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.
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.
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.
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.
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This work is dedicated in memory of our colleague and mentor Dr. Aaron J. Marcus, an exceptionally talented scientist and expert in thrombosis and platelet dysfunction, who made enormous contributions to the field of Hematology and was continuously funded by the National Institutes of Health for over 50 years.
This work was supported by National Institutes of Health grants HL089521 (A.J.M.) and HL047073 (A.J.M., J.H.F.D.), a Merit Review grant I01BX002122 from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Program (A.J.M., J.H.F.D.), and a National Heart Lung and Blood Institute grant K23 HL094358 (A.C.K.). We also received support from the Clinical Translational Research Center at Rockefeller University Hospital, grant UL1 TR001866 from the National Center for Advancing Translational Sciences, National Institutes of Health and Clinical and Translational Science Award programs, and grant UL1 TR000457-06 from the Clinical and Translational Science Center at Weill Cornell Medicine.
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The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Krieger, A.C., Anand, R., Hernandez-Rosa, E. et al. Increased platelet activation in sleep apnea subjects with intermittent hypoxemia. Sleep Breath 24, 1537–1547 (2020). https://doi.org/10.1007/s11325-020-02021-4