Department of Neurology, Weill Cornell Medicine, New York, NY, 10065, USA.
Department of Medicine, Weill Cornell Medicine, New York, NY, 10065, USA.
Sleep Breath. 2020 Dec;24(4):1537-1547. doi: 10.1007/s11325-020-02021-4. Epub 2020 Feb 8.
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.
NCT00859950.
阻塞性睡眠呼吸暂停（OSA）与中风和其他心血管疾病的风险增加独立相关。由于激活的血小板在心血管疾病中起重要作用，本研究的目的是确定间歇性夜间低氧血症的 OSA 患者的血小板反应性是否发生改变。
31 名受试者无高血压或心血管疾病且未服用药物，参与了这项研究。根据整夜多导睡眠图记录的与 OSA 相关的氧减指数（ODI）将受试者分层。通过监测血小板聚集和三磷酸腺苷（ATP）分泌来测量血小板对广泛的激动剂（胶原、凝血酶、蛋白酶激活受体 1 六肽、肾上腺素、ADP）的反应性。通过流式细胞术定量血小板活化标志物 CD154（CD40L）和 CD62P（P-选择素）以及血小板-单核细胞聚集体（PMA）的表达。
与低氧血症程度较轻的患者（ODI<15）相比，伴有明显间歇性低氧血症（ODI≥15）的 OSA 患者肾上腺素诱导的血小板聚集显著降低（曲线下面积，p=0.01）。此外，ODI≥15 的 OSA 患者的凝血酶诱导的血小板聚集（p=0.02）和 CD40L 血小板表面表达（p=0.05）降低。各组之间对其他激动剂、CD62P 血小板表面表达和 PMA 水平的血小板反应没有显著差异。在间歇性夜间低氧血症的 OSA 患者中，肾上腺素和凝血酶的血小板反应降低，CD40L 表面标志物表达降低，这表明其血小板处于激活状态。
在有间歇性夜间低氧血症的健康受试者中，存在由于潜在的 OSA 引起的血小板过度激活。这种血管中的血栓前环境可能是血栓形成和心血管疾病发展的关键因素。
NCT00859950。
