INQUIRY

Breathing DisordersComorbid conditions

Fig 1.—Mechanisms bywhich SRBDmay cause or contribute to thedevelopment of various medical conditions. (Courtesy of NormanD, Haberman PB, Valladares EM: Medical consequences and associ-ations with untreated sleep-related breathing disorders and out-comes of treatments. J Calif Dent Assoc 40:141-149, 2012.)

Background.—The term sleep-related breathing disor-ders (SRBD) includes several specific disorders, such as ob-structive sleep apnea (OSA), central sleep apnea (CSA), andperiodic breathing disorders. Symptoms these disordersshare include restless sleep, recurrent nighttime awaken-ings, and/or excessive daytime somnolence. The physio-logic consequences of having a narrow airway and thebody’s responses to the condition contribute to an in-creased risk of medical morbidity and mortality. As a result,SRBD and several medical conditions may be linkedthrough multiple pathophysiologic mechanisms. Amongthe possible medical conditions are hypertension, cardiacarrhythmias, heart failure, coronary artery disease, depres-sion, stroke, diabetes mellitus, and obesity. Various inter-ventions may be effective in reducing these risks.

SRBDLMedical Condition Links.—The mechanismsof SRBD that increase the risk of various medical conditionsbegin with apnea and hypopneas, which cause transient car-bon dioxide retention (Fig 1). Chemoreflex-mediated acti-vation of the sympathetic nervous system then develops,which causes a transient spike in blood pressure and heartrate during these apneic/hypopneic episodes. Significantnegative intrathoracic pressure results from ongoing respi-ratory effort related to airway obstruction. The effects canadversely influence the cardiovascular system. Initiallythese changes are transient but with time in patients withuntreated OSA, sympathetic nervous system activity isheightened both day and night.

The intermittent hypoxia also increases oxidative stress,contributes to endothelial dysfunction, and increases therelease of vasoactive substances. Together these influencescontribute to reduced daytime heart rate variability and in-creased blood pressure variability. Injury to brain regionsthat mediate autonomic control alters autonomic func-tions. Patients with intermittent hypoxemia and sleep dis-ruption or deprivation can have increased inflammatoryresponses and activation of fibrinogen and platelets, con-tributing to increased insulin resistance.

These mechanisms lead to an increased risk for variousmedical problems. Half of OSA patients suffer from hyper-tension. A stepwise association has been noted between

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increasing OSA severity and higher risk for and greater se-verity of hypertension. This effect persists even after con-trolling for age, gender, ethnicity, body mass index,smoking and alcohol use, neck size, and waist-to-hip ratio.

Complex cardiac arrhythmias are more likely to developin patients with severe SRBD than in controls withoutSRBD. The type of arrhythmia also appears to be relatedto the type of SRBD. Among older men, atrial fibrillationis linked to central sleep apnea and complex ventricular ec-topy is linked to OSA. Nonsustained ventricular tachycardiawas found more commonly in patients with severe CSA inone study, and the prevalence of OSA is significantly higherin patients with atrial fibrillation compared to patients ina general cardiology practice.

OSA is found in 40%–70% of patients with heart failure.Mortality is significantly higher for such patients whosemoderate to severe OSA is untreated than for those withless severe disease. Both systolic and diastolic heart failurehave been linked to OSA. The presence of OSA is also asso-ciated with increased risk of coronary artery disease.Patients without OSA are at highest risk of sudden cardiac

death between 6 and 11 AM, whereas those with OSA are athighest risk between 10 PM and 6 AM, which is when mostpeople are sleeping.

Depression, stroke, diabetesmellitus, andobesity are alsomore likely in patients with SRBD, but the evidence variesconcerning the exact relationships. Patients with untreatedsevere sleep apnea are more likely to suffer fatal cardiovascu-lar events than thosewith simply snoring or no SRBD, but thedifference is not statistically significant. Motor vehicle acci-dents are more likely in patients with untreated OSA, andthese incidents can contribute to higher mortality rates.

Effects of Interventions.—Continuous positive airwaypressure (CPAP) therapy can help to normalize respiratorydisturbances and oxyhemoglobin saturation during sleep,especially in patients with more severe apnea. Its usefulnesshas been shown against hypertension, with reductions inboth daytime and nighttime mean arterial pressure (MAP)shown in a number of randomized placebo-controlled trials.CPAP is also strongly associated with a reduced rate of ar-rhythmias in patients with OSA. Treatment with CPAP cansignificantly reduce the risk of occurrence of both fataland nonfatal cardiovascular events in patients with coronaryartery disease. In addition, CPAP will reduce the risk of mo-tor vehicle accidents in patients withOSA.However, compli-ance with CPAP therapy tends to be poor, which affects itsability to improve health status in patients with SRBD.

Oral appliance therapy (OAT) is supported by a growingbody of evidence as an effective intervention. Mandibularadvancement devices (MADs) reduce both systolic and dia-stolic blood pressure. However, compliance is also an issuewith OAT.

At times CPAP and OAT may both be ineffective andalternatives are needed. Adaptive servo-ventilation may behelpful in patients with heart failure, producing fewer respi-ratory events and better outcomes in terms of left ventricu-lar ejection fraction and SRBD treatment. Upper airwaysurgery, including uvulopalatopharyngeoplasty, genioglos-sus advancement, hyoid suspension, and maxillomandibu-lar advancement (MMA) surgery, may positively affectSRBD and help with associated medical problems. Adeno-tonsillectomy is the preferred intervention for children

with OS and can decrease diastolic blood pressure signifi-cantly. However, one study found that children whose ob-structive OSA recurs after this surgery are at higher riskfor developing hypertension a year after surgery than chil-dren who do not experience recurrence. Overall, soft-tissue upper airway surgeries have lower success ratesthan CPAP or OAT. Patients having MMA surgery may expe-rience substantial improvements in apnea hypopnea index(AHI), but the long-term effects remain in question.

Clinical Significance.—Both physicians anddentists need to identify patients who might beat risk for medical conditions associated withtheir SRBD. These practitioners can then helppatients understand the risks and benefits ofthe various treatment options and of not havingtreatment or not adhering to the treatment plan.Long-term follow-up should be a part of themanagement plan so that potential side effectsof treatment can be handled appropriately andto ensure the prescribed treatment is still beingused. Changes related to altered patient status(e.g., weight gain or loss, additional medica-tions, symptom recurrence, or worsening ofsigns and symptoms) may necessitate a re-evaluation of the patient by a sleep specialist.Should residual OSA be found, CPAP settings ororal appliances may be adjusted or additionalairway surgery considered. Other therapies,such as adaptive servo-ventilation, may also beneeded if CSA or periodic breathing distur-bances of sleep are present. Combination treat-ments can also be tried. During follow-up,practitioners should carefully evaluate the pa-tient for exacerbations of existing diseases orthe development of new comorbid conditions.

Norman D, Haberman PB, Valladares EM: Medical consequencesand associations with untreated sleep-related breathing disordersand outcomes of treatments. J Calif Dent Assoc 40:141-149, 2012

Reprints available from D Norman, 1301 20th St. Suite 360/370,Santa Monica, CA 90404, USA

FeminizationGender effects on the profession

Background.—Feminization refers to the increase infemale presence and corresponding shifts in occupation.Dentistry has traditionally been dominated by men, but

since the 1970s, women have been making significantgains, principally as a result of professional initiatives andwomen’s movements. In 2008 in Canada, women

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