Dataset Information

Changes in Expression of the CLOCK Gene in Obstructive Sleep Apnea Syndrome Patients Are Not Reverted by Continuous Positive Airway Pressure Treatment.

ABSTRACT: Purpose:Metabolic syndrome and cardiovascular disease are strongly associated with obstructive sleep apnea syndrome (OSAS), which causes substantial changes to normal circadian physiological functions, including metabolic pathways. Because core clock genes are known to be modulated by sleep/vigilance cycles, we asked whether the expression level of mRNA coding for clock genes is altered in non-treated OSAS patients and if it can be corrected by standard continuous positive airway pressure (CPAP) treatment. Methods:Peripheral blood was collected from male patients diagnosed with severe OSAS (apnea-hypopnea index???30/h) before and after treatment initiation. qPCR was used to measure mRNA levels of genes associated with the central circadian pacemaker including CLOCK, BMAL1, Cry1, Cry2, and three Period genes (Per 1, 2, 3) in peripheral blood mononuclear cells (PBMCs). Results:We found statistically significant differences for CLOCK (p-value?=?0.022) expression in PBMCs of OSAS patients which were not reverted by treatment with CPAP. We have also found a substantial decrease in the slow wave sleep (SWS) content in OSAS patients (p-value?

SUBMITTER: Moreira S

PROVIDER: S-EPMC5681745 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Changes in Expression of the <i>CLOCK</i> Gene in Obstructive Sleep Apnea Syndrome Patients Are Not Reverted by Continuous Positive Airway Pressure Treatment.

Moreira Susana S Rodrigues Raquel R Barros André B AB Pejanovic Nadja N Neves-Costa Ana A Pedroso Dora D Pereira Cláudia C Fernandes Dina D Rodrigues João Valença JV Barbara Cristina C Moita Luís Ferreira LF

Frontiers in medicine 20171106

<h4>Purpose</h4>Metabolic syndrome and cardiovascular disease are strongly associated with obstructive sleep apnea syndrome (OSAS), which causes substantial changes to normal circadian physiological functions, including metabolic pathways. Because core clock genes are known to be modulated by sleep/vigilance cycles, we asked whether the expression level of mRNA coding for clock genes is altered in non-treated OSAS patients and if it can be corrected by standard continuous positive airway pressur ...[more]

PMID: 29164122

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Project description:Study objectiveTo determine the neurocognitive effects of continuous positive airway pressure (CPAP) therapy on patients with obstructive sleep apnea (OSA).Design, setting, and participantsThe Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blind, 2-arm, sham-controlled, multicenter trial conducted at 5 U.S. university, hospital, or private practices. Of 1,516 participants enrolled, 1,105 were randomized, and 1,098 participants diagnosed with OSA contributed to the analysis of the primary outcome measures.InterventionActive or sham CPAP MEASUREMENTS: THREE NEUROCOGNITIVE VARIABLES, EACH REPRESENTING A NEUROCOGNITIVE DOMAIN: Pathfinder Number Test-Total Time (attention and psychomotor function [A/P]), Buschke Selective Reminding Test-Sum Recall (learning and memory [L/M]), and Sustained Working Memory Test-Overall Mid-Day Score (executive and frontal-lobe function [E/F])ResultsThe primary neurocognitive analyses showed a difference between groups for only the E/F variable at the 2 month CPAP visit, but no difference at the 6 month CPAP visit or for the A/P or L/M variables at either the 2 or 6 month visits. When stratified by measures of OSA severity (AHI or oxygen saturation parameters), the primary E/F variable and one secondary E/F neurocognitive variable revealed transient differences between study arms for those with the most severe OSA. Participants in the active CPAP group had a significantly greater ability to remain awake whether measured subjectively by the Epworth Sleepiness Scale or objectively by the maintenance of wakefulness test.ConclusionsCPAP treatment improved both subjectively and objectively measured sleepiness, especially in individuals with severe OSA (AHI > 30). CPAP use resulted in mild, transient improvement in the most sensitive measures of executive and frontal-lobe function for those with severe disease, which suggests the existence of a complex OSA-neurocognitive relationship.Clinical trial informationRegistered at clinicaltrials.gov. Identifier: NCT00051363.CitationKushida CA; Nichols DA; Holmes TH; Quan SF; Walsh JK; Gottlieb DJ; Simon RD; Guilleminault C; White DP; Goodwin JL; Schweitzer PK; Leary EB; Hyde PR; Hirshkowitz M; Green S; McEvoy LK; Chan C; Gevins A; Kay GG; Bloch DA; Crabtree T; Demen WC. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the Apnea Positive Pressure Long-term Efficacy Study (APPLES). SLEEP 2012;35(12):1593-1602.

Project description:Excessive daytime sleepiness (EDS) is a symptom of obstructive sleep apnea (OSA) that resolves under treatment with continuous positive airway pressure (CPAP). In some patients, sleepiness persists despite CPAP treatment. We retrospectively analyzed data on subjective residual EDS, assessed as an Epworth Sleepiness Scale score (ESS) >10, in patients from the European Sleep Apnea Database (n = 4,853, mean age ± SD 54.8 ± 11.8 years, 26.1% females), at baseline and at the first visit (median follow-up: 5 months, interquartile range 3-13). An ESS > 10 occurred in 56% of patients at baseline and in 28.2% of patients at follow-up. Residual EDS was analyzed in 2,190 patients (age: 55.1 ± 12.0 years, 26.1% females) with sleep monitoring data (median follow-up: 3 months, interquartile range 1-15). Sleep studies during CPAP use were obtained in 58% of these patients; EDS was reported by 47.2% of patients at baseline and by 30.3% at follow-up. Residual OSA, defined as an apnea-hypopnea index >10/h, and insufficient CPAP adherence, defined as nightly use <4 h, occurred with similar frequency in patients with and without EDS at follow-up. Prevalence of residual EDS was highest (40%) in patients with a first follow-up visit at 0-3 months, then it was 13-19% in patients with a first follow-up visit after 4 months to 2 years. The change in ESS (n = 2,190) was weakly correlated with CPAP use (R2 = 0.023, p < 0.0001). Logistic regression showed that an ESS score >10 at the first follow-up visit was associated directly with ESS at baseline and inversely with duration of follow-up, and CPAP use (R2 of the model: 0.417). EDS showed heterogeneity in different European countries both at baseline and at the first follow-up visit, suggesting modulation by cultural and lifestyle factors. In conclusion, residual EDS in CPAP-treated OSA occurred in approximately one in four patients at follow-up; its prevalence was highest (40%) in the first 3 months of treatment and subsequently decreased. The finding of residual EDS in a significant percentage of optimally treated OSA patients suggests that wake-promoting agents may be useful, but their indication should be evaluated after at least 3 months of treatment.

Dataset Information

Changes in Expression of the CLOCK Gene in Obstructive Sleep Apnea Syndrome Patients Are Not Reverted by Continuous Positive Airway Pressure Treatment.

Publications

Changes in Expression of the <i>CLOCK</i> Gene in Obstructive Sleep Apnea Syndrome Patients Are Not Reverted by Continuous Positive Airway Pressure Treatment.

Similar Datasets

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