Nature and Science of Sleep (Jun 2018)

Use of blood biomarkers to screen for obstructive sleep apnea

  • Fleming WE,
  • Holty JEC,
  • Bogan RK,
  • Hwang D,
  • Ferouz-Colborn AS,
  • Budhiraja R,
  • Redline S,
  • Mensah-Osman E,
  • Osman NI,
  • Li Q,
  • Azad A,
  • Podolak S,
  • Samoszuk MK,
  • Cruz AB,
  • Bai Y,
  • Lu J,
  • Riley JS,
  • Southwick PC

Journal volume & issue
Vol. Volume 10
pp. 159 – 167

Abstract

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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 Southwick8 1Sleep Center Orange County, Irvine, CA, USA; 2Stanford Medical School, VA Palo Alto Health Care System, Pulmonary, Critical Care and Sleep Medicine Section, Palo Alto, CA, USA; 3SleepMed Inc., Bogan Sleep Consultants, LLC, Columbia, SC, USA; 4Sleep Medicine Department, Southern California Permanente Medical Group, Kaiser Permanente, Fontana Medical Center, Fontana, CA, USA; 5Division of Sleep Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA; 6EENA Comprehensive Neurology and Sleep Center, Boynton Beach, FL, USA; 7South Bend Medical Foundation, New Technology and Test Development, South Bend, IN, USA; 8Clinical Research Department, Beckman Coulter, Inc., Brea, CA, USAPurpose: 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: obstructive sleep apnea, OSA, screening, diagnosis, biomarkers, CRP, HbA1c, erythropoietin, EPO, uric acid, IL-6 

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