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Nat Sci Sleep. 2018 Jun 14;10:159-167. doi: 10.2147/NSS.S164488. eCollection 2018.

Use of blood biomarkers to screen for obstructive sleep apnea.

Author information

Sleep Center Orange County, Irvine, CA, USA.
Stanford Medical School, VA Palo Alto Health Care System, Pulmonary, Critical Care and Sleep Medicine Section, Palo Alto, CA, USA.
SleepMed Inc., Bogan Sleep Consultants, LLC, Columbia, SC, USA.
Sleep Medicine Department, Southern California Permanente Medical Group, Kaiser Permanente, Fontana Medical Center, Fontana, CA, USA.
Division of Sleep Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
EENA Comprehensive Neurology and Sleep Center, Boynton Beach, FL, USA.
South Bend Medical Foundation, New Technology and Test Development, South Bend, IN, USA.
Clinical Research Department, Beckman Coulter, Inc., Brea, CA, USA.



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).


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%).


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.


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

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.

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