Impact of Nasal Continuous Positive Airway Pressure Therapy on Markers of Platelet Activation in Patients with Obstructive Sleep Apnea

Abstract

Background: Considerable evidence implicates CD40 signaling in the pathogenesis of atheromas. Exposure to CD40 ligand induces platelet-leukocyte conjugation, a heightened expression of inflammatory cytokines, matrix-degrading enzymes, and procoagulant factors. Objectives: To investigate the association between plasma soluble CD40 ligand (sCD40L) and platelet-monocyte aggregates in patients with obstructive sleep apnea (OSA) and to determine whether treatment of OSA with nasal continuous positive airway pressure (nCPAP) alters this relationship. Methods: Twelve patients with OSA who were free of other diseases and 12 healthy controls matched for age, gender, and body mass index had blood drawn for sCD40L and platelet-monocyte aggregate measurements. A repeat assessment was obtained following 8 weeks of nCPAP therapy. Results: Subjects with OSA had significantly higher plasma sCD40L levels and exhibited elevated platelet-monocyte aggregates compared to nonapneic subjects (7.6 ± 4.3 versus 1.7 ± 1.1, p = 0.004; and 41.3 ± 23.7 versus 6.7 ± 4.9, p = 0.001, respectively). Both parameters correlated positively with the percentage of time spent with SpO₂ <90% (r = 0.69, p = 0.01 and r = 0.6, p = 0.03, respectively). After 8 weeks of nCPAP treatment, sCD40 levels declined by 47% (p = 0.003) and platelet-monocyte aggregates by 42% (p = 0.002). None of the controls showed any changes in either sCD40L or platelet- monocyte aggregates after nCPAP therapy. Conclusions: OSA is associated with upregulation of circulating sCD40L levels and platelet-monocyte aggregation that may account for the increased incidence of cardiovascular events in this population. Treatment with nCPAP may alleviate this risk.

Complicated Course of Ischemic Heart Disease in a Patient With Obstructive Sleep Apnea

“…In the same manner, Doherty et al 15 have confirmed reduced cardiovascular mortality in patients with treated OSA in comparison with the control group. CPAP treatment leads to a decrease in thrombocyte activation and this may explain the stabilization of the health status of our patient following long-term use of the CPAP device 16 . Cassar et al 17 showed that patients with OSA who are treated with CPAP have a lower incidence of post PCI cardiac death in comparison with patients without treatment.…”

Withdrawal of Continuous Positive Airway Pressure Therapy for 2 Weeks in Obstructive Sleep Apnoea Patients Results in Increased Circulating Platelet and Leucocyte-Derived Microvesicles

“…Although there is a paucity of robust randomised and controlled studies and conflicting data, CPAP therapy and the consequent reduction in intermittent hypoxia and catecholamine levels may reduce platelet activation [11] and inflammation [12], processes thought to trigger MV release, thus potentially explaining the changes in circulating MVs found with the commencing or withdrawal of CPAP. Thus, CPAP therapy may reduce the risk of patients developing co-morbidities such as cardiovascular disease [13], and if this link is firmly established, then lowered circulating MVs may be a part of the explanation.…”

Continuous Positive Airway Pressure and Platelet Activation in Obstructive Sleep Apnoea

“…ma sCD40L levels and platelet-monocyte aggregates in sleep apnoea patients and that this is correlated with hypoxia severity and that these effects are ameliorated by continuous positive airway pressure (CPAP), a treatment that relieves the obstruction and the hypoxia [8] . Previous studies failed to find an effect of CPAP on platelet aggregation in sleep apnoea patients [12,13] , but several other studies have reported increased platelet activation and aggregation [14][15][16][17][18] .…”

“…The interaction of CD40L with its receptor CD40 plays a major role in inflammation, and increased levels of Obstructive sleep apnoea (OSA) is a complex condition associated with a number of cardiovascular sequelae including hypertension (both systemic and pulmonary), congestive heart failure, arrhythmias, myocardial infarction and stroke [1][2][3][4][5][6] . However, the recent American Heart Association/American College of Cardiology scientific statement on sleep apnoea suggests that there is a paucity of data for a causal role of OSA in cardiovascular disease [7] , which underlines the importance of studies such as that of Akinnusi et al [8] in this edition of Respiration that are aimed at understanding the pathophysiology of OSA. The condition is caused by multiple episodes of airway collapse during the course of sleep which causes large oscillations in intrathoracic pressure and in arterial blood gases.…”

“…Recently CPAP has been shown to improve endothelial function [28] and to reduce blood pressure [29,30] , sympathetic tone [31] and platelet activation [8,18] in patients with OSA. Thus, CPAP clearly reduces many of the risk factors for adverse cardiac events, although the exact mechanism is not clear.…”