |  Volume : 27  |  Issue : 4  |  Page : 671-676

Predictors of cardiovascular risks in obstructive sleep apnea syndrome


1 Department of Internal Medicine, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt
2 Department of Internal Medicine, Sidi Salim Hospital, Kafr El Sheikh, Egypt

Date of Submission24-Nov-2013
Date of Acceptance10-Apr-2014
Date of Web Publication22-Jan-2015

Correspondence Address:
Mahmoud H Mohamed
Sidi Salim, Kafr El Sheikh
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.149658

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  Abstract 

Objective
The aim of the study was to assess the predictors of cardiovascular risks in obstructive sleep apnea (OSA) syndrome.
Data sources
They included medical text books, medical journals, and medical websites that have updated research with keywords 'cardiovascular risks' in the title of the paper.
Study selection
Systematic reviews that addressed OSA syndrome and studies that addressed cardiovascular risks in OSA syndrome were included.
Data extraction
Special search was performed at midline with keywords 'cardiovascular risks' in the title of the papers; extraction was made, including assessment of the quality and validity of papers that met with the prior criteria that describe cardiovascular risks in OSA syndrome.
Data synthesis
Each study was reviewed independently; obtained data were rebuilt in new language according to the need of the researcher and arranged in topics through the article.
Recent findings
There is also strong evidence supporting the association between sleep apnea and hypertension, arrhythmias, and coronary heart disease, as well as overall cardiovascular mortality. OSA is accompanied by activation of multiple cardiovascular disease mechanisms.
Conclusion
OSA, presumably mainly through intermittent hypoxia, is associated with oxidative stress, systemic inflammation, and vascular endothelium damage and dysfunction. Both systemic inflammation and endothelial dysfunction are aggravated when sleep-disordered breathing is associated with other comorbid conditions, such as morbid obesity. There are new directions regarding upper airway collapse mechanisms, such as pharyngeal denervation. There is also strong evidence supporting the association between sleep apnea and hypertension, arrhythmias, and coronary heart disease, as well as overall cardiovascular mortality.

Keywords: Cardiovascular risks, mortality, obstructive sleep apnea


How to cite this article:
Gazareen SS, Abd-El Atty EA, Dala AG, Mohamed MH. Predictors of cardiovascular risks in obstructive sleep apnea syndrome. Menoufia Med J 2014;27:671-6

How to cite this URL:
Gazareen SS, Abd-El Atty EA, Dala AG, Mohamed MH. Predictors of cardiovascular risks in obstructive sleep apnea syndrome. Menoufia Med J [serial online] 2014 [cited 2020 Feb 28];27:671-6. Available from: http://www.mmj.eg.net/text.asp?2014/27/4/671/149658


  Introduction Top


Obstructive sleep apnea (OSA) is a condition that causes intermittent and repeated upper airway narrowing or collapse; usually at multiple levels, this results in partial or total obstruction of the upper respiratory tract, also referred to hypopnea and apnea [1].

Obstructive apnea is often terminated by an arousal, which is accompanied with an increase in the sympathetic activity. Besides, repetitive hypoxia and large swings in intrathoracic pressure due to airway collapse in OSA patients may cause an overactive sympathetic system. OSA patients continue to have repetitive bursts of sympathetic activity and increased sympathetic activity even during the day as demonstrated by microneurography and elevated catecholamine levels both in plasma and urine. Indeed, increased and variable heart rate (HR) and blood pressure (BP) were demonstrated in OSA patients compared with normal individuals during wakefulness. As the altered cardiovascular variability due to the dysfunction of autonomic cardiovascular regulation predicts morbidity and mortality in patients with hypertension, diabetes, heart failure, and coronary artery disease, this may be the case even for OSA patients [2].

The physiologic consequences of these episodes are repetitive bursts of sympathetic activity, hypoxia, hypercapnia, increased left ventricular (LV) afterload, acute hypertension, and endothelial dysfunction [3].

OSA is a risk factor for several cardiovascular conditions, including arterial hypertension, congestive heart failure, coronary arterial disease, and cardiac arrhythmias [4].

Polysomnography is the gold standard method to diagnose sleep apnea syndrome; nevertheless, it has potential limitations to its widespread use in clinical practice. The Berlin Questionnaire is a simple and validated method to diagnose OSA in the general population and, recently, it has also been validated in cardiovascular patients [5].

Nasal continuous positive airway pressure (CPAP), which prevents apnea by maintaining adequate upper airway patency, is currently the treatment of choice for OSA [6].


  Materials and methods Top


The guidance published by the Centre for Reviews and Dissemination was used to assess the methodology and outcomes of the studies. This review was reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. An institutional review board and ethics committee approved this study.

Search strategy

A systematic search was performed of several bibliographical databases to identify relevant reports in any language. These included MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, TRIP database, Clinical Trials Registry, ISI Web of Knowledge, and Web of Science. Articles electronically published ahead of print were included. The search was performed in the electronic databases from the start of the database up to 2012.

Study selection

All studies were independently assessed for inclusion. They were included if they fulfilled the following criteria:

  1. Participants: Patients with OSA.
  2. Interventions: Predictors of cardiovascular risk in OSA syndrome.
  3. Outcomes: Regression of cardiac diseases in sleep apnea.


If the studies did not fulfill the above criteria, they were excluded. Articles in non-English languages were translated. The article title and abstracts were initially screened and then, the selected articles were read in full and further assessed for eligibility. All references from the eligible articles were reviewed to identify additional studies.

Data extraction

Study quality assessment included whether ethical approval was gained, prospective design, eligibility criteria specified, appropriate controls used, adequate follow-up achieved, and defined outcome measures such as regression of cardiac diseases in OSA syndrome.

Quality assessment

The quality of all studies was assessed. Important factors included prospective study design, attainment of ethical approval, evidence of a power calculation, specified eligibility criteria, appropriate controls, specified outcome measures, and adequate follow-up. It was expected that confounding factors would be reported and controlled for and appropriate data analysis made in addition to an explanation of missing data.

Data synthesis

Because of heterogeneity in postoperative follow-up periods and outcome measures reported, it was not possible to pool the data and perform meta-analysis. Comparisons were made by structured review.


  Results (findings) Top


OSA, presumably mainly through intermittent hypoxia, is associated with oxidative stress, systemic inflammation, and vascular endothelium damage and dysfunction. Both systemic inflammation and endothelial dysfunction are aggravated when sleep-disordered breathing (SDB) is associated with other comorbid conditions, such as morbid obesity. Sleep apnea is identified as being part of the cluster of chronic metabolic disorders linked to obesity and associated with low-grade inflammation. There are new directions regarding upper airway collapse mechanisms, such as pharyngeal denervation. There is also strong evidence supporting the association between sleep apnea and hypertension, stroke, arrhythmias, and coronary heart disease, as well as overall cardiovascular mortality.

Objective

The aim of the study was to assess the predictors of cardiovascular risks in OSA syndrome.

Data analysis

Data sources

They included medical text books, medical journals, and medical websites that have updated research with keywords 'cardiovascular risks' in the title of the paper.

Study selection

Systematic reviews that addressed OSA syndrome and studies that addressed cardiovascular risks in OSA syndrome were included.

Data extraction

Special search was performed at midline with keywords 'cardiovascular risks' in the title of the papers; extraction was made, including assessment of the quality and validity of papers that met with the prior criteria that describe cardiovascular risks in OSA syndrome.

Data synthesis

Each study was reviewed independently; obtained data were rebuilt in new language according to the need of the researcher and arranged in topics through the article.


  Discussion Top


Definition of sleep

Sleep is an essential biological process, a periodical state of quiescence in which there is minimal processing of sensory information and no interaction with the environment. However, sleep is more than the absence of being awake; it is a homeostatically regulated process [7].

Regulation of sleep

Sleep is a state of unconsciousness in which the brain is relatively more responsive to internal than external stimuli. The predictable cycling of sleep and the reversal of relative external unresponsiveness are features that assist in distinguishing sleep from other states of unconsciousness. The brain gradually becomes less responsive to visual, auditory, and other environmental stimuli during the transition from wake to sleep, which is considered by some to be stage I of sleep [8].

Definition of obstructive sleep apnea

SDB disrupts sleep pattern and quality. OSA is the most common sleep disorder being diagnosed. It is a chronic condition characterized by repetitive episodes of the upper airway collapse during sleep. The effects of intermittent hypoxia and reoxygenation may provoke a number of pathological cascades that involve sympathetic overactivity, systemic inflammation, oxidative stress, and endothelial dysfunction [9].

Epidemiology

Population-based studies suggest that OSA prevalence is as high or higher in African-Americans compared with Whites aged 65 years or greater, by in-home monitoring, and found that the odds of having an AHI of 30 or higher was 2.5 times greater in African-Americans compared with Whites, controlling for BMI and other confounding factor [10].

Pathophysiology

Patients with very severe OSA may exhibit increased airway resistance to inspiratory airflow even during supine wakefulness. However, it is only during sleep that obstructive apnea usually becomes evident. Thus, while mandibular and upper airway structure may be important in predisposing to OSA, the occurrence of obstruction primarily during sleep speaks directly to the importance of functional contributions to inspiratory airway occlusion.

OSA is the most common form of SDB and is characterized by repetitive partial or complete closure of the upper airway during sleep. Acute physiologic stresses occur during these episodes of asphyxia, including arterial oxygen desaturation, sympathetic activity, and acute hypertension [11].

Acute hemodynamic changes during obstructive sleep apnea

Large swings in the systemic and pulmonary arterial pressures during obstructive apneic events were described. It has been revealed that there is an initial decrease in BP and bradycardia during the early period of apnea. During the second phase of apnea, arterial oxygen saturation (SaO2) decreases, pleural pressure swings increase as well as HR and BP rise. During the third phase, after apnea termination and arousal, SaO2 starts to rise, pleural pressure swings are reduced compared with the second phase, HR further increases, and BP is sharply elevated to reach a peak within the first immediate postapneic breaths. The initial depressor effect has been related to an increased parasympathetic activity resulting in a decreased HR. LV stroke volume is reduced due to the negative intrathoracic pressure - that is, increased LV afterload - as well as decreased pulmonary venous return - that is, decreased LV preload - accounting for a decrease in cardiac output [2].

Cardiomechanical effects

During obstructive apneas, negative inspiratory intrathoracic pressure generated against the occluded pharynx increases LV transmural pressure, and hence afterload. It also increases venous return, augmenting right ventricular (RV) preload, whereas OSA-induced hypoxic pulmonary vasoconstriction increases RV afterload. Consequent RV distension and leftward septal displacement during diastole impairs LV filling. This combination of increased LV afterload and diminished preload reduces stroke volume and cardiac output more in HF patients than in healthy individuals. However, stroke volume recovers abruptly to baseline in healthy individuals at apnea termination, whereas recovery is delayed in patients with HF [12].

Oxidative, inflammatory, and vascular endothelial effects

Intermittent hypoxia and postapneic reoxygenation induce oxidative stress, generate reactive oxygen species, and provoke inflammation. Reactive oxygen species diminish nitric oxide levels, and hence impair endothelial-mediated vasodilation that could contribute to development of hypertension [13].

Obstructive sleep apnea and arrhythmia

Arrhythmogenic effects: Intermittent hypoxia can cause HR to decrease, increase, or remain constant depending on whether parasympathetic or sympathetic activity dominates, or whether their influences are relatively equal [14].

Obstructive sleep apnea and atrial fibrillation

It is well known that sympathetic overactivation may promote ventricular dysfunction and arrhythmia. Patients with severe OSA often have a much higher prevalence of atrial fibrillation, nonsustained ventricular tachycardia, and complex ectopic excitation compared with individuals without OSA [15].

Obstructive sleep apnea and acute coronary syndrome

Coronary artery disease is more prevalent in OSA patients, and the respiratory disturbance index is a predictor of cardiovascular mortality [16].

Obesity as a risk factor for obstructive sleep apnea

OSA is a potential risk factor for cardiovascular disease and metabolic disorders, such as insulin resistance, type 2 diabetes mellitus, and hypertension, and obesity is a very common disorder among patients with OSA [17].

Obstructive sleep apnea and hypertension

OSA plays a significant role in increasing BP. Systemic hypertension in OSA, often underdiagnosed, is a large clinical problem, as it may increase the cardiovascular risk for OSA [18].

Obstructive sleep apnea and resistant hypertension

OSA is common in patients with resistant hypertension, which is defined as BP that remains uncontrolled with three or more medications. In a prospective evaluation of 41 patients with resistant hypertension, it was found that 96% of the men and 65% of the women had significant OSA (AHI more than 10 events/h) [19].

Pulmonary arterial hypertension and obstructive sleep apnea

OSA is associated with mild pulmonary arterial hypertension, most often when there is coexisting chronic lung or heart disease. Two observational studies have demonstrated that, among patients with OSA, cor pulmonale occurred predominantly in those who had daytime hypoxemia [20].

Obstructive sleep apnea and heart failure

The most direct mechanism by which long-standing OSA might induce LV systolic dysfunction is by raising BP. Hypertension is the most common risk factor for ventricular hypertrophy and failure. Nocturnal oxygen desaturation is an independent predictor of impaired ventricular relaxation during diastole; moreover, increased BMI, an important predisposing factor for OSA, also was associated with greater risk of developing heart failure [21].

Ventricular arrhythmias and sudden cardiac death

Patients with OSA have a higher prevalence of premature ventricular contractions (PVCs) than normal individuals [15]. Furthermore, in patients with HF with left ventricular ejection fraction less than 45% and more than 10 concomitant PVCs per hour, treatment with CPAP experienced 58% reduction in PVCs. Results were accompanied by reductions in AHI, frequency of arousals, and overnight urinary epinephrine concentration as well as an increase in minimum arterial oxygen saturation [22].

Diagnosis of obstructive sleep apnea

Symptoms

Excessive daytime sleepiness, fatigue, snoring, choking during sleep, nocturia, headache on waking, personality change, depression, and road traffic incidents.

Causes

The causes are obesity, neck circumference (men >43.2 cm, women >40.6 cm), smoking, alcohol intake, and use of medication with sedating properties.

Comorbidities

These include hypertension, full stroke, transient ischemic attack, pulmonary hypertension, and cardiac arrhythmias [23].

Types according to attacks of apnea and hypopnea per hours of sleep [24]

  1. Mild OSA: AHI of 5-15 attacks of apnea-hypopnea per hours of sleep; involuntary sleepiness during activities that require little attention, such as watching TV or reading.
  2. Moderate OSA: AHI of 16-30 attacks of apnea-hypopnea per hours of sleep; involuntary sleepiness during activities that require some attention, such as meetings or presentations.
  3. Severe OSA: AHI of more than 30 attacks of apnea-hypopnea per hours of sleep; involuntary sleepiness during activities that require more active attention, such as talking or driving.


Investigations of obstructive sleep apnea

A high index of suspicion is required by practitioners and dietitians or nutritionists to recognize the symptoms of OSA, so that patients can be referred for an appropriate diagnostic test. The diagnosis of OSA is confirmed by means of an overnight sleep study or polysomnogram, which measures various parameters, including airflow, breathing activity and respiratory effort, oxygen concentration, brain electroencephalographic activity, leg muscle activity, and sleeping position [25].

  1. Polysomnography.
  2. Lateral cephalometric radiographs.
  3. Computed tomography.
  4. Pharyngoscopy.
  5. MRI.


Treatment of obstructive sleep apnea

Continuous positive airway pressure

CPAP is the standard treatment option for moderate-to-severe cases of OSA and a good option for mild sleep apnea. First introduced for the treatment of sleep apnea in 1981, CPAP provides a steady stream of pressurized air to patients through a mask that they wear during sleep. This airflow keeps the airway open, preventing pauses in breathing and restoring normal oxygen levels. Newer CPAP models are small, light, and virtually silent. Patients can choose from numerous mask sizes and styles to achieve a good fit. Heated humidifiers that connect to CPAP units contribute to patient comfort [24].

Oral appliances

Customized dental appliances are designed to increase airway size and to facilitate airflow by advancing the mandible or tongue or lifting the soft palate. Although success with oral appliances often is difficult to predict, these devices may offer a viable treatment option in nonobese patients with micrognathia or retrognathia who have snoring or mild-to-moderate OSA, particularly those who do not tolerate CPAP therapy [26].

Surgery

Patient selection is very important to identify appropriate candidates for the procedure, and it has been suggested that patients who have the obstruction localized to the oropharynx would be the most suitable for UPPP. Studies have also shown that severity is not a prognostic factor for success. Patients with mild AHI classification can have a poor result with UPPP, whereas a candidate with severe disease can be fully cured. Obesity is a negative prognostic factor and BMI greater than 40 is a contraindication to UPPP due to poor outcome of the procedure. The main complications to UPPP are intraoperative and postoperative bleeding, airway obstruction during the initial postoperative period caused by significant edema, and dysphagia.

Genioglossus and hyoid advancement

The genioglossus advancement (GA) involves osteotomy of the chin (usually square shaped on the symphysis) to be able to move the geniotubercle with the genioglossus insertion forward without moving the mandible. This advancement places tension on the tongue musculature, and thereby limits posterior displacement during sleep. The hyoid advancement technique implies an anterior movement of the hyoid bone by attaching it to the thyroid cartilage. The operation is usually performed in conjunction with GA or UPPP to reduce the severity of OSA. The success rates for GA and hyoid advancement have been variable, ranging from 23 to 77%. In general, the associated surgical risks for these procedures are low but include infection, edema, and dysphagia [27].

Phase II surgery

Maxillomandibular advancement, also called phase II surgery, expands the skeleton that encircles the airway and the entire airway is thereby enlarged. The operation consists of a bilateral osteotomy (Le Fort I osteotomy and bilateral sagittal split osteotomy of the mandible) and the maxillomandibular complexes are mobilized and displaced anteriorly. Fixation is performed with titanium plates when a good occlusion is established. An advancement of 10-14 mm is usually recommended to achieve a successful improvement of the obstructed airways. Maxillomandibular advancement is considered the most effective surgical sleep apnea procedure currently available, and the long-term success rate is usually over 90%. Despite that bimaxillary surgery is considered a fairly invasive procedure, the associated surgical risks are low but include bleeding, sensory disturbance of the inferior alveolar nerve, and malocclusion [28].

Behavioral changes

Lifestyle changes can be the most difficult changes to accomplish, but they can make a major impact on OSA severity. Weight loss is effective in reducing OSA severity in selected patients [29].

Over-the-counter remedies

Although some external nasal dilator strips, internal nasal dilators, and lubricant sprays may reduce snoring, there is no evidence that they help treat OSA. They may even mask the problem by muting the loud snoring that is a warning sign for sleep apnea [24].

Position therapy

This is a treatment used for patients suffering from mild OSA. Patients are advised to stay off of the back while sleeping and raise the head of the bed to reduce symptoms [24].


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
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