There is growing evidence that obstructive sleep apnea (OSA) may contribute to the initiation and progression of hypertension, heart failure, cardiac ischaemia and stroke. Chronic sympathetic activation appears to be a key mechanism underlying the relationship between OSA and cardiovascular morbidity. Several studies have consistently shown that patients with OSA have high levels of sympathetic nerve traffic. During sleep, repetitive episodes of hypoxia, hypercapnia and obstructive apnea act through chemoreceptor reflexes and other mechanisms to increase sympathetic drive. Resumption of breathing results in increased venous return and increased cardiac output. This increased cardiac output is delivered into a severely vasoconstricted peripheral vasculature resulting in surges in blood pressure, and may contribute in part to the phenomenon widely described as 'non-dipping'.
Remarkably, the high sympathetic drive is present even during daytime wakefulness when subjects are breathing normally and no evidence of hypoxia or chemoreflex activation is apparent. In addition to high levels of sympathetic activity, OSA patients have clear-cut abnormalities in cardiovascular variability during wakefulness. Blood pressure variability is markedly increased and RR variability is decreased in patients with OSA. Several mechanisms may contribute to maintenance of higher sympathetic activity and blood pressure. These mechanisms include chemoreflex and baroreflex dysfunction, vasoconstrictor effects of nocturnal endothelin release and endothelial dysfunction.
Treatment with continuous positive airway pressure (CPAP) results in acute and marked reduction in nocturnal sympathetic nerve traffic and blunts blood pressure surges during sleep. Long-term continuous positive airway pressure treatment decreases muscle sympathetic nerve activity in OSA patients.
We have recently shown that catheter-based renal sympathetic denervation lowers blood pressure and improves glycemic control in resistant hypertensive patients with OSA. This was accompanied by amelioration of OSA. Renal sympathetic denervation may conceivably be a potentially useful therapeutic option for patients with refractory hypertension and severe OSA, particularly in those with comorbid metabolic dysregulation. More definitive randomized, controlled clinical trials are needed to confirm these initial proof-of-concept data.