Urine 5-Eicosatetraenoic Acids as Diagnostic Markers for Obstructive Sleep Apnea
Abstract
:1. Introduction
2. Materials and Methods
2.1. Pilot, Verification, and Validation Cohorts
2.2. Patients and Exclusion Criteria in the Pilot and Verification Cohorts
2.3. Patients in the Validation Cohorts
2.4. Cell Culture
2.5. Animals and Hypoxic Exposures
2.6. Metabolite Analyses Using LC/Q-TOF MS
2.7. Quantification of Biomarkers
2.8. Immunoblotting
2.9. Glutathione Peroxidase Activity
2.10. siRNA and Plasmid DNA Transfection
2.11. Statistics
3. Results
3.1. Characteristics of the Study Population
3.2. Identification of Urine 5-HETE as an OSA Marker
3.3. Analyses of Metabolites in the 5-Lipoxygenase Pathway
3.4. Verification and Validation of 5-HETE and 5-oxoETE as Diagnostic Markers for OSA
3.5. Mechanism Study in Human Mononuclear Cells
3.6. Verification of 5-HETE and 5-oxoETE as Intermittent Hypoxia Markers in Mice
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Pilot Cohort | Verification Cohort | |||||
---|---|---|---|---|---|---|
Characteristic | Control | Patients with OSA | p Value | Control | Patients with OSA | p Value |
n | 38 | 20 | - | 25 | 60 | - |
Age (yrs) | 32.0 ± 10.9 | 39.4 ± 13.5 | 0.040 | 36.4 ± 10.3 | 38.8 ± 7.4 | 0.067 |
BMI (kg/m2) † | 21.9 ± 3.1 | 25.1 ± 3.0 | <0.001 | 24.8 ± 1.9 | 25.9 ± 2.8 | 0.068 |
Neck circumference (cm) | 34.7 ± 3.2 | 38.0 ± 3.1 | <0.001 | 38.4 ± 1.9 | 39.0 ± 2.3 | 0.240 |
Waist Hip Ratio | 0.84 ± 0.05 | 0.93 ± 0.07 | <0.001 | 0.89 ± 0.05 | 0.92 ± 0.05 | 0.083 |
Systolic blood pressure (mmHg) | 123.0 ± 16.1 | 126.0 ± 15.5 | 0.413 | 128.7 ± 18.8 | 135.7 ± 20.1 | 0.291 |
Diastolic blood pressure (mmHg) | 79.1 ± 10.5 | 80.3 ± 10.5 | 0.313 | 81.8 ± 13.9 | 87.6 ± 16.1 | 0.060 |
Epworth sleepiness scale | 7.4 ± 4.4 | 11.0 ± 4.1 | 0.006 | 7.4 ± 4.6 | 10.6 ± 4.6 | 0.010 |
Apnea-hypopnea index (events/h) | 1.4 ± 1.6 | 43.7 ± 24.1 | <0.001 | 1.4 ± 1.5 | 32.8 ± 22.5 | <0.001 |
RDI (events/h) | 7.9 ± 5.9 | 54.3 ± 22.1 | <0.001 | 8.6 ± 6.8 | 32.8 ± 22.5 | <0.001 |
Mean SaO2 (%) | 96.7 ± 0.8 | 94.7 ± 1.6 | <0.001 | 96.6 ± 1.1 | 94.3 ± 2.1 | <0.001 |
Minimal SaO2 (%) | 92.7 ± 2.5 | 80.0 ± 9.0 | <0.001 | 92.3 ± 2.5 | 79.3 ± 8.5 | <0.001 |
SaO2 < 90% (% Total Sleep Time) | 0.01 ± 0.03 | 6.32 ± 9.2 | <0.001 | 0.01 ± 0.03 | 10.7 ± 16.8 | <0.001 |
Oxygen desaturation index (events/hr) | 4.2 ± 12.8 | 41.4 ± 25.1 | <0.001 | 3.0 ± 3.0 | 37.3 ± 22.6 | <0.001 |
Validation Cohort (n = 120) | |||||
---|---|---|---|---|---|
Characteristic | Control | Mild OSA | Moderate OSA | Severe OSA | p Value ** |
n | 18 | 28 | 27 | 47 | - |
M:F (n) | 14:4 | 21:7 | 20:7 | 42:5 | - |
Age (yr) | 35.8 ± 13.9 | 40.6 ± 12.6 | 45.5 ± 15.3 | 44.7 ± 14.1 | 0.080 |
BMI (kg/m2) † | 22.6 ± 3.6 | 24.9 ± 2.8 | 24.9 ± 3.2 | 27.1 ± 3.8 | <0.001 |
Hypertension (n) | 4 | 4 | 5 | 21 | - |
Diabetes (n) | 1 | 0 | 1 | 3 | - |
Smoking (n) | 6 | 2 | 6 | 16 | - |
Systolic blood pressure (mmHg) | 133.4 ± 16.2 | 128.1 ± 12.8 | 129.4 ± 14.9 | 138.1 ± 21.6 | 0.092 |
Diastolic blood pressure (mmHg) | 81.1 ± 11.8 | 78.0 ± 8.6 | 79.3 ± 8.6 | 85.3 ± 14.7 | 0.060 |
Apnea-hypopnea index (events/h) | 2.3 ± 1.4 | 9.8 ± 3.2 | 22.2 ± 4.5 | 52.6 ± 20.2 | <0.001 |
Mean SaO2 (%) | 97.0 ± 1.0 | 96.1 ± 0.8 | 96.0 ± 1.1 | 94.2 ± 2.7 | <0.001 |
Minimal SaO2 (%) | 90.9 ± 3.6 | 88.6 ± 3.7 | 85.7 ± 4.1 | 78.4 ± 8.3 | <0.001 |
5-HETE (ng/mg creatinine) | 25.7 ± 9.4 | 28.4 ± 8.6 | 42.2 ± 16.6 | 45.9 ± 21.2 | <0.001 |
5-oxoETE (ng/mg creatinine) | 23.8 ± 7.6 | 23.8 ± 6.8 | 36.3 ± 14.7 | 38.6 ± 18.2 | <0.001 |
Estimated Odds Ratio (95% CI) | |||||
---|---|---|---|---|---|
No. of Subjects | Unadjusted | p Value | Multivariate a | p Value | |
5-HETE (<27.5 ng/mg) | 39 | reference | reference | ||
5-HETE (≥27.5 ng/mg) | 81 | 7.60 (2.47–23.37) | <0.001 | 11.71 (2.55–48.58) | 0.001 |
5-oxoETE (<24.0 ng/mg) | 44 | reference | reference | ||
5-oxoETE (≥24.0 ng/mg) | 76 | 3.29 (1.17–9.25) | 0.024 | 4.71 (1.29–17.24) | 0.019 |
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Shin, H.-W.; Cho, K.; Rhee, C.-S.; Hong, I.-H.; Cho, S.H.; Kim, S.W.; Kim, J.; So, D.; Cho, J.-Y.; Park, J.-W. Urine 5-Eicosatetraenoic Acids as Diagnostic Markers for Obstructive Sleep Apnea. Antioxidants 2021, 10, 1242. https://doi.org/10.3390/antiox10081242
Shin H-W, Cho K, Rhee C-S, Hong I-H, Cho SH, Kim SW, Kim J, So D, Cho J-Y, Park J-W. Urine 5-Eicosatetraenoic Acids as Diagnostic Markers for Obstructive Sleep Apnea. Antioxidants. 2021; 10(8):1242. https://doi.org/10.3390/antiox10081242
Chicago/Turabian StyleShin, Hyun-Woo, Kumsun Cho, Chae-Seo Rhee, Il-Hee Hong, Seok Hyun Cho, Sung Wan Kim, Jiyoung Kim, Daeho So, Joo-Youn Cho, and Jong-Wan Park. 2021. "Urine 5-Eicosatetraenoic Acids as Diagnostic Markers for Obstructive Sleep Apnea" Antioxidants 10, no. 8: 1242. https://doi.org/10.3390/antiox10081242
APA StyleShin, H.-W., Cho, K., Rhee, C.-S., Hong, I.-H., Cho, S. H., Kim, S. W., Kim, J., So, D., Cho, J.-Y., & Park, J.-W. (2021). Urine 5-Eicosatetraenoic Acids as Diagnostic Markers for Obstructive Sleep Apnea. Antioxidants, 10(8), 1242. https://doi.org/10.3390/antiox10081242