Gravitational influences and shifting propensity for sleep apnea: another source of heterogeneity or a new intervention target?

Sleep-disordered breathing occurs in as many as 17% of adults and is associated with increased mortality.1 Characterized by the occurrence of repetitive episodes of apneas and hypopneas resulting in intermittent oxyhemoglobin desaturation and sleep disruption, it is a common comorbid condition in patients with heart disease, who may have both obstructive and central variants. Apneas and hypopneas are classified as obstructive when reductions in ventilation result from episodic pharyngeal occlusion accompanied by concomitant respiratory effort. Obstructive sleep apnea (OSA) is diagnosed when an overnight sleep study shows that the total number of apneas plus hypopneas exceeds some threshold, with a predominance of events consisting of obstructive breathing events. Patients diagnosed with OSA are frequently overweight, tend to be male, and have a high prevalence of comorbidities, including hypertension and diabetes mellitus.2 The pathogenesis of OSA is complex and is likely influenced by both anatomic and physiological risk factors that reduce oropharyngeal area, including obesity with increased peripharyngeal fat deposition, certain craniofacial morphologies, and ventilatory deficits that predispose to pharyngeal collapsibility during sleep, a time when neuromuscular output is reduced. In contrast, apneas that occur without evidence of increased upper-airway resistance and with absence of respiratory effort are considered to be central apneas. A predominance of this event subtype constitutes central sleep apnea (CSA), a disorder that may occur in individuals with a variety of genetic and neuromuscular disorders. However, central apneas also may manifest as components of Cheyne-Stokes respiration, a form of periodic breathing characterized by long cycles of alternating hyperventilation and hypoventilation associated with hypocapnia, prolonged circulation time, and/or reduction in ventilatory reserve.3 The combination of CSA and Cheyne-Stokes respiration occurs in as many as 40% of patients with heart failure, which reflects the predilection of this patient group to respiratory control system instability due to the effects of pulmonary congestion on stimulating pulmonary irritant receptors, increased chemoreceptor sensitivity, and reduced cardiac output and cerebrovascular blood flow, and possibly because of abnormalities in autonomic function. An increased risk of both Cheyne-Stokes respiration and CSA occurring in heart failure is associated with male gender, atrial fibrillation, older age, and hypocapnia (pCO2 38 mm Hg during wakefulness).4 Patients with heart failure and both Cheyne-Stokes respiration and CSA generally have poorer cardiac function than do other patients with heart failure, have augmented levels of sympathetic nervous system activity, and may be at risk for pulmonary hypertension and increased mortality.3 However, the specific role of treatment of this breathing disorder in attenuating risk is unclear.5