Original Contribution
Association of urinary 15-F2t-isoprostane level with oxygen desaturation and carotid intima–media thickness in nonobese sleep apnea patients

https://doi.org/10.1016/j.freeradbiomed.2009.12.008Get rights and content

Abstract

Obstructive sleep apnea (OSA) is characterized by recurrent apnea during sleep that may unbalance oxidative stress, increasing atherosclerosis. Among oxidative stress markers, 15-F2t-isoprostane is considered one of the most sensitive and specific metabolites of lipid peroxidation. To explore the relationship between urinary 15-F2t-isoprostane with sleep apnea severity and carotid modifications in nonobese OSA patients, 31 nonobese sleep apnea patients were studied, along with 10 lean subjects without OSA. Patients were assessed by polysomnography, blood pressure measurement, and ultrasonography to determine the carotid intima–media thickness (IMT). Urinary 15-F2t-isoprostanes were measured by liquid chromatography–tandem mass spectrometry. Urinary 15-F2t-isoprostane concentrations were increased in severe OSA patients compared to control subjects (20.2 ± 7.3 vs 12.3 ± 2.8 ng/mmol creatinine; P = 0.020). Mean carotid IMT was correlated with 15-F2t-isoprostane (r = 0.532; P < 0.001) and with the apnea–hypopnea index (r = 0.345; P = 0.029). 15-F2t-Isoprostane level was related to the night time spent at SaO2 < 90% (r = 0.478; P = 0.002), the apnea–hypopnea index (r = 0.465; P = 0.003), and the mean nocturnal SaO2 (r = − 0.424; P = 0.007). These results showed a relationship between lipid peroxidation, carotid intima–media thickness, and intermittent hypoxia in nonobese OSA patients, thus reinforcing the hypothesis that oxidative stress could be involved in the early atherosclerotic process.

Section snippets

Subjects and methods

All subjects underwent an overnight polysomnography in the sleep laboratory of Grenoble University Hospital to evaluate sleep breathing patterns. Upon waking, urinary and fasting blood samples were obtained and quickly sent to the laboratory for treatment and analysis. This was followed by arterial blood gas analysis and by ultrasonography for carotid IMT assessment. None of the patients had known coronary artery disease, hypertension, diabetes mellitus, or vasoactive treatment. None of the

Results

Patients were divided into three groups according to their AHI: control subjects (n = 10) had an AHI < 15, nonobese mild-to-moderate OSA patients (n = 19) had an AHI between 15 and 30, and nonobese severe OSA patients (n = 12) had an AHI ≥ 30 events/h of sleep. Anthropometric and biological parameters as well as clinical history of the three groups of patients are shown in Table 1. Patients were similar regarding age, BMI, anthropometric measurements, and glucolipidic parameters. Overall, there was no

Discussion

In this study, we have shown that urinary 15-F2t-isoprostane level was higher in nonobese severe OSA patients than in control patients. There was a relationship between urinary 15-F2t-isoprostane excretion and carotid remodeling and both were correlated with sleep apnea severity. This is of particular interest because it reinforces the hypothesis that intermittent hypoxia-induced lipid peroxidation could contribute to the deleterious cardiovascular consequences of OSA.

Isoprostanes are generated

Perspectives and conclusion

This study has shown that overnight urinary 15-F2t-isoprostane level is increased and correlated with the severity of oxygen desaturation and carotid IMT in nonobese obstructive sleep apnea patients. However, even in lean individuals, not only oxidative stress but also inflammation, dyslipidemia, and insulin resistance can be responsible for deleterious cardiovascular and metabolic consequences of OSA.

Treating OSA patients with various antioxidant drugs can potentially lower isoprostane

Acknowledgments

We thank Dominique Blondelle for her technical support in this work.

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