Essential Lab Tests for Diagnosing and Managing Sleep Apnea

Sleep apnea, characterized by recurrent pauses in breathing during sleep, is a sleep disorder that is estimated to affect 20% of adults. Despite this high prevalence, this condition is wildly underdiagnosed: at least 85% of patients with sleep apnea have not been diagnosed. (26) 

The implications of untreated sleep apnea are far-reaching. This condition not only disrupts sleep patterns but also poses significant health risks, including cardiovascular disease, diabetes, and cognitive impairment. Accurate diagnosis and effective management improve sleep quality, mitigate these risks, and enhance quality of life. 

[signup]

Understanding Sleep Apnea

Sleep apnea is a sleep disorder characterized by repeated interruptions in breathing during sleep. These interruptions, or apneas, can last from a few seconds to minutes and may occur multiple times throughout the night, leading to fragmented and poor-quality sleep.

There are three primary types of sleep apnea: 

• Obstructive Sleep Apnea (OSA): OSA is the most common form and occurs when the muscles at the back of the throat fail to keep the airway open despite efforts to breathe. 
• Central Sleep Apnea (CSA): CSA involves the brain failing to send proper signals to the muscles that control breathing, leading to pauses in breathing. 
• Complex Sleep Apnea Syndrome (CompSAS): Also known as treatment-emergent central sleep apnea, CompSAS is a combination of OSA and CSA, typically arising when OSA persists even after continuous positive airway pressure (CPAP) therapy.

Common symptoms of sleep apnea include:

• Loud snoring
• Episodes of breathing cessation observed by another person
• Frequent awakenings throughout the night accompanied by gasping or choking
• Daytime sleepiness
• Difficulty concentrating
• Irritability
• Morning headaches
• Dry mouth upon waking 

Risk factors for sleep apnea encompass: 

• Obesity 
• Large neck circumference
• Narrowed airway
• Male gender
• Older age
• Family history
• Use of alcohol, sedatives, or opioids
• Smoking
• Certain medical conditions, including hypertension, diabetes, heart failure, and stroke

The hypoxia (insufficient oxygen levels) caused by sleep apnea increases a person's risk for cardiometabolic disease, respiratory disease, and mental health disorders. The frequent nighttime awakenings and poor sleep quality associated with this sleep disorder cause excessive daytime fatigue, which impairs concentration and increases the risk of accidents. People with untreated sleep apnea are at a greater risk for poor quality of life and shortened lifespan due to increased all-cause mortality.

Initial Evaluation and Screening

Given untreated sleep apnea's negative implications on health, screening and early detection are important so that treatment can be initiated promptly to mitigate health risks and improve the quality of life of those affected.

Patient History

The American Academy of Sleep Medicine advocates that all adults be asked about the signs and symptoms of sleep apnea as part of an annual wellness exam (32). They also recommend that patients with the following be screened annually for sleep apnea with a validated screening questionnaire:

• Heart failure
• Elevated blood pressure
• Atrial fibrillation
• Resistant hypertension
• Type 2 diabetes
• Stroke
• Body mass index > 30 kg/m²
• Nocturnal cardiac arrhythmias
• Pulmonary hypertension
• Coronary artery disease

Screening Questionnaires

The STOP-Bang questionnaire is a widely used screening tool to identify individuals at risk for OSA. The acronym "STOP-Bang" stands for: Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and Gender, encompassing the key risk factors associated with OSA. Each "yes" answer scores one point, with a total possible score of eight points. A higher score indicates a higher risk of OSA. Specifically:

• 0-2: low risk
• 3-4: intermediate risk
• 5-8: high risk

The Epworth Sleepiness Scale is a self-administered questionnaire used to measure a person's general level of daytime sleepiness. It helps assess the likelihood of falling asleep in different situations, which can indicate sleep apnea. The questionnaire consists of eight questions about the chance of dozing off or falling asleep in specific situations. The scores for each situation are added to obtain a total score ranging from 0 to 24:

• 0-7: Unlikely to have abnormal daytime sleepiness
• 8-9: Average amount of daytime sleepiness
• 10-15: Excessive daytime sleepiness, may require medical attention
• 16-24: Severe excessive daytime sleepiness, strongly suggests the need for medical intervention

The Berlin questionnaire is another validated tool to identify patients at risk for sleep apnea. It is structured around three main categories: snoring behavior, daytime sleepiness or fatigue, and the presence of obesity or hypertension. Each category consists of specific questions, and responses are used to stratify patients into high or low risk for OSA. Compared to other apnea screening tools, the scoring process is rather complex, so it is often recommended for use by sleep specialists or other similarly trained individuals. 

Physical Examination

Physical exam findings that are predictive of sleep apnea include:

• Large neck circumference (greater than 17 inches in men and 15 inches in women)
• High body mass index (greater than 30 kg/m ²)
• Posterior chin position
• Reduced distance and increased angles from the chin to the thyroid
• High-arched hard palate 
• Narrow oropharyngeal opening
• Enlarged tonsils
• High blood pressure (32, 45) 

Polysomnography (PSG)

Patients at high risk for sleep apnea based on an initial screening should receive a comprehensive sleep evaluation by a board-certified sleep medicine expert. 

PSG, or a sleep study, is the diagnostic standard for sleep apnea. Sleep studies can be performed at home or in a laboratory setting. Patients are monitored for the following parameters as they sleep during a PSG:

• Sleep stages via electroencephalogram (EEG), electrooculogram (EOG), and chin electromyogram (EMG)
• Heart rate and rhythm via electrocardiogram (ECG)
• Leg movements via anterior tibialis EMG
• Airflow, respiratory effort, and oxygen saturation

Patients are monitored for apneic and hypoxic events as they sleep. The apnea-hypopnea index (AHI) is calculated by adding all apneas and hypopneas and then dividing by total sleep time. (32)  

• An AHI of 15 or more events per hour, or five or more events per hour in the presence of symptoms or cardiovascular comorbidities, is diagnostic for OSA (46). 
• An AHI of five or more events per hour, in which a cessation or absence of ventilatory effort is identified in at least half of the apneas or hypopneas, is diagnostic for CSA.

Additional Lab Tests for Sleep Apnea Patients

The cardiometabolic risk associated with sleep apnea warrants additional screening and monitoring for comorbid conditions to ensure comprehensive management and improve patient outcomes.

Blood Tests

Polycythemia, characterized by an elevated red blood cell (RBC) count, often arises in patients with untreated sleep apnea as a compensatory response to chronic hypoxia. The repeated drops in blood oxygen levels trigger the body to stimulate RBC production to increase the blood's oxygen-carrying capacity. Polycythemia can exacerbate cardiovascular risks in patients with sleep apnea. Elevated RBCs, hemoglobin, and hematocrit on a complete blood count are indicative of polycythemia. 

Patients with hypothyroidism are more likely to have sleep apnea. Some studies have calculated an incidence of up to 82% in patients with hypothyroidism. Hypothyroidism may contribute to OSA by increasing mucoprotein deposition in the upper airways, altering respiratory muscular function, and predisposing patients to weight gain/obesity. A thyroid panel, including TSH, free T3, and free T4, can monitor thyroid health and function. Elevations of TSH in conjunction with low levels of T3 and/or T4 are diagnostic for hypothyroidism. 

Blood tests can help assess cardiovascular risk by providing valuable insights into lipid metabolism, blood sugar regulation, and inflammation:

• A lipid panel can diagnose high cholesterol
• Hemoglobin A1c is a 3-month average of blood sugar levels and a diagnostic marker for diabetes
• Insulin resistance, which corresponds to elevated fasting insulin levels, is a hallmark and predisposing feature of prediabetes and type 2 diabetes. 
• Sleep apnea perpetuates chronic, low-grade inflammation, which is a driving factor in cardiovascular disease and adverse events. High-sensitivity C-reactive protein (hs-CRP) is a marker of inflammation that can help predict the risk of cardiovascular disease and mortality. (8)  

Cardiac Evaluations

Additional cardiovascular evaluation by a cardiologist may be warranted for patients at increased risk for cardiovascular disease. In addition to the blood tests discussed above, cardiologists may recommend the following tests to better evaluate heart health:

• ECG: Sleep apnea can increase susceptibility to heart arrhythmias, which are abnormalities in how the heart beats to pump blood through the body. An ECG records the heart's electrical activity and can identify irregularities in the heart's rhythm and electrical conduction system.
• Holter Monitor: Holter monitors are small, portable ECGs that patients can wear to continuously monitor the heart's electrical activity over a 24- to 48-hour period. Patients with sleep apnea often have more abnormalities in 24-hour Holter monitoring.
• Echocardiogram: Sleep apnea is linked to higher rates of left ventricular diastolic dysfunction, which increases the risk of heart failure. An echocardiogram is an ultrasound that evaluates the structure and function of the heart. It is used to calculate left ventricular ejection fraction (LVEF), which measures left ventricular function. 

Specialty Tests

In addition to hypothyroidism, the prevalence of obstructive sleep apnea is also increased in patients with acromegaly and Cushing syndrome. 

Acromegaly is a rare hormonal disorder caused by excessive growth hormone. This results in the abnormal growth of tissues and bones, particularly in the hands, feet, and face. Due to tongue enlargement and tissue thickening in the neck, airway obstruction may occur.

Cushing syndrome, also known as hypercortisolism, is a disorder caused by prolonged exposure to high levels of cortisol, a hormone produced by the adrenal glands. Evidence suggests that hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis contributes to the cardiometabolic complications of sleep apnea. Repeated episodes of hypoxia and disrupted sleep patterns trigger chronic stress responses that elevate cortisol levels and disturb the HPA axis function. This chronic activation contributes to systemic inflammation, insulin resistance, and other metabolic abnormalities. Multi-point salivary cortisol tests, such as the Diurnal Cortisol test by ZRT Laboratory, are often ordered to assess the body's stress response, HPA axis function, and cortisol levels. 

Family history is a risk factor for both sleep apnea and cardiovascular disease, suggesting a genetic predisposition to their development. Genetic factors likely contribute to sleep apnea by influencing the structural and functional components of the upper airway, inflammation, and the ability to regulate blood oxygen levels. Similarly, genetic variants can impact cardiovascular health by influencing lipid metabolism, blood pressure regulation, and vascular function. A test like the 3X4 Genetics Test + Blueprint Report by 3X4 Genetics can help identify at-risk individuals earlier.

Follow-Up and Monitoring

Regular follow-up and ongoing management ensure optimal treatment outcomes for patients with sleep apnea. Periodic clinical evaluations are important to assess patient adherence and response to treatment interventions, such as continuous positive airway pressure (CPAP) therapy. Monitoring changes in relevant laboratory values over time helps track disease progression and treatment efficacy. Adjusting treatment plans based on these findings ensures that therapy reduces symptoms, improves sleep quality, and mitigates associated health risks.

[signup]

Key Takeaways

• A comprehensive evaluation for diagnosing and managing sleep apnea relies heavily on polysomnography for definitive diagnosis and ancillary tests to stratify cardiovascular risk.
• Regular monitoring of these parameters tailors personalized treatment plans and ensures ongoing effectiveness. 
• By emphasizing the importance of thorough evaluation and personalized care, healthcare providers can optimize outcomes, improve patient adherence to treatment, and reduce the long-term health consequences of untreated sleep apnea.