Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jun 14:10:159-167.
doi: 10.2147/NSS.S164488. eCollection 2018.

Use of blood biomarkers to screen for obstructive sleep apnea

Wesley Elon Fleming  1 , Jon-Erik C Holty  2 , Richard K Bogan  3 , Dennis Hwang  4 , Aliya S Ferouz-Colborn  4 , Rohit Budhiraja  5 , Susan Redline  5 , Edith Mensah-Osman  6 , Nadir Ishag Osman  6 , Qing Li  7 , Armaghan Azad  1 , Susann Podolak  1 , Michael K Samoszuk  8 , Amabelle B Cruz  8 , Yang Bai  8 , Jiuliu Lu  8 , John S Riley  8 , Paula C Southwick  8
Affiliations

Use of blood biomarkers to screen for obstructive sleep apnea

Wesley Elon Fleming et al. Nat Sci Sleep. .

Abstract

Purpose: Obstructive sleep apnea (OSA) is a highly prevalent disorder associated with increased risk for cardiovascular disease, diabetes, and other chronic conditions. Unfortunately, up to 90% of individuals with OSA remain without a diagnosis or therapy. We assess the relationship between OSA and blood biomarkers, and test the hypothesis that combinations of markers provide a characteristic OSA signature with diagnostic screening value. This validation study was conducted in an independent cohort in order to replicate findings from a prior feasibility study.

Patients and methods: This multicenter prospective study consecutively enrolled adult male subjects with clinically suspected OSA. All subjects underwent overnight sleep studies. An asymptomatic control group was also obtained. Five biomarkers were tested: glycated hemoglobin (HbA1c), C-reactive protein (CRP), uric acid, erythropoietin (EPO), and interleukin-6 (IL-6).

Results: The study enrolled 264 subjects. The combination of HbA1c+CRP+EPO (area under the curve 0.78) was superior to the Epworth Sleepiness Scale (ESS; 0.53) and STOP-Bang (0.70) questionnaires. In non-obese subjects, the combination of biomarkers (0.75) was superior to body mass index (BMI; 0.61). Sensitivity and specificity results, respectively, were: HbA1c+CRP+EPO (81% and 60%), ESS (78% and 19%), STOP-Bang (75% and 52%), BMI (81% and 56%), and BMI in non-obese patients (81% and 38%).

Conclusion: We verify our hypothesis and replicate our prior feasibility findings that OSA is associated with a characteristic signature cluster of biomarker changes in men. Concurrent elevations of HbA1c, CRP, and EPO levels should generate a high suspicion of OSA and may have utility as an OSA screening tool. Biomarker combinations correlate with OSA severity and, therefore, may assist sleep centers in identifying and triaging higher risk patients for sleep study diagnosis and treatment.

Keywords: CRP; EPO; HbA1c; IL-6; OSA; biomarkers; diagnosis; erythropoietin; obstructive sleep apnea; screening; uric acid.

PubMed Disclaimer

Conflict of interest statement

Disclosure This work was supported by research grant funding from Beckman Coulter, Inc. (Brea, CA, USA) provided to the respective institutions of Drs. Fleming, Holty, Bogan, Hwang, Ferouz-Colborn, Budhiraja, Redline, Mensah-Osman, Osman, and Li. Drs. Samoszuk, Riley, and Southwick, as well as Ms. Cruz, Mr. Bai, and Mr. Lu are employed by Beckman Coulter. Dr. Azad and Ms. Podolak report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Probability of moderate/severe OSA by CRP and HbA1c values in combination. Notes: When CRP was ≥0.2 mg/dL and HbA1c ≥5.7%, the probability of moderate/severe OSA was 81%. When neither marker was elevated, the probability was 37%, which was less than half that observed when both markers are elevated. Abbreviations: CRP, C-reactive protein; OSA, obstructive sleep apnea.
Figure 2
Figure 2
ROC curves for detection of OSA in non-obese subjects (BMI <30). Notes: In non-obese subjects, the AUC for the combination of biomarkers (0.75) was higher than BMI (0.61), as well as the STOP-Bang (0.66) and ESS (0.56) scores. Abbreviations: AUC, area under the curve; BMI, body mass index; BP, blood pressure; CRP, C-reactive protein; EPO, erythropoietin; ESS, Epworth Sleepiness Scale; FPF, false positive fraction; OSA, obstructive sleep apnea; ROC, receiver operating characteristic; TPF, true positive fraction.
See this image and copyright information in PMC

Comment in

References

    1. Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol. 2013;177(9):1006–1014. - PMC - PubMed
    1. Watson NF. Health care savings: the economic value of diagnostic and therapeutic care for obstructive sleep apnea. J Clin Sleep Med. 2016;12(8):1075–1077. - PMC - PubMed
    1. Bousquet J, Khaltaev N, World Health Organization, editors. Global surveillance, prevention and control of chronic respiratory diseases: a comprehensive approach. Geneva: WHO; 2007. [Accessed February 03, 2018]. Available from: http://www.who.int/gard/publications/GARD%20Book%202007.pdf.
    1. Kapur V, Strohl KP, Redline S, Iber C, O’Connor G, Nieto J. Underdiagnosis of sleep apnea syndrome in U.S. communities. Sleep Breath. 2002;6(2):49–54. - PubMed
    1. Young T, Evans L, Finn L, Palta M. Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle-aged men and women. Sleep. 1997;20(9):705–706. - PubMed