title: The influence of intermittent hypoxemia on platelet activation in obese patients with obstructive sleep apnea.
abstract: OBJECTIVE
  Literature regarding platelet function in obstructive sleep apnea (OSA) has considerable limitations. Given the central role of platelets in atherothrombosis and the known cardiovascular risk of OSA, we hypothesized that OSA severity is predictive of platelet function, independent of known comorbidities.
  
  
  METHODS
  Obese subjects, without comorbidities, underwent overnight, in-lab polysomnography. The following morning, 5 biomarkers of platelet activation were measured by whole-blood flow cytometry at baseline and in response to agonists (no stimulation, stimulation with 5 μM ADP agonist, and stimulation with 20 μM ADP agonist): platelet surface P-selectin, activated glycoprotein (GP) IIb/IIIa, and GPIb receptor expression, platelet-monocyte aggregation (PMA) and platelet-neutrophil aggregation (PNA).
  
  
  RESULTS
  Of the 77 subjects, 47 were diagnosed with OSA (median apnea-hypopnea index [AHI] of 24.7 ± 28.1/h in subjects with OSA and 3.0 ± 3.9/h in subjects without OSA, p < 0.001). The groups were matched for body mass index, with a mean body mass index of 40.3 ± 9.6 kg/m(2) in subjects with OSA and 38.9 ± 6.0 kg/m(2) in subjects without OSA (p = 0.48). A comparison of time spent with an oxygen saturation of less than 90% showed that subjects who had 1 minute or more of desaturation time per hour of sleep had lower GPIb fluorescence in circulating platelets, as compared with those subjects who had less than 1 minute of desaturation time per hour of sleep; similar findings were observed following 5 μM and 20 μM of ADP stimulation, as compared with control vehicle, suggesting higher levels of circulating platelet activity. In multivariate analyses, only nocturnal hypoxemia and female sex predicted agonist response. Platelet surface P-selectin, platelet surface-activated GPIIb/IIIa, PMA, and PNA were not significantly correlated with markers of OSA.
  
  
  CONCLUSIONS
  In obese patients with OSA, platelet activation is associated with greater levels of oxygen desaturation, compared with matched control subjects. Metrics other than AHI (e.g., hypoxemia) may determine OSA-related thrombotic risk.
authors.affiliation: Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. srahangdale@northshore.org
authors.forename: Shilpa
authors.initials: S
authors.lastname: Rahangdale
authors.forename: Susie Yim
authors.initials: SY
authors.lastname: Yeh
authors.forename: Victor
authors.initials: V
authors.lastname: Novack
authors.forename: Karen
authors.initials: K
authors.lastname: Stevenson
authors.forename: Marc R
authors.initials: MR
authors.lastname: Barnard
authors.forename: Mark I
authors.initials: MI
authors.lastname: Furman
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Frelinger
authors.forename: Alan D
authors.initials: AD
authors.lastname: Michelson
authors.forename: Atul
authors.initials: A
authors.lastname: Malhotra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D016009:Chi-Square Distribution; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000860:Hypoxia / Q000097:blood* / Q000209:etiology; D008297:Male; D009765:Obesity / Q000097:blood* / Q000150:complications; D015539:Platelet Activation / Q000502:physiology*; D017286:Polysomnography; D020181:Sleep Apnea, Obstructive / Q000097:blood* / Q000150:complications; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D015415:Biomarkers