## 4 Discussion  
Generally, a sleep disorder causes a worsening of life quality and increases morbidity and mortality in a large part of patients. In particular, patients with OSA often have comorbid conditions, which can contribute to the onset of more serious clinical situations. Several studies have reported the presence of common comorbidities with OSA, such as cardiovascular disease (CVD), cognitive impairment, psychiatric problems (including depression), diabetes and obesity, although the etiopathogenesis pathway is not completely understood, therefore it is not clear if a condition is a consequence of OSA or a risk factor [31]. It was also demonstrated that OSA can predispose patients to an augmented prevalence of hypertension, heart failure, arrhythmias and mortality. This relationship involves not only the early onset of cardiovascular and metabolic diseases but also their progression. Obstructed breathing causes negative intrathoracic pressure in association with hypoxia and hypercapnia. Hypoxemic stress is further amplified by subsequent reoxygenation (intermittent hypoxia), which leads to a production of reactive oxygen species (ROS), activation of the sympathetic system and inflammation. Every time that an apnea occurs, hypoxia-hypercapnia followed by reoxygenation also alter the exchange of physiological blood gases. When chemoreflex activation occurs, electroencephalography alterations (microarousals) are also evident; each inspiratory effort against the occluded upper airways induces an increase in negative intrathoracic pressure leaving significant consequences on the heart's anatomy, such as atrial enlargement and remodeling and stretching of the ostia of the pulmonary vein. All these acute mechanisms of obstructive apnea will activate several biological pathways. The most relevant one being the autonomic nervous system (ANS) deregulation, with recurrent bursts of sympathetic activity elicited by the activation of chemoreflexes and by the sympathetic and parasympathetic coactivation, which occur repeatedly during the onset of apnea. This sympathetic/parasympathetic coactivation is very typical of OSA and it may represent a decisive factor in triggering major life-threatening arrhythmias in such patients. Moreover, apneic events may also activate a wide range of intermediate mechanisms, such as oxidative stress, the systemic inflammatory response, platelet activation and aggregation, endothelial dysfunction and metabolic alterations [32]. The first-line treatment of breathing-related sleep disorders may include behavioral modifications and CPAP [33]. Alternatives for patients unable to adhere to CPAP therapy include upper airway surgery [33,34] or the use of MADs [35]. In children there are also other options that are being studied, such as palatal expansion [36,37,38]. Studies comparing the effectiveness of CPAP and MAD therapy reported a significant decrease in the AHI compared with baseline over a two-year treatment period for both interventions, suggesting the use of oral appliances as a viable alternative to CPAP therapy in patients with mild to moderate OSA [35]. In this research, we also found a significant variation of HR values after using MAD therapy. The average minimum HR increased, while the average maximum HR decreased. These findings are in accordance with those of previous studies. [PERSON] et al. observed that both MAD therapy and CPAP therapy led to improvements in blood pressure and episodes of breathing cessation in patients with mild to severe OSA [39]; similarly, in a systematic review of the literature, the HR reduction after MAD therapy was concluded to be comparable to that observed after CPAP therapy [40]. Several authors have demonstrated how variations of HR can represent a risk factor for the onset of CVD. Many biological mechanisms can elucidate the relationship between high HR, atherosclerosis and cardiovascular events. tachycardia may be the consequence of an unbalanced tone of the ANS.