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Medical and dental conditions related to sleep-related breathing disorders

CONCEPTUAL OVERVIEW

Research during the past decade has confirmed that sleep disorders adversely affect various physiological systems, including cardiovascular, metabolic, psychobiologic, endocrine, nervous, and immune.

Almost from the onset of the recognition of sleep-related breathing disorders (SRBD) in patients, there has been an awareness that this particular sleep disorder could increase the risk for health-related consequences. Although cardiovascular disease has been found to be one of the more significant consequences of SRBD, the risk for other health problems has also been demonstrated.

The most widely recognized and often referred to study regarding the health-related risks with SRBD is the Sleep Heart Health Study.¹ Additional studies have also been published that support the association between SRBD and the risk for many common medical conditions.

HEALTH CONSEQUENCES ASSOCIATED WITH SRBD

An increasing prevalence of metabolic syndrome is linked with SRBD. Metabolic syndrome is the term for a group of risk factors that are associated with specific health issues, including but not limited to cardiovascular disease, diabetes, and stroke. This syndrome, which is also known as Syndrome X, insulin resistance, and obesity syndrome, may be associated with SRBD. In one study, the presence of metabolic syndrome was found to be almost 40% greater in SRBD subjects than in control subjects.² There is ongoing research and discussion in the medical field relative to further clarifying this syndrome.

The criterion by which metabolic syndrome is diagnosed is predicated on an individual having a minimum of three of the five following metabolic risk factors:³ (1) increased girth of the waist or having a gut with an increased body mass index (BMI), (2) increased blood levels of triglycerides, (3) decreased blood levels of high-density lipoprotein (HDL) cholesterol, (2) increased blood pressure, and (5) impaired fasting glucose.

The prevalence of diabetes and obesity in the United States is increasing, and the link of these risk factors to metabolic syndrome lends to the estimation of almost 50 million adults with this syndrome.⁴ In addition, obesity is associated with other health problems such as increased insulin resistance, increased levels of cholesterol and triglycerides, and a variety of other health consequences, primarily related to cardiovascular disease.

The most widely acknowledged association with SRBD and even just sleep loss or restriction relates to the presence of obesity,^5–7 although SRBD does not have to be present for obesity to occur. Sleep restriction or a decrease in adequate hours of sleep may also lead to the obesity.^{8, 9} The sleep loss and obesity association is not exclusive to adults. Obesity in children and adolescents is an increasing concern and appears to also be related to a lack of adequate number of hours of sleep.^{10, 11}

Not all patients with SRBD are obese. Even the nonobese are at risk for similar health problems, mostly associated with short sleep duration.¹² An increase in abdominal girth or central (visceral) size is the one common finding that most often indicates SRBD as increasing the risk for health-related consequences.⁹

Hypertension

Since the early 1990s, studies have recognized that an individual with SRBD is at an increased risk for elevated blood pressure or hypertension. One study looked at the incidence of hypertension in obstructive sleep apnea (OSA) patients independent of obesity,¹³ and it demonstrated the following: (1) the incidence of elevated blood pressure existed in 20–70% of OSA patients, (2) significant OSA was found in 30–40% of hypertensive patients, and (3) nocturnal SRBD was more closely related to elevated blood pressure.

Arousals from sleep are also a factor in the elevation of blood pressure.¹⁴ These repeated arousals are associated with an increase in blood pressure during the day, and they appear to be related to an increase in sympathetic activity or tone that occurred during sleep and resulted in a rise in daytime blood pressure.¹⁵ The Sleep Heart Health Study further confirmed an association between SRBD and hypertension.¹

Snoring alone can also lead to an elevation in blood pressure. A study demonstrated that snoring without any significant apnea or hypopnea can result in hypertension, but the risk is lower.¹⁶ Another study showed that SRBD and the risk for hypertension were greater in younger males than in males over the age of 60.¹⁷ Given the fact that snoring over time may lead to OSA, this should not be taken lightly.

Cardiovascular disease

The development of cardiovascular disease takes on a variety of related conditions, all of which have been found to be prevalent in the presence of SRBD. Studies may vary on the degree of risk, but it is generally agreed upon that SRBD is a significant factor in the presentation of cardiovascular disease.

Arrhythmias

Various arrhythmias have been documented during episodes of OSA, and they are resolved with continuous positive airway pressure therapy.¹⁸ In addition, bradycardia and tachycardia have been implicated as associated with OSA. Hypoxia’s main outcome is bradycardia. Arrhythmia appears to be associated with oxygen desaturation, is common in patients with coronary heart disease, and appears to resolve with the management of the apnea.

Atrial fibrillation

There is an association between sleep apnea and the presence of atrial fibrillation.¹⁹ The odds ratio for the association of atrial fibrillation with OSA was found to be 2.19. All the patients studied were similar, especially as it related to the presence of diabetes, hypertension, and congestive heart failure (CHF).

Atherosclerosis, endothelial dysfunction, and coronary heart disease

OSA and the presence of coronary artery disease is significant. A study found that in a population of patients who had symptomatic angina diagnosed with angiography, 30.5% had OSA.²⁰ This group had a higher apnea–hypopnea index and more of a tendency to be overweight or obese.

The potential for atherosclerosis is also greater among OSA patients.²¹ Although these patients may be free of signs and symptoms of cardiovascular disease, atherosclerosis and coronary heart disease were found to be significantly higher as the degree of OSA worsened. The significance of this is critical if one considers that only 12.5% of a control group had signs of coronary heart disease while mild OSA patients demonstrated a 42% incidence and moderate to severe patients had an 80% incidence of disease in multiple vessels.²² Sleeping less than 7 hours a night or more than 8 hours may increase the risk for coronary heart disease (Table 5.1).

Table 5.1 Risks for coronary heart disease relative to hours of sleep.

Source: Adapted from Ayas NT. The adverse health effects of sleep restriction. Sleep Rev. 2003; (May/June):16.

Endothelial dysfunction can also be associated with OSA. There can be subsequent relaxation in the vascular structures as well as atherosclerotic changes and cardiovascular disease, and the endothelial injury at a tissue level leads to atherogenesis.²³ The progression of atherosclerosis may be related to apnea events that alter inflammatory mediators and metabolic factors, which can result in hypertension.²⁴ These related events lead to atherosclerosis and cardiovascular disease.

A recent study has demonstrated that snoring alone may put patients at risk for atherosclerosis of the carotid artery.²⁵ The proposed mechanism involves vibrations in the pharyngeal airway that are in close proximity to the artery, and these vibrations may cause endothelial damage that results in inflammation and thereby promotes changes that may lead to atherosclerosis. The prevalence of the atherosclerosis worsened in direct proportion to the degree of snoring, and the prevalence ranged from 20% in mild snorers to 64% in heavy snorers.

Congestive heart failure

The association of cardiovascular disease and sleep apnea is well known. CHF has been found to be prevalent in patients mainly with central sleep apnea (CSA).²⁶ The recurring respiratory events are associated with sleep disruption, arousals, hypoxia, and hypercapnia. It appears that a high percentage of patients with heart failure when screened for SRBD tested positive.²⁷ In addition, there is oftentimes a relation between Cheyne–Stokes respiration and CHF that is present in CSA patients.

Interestingly, the use of an oral appliance (OA) can beneficially impact CHF.^{28, 29} In these studies, the focus in determining the effect of OAs was based on the measurement of brain natriuretic peptide (BNP), which has been found to be elevated in OSA. This increase is linked to left ventricular pressure and volume levels. In patients with CHF, the BNP levels rise and are associated with sudden death, and it may predict morbidity and mortality.

Cerebrovascular function and stroke

Stroke is the third leading cause of death and long-term disability.³⁰ The incidence of cerebrovascular disease and stroke is related to SRBD, and it is independent of other known risk factors for stroke.³¹ The risk for stroke associated with OSA is also independent of hypertension, but the existence of hypertension, especially diurnal hypertension, further increases the risk. The mechanism is related to a decrease in cerebral perfusion and increased coagulation. There is an increased incidence of sudden death during sleep.³² In addition, after a stroke, there is an increase in the prevalence of OSA, which affects the ability of the patient to rehabilitate and recover following the stroke.

Triglycerides and cholesterol

HDL, or the good cholesterol, functions as both an antioxidant and antiatherogenic. HDL dysfunction has been found to be present in OSA patients.³³ This association is related to oxidative stress, which is present in patients with coronary heart disease. Lower levels of HDL have also been linked to issues with short-term memory deficits. Difficulty with memory has also been linked to OSA as one of the common symptoms.

Diabetes type 2

2 diabetes is linked to SRBD such as snoring and OSA. In fact, snoring alone has been shown to be an independent risk factor for this type of diabetes.³⁴ The impact of snoring and OSA, by virtue of upper airway obstruction, may lead to oxygen desaturation that in turn may cause a rise in the level of cortisol and catecholamines. The outcome of this cascade may be an increase in insulin resistance, which is considered to be a precursor to diabetes. The Sleep Heart Health Study demonstrated that hypoxia during sleep resulted in glucose intolerance which was independent of age, sex, BMI, or the size of the waist.¹ Other studies have also shown that SRBD, irrespective of obesity, may serve as a contributing factor to diabetes through its association with glucose and insulin metabolism.^{35– 37}

Sleep disruption has also been shown to be common among those with type 2 diabetes.^{38, 39} Three main factors were found that are related to sleep disruption: obesity, pain, and an increase in the need to use the bathroom during the night. One-third of those who have type 2 diabetes experience sleep problems. In addition, the severity of the diabetes is directly related to the sleep disruption.

Sleep restrictions and excessive sleep are other issues that may impact the risk for diabetes (Table 5.2).⁴⁰ Getting between 7 and 8 hours of sleep a night is optimum. Less than 6–7 hours and over 8–9 hours may lead to an increased risk for diabetes.^{1, 41} After adjusting for BMI, where the tendency for being overweight or obese was corrected, the increased risk for diabetes became modest (Table 5.2).

Table 5.2 Risks for symptomatic diabetes relative to hours of sleep.

Source: Adapted from Ayas NT. The adverse health effects of sleep restriction. Sleep Rev. 2003; (May/June):16.

Gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) (Table 5.3) is estimated in the United States to be experienced daily by 7% of the adult population and weekly by 70%.⁴² Until more recently, though, there has been a slow acknowledgement of sleep-related GERD as well as its impact on daily function.⁴³

Many people who have SRBD also may complain or may have been diagnosed with GERD.⁴⁴ The prevalence of GERD is much higher in patients with OSA as compared to the general population.⁴⁵ This is a condition that is associated with the relaxation of the phreno-esophageal sphincter where the esophagus enters the stomach, and it is oftentimes associated with obesity and diabetes.

GERD may be more prevalent in SRBD because of the following:

Table 5.3 Common symptoms of gastroesophageal reflux disease.

Source: Adapted from Demeter P and Pap A. The relationship between gastroesophageal reflux disease and obstructive sleep apnea. J Gastroenterol. 2004; 39(9):815–820.

In like manner, GERD, particularly when present at night along with OSA, was found to be a cause of sleep disturbance.⁴⁷ The presence of GERD-type symptoms is also associated with awakenings from sleep. It has been estimated that the symptoms of GERD can cause awakenings in 58.6% of these patients.⁴⁸ Other symptoms associated with these awakenings are difficulty in initiating sleep and experiencing nightmares. It was also demonstrated that patients with GERD had more symptoms of excessive daytime sleepiness (EDS) as well.⁴⁹

Asthma

The presence of asthma, along with other respiratory conditions, may be associated with SRBD. In the general population, the prevalence of asthma is 5%. The coexistence of asthma and OSA is not well documented, although from a clinical perspective, many people who have SRBD also have asthma.

The one significant association that exists between asthma and SRBD is between asthma and GERD, the common denominator being the presence of inflammation. This same inflammatory condition has also been implicated in the progression of OSA. Nocturnal GERD associated with OSA can lead to the presentation of asthma.⁵⁰ The presence of airway obstruction and obesity are also common findings. The role of reflux in the precipitation of asthma has been linked to an elevation in BMI. As the BMI increases and obesity is more prevalent, the incidence of asthma also increases.

Alzheimer’s disease

The link between OSA and Alzheimer’s disease is becomi/>

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