Subclinical Atherosclerosis and Regulatory T Cells in Obstructive Sleep Apnea

Abstract

SESSION TITLE: Pulmonary and Sleep MedicineSESSION TYPE: Slide PresentationPRESENTED ON: Saturday, March 22, 2014 at 09:00 AM - 10:00 AMPURPOSE: Intermittent hypoxia and increase sympathetic activity during apnea episodes may cause systemic inflammation via down-regulation of regulatory T-cell (Treg cells). This may contribute to premature atherosclerosis leading to an increase in the size of arterial intima-media thickness (IMT). To evaluate the relationship between Treg plasma cells and intima-media thickness (IMT) in non-OSA and OSA patients without comorbiditiesMETHODS: During a 10 months period, we enrolled 100 adults (age range: 20 to 55) among those referred for sleep study due to suspected OSA. Exclusion criteria were: history of tobacco or alcohol consumption, hypertension, dyslipidemia, diabetes, cardiovascular, cerebrovascular, renal, neuromuscular, inflammatory or autoimmune chronic diseases. OSA diagnosis was made on the basis of an apnea/hypopnea index (AHI) > 5. IMT was assessed in common carotid arteries by high-resolution B-mode ultrasonography. By flow-cytometry analysis, CD+CD25+Foxp3+ cells as were acquired (BD Pharmigen) and identified as Treg cells.RESULTS: Non-OSA subjects (n = 30) were younger (41 ± 8 vs 45 ± 8 years, p = 0.02) and had a lower body mass index (26.4 ± 3.8 vs 30.1 ± 5.5 kg/m2, p < 0.001) than OSA patients (n = 70). IMT was 0.53 ± 0.08 (95 percentile: 0.65 mm) and 0.66 ± 0.12 mm respectively (p<0.001). Abnormal IMT (> 0.65 mm) was identified in 41% of OSA group. In multivariate linear regression analyses, age, BMI and baseline systolic blood pressure but not AHI, were related with IMT. Treg cells represent 7.5 ± 1.6% of all CD3 (lymphocytes) in non-OSA subjects and 6.7 ± 1.4 % in OSA patients. IMT and Treg cells were significantly related (r = -0.29, p =0.007).CONCLUSIONS: Down regulation of Treg cells but not AHI is associated with subclinical atherosclerosis suggesting different epigenetic adaptations to apnea episodes in OSA.CLINICAL IMPLICATIONS: The effect of nocturnal intermittent hypoxia and increase sympathetic activity is not homogeneous among all patients with OSA. It seems that a subset of patients exhibit an increased risk of subclinical atherosclerosis associated with a down-regulation of regulatory T-cells. This subgroup of patients probably represents a particular phenotypic presentation of OSA that merits a specific treatment. Supported by ISCIII grant PI12/02175 and SEPAR-2014DISCLOSURE: The following authors have nothing to disclose: Marta Marin-Oto, Teresa Martin, Javier Godino, Marta Andres, Victoria Gil, Jose MarinNo Product/Research Disclosure Information.