Relationship between serum asymmetric dimethylarginine (ADMA) level and obstructive sleep apnea syndrome (OSAS) severity

Introduction and Aim: The repetitive hypoxemia occurs in patients with obstructive sleep apnea and reoxygenation can induce oxidative stress mechanisms. Oxidative stress by changing the activity of the enzymes involved in ADMA, leads a change in the amount of ADMA. The main stimulus of erythropoietin (EPO) production is tissue hypoxia. Blood EPO level rises among patients with OSAS due to the hypoxia. Rising levels of EPO restrains hydrolysis of ADMA by inhibiting Dimethylarginine Dimethylaminohydrolase (DDAH) and serum ADMA level increases. It's thought that this mechanism increases serum ADMA levels in patients with OSAS. ADMA may be used as a marker for determining the severity of the disease. The aim of our study was to investigate the relationship between serum levels of ADMA and OSAS severity. Materials and Methods: Three hundred thirty patient's records, who applied to sleep laboratory of Düzce University Medical Faculty Department of Chest Diseases with OSAS clinic and underwent overnight polysomnography (PSG) consecutively, were retrospectively examined. Seventy two patients were found to be eligible for study. Patients were categorized into five groups according to the apnea hipopnea index (AHI). Measurement of ADMA levels was performed by ELİSA kit for ADMA on the blood specimens obtained in the morning. Results: Twenty six point four percent of patients was in normal ( n = 19) group, 25% in severe (n = 18), 25% in positional–rem dependent ( n = 18), 16.7% in mild (n = 12), 6.9 % in medium (n = 5) OSAS groups. The mean age was 44.19 ± 14.24 years. 31.9 % (n = 23) of the patients who participated in the study were female, 68.1 % were men (n = 49 ). A significant positive correlation was found between the mean levels of AHI and ADMA (r= 0,483; p<0,001). There were significant differences among the groups according to the mean SO2 levels ( p = 0.001). A significant negative correlation between the mean Min S02 and ADMA levels was found when the influence of confounders (age ) was under the control (r= -0,291; p=0,014). A significant positive correlation between the mean desaturation index and ADMA levels was found when the influence of confounders (age) was under the control ((r= 0,439; p<0,001). Appropriate cut-off criterion was set at 1.39 for ADMA. Sensitivity for this value was 73.58 % (95 % Confidence Interval (CI) : 61,71- % 85.45 % ) and specificity was 94.74 % ( 95 % CI: 84,70- % to 100% ). Accuracy or correct classification rate was found to be 79.17 %. The positive predictive value was 97.5 % and negative predictive value was 56.25 %. The positive likelihood ratio ( LR + ) was 13.98 ( LR + > 10) and the negative likelihood ratio was ( R- ) 0.28 ( R- <1 ). Conclusion: ADMA was found to be a strong and good diagnostic tool among patients with normal levels for glucose, LDL, triglyceride, TSH, creatinine and liver function tests. Key Words: OSAS, ADMA, oxidative stress