Obstructive sleep apnea (OSA) is known to be an independent cardiovascular risk factor. Among arousal from sleep, increased thoracic pressure and enhanced sympathetic activation, intermittent hypoxia is now considered as one of the most important pathophysiological mechanisms contributing to the development of endothelial dysfunction. Nevertheless, not much is known about blood components, which justifies the current review. This review focuses on molecular mechanisms triggered by sleep apnea. The recurrent periods of hypoxemia followed by reoxygenation promote reactive oxygen species (ROS) overproduction and increase inflammatory response. In this review paper we also intend to summarize the effect of treatment with continuous positive airway pressure (CPAP) on changes in the profile of the endothelial function and its subsequent potential clinical advantage in lowering cardiovascular risk in other comorbidities such as diabetes, atherosclerosis, hypertension, atrial fibrillation. Moreover, this paper is aimed at explaining how the presence of OSA may affect platelet function and exert effects on rheological activity of erythrocytes, which could also be the key to explaining an increased risk of stroke.

Coronary artery disease (CAD) and stroke are the most common and serious long-term complications of hypertension. Acetylsalicylic acid (ASA) significantly reduces their incidence and cardiovascular mortality. The RAAS activation plays an important role in pathogenesis of CVD, resulting in increased vascular resistance, proliferation of vascular-smooth-muscle-cells, and cardiac hypertrophy. Drugs acting on the renin-angiotensin-aldosterone system (RAAS) are demonstrated to reduce cardiovascular events in population with cardiovascular disease (CVD). The cyclooxygenase inhibitors limit the beneficial effect of RAAS-inhibitors, which in turn may be important in subjects with hypertension, CAD, and congestive heart failure. These observations apply to most of nonsteroidal anti-inflammatory drugs and ASA at high doses. Nevertheless, there is no strong evidence confirming presence of similar effects of cardioprotective ASA doses. The benefit of combined therapy with low-doses of ASA is—in some cases—significantly higher than that of monotherapy. So far, the significance of ASA in optimizing the pharmacotherapy remains not fully established. A better understanding of its influence on the particular CVD should contribute to more precise identification of patients in whom benefits of ASA outweigh the complication risk. This brief review summarizes the data regarding usefulness and safety of the ASA combination with drugs acting directly on the RAAS.

Introduction: Endothelial dysfunction resulting from decreased nitric oxide (NO) bioavailability is an important mechanism that increases cardiovascular risk in subjects with obstructive sleep apnea (OSA). NO is produced by nitric oxide synthase (NOS) in a reaction that converts L-arginine to L-citrulline. Asymmetric-dimethylarginine (ADMA) is created by L-arginine and is a naturally occurring competitive inhibitor of nitric oxide synthase (NOS). The aim of our study was to verify if erythrocytes could play a role in the storage and accumulation of ADMA in OSA patients. The crosstalk between erythrocyte-ADMA, SDMA, L-arginine, and L-citrulline levels and endothelial function was investigated in OSA subjects both at baseline and prospectively following 1-year CPAP (continuous positive airway pressure) treatment. Material and Methods: A total of 46 subjects with OSA were enrolled in this study and divided into two groups: those with moderate-to-severe OSA and those with mild or no OSA. A physical examination was followed by blood collection for the assessment of biochemical cardiovascular risk factors and the nitric oxide bioavailability parameters both in plasma and erythrocytes. Vasodilative endothelial function was assessed using Laser Doppler Flowmetry (LDF). Results: No significant changes regarding the NO pathway metabolites were noted apart from the plasma L-citrulline concentration, which was decreased in patients with OSA (26.9 ± 7.4 vs. 33.1 ± 9.4 μM, p < 0.05). The erythrocyte ADMA concentration was lower than in plasma irrespective of the presence of OSA (0.33 ± 0.12 vs. 0.45 ± 0.08 μM in OSA, p < 0.05 and 0.33 ± 0.1 vs. 0.45 ± 0.07 μM in the control, p < 0.05). No significant changes regarding the LDF were found. CPAP treatment did not change the levels of NO metabolites in the erythrocytes. Conclusions: The erythrocyte pool of the NO metabolic pathway intermediates does not depend on OSA and its treatment, whereas the erythrocytes could constitute a high-volume buffer in their storage Hence, the results from this prospective study are a step forward in understanding the role of the erythrocyte compartment and the intra-erythrocyte pathways regulating NO bioavailability and paracrine endothelial function in the hypoxia-reoxygenation setting, such as obstructive sleep apnea.

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