Author(s): Emrah Bolca*, Dilek Ergun, Recai Ergun, Fikret Kanat, Ali Unlu, Duygu Eryavuz Onmaz, Muslu Kazim Korez
Background: Recurrent hypoxaemia and reoxygenation in patients with Obstructive Sleep Apnea Syndrome (OSAS) may trigger oxidative stress mechanisms. Oxidative stress alters the activities of enzymes involved in the production of Asymmetric Dimethylarginine (ADMA), Symmetric Dimethylarginine (SDMA) and N-Monomethyl L-arginine (L-NMMA), leading to changes in their amounts. In previous studies, it was observed that intermittent hypoxia and hypoxia-re-oxygenation events increased Nitric Oxide (NO) synthesis by increasing endothelial Nitric Oxide Synthase (eNOS) synthase activity in OSAS patients. In our study, we examined the balance between L-arginine-nitric oxide and L-arginine-methylated arginine metabolites (ADMA, SDMA and L-NMMA) pathways due to intermittent hypoxia in newly diagnosed OSAS patients who have not yet developed OSAS-related complications and which pathways are activated. At the end of our study, we aimed to examine the effect of increased metabolites in predicting complications that may develop in the future due to OSAS.
Materials and methods: Male and female patients aged 18 years and older who voluntarily agreed to participate in the study were included in the study. Patients with an apnea-hypopnea index of 5 and above were included in the study. Patients with central apnea and laboratory abnormalities (Hg, AST, ALT, HbA1c, bilirubin, electrolytes, urea, homocysteine, folic acid and thyroid function tests) were excluded. Detailed anamnesis was obtained from the patients and those with comorbidities that would affect the study; cardiovascular system diseases (essential hypertension, hypercholesterolemia, hyperhomocysteinaemia, acute coronary events, congestive heart failure), diabetes, hyperthyroidism, chronic renal failure, insulin resistance and metabolic syndrome, low serum folic acid and high homocysteine levels were excluded from the study. Blood samples were obtained from the other patients with their informed consent for ADMA, SDMA, L-NMMA, arginine, complete blood count, renal function tests, lipid panel, thyroid function tests, fasting blood glucose, HbA1c, folic acid and homocysteine controls.
The study included 121 patients including 31 healthy and newly diagnosed mild ouas 30, moderate ouas 30 and severe ouas 31. The demographic characteristics, laboratory findings and clinical indices of the study participants according to the study groups were compared by One-Way Analysis of Variance, Welch F test or Kruskal Wallis tests. Tukey HSD, Games-Howell and Bonferroni corrected Dunn's tests were used for multiple comparisons for the parameters found to be significant as a result of these tests, respectively. The level of significance was taken as 5% in the evaluation of statistical hypotheses.
Results: As a result of our study, we found that arginine metabolites (ADMA and L-NMMA) levels were lower in patients with OSAS compared to the healthy group. SDMA values of healthy controls and OSAS patient groups were similar. When the laboratory findings of the study groups were analysed, TMAL value was significantly lower in OSAS patients compared to healthy controls.
Conclusion: The patients we included in the study were newly diagnosed with the polysomnography results and had not developed any complications related to the disease because of the early stage of the disease. Therefore, we did not observe an increase in arginine metabolites (ADMA and L-NMMA) due to the fact that the L-arginine pathway was registered to nitric oxide synthesis for compensation and therefore the methylated arginine pathway was not yet activated. There is a need for further controlled, prospective, prospective studies including NO measurement and nitric oxide synthase enzyme activities in terms of monitoring treatment efficacy, monitoring of complications and monitoring of disease progression in patients with OSAS.
