Ana C Krieger1,2, Ranjini Anand3,4,5, Evelyn Hernandez-Rosa3,4,6, Allison Maidman2,7, Sara Milrad2,8, Miles Q DeGrazia2, Alexander J Choi2,9, Clara Oromendia10,11, Aaron J Marcus3,4,12, Joan H F Drosopoulos13,14. 1. Department of Neurology, Weill Cornell Medicine, New York, NY, 10065, USA. 2. Department of Medicine, Weill Cornell Medicine, New York, NY, 10065, USA. 3. Thrombosis Research Laboratory, Research Service, VA New York Harbor Healthcare System, 423 East 23rd Street, Room 13026W, New York, NY, 10010, USA. 4. Department of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, 10065, USA. 5. Medical Department, PureSinse Inc., Mississauga, ON, L4W 5K4, Canada. 6. Department of Pathology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, 10032, USA. 7. Department of Pediatrics, NYU Langone Hospital, Brooklyn, NY, 11220, USA. 8. Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, 33431, USA. 9. University of Michigan Medical School, Ann Arbor, MI, 48109, USA. 10. Department of Healthcare Policy and Research, Division of Biostatistics and Epidemiology, Weill Cornell Medicine, New York, NY, 10065, USA. 11. Project Rōnin Inc., San Mateo, CA, 94401, USA. 12. Department of Pathology and Laboratory Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, 10065, USA. 13. Thrombosis Research Laboratory, Research Service, VA New York Harbor Healthcare System, 423 East 23rd Street, Room 13026W, New York, NY, 10010, USA. jhfliess@med.cornell.edu. 14. Department of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, 10065, USA. jhfliess@med.cornell.edu.
Abstract
PURPOSE: Obstructive sleep apnea (OSA) is independently associated with increased risk for stroke and other cardiovascular diseases. Since activated platelets play an important role in cardiovascular disease, the objective of this study was to determine whether platelet reactivity was altered in OSA subjects with intermittent nocturnal hypoxemia. METHODS: Thirty-one subjects, without hypertension or cardiovascular disease and not taking medication, participated in the study. Subjects were stratified based on OSA-related oxygen desaturation index (ODI) recorded during overnight polysomnography. Platelet reactivity to a broad panel of agonists (collagen, thrombin, protease-activated receptor1 hexapeptide, epinephrine, ADP) was measured by monitoring platelet aggregation and ATP secretion. Expression of platelet activation markers CD154 (CD40L) and CD62P (P-selectin) and platelet-monocyte aggregates (PMA) was quantified by flow cytometry. RESULTS: Epinephrine-induced platelet aggregation was substantially decreased in OSA subjects with significant intermittent hypoxemia (ODI ≥ 15) compared with subjects with milder hypoxemia levels (ODI < 15) (area under curve, p = 0.01). In addition, OSA subjects with ODI ≥ 15 exhibited decreased thrombin-induced platelet aggregation (p = 0.02) and CD40L platelet surface expression (p = 0.05). Platelet responses to the other agonists, CD62P platelet surface expression, and PMA levels were not significantly different between groups. Reduction in platelet responses to epinephrine and thrombin, and decreased CD40L surface marker expression in significant hypoxemic OSA individuals, is consistent with their platelets being in an activated state. CONCLUSIONS: Increased platelet activation was present in otherwise healthy subjects with intermittent nocturnal hypoxemia due to underlying OSA. This prothrombotic milieu in the vasculature is likely a key contributing factor toward development of thrombosis and cardiovascular disease. TRIAL REGISTRATION: NCT00859950.
PURPOSE: Obstructive sleep apnea (OSA) is independently associated with increased risk for stroke and other cardiovascular diseases. Since activated platelets play an important role in cardiovascular disease, the objective of this study was to determine whether platelet reactivity was altered in OSA subjects with intermittent nocturnal hypoxemia. METHODS: Thirty-one subjects, without hypertension or cardiovascular disease and not taking medication, participated in the study. Subjects were stratified based on OSA-related oxygen desaturation index (ODI) recorded during overnight polysomnography. Platelet reactivity to a broad panel of agonists (collagen, thrombin, protease-activated receptor1 hexapeptide, epinephrine, ADP) was measured by monitoring platelet aggregation and ATP secretion. Expression of platelet activation markers CD154 (CD40L) and CD62P (P-selectin) and platelet-monocyte aggregates (PMA) was quantified by flow cytometry. RESULTS:Epinephrine-induced platelet aggregation was substantially decreased in OSA subjects with significant intermittent hypoxemia (ODI ≥ 15) compared with subjects with milder hypoxemia levels (ODI < 15) (area under curve, p = 0.01). In addition, OSA subjects with ODI ≥ 15 exhibited decreased thrombin-induced platelet aggregation (p = 0.02) and CD40L platelet surface expression (p = 0.05). Platelet responses to the other agonists, CD62P platelet surface expression, and PMA levels were not significantly different between groups. Reduction in platelet responses to epinephrine and thrombin, and decreased CD40L surface marker expression in significant hypoxemic OSA individuals, is consistent with their platelets being in an activated state. CONCLUSIONS: Increased platelet activation was present in otherwise healthy subjects with intermittent nocturnal hypoxemia due to underlying OSA. This prothrombotic milieu in the vasculature is likely a key contributing factor toward development of thrombosis and cardiovascular disease. TRIAL REGISTRATION: NCT00859950.
Authors: Wael Alkhiary; Nesreen E Morsy; Aida M Yousef; Amr Mohamed El-Saddik; Eman O Arram Journal: Clin Appl Thromb Hemost Date: 2015-08-14 Impact factor: 2.389
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