obstructive sleep apnea ( osa ) is a highly prevalent and underdiagnosed disease.1 a recent large clinical trial established osa as a novel risk factor for sudden cardiac death ( scd).2 after 20 years of followup , the busselton health study cohort showed that moderate to severe sleep apnea was independently associated with an increased risk of allcause mortality.3 in a longitudinal study of 10  701 adults , osa was associated with scd , and the magnitude of risk varied with osa severity.2 
  qt prolongation is an independent risk factor for scd,4 , 5 , 6 and osa is associated with longer qt intervals.7 , 8 this electrocardiographic effect is thought to be caused by systemic hypoxia , hypercarbia , or acidosis .
the most effective treatment for osa is continuous positive airway pressure ( cpap ) therapy , which improves oxygenation and decreases sleep fragmentation .
cpap improves prolonged cardiac repolarization9 and decreases the rate of death.10 cpap withdrawal is associated with prolongation of the corrected qt interval.11 
  the genetic link of scd and qt interval to potassium channels has been well established in inherited long qt syndromes.12 lossoffunction gene mutations of cardiac potassium channels contribute to different types of long qt syndromes , such as kcnq1 ( long qt syndrome type 1 [ lqt1 ] ) , kcnh2 ( lqt2 ) , kcne1 ( lqt5 ) , kcne2 ( lqt6 ) , and kcnj2 ( lqt7).13 , 14 other potassium channels expressed in the heart include kcnd3 , encoding the potassium channel that underlies the transient outward current ito15 ; kcna5 , encoding the potassium channel that underlies ikur 
 16 ; and kcnj11 , encoding kir6.2 , which underlies the inward rectifying channel.17 
  in summary , osa is associated with qt prolongation and scd .
cpap improves qt prolongation.9 , 11 qt interval is influenced by potassium channels . in our previously published study , the levels of circulating cardiac sodium channel fulllength mrna and splicing variants in white blood cells were representative of levels in the myocardium.18 based on these observations , we reasoned that circulating white blood cells may experience conditions similar to those of cardiomyocytes and may reveal insights into the mechanism of qt changes with osa and cpap .
we hypothesized that prolonged qt in osa represented altered potassium channel regulation and that this regulation would be reflected in circulating white blood cells .
sodium channel splicing in obstructive sleep apnea ( socsosa )  and was conducted at the lifespan health system ( rhode island hospital and the miriam hospital ) in providence , rhode island , and at the university of illinois at chicago ( uic ) in chicago , illinois .
participants were adults ( aged 18  years ) with osa newly diagnosed by polysomnogram who agreed to cpap treatment ( osa group ) or adults without osa ( control group ) .
all trial participants were screened with the stopbang questionnaire19 before proceeding to the sleep study .
based on the severity of apnea  hypopnea index ( ahi ) , osa patients were assigned to 3 groups : mild ( ahi 515 ) , moderate ( ahi 1530 ) , or severe ( ahi > 30).20 the ahi was defined as the number of apneas and hypopneas per hour and calculated by adding the total number of apnea and hypopnea events and dividing by the total number of minutes of actual sleep time multiplied by 60 .
the overnight sleep study consisted of continuous polygraphic recordings from 10  pm to 7  am , and the baseline parameters were measured .
arterial oxygen saturation was recorded by digital pulse oximeter , and the nadir arterial oxygen saturation levels ( nadir o2 ) were obtained . the oxygen desaturation index is the number of times per hour of sleep that the blood 's oxygen level drops by 3% or 4% ( ie , odi4 ) from baseline . to quantify overall nocturnal desaturation , we used the cumulative percentages of sleep time spent at saturations < 90% or < 85% .
respiratory disturbance index was defined as the average number of episodes of apnea , hypopnea , and respiratory event  related arousals per hour of sleep documented in the polysomnography .
after 4  weeks of cpap therapy , an ahi score was measured and documented as residual ahi , which was used to assess the efficacy of cpap therapy .
the osa patients were evaluated with the epworth sleepiness scale ( ess)21 and the functional outcome of sleep questionnaire 10 ( fosq10)22 at the time of initial diagnosis .
improvement of the symptoms were reevaluated by the ess and fosq10 after 1  month of cpap treatment .
the exclusion criteria included chronic use of hypnotics ; current drug or alcohol addiction ; a rhythm other than sinus at enrollment ; mandatory and biventricular pacing ; a history of heart transplant or left ventricular assist device ; active use of intravenous vasodilators , vasopressors , or inotropes ; hemodialysis or peritoneal dialysis ; active infection ; acute coronary syndrome ; major trauma or surgery ; malignant neoplastic disease on active treatment including chemotherapy and radiation therapy ; life expectancy < 1  year ; collagen vascular disease on active treatment including steroids and other immunomodulating drugs ; systemic steroid use ; or concomitant use of an investigational drug .
blood samples were collected in paxgene blood rna tubes ( qiagen ) and were stored in a freezer at 80c before processing .
total rna was isolated with the use of the paxgene blood rna isolation kit and was then converted to cdna with the use of the superscript iii cdna reverse transcription kit ( life technologies ) . only samples with an optical density of 260/280>2.0 and 260/230>1.7
quantitative reverse transcriptase polymerase chain reaction was performed to detect the abundance of potassium channels using iqsybr green supermix ( biorad laboratories ) and the 7500 fast realtime pcr system ( life technologies ) .
the primer sequences used were hkcnq1f ( 5ttgggaagccctcactgttc3 ) , hkcnq1r ( 5ctggtg aagcatgtcggtga3 ) , hkcnh2f ( 5tcaccgccctgtacttcatct3 ) , hkcnh2r ( 5caggccttgcataca ggttca3 ) , hkcne1f ( 5gaaccccaccactggctaaa3 ) , hkcne1r ( 5taatcca cccctcacccctt3 ) , hkcne2f ( 5atttcatcctgcccacacact3 ) , hkcne2r ( 5 ccagcgtctgtgtgaaattgg3 ) , hkcna5f ( 5agaggagtccagcggaaggt3 ) , hkcna5r ( 5actgtctgcattctccagggt3 ) , hkcnj11f ( 5tccagggtgttacaa ggcac3 ) , hkcnj11r ( 5gaattgggttgggaggagca3 ) , hkcnj2f ( 5tgtcacgg atgaatgcccaa3 ) , hkcnj2r ( 5ctgcgccaatgatgaaagca3 ) , hkcnd3f ( 5t gtacgaacctccaccatcaa3 ) , and hkcnd3r ( 5atgggtagttctgcattgaact ct3 ) .
quantitative reverse transcriptase polymerase chain reaction thermal cycling conditions were initial incubation at 50c for 60  minutes and then termination of the reactions at 85c for 5  minutes .
polymerase chain reaction was performed with an initial denaturation step at 95c for 20  seconds , followed by 40 cycles of denaturation at 95c for 3  seconds and annealing and nucleotide prolongation at 60c for 30  seconds .
each sample was measured for the target genes kcnq1 , kcnh2 , kcne1 , kcne2 , kcna5 , kcnj11 , kcnj2 , kcnd3 , and actin .
continuous variables were described in terms of descriptive statistics ( mean and standard deviation ) .
independent samples t tests and pearson chisquare tests were used for bivariate analysis comparisons of continuous and categorical variables , respectively .
the pearson correlation coefficient was used to assess the correlation between the parameters measured in the sleep study , the severity of osa , and the mrna levels of potassium channels .
differences between gene expression at baseline and at the followup visit were examined by means of paired wilcoxon tests .
sodium channel splicing in obstructive sleep apnea ( socsosa )  and was conducted at the lifespan health system ( rhode island hospital and the miriam hospital ) in providence , rhode island , and at the university of illinois at chicago ( uic ) in chicago , illinois .
participants were adults ( aged 18  years ) with osa newly diagnosed by polysomnogram who agreed to cpap treatment ( osa group ) or adults without osa ( control group ) .
all trial participants were screened with the stopbang questionnaire19 before proceeding to the sleep study .
based on the severity of apnea  hypopnea index ( ahi ) , osa patients were assigned to 3 groups : mild ( ahi 515 ) , moderate ( ahi 1530 ) , or severe ( ahi > 30).20 the ahi was defined as the number of apneas and hypopneas per hour and calculated by adding the total number of apnea and hypopnea events and dividing by the total number of minutes of actual sleep time multiplied by 60 .
the overnight sleep study consisted of continuous polygraphic recordings from 10  pm to 7  am , and the baseline parameters were measured .
arterial oxygen saturation was recorded by digital pulse oximeter , and the nadir arterial oxygen saturation levels ( nadir o2 ) were obtained . the oxygen desaturation index is the number of times per hour of sleep that the blood 's oxygen level drops by 3% or 4% ( ie , odi4 ) from baseline . to quantify overall nocturnal desaturation , we used the cumulative percentages of sleep time spent at saturations < 90% or < 85% .
respiratory disturbance index was defined as the average number of episodes of apnea , hypopnea , and respiratory event  related arousals per hour of sleep documented in the polysomnography .
after 4  weeks of cpap therapy , an ahi score was measured and documented as residual ahi , which was used to assess the efficacy of cpap therapy .
the osa patients were evaluated with the epworth sleepiness scale ( ess)21 and the functional outcome of sleep questionnaire 10 ( fosq10)22 at the time of initial diagnosis .
improvement of the symptoms were reevaluated by the ess and fosq10 after 1  month of cpap treatment .
the exclusion criteria included chronic use of hypnotics ; current drug or alcohol addiction ; a rhythm other than sinus at enrollment ; mandatory and biventricular pacing ; a history of heart transplant or left ventricular assist device ; active use of intravenous vasodilators , vasopressors , or inotropes ; hemodialysis or peritoneal dialysis ; active infection ; acute coronary syndrome ; major trauma or surgery ; malignant neoplastic disease on active treatment including chemotherapy and radiation therapy ; life expectancy < 1  year ; collagen vascular disease on active treatment including steroids and other immunomodulating drugs ; systemic steroid use ; or concomitant use of an investigational drug .
blood samples were collected in paxgene blood rna tubes ( qiagen ) and were stored in a freezer at 80c before processing .
total rna was isolated with the use of the paxgene blood rna isolation kit and was then converted to cdna with the use of the superscript iii cdna reverse transcription kit ( life technologies ) . only samples with an optical density of 260/280>2.0 and 260/230>1.7 were used .
quantitative reverse transcriptase polymerase chain reaction was performed to detect the abundance of potassium channels using iqsybr green supermix ( biorad laboratories ) and the 7500 fast realtime pcr system ( life technologies ) .
the primer sequences used were hkcnq1f ( 5ttgggaagccctcactgttc3 ) , hkcnq1r ( 5ctggtg aagcatgtcggtga3 ) , hkcnh2f ( 5tcaccgccctgtacttcatct3 ) , hkcnh2r ( 5caggccttgcataca ggttca3 ) , hkcne1f ( 5gaaccccaccactggctaaa3 ) , hkcne1r ( 5taatcca cccctcacccctt3 ) , hkcne2f ( 5atttcatcctgcccacacact3 ) , hkcne2r ( 5 ccagcgtctgtgtgaaattgg3 ) , hkcna5f ( 5agaggagtccagcggaaggt3 ) , hkcna5r ( 5actgtctgcattctccagggt3 ) , hkcnj11f ( 5tccagggtgttacaa ggcac3 ) , hkcnj11r ( 5gaattgggttgggaggagca3 ) , hkcnj2f ( 5tgtcacgg atgaatgcccaa3 ) , hkcnj2r ( 5ctgcgccaatgatgaaagca3 ) , hkcnd3f ( 5t gtacgaacctccaccatcaa3 ) , and hkcnd3r ( 5atgggtagttctgcattgaact ct3 ) .
quantitative reverse transcriptase polymerase chain reaction thermal cycling conditions were initial incubation at 50c for 60  minutes and then termination of the reactions at 85c for 5  minutes .
polymerase chain reaction was performed with an initial denaturation step at 95c for 20  seconds , followed by 40 cycles of denaturation at 95c for 3  seconds and annealing and nucleotide prolongation at 60c for 30  seconds .
each sample was measured for the target genes kcnq1 , kcnh2 , kcne1 , kcne2 , kcna5 , kcnj11 , kcnj2 , kcnd3 , and actin .
continuous variables were described in terms of descriptive statistics ( mean and standard deviation ) .
independent samples t tests and pearson chisquare tests were used for bivariate analysis comparisons of continuous and categorical variables , respectively .
the pearson correlation coefficient was used to assess the correlation between the parameters measured in the sleep study , the severity of osa , and the mrna levels of potassium channels .
differences between gene expression at baseline and at the followup visit were examined by means of paired wilcoxon tests .
overall , 28 osa patients and 6 participants without osa met eligibility criteria and completed the baseline and followup visits .
the mean age ( sd ) was 50.710.1  years in osa patients and 43.616.3  years in participants without osa .
the baseline body mass index was 36.48.1 in osa patients and 39.510.7 in participants without osa . at baseline
, there was no significant difference in demographic characteristics between groups ( table  1 ) .
clinical characteristics of the socsosa study ahi indicates apnea  hypopnea index ; bmi , body mass index ; cpap , continuous positive airway pressure ; ct85 , the cumulative percentages of sleep time spent at saturations < 85% ; ct90 , the cumulative percentages of sleep time spent at saturations < 90% ; odi3 , the number of times per hour of sleep that the blood 's oxygen level drops by 3% from baseline ; odi4 , the number of times per hour of sleep that the blood 's oxygen level drops by 4% from baseline ; osa , obstructive sleep apnea ; rdi , respiratory disturbance index ; residual ahi , the apnea  hypopnea index after 4  weeks of continuous positive airway pressure therapy . 
 p value from t tests for continuous variables and chisquare tests for categorical variables .
the sleep characteristics and cpap treatment among participants with osa are shown in table  1 .
as expected , cpap therapy was associated with significant reductions in ahi . nevertheless , compared with patients with mild or moderate osa , patients with severe osa had significantly higher residual ahi ( mild 2.01.8 , moderate 1.00.9 , severe 5.85.6 ; p=0.015 ) .
the stopbang questionnaire was used to screen for osa . compared with patients with mild osa , patients with moderate osa had markedly higher scores ( mild 4.11.4 , moderate 6.01.3 , severe 5.41.1 ; p=0.022 ) .
there was no statistically significant difference between moderate and severe osa , and that might be explained by use of the stopbang questionnaire , which is highly sensitive at low scores and highly specific at high scores for osa.23 the osa patients were evaluated with the ess questionnaire to measure daytime sleepiness before and after cpap therapy .
the ess score significantly decreased after 4  weeks of cpap in mild and moderate osa patients ( mild 12.65.2 versus 9.26.1 , p=0.028 ; moderate 11.74.5 versus 7.35.7 , p=0.034 ; severe 12.36.6 versus 10.75.3 , p=0.497 ) .
we observed a significant inverse correlation between the severity of osa stratified by ahi and the 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 ) ( figure  1 and table  2 ) .
in addition , kcnq1 ( r=0.404 , p=0.027 ) , kcnh2 ( r=0.416 , p=0.022 ) , and kcne1 ( r=0.465 , p=0.010 ) inversely correlated with odi4 , indicating the oxygen desaturation status ( figure  2 and table  2 ) .
a , correlation between mrna level of kcnq1 ( ordinate ) and ahi ( abscissa ) .
b , correlation between mrna level of kcnj2 ( ordinate ) and ahi ( abscissa ) .
correlation of the expression of baseline potassium channels with hypoxia ahi indicates apnea  hypopnea index ; nadir o2 , nadir arterial oxygen saturation levels ; odi4 , the number of times per hour of sleep that the blood 's oxygen level drops by 4% from baseline .
a , correlation between mrna level of kcnq1 ( ordinate ) and odi4 ( abscissa ) .
b , correlation between mrna level of kcnj2 ( ordinate ) and odi4 ( abscissa ) .
odi4 indicates the number of times per hour of sleep that the blood 's oxygen level drops by 4% from baseline . for patients with
newly diagnosed osa initiating cpap for the first time , circulating kcnq1 and kcnj2 were increased 1.40.4fold ( p=0.040 ) and 2.11.4fold ( p=0.046 ) , respectively , after 4  weeks of cpap therapy in the moderate group ( figure  3 ) . although they did not reach statistical significance , cpap improved most potassium channel gene expression in moderate osa : kcne1 1.5fold , kcne2 2.9fold , kcna5 1.9fold , kcnd3 1.3fold , and kcnj11 1.6fold . 

p<0.05 comparing the postcpap fold change of kcnq1 or kcnj2 to the baseline in the moderate osa group .
overall , 28 osa patients and 6 participants without osa met eligibility criteria and completed the baseline and followup visits .
the mean age ( sd ) was 50.710.1  years in osa patients and 43.616.3  years in participants without osa .
the baseline body mass index was 36.48.1 in osa patients and 39.510.7 in participants without osa . at baseline
, there was no significant difference in demographic characteristics between groups ( table  1 ) .
clinical characteristics of the socsosa study ahi indicates apnea  hypopnea index ; bmi , body mass index ; cpap , continuous positive airway pressure ; ct85 , the cumulative percentages of sleep time spent at saturations < 85% ; ct90 , the cumulative percentages of sleep time spent at saturations < 90% ; odi3 , the number of times per hour of sleep that the blood 's oxygen level drops by 3% from baseline ; odi4 , the number of times per hour of sleep that the blood 's oxygen level drops by 4% from baseline ; osa , obstructive sleep apnea ; rdi , respiratory disturbance index ; residual ahi , the apnea  hypopnea index after 4  weeks of continuous positive airway pressure therapy . 
 p value from t tests for continuous variables and chisquare tests for categorical variables .
the sleep characteristics and cpap treatment among participants with osa are shown in table  1 .
as expected , cpap therapy was associated with significant reductions in ahi . nevertheless , compared with patients with mild or moderate osa ,
patients with severe osa had significantly higher residual ahi ( mild 2.01.8 , moderate 1.00.9 , severe 5.85.6 ; p=0.015 ) .
the stopbang questionnaire was used to screen for osa . compared with patients with mild osa , patients with moderate osa had markedly higher scores ( mild 4.11.4 , moderate 6.01.3 , severe 5.41.1 ; p=0.022 ) .
there was no statistically significant difference between moderate and severe osa , and that might be explained by use of the stopbang questionnaire , which is highly sensitive at low scores and highly specific at high scores for osa.23 the osa patients were evaluated with the ess questionnaire to measure daytime sleepiness before and after cpap therapy .
the ess score significantly decreased after 4  weeks of cpap in mild and moderate osa patients ( mild 12.65.2 versus 9.26.1 , p=0.028 ; moderate 11.74.5 versus 7.35.7 , p=0.034 ; severe 12.36.6 versus 10.75.3 , p=0.497 ) .
we observed a significant inverse correlation between the severity of osa stratified by ahi and the 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 ) ( figure  1 and table  2 ) .
in addition , kcnq1 ( r=0.404 , p=0.027 ) , kcnh2 ( r=0.416 , p=0.022 ) , and kcne1 ( r=0.465 , p=0.010 ) inversely correlated with odi4 , indicating the oxygen desaturation status ( figure  2 and table  2 ) .
a , correlation between mrna level of kcnq1 ( ordinate ) and ahi ( abscissa ) .
b , correlation between mrna level of kcnj2 ( ordinate ) and ahi ( abscissa ) .
correlation of the expression of baseline potassium channels with hypoxia ahi indicates apnea  hypopnea index ; nadir o2 , nadir arterial oxygen saturation levels ; odi4 , the number of times per hour of sleep that the blood 's oxygen level drops by 4% from baseline .
a , correlation between mrna level of kcnq1 ( ordinate ) and odi4 ( abscissa ) .
b , correlation between mrna level of kcnj2 ( ordinate ) and odi4 ( abscissa ) .
odi4 indicates the number of times per hour of sleep that the blood 's oxygen level drops by 4% from baseline .
for patients with newly diagnosed osa initiating cpap for the first time , circulating kcnq1 and kcnj2 were increased 1.40.4fold ( p=0.040 ) and 2.11.4fold ( p=0.046 ) , respectively , after 4  weeks of cpap therapy in the moderate group ( figure  3 ) . although they did not reach statistical significance , cpap improved most potassium channel gene expression in moderate osa : kcne1 1.5fold , kcne2 2.9fold , kcna5 1.9fold , kcnd3 1.3fold , and kcnj11 1.6fold . 

p<0.05 comparing the postcpap fold change of kcnq1 or kcnj2 to the baseline in the moderate osa group .
the main findings of this prospective study are that the mrna expression of at least 5 of 8 cardiac potassium channels correlated with the severity of osa and that cpap treatment improved circulating kcnq1 and kcnj2 in patients with moderate osa .
there were trends toward increases in 7 of 8 potassium channels in patients with moderate osa .
qt prolongation is an independent risk factor for scd . in the oregon sudden unexpected death study , idiopathic abnormal prolongation of the corrected qt interval
was associated with 5fold increased odds of scd.5 recent genetic studies have established a clear inverse relationship between qt interval and expression and function of potassium channels .
gene defects resulting in loss of function of voltagegated potassium channels , for example , are associated with long qt syndromes : lqt1 ( kcnq1 ) and lqt2 ( kcnh2 ) , encoding subunits of the potassium channels iks and ikr ; lqt5 ( kcne1 ) and lqt6 ( kcne2 ) , encoding subunits of the potassium channels iks and ikr ; and lqt7 ( kcnj2 ) , encoding the inward rectifier potassium channel kir2.1.12 , 13 , 14 , 15 , 16 , 17 
  osa is associated with scd and long qt .
osa predicted incident scd in a longitudinal study of 10  701 adults.3 in osa patients who had no evidence of underlying cardiac , pulmonary , or central nervous system disease , the qt interval was prolonged at the onset of apnea.7 
  because osa is associated with long qt , and long qt can be caused by potassium channel loss of function , we tested whether osa was associated with circulating potassium channel changes .
a total of 8 potassium channel genes were studied , and we found that the mrna levels of at least 5 of 8 potassium channel genes assessed correlated inversely with hypoxemia and osa severity .
of these channel genes , 2 were statistically significantly increased and 5 more showed trends toward an increase with cpap therapy .
this could be explained if correction of hypoxia were the major driver for improvements in channel levels .
consistent with this idea , in a population of 10  701 adults , the magnitude of scd risk was predicted by ahi and nocturnal oxygen desaturation.3 in our study , even with cpap , severe osa patients had higher residual ahi with statistical difference , and there was no change in potassium channel levels with cpap .
this supports the idea that the degree of hypoxia , rather than some other aspect of cpap , was mediating the changes in mrna abundance . in our patients with mild osa , hypoxia was not severe and changed little with cpap .
the transcription factor hypoxiainducible factor 1 ( hif1 ) plays a key role in cellular response to systemic oxygen levels in humans .
hif1 is a subunit of a heterodimeric hif1.24 , 25 there are 3 putative hif1 transcription factor binding sites located in the upstream sequence of the human kcnq1 gene and 4 hif1 binding sites located in the upstream sequence of the human kcnj2 gene ( data not shown ) .
the systemic oxygen level affects hif1 through multiple mechanisms , such as hif1 conformational changes and stability , subcellular localization , and transcriptional activity .
hif1 regulates the expression of > 60 genes involved in angiogenesis , cell proliferation , cell survival , and glucose and iron metabolism.26 the presence of hif1 binding sites in the promoters of potassium channels may provide the mechanism by which systemic oxygen level affects the gene expression of potassium channels .
although the paired design controlled for interparticipant variability , the small sample size precluded comprehensive multivariable adjustment . in addition , because of the short study duration , it is not clear if the changes in potassium channel expression with cpap will be durable or if they correlate with improved outcomes .
furthermore , we did not correlate potassium channel mrna levels in white blood cells with levels or currents in the myocardium .
the mrna expression of most potassium channels inversely correlated with the severity of osa and hypoxemia .
if downregulations in circulating potassium channel genes with osa are mirrored in the heart , as may happen if systemic hypoxemia is a causal factor , then downregulation of potassium channel genes in the heart may explain the long qt and increased risk of scd in osa .
moreover , it suggests that potassium channel gene levels may represent a new circulating marker for arrhythmic risk in osa .
the present work was supported in part by national institutes of health grants r01 hl104025 and hl106592 .
 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 4week followup 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 1.40.4fold ( p=0.040 ) and 2.11.4fold ( 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 2.01.8 , moderate 1.00.9 , severe 5.85.6 ; 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 . 
Introduction
Materials and Methods
Clinical Characteristics of the OSA Population and Inclusion Criteria
Sample Collection and Processing
Statistical Analysis
Results
Demographic and Clinical Characteristics
Comparison of the Questionnaires Among OSA Groups
Baseline Potassium Channel mRNA Expression Correlated With the Severity of OSA
CPAP Improved Circulating KCNQ1 and KCNJ2 in Moderate OSA Patients
Discussion
Conclusions
Sources of Funding
Disclosures