Epigenetics modifications and Subclinical Atherosclerosis in Obstructive Sleep Apnea: The EPIOSA study

Abstract

BackgroundObstructive sleep apnea (OSA) is associated with increased risk for cardiovascular morbidity and mortality. Epidemiological and animal models studies generate hypotheses for innovative strategies in OSA management by interfering intermediates mechanisms associated with cardiovascular complications. We have thus initiated the Epigenetics modification in Obstructive Sleep Apnea (EPIOSA) study (ClinicalTrials.gov identifier: NCT02131610).Methods/designEPIOSA is a prospective cohort study aiming to recruit 350 participants of caucasian ethnicity and free of other chronic or inflammatory diseases: 300 patients with prevalent OSA and 50 non-OSA subjects. All of them will be follow-up for at least 5 years. Recruitment and study visits are performed in single University-based sleep clinic using standard operating procedures. At baseline and at each one year follow-up examination, patients are subjected to a core phenotyping protocol. This includes a standardized questionnaire and physical examination to determine incident comorbidities and health resources utilization, with a primary focus on cardiovascular events. Confirmatory outcomes information is requested from patient records and the regional Department of Health Services. Every year, OSA status will be assessed by full sleep study and blood samples will be obtained for immediate standard biochemistry, hematology, inflammatory cytokines and cytometry analysis. For biobanking, aliquots of serum, plasma, urine, mRNA and DNA are also obtained. Bilateral carotid echography will be performed to assess subclinical atherosclerosis and atherosclerosis progression. OSA patients are treated according with national guidelines.DiscussionEPIOSA will enable the prospective evaluation of inflammatory and epigenetics mechanism involved in cardiovascular complication of treated and non-treated patients with OSA compared with non OSA subjects.

Mechanisms of microglial activation in models of inflammation and hypoxia: Implications for chronic intermittent hypoxia

“…There is at least one ongoing 5‐year study evaluating DNA methylation and RNA transcriptome changes in the blood of OSA patients (Marin et al . ); results of this study will be of considerable interest.…”

Low Oxygen Consumption is Related to a Hypomethylation and an Increased Secretion of IL-6 in Obese Subjects with Sleep Apnea-Hypopnea Syndrome

“…Additionally, only one study with adults has aimed to evaluate the epigenetic mechanism involved in SAHS, but it has only published methodological data so far [54]. On the other hand, studies of DNA methylation patterns carried out in children with SAHS suggested an epigenetic dysregulation of vascular function [55].…”

Forkhead Box P3 Methylation and Expression in Men with Obstructive Sleep Apnea

“…Demographic, anthropometric, and clinical data were obtained at recruitment using specific questionnaires and standard measurements [12]. Daytime somnolence was assessed with the Epworth test [28].…”

“…The Epigenetics Status and Subclinical Atherosclerosis in Obstructive Sleep Apnea (EPIOSA) Study is a longitudinal study with the main objective of identifying epigenetic markers associated to the prevalence and progression of subclinical atherosclerosis in individuals with OSA without co-morbid conditions (ClinicalTrials.gov: NCT02131610) [12]. We hypothesized that adults with OSA may have different systemic inflflammatory responses reflflecting different patterns in FOXP3 gene methylation and expression.…”