Obstructive Sleep Apnea and Circulating Potassium Channel Levels

Abstract

BackgroundCardiac arrhythmias and sudden cardiac death are more frequent in patients with obstructive sleep apnea (OSA). OSA is associated with QT prolongation, and QT prolongation is an independent risk factor for sudden cardiac death. Because QT prolongation can be mediated by potassium channel loss of function, we tested whether OSA or continuous positive airway pressure therapy altered mRNA expression of circulating white blood cell potassium channels.Methods and ResultsIn total, 28 patients with OSA newly diagnosed by polysomnogram and 6 participants without OSA were enrolled. Potassium channel levels in white blood cells at baseline and at a 4‐week follow‐up visit were compared. There was a significant inverse correlation between the severity of the OSA stratified by apnea–hypopnea index and mRNA expression of the main potassium channels assessed: KCNQ1 (r=−0.486, P=0.007), KCNH2 (r=−0.437, P=0.016), KCNE1 (r=−0.567, P=0.001), KCNJ2 (r=−0.442, P=0.015), and KCNA5 (r=−0.468, P=0.009). In addition, KCNQ1, KCNH2, and KCNE1 inversely correlated with the oxygen desaturation index 4. After 4 weeks of continuous positive airway pressure therapy, circulating KCNQ1 and KCNJ2 were increased 1.4±0.4‐fold (P=0.040) and 2.1±1.4‐fold (P=0.046) in the moderate OSA group. Compared with patients with mild or moderate OSA, patients with severe OSA had a persistently higher apnea–hypopnea index (mild 2.0±1.8, moderate 1.0±0.9, severe 5.8±5.6; P=0.015), perhaps explaining why the potassium channel changes were not seen in the severe OSA group.ConclusionsThe mRNA expression of most potassium channels inversely correlates with the severity of OSA and hypoxemia. Continuous positive airway pressure therapy improves circulating KCNQ1 and KCNJ2 in patients with moderate OSA.

Sleep‐disordered breathing and electrocardiographic QRS‐T angle: The MESA study

“…Obstructive respiratory events lead to intermittent hypoxemia, increase in ventricular afterload and disruption of sympatho‐vagal balance (Dempsey, Veasey, Morgan, & O'Donnell, ). These episodes can increase nocturnal ventricular arrhythmogenicity possibly through ion channel dysfunction (Jiang et al., ; Verrier & Josephson, ). Such immediate effect of SDB is illustrated by dynamic change in ECG markers of ventricular repolarization in sleep in patients with SDB and its attenuation with continuous positive airway pressure (Kilicaslan et al., ; Roche et al., , ).…”

Clues to the Pathophysiology of Sudden Cardiac Death in Obstructive Sleep Apnea

“…Such mechanisms can contribute to life-threatening ventricular arrhythmias and SCD. One such proof of balance changes in intracellular potassium ions was demonstrated by the research of Jiang et al [22], which suggested the mechanistic links between OSA and the extension of repolarization elongation. Examining matrix RNA OSA patients, the authors established a decrease in the expression of the KCNQ1, KCNH2, KCNE1, KCNJ2, and KCNA5 potassium-channel genes, which were inversely related to AHI.…”

Ion Channel Remodeling—A Potential Mechanism Linking Sleep Apnea and Sudden Cardiac Death

“…In an elegant prospective observational cohort study in this issue of the Journal, Dudley and colleagues report a possible mechanistic link between OSA and prolonged QT interval and thus SCD. 11 Given the inherent procedural risks associated with endomyocardial biopsy of the different regions of the heart, the authors used mRNA in circulating white blood cells as surrogate reflectors of ion channel expression in unaffected controls and patients with OSA before and after 4 weeks of continuous positive airway pressure (CPAP) therapy. The authors found expression of potassium channels KCNQ1, KCNH2, KCNE1, KCNJ2, and KCNA5 to be inversely associated with severity of OSA by the apnea-hypopnea index.…”

“…Obstructive sleep apnea (OSA) may be an independent risk factor for nocturnal MI, SCD, atrial fibrillation (AF), heart failure, and pulmonary and systemic hypertension 3, 4, 5, 6, 7, 8, 9, 10. In this issue of the Journal , Dudley and colleagues elegantly propose a potential mechanistic link between OSA and ion channel remodeling (ICR) by measuring circulating mRNA levels of K + channels in OSA patients and controls and compare changes in those treated with continuous positive airway pressure (CPAP) 11. In this accompanying editorial we provide background on arrhythmia propensity and the role of OSA in SCD.…”