Evaluation of arterial stiffness and quality of life in the treatment of moderate to severe obstructive sleep apnea with Continuous Positive Airway Pressure or Mandibular Advancement Appliance: a cross-sectional study
Obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial (hypopnea) or total (apnea) obstruction of the Upper Airway (UA) during sleep, accompanied by decreased oxyhemoglobin saturation with or without awakening . The diagnosis of OSA is based on clinical symptoms and polysomnography (PSG) findings. Patients with OSA may experience excessive daytime sleepiness, fatigue, loud snoring, morning headaches, mood changes, and difficulty concentrating. Once the suspicion has been raised by clinical examination and anamnesis, full-night PSG must be performed for an accurate classification of the severity of the condition based on the number of respiratory events (Apneas and Hypopneas) occurring per hour during sleep (AIH) . AHI greater than 15 classifies the patient as having moderate apnea and values above 30 represent a severe condition . The use of Continuous Positive Airway Pressure (CPAP) and intraoral Mandibular Advancement Appliance (MAA) is considered the main treatment for most patients with OSA . Usually, CPAP is more indicated in moderate to severe conditions, while the indication of MAA is more common in mild to moderate conditions . However, MAA can also be indicated in cases of severe OSA  in patients with low adherence to CPAP and also can be prescribed in cases of mild OSA that present important symptoms or exhibit a low response to other types of treatment . OSA is related to a considerable worsening of Quality of Life (QoL) and increased mortality. Its treatment, when carried out correctly and with good monitoring, has been associated with both improved quality of life and improved survival . OSA is considered a public health problem due to its high prevalence in the general population and its deleterious effects, especially on the cardiovascular system . Intermittent hypoxia, micro-arousals, and greater negativity of intrapleural pressure during recurrent UA obstructive events are responsible for cardiovascular dysfunction in OSA . A series of neurohumoral, inflammatory, and metabolic changes as well as vascular diseases triggered by OSA are described, including increased sympathetic activity, release of oxidative stress products, endothelial dysfunction, increased plasma leptin concentration, C-reactive protein and cytokines, increased insulin resistance, and arterial stiffness . OSA is associated with accelerated vascular aging process as seen in two European community-based cohort studies . Currently, new markers of cardiovascular disease such as pulse wave velocity (PWV) have been proposed since it is considered a great indicator of arterial stiffness  and is considered an independent predictor of future cardiovascular events and mortality . Considered intrinsic to the aging process, arterial stiffness is also influenced by factors and diseases such as OSA although the correlation between pulse wave velocity (PWV) and OSA severity has not yet been scientifically confirmed . Unlike other sleep disorders, 80% of patients with OSA have multiple comorbidities, mostly cardiovascular diseases . Some authors suggest that the burden of comorbidity increases progressively with the severity of OSA . The coexistence of OSA and conventional risk factors such as hypertension, diabetes, hyperlipidemia, and obesity contributes to increased arterial stiffness, making it difficult to establish a causal relationship . Based on the above information, this study aimed to compare arterial stiffness and other cardiovascular parameters as well as QoL in patients diagnosed with moderate to severe OSA without treatment and treated with CPAP and MAA therapies. 

Participants This is a cross-sectional study conducted from March 2019 to November 2023 involving adults aged 50 years and over, of both sexes and diagnosed with moderate to severe OSA previously confirmed by type 1 polysomnography (PSG) categorized into three independent groups as described below: Control group: participants diagnosed with moderate to severe OSA without treatment for the disease. CPAP group: participants initially diagnosed with moderate to severe OSA, who have been treated with CPAP for at least 6 months. MAA group: participants initially diagnosed with moderate to severe OSA, who were treated with a mandibular advancement appliance for at least 6 months. Participants in the CPAP group were enrolled in the Pulmonology outpatient clinic of the Hospital Militar de Minas Gerais (HPM-MG). The equipment used by participants in this group was continuously adjusted and monitored by a respiratory physiotherapist with technical knowledge in CPAP adjustment. The participants enrolled in the MAA group derived from a private dental clinic specializing in sleep disorders. The same experienced dentist treated all patients, and a dental technician was responsible for manufacturing all appliances. A better description of the MMA model utilized in this study can be seen in a case report by Guimaraes et al. (2018) . This group was also continuously followed up to monitor symptoms related to apnea and adjust the appliance when necessary. The control group consisted of patients derived from both institutions mentioned above before implementing specific treatment for OSA condition. Exclusion criteria included cardiovascular disorders such as cerebrovascular diseases, acute myocardial infarction and coronary artery disease, peripheral vascular disease, congenital heart disease, valvular heart disease, and arrhythmia. These conditions could impact our results, as they are strongly associated with increased arterial stiffness . We also excluded patients with other sleep disorders such as insomnia, neuromuscular diseases, chronic obstructive pulmonary disease, renal failure, severe cognitive disorders, history of recent UA surgery, use of other types of treatment for OSA, and lack of results of PSG. CPAP and MAA users reported initiation and adherence to therapy and were excluded from the study if the use of these devices was less than 4 h per night/ 5 days per week, following the recommendations of the American Academy of Sleep Medicine . Although participants with diabetes, dyslipidemia, and arterial hypertension were not excluded, all participants with these comorbidities were on strict medication regimens and were clinically stable. The variables investigated in both groups were demographic and anthropometric data, associated comorbidities, arterial stiffness indices, PSG data, and QoL. Information regarding anthropometric variables, clinical history, and clinical examination were obtained through anamnesis using a standardized collection form. After collecting anthropometric and clinical data, the QoL questionnaire was applied, and hemodynamic and vascular parameters related to arterial stiffness indices were evaluated. All participants were evaluated in the morning. This study was approved by the Research Ethics Committee of Faculdade de Ciências Médicas de Minas Gerais (CAAE 92822918.700005134 / approval report number: 5513761). It was undertaken in agreement with the principles of the Declaration of Helsinki. All participants were previously informed about the research objectives and procedures and, after agreement, signed the consent form. Polysomnography data All participants had a previous diagnosis of OSA confirmed by PSG (baseline), defined as performed in the sleep laboratory and observed by a professional who should be present during data collection to oversee the extraction of the variables of interest . The following polysomnographic data were considered for analysis: AHI, sleep efficiency, average and minimum oxygen saturation (SpO 2 ), saturation time ˂ 90%, awakening, phases of sleep, and sleep-phase distribution (N1, N2, N3, and rapid eye movement or REM). Anthropometric assessment Anthropometric data were collected as recommended by the World Health Organization . Quality of life The Quebec Sleep Questionnaire (QSQ) is an instrument comprising 32 items that assess the impact of OSA on five distinct domains: daytime sleepiness; diurnal symptoms; nocturnal symptoms; emotions; and social interactions. Each domain consists of 4 to 10 items rated on a 1- to 7-point Likert scale. The results are expressed as the mean score for each separate domain and the higher the score, the milder the symptom and therefore, better outcomes. Thus, a higher score across domains reflects a lower symptom burden and a more favorable health status in relation to OSA. The QSQ was originally designed in French and translated by its authors from French into English and was shown to have excellent psychometric properties. In 2017, the QSQ was translated and culturally adapted for the Brazilian population . Vascular and hemodynamic parameters and arterial stiffness indices To assess hemodynamic and vascular parameters related to arterial stiffness indices, an oscillometric, 24-hour ambulatory blood pressure monitoring device (Mobil-O-Graph ® ; IEM, Germany) was used . This non-invasive method was validated by the American Heart Association’s Council on Hypertension and The British Hypertension Society . This device contains the ARC Solver algorithm (ARC Solver method, Austrian Institute of Technology) that provides the variables PWV and Augmentation Index adjusted for a Heart Rate (HR) of 75 beats per minute (Alx@75) to estimate arterial stiffness. PWV was determined by a mathematical model considering pulse wave parameters and wave separation analysis . AIx@75 was calculated from the difference between the peak of the reflection wave (P2) and the peak of the incident wave (P1) and was expressed as a percentage of the central pulse pressure (cPP), corrected for a heart rate of 75 bpm [AIx@75 = 100 × (P2 - P1) / cPP] . The monitor also provided the measurements of HR, Systolic (SBP) and Diastolic (DBP) Blood Pressure, and peripheral and central Pulse Pressure (PP). These factors have been recently proposed to estimate cardiovascular risk in many populations . To obtain reliable data, participants were instructed to remain seated with their feet and arms supported. The examination was performed after 10 min of rest . Three consecutive measurements of all parameters were performed, and their mean, when acceptable, was considered for analysis. Participants received prior instructions to abstain from stimulating foods (coffee, cola-based soft drinks, chocolate, etc.), alcoholic beverages, and nicotine as well as to avoid physical activity for a minimum of 24 h before the exam . Statistical analysis The data were presented in frequency tables with absolute frequencies and their respective percentages, as well as descriptive measures (mean, standard deviation, and 25th and 75th percentiles) for quantitative data. Quantitative variables were tested for Normality using the Shapiro-Wilk test. ANOVA was used to compare means between groups, followed by Bonferroni tests for multiple comparison analyses. The Kruskal-Wallis test was used to compare non-parametric data, followed by Mann-Whitney tests for two-by-two comparisons. The Chi-Square test with Monte Carlo simulations was applied to evaluate the association between the presence of comorbidities and the groups. A significance level of 0.05 ( p < 0.05) was adopted for all statistical analyses. All analyses were performed using SPSS statistical software. 

This is a cross-sectional study conducted from March 2019 to November 2023 involving adults aged 50 years and over, of both sexes and diagnosed with moderate to severe OSA previously confirmed by type 1 polysomnography (PSG) categorized into three independent groups as described below: Control group: participants diagnosed with moderate to severe OSA without treatment for the disease. CPAP group: participants initially diagnosed with moderate to severe OSA, who have been treated with CPAP for at least 6 months. MAA group: participants initially diagnosed with moderate to severe OSA, who were treated with a mandibular advancement appliance for at least 6 months. Participants in the CPAP group were enrolled in the Pulmonology outpatient clinic of the Hospital Militar de Minas Gerais (HPM-MG). The equipment used by participants in this group was continuously adjusted and monitored by a respiratory physiotherapist with technical knowledge in CPAP adjustment. The participants enrolled in the MAA group derived from a private dental clinic specializing in sleep disorders. The same experienced dentist treated all patients, and a dental technician was responsible for manufacturing all appliances. A better description of the MMA model utilized in this study can be seen in a case report by Guimaraes et al. (2018) . This group was also continuously followed up to monitor symptoms related to apnea and adjust the appliance when necessary. The control group consisted of patients derived from both institutions mentioned above before implementing specific treatment for OSA condition. Exclusion criteria included cardiovascular disorders such as cerebrovascular diseases, acute myocardial infarction and coronary artery disease, peripheral vascular disease, congenital heart disease, valvular heart disease, and arrhythmia. These conditions could impact our results, as they are strongly associated with increased arterial stiffness . We also excluded patients with other sleep disorders such as insomnia, neuromuscular diseases, chronic obstructive pulmonary disease, renal failure, severe cognitive disorders, history of recent UA surgery, use of other types of treatment for OSA, and lack of results of PSG. CPAP and MAA users reported initiation and adherence to therapy and were excluded from the study if the use of these devices was less than 4 h per night/ 5 days per week, following the recommendations of the American Academy of Sleep Medicine . Although participants with diabetes, dyslipidemia, and arterial hypertension were not excluded, all participants with these comorbidities were on strict medication regimens and were clinically stable. The variables investigated in both groups were demographic and anthropometric data, associated comorbidities, arterial stiffness indices, PSG data, and QoL. Information regarding anthropometric variables, clinical history, and clinical examination were obtained through anamnesis using a standardized collection form. After collecting anthropometric and clinical data, the QoL questionnaire was applied, and hemodynamic and vascular parameters related to arterial stiffness indices were evaluated. All participants were evaluated in the morning. This study was approved by the Research Ethics Committee of Faculdade de Ciências Médicas de Minas Gerais (CAAE 92822918.700005134 / approval report number: 5513761). It was undertaken in agreement with the principles of the Declaration of Helsinki. All participants were previously informed about the research objectives and procedures and, after agreement, signed the consent form. 

All participants had a previous diagnosis of OSA confirmed by PSG (baseline), defined as performed in the sleep laboratory and observed by a professional who should be present during data collection to oversee the extraction of the variables of interest . The following polysomnographic data were considered for analysis: AHI, sleep efficiency, average and minimum oxygen saturation (SpO 2 ), saturation time ˂ 90%, awakening, phases of sleep, and sleep-phase distribution (N1, N2, N3, and rapid eye movement or REM). 

Anthropometric data were collected as recommended by the World Health Organization . 

The Quebec Sleep Questionnaire (QSQ) is an instrument comprising 32 items that assess the impact of OSA on five distinct domains: daytime sleepiness; diurnal symptoms; nocturnal symptoms; emotions; and social interactions. Each domain consists of 4 to 10 items rated on a 1- to 7-point Likert scale. The results are expressed as the mean score for each separate domain and the higher the score, the milder the symptom and therefore, better outcomes. Thus, a higher score across domains reflects a lower symptom burden and a more favorable health status in relation to OSA. The QSQ was originally designed in French and translated by its authors from French into English and was shown to have excellent psychometric properties. In 2017, the QSQ was translated and culturally adapted for the Brazilian population . 

To assess hemodynamic and vascular parameters related to arterial stiffness indices, an oscillometric, 24-hour ambulatory blood pressure monitoring device (Mobil-O-Graph ® ; IEM, Germany) was used . This non-invasive method was validated by the American Heart Association’s Council on Hypertension and The British Hypertension Society . This device contains the ARC Solver algorithm (ARC Solver method, Austrian Institute of Technology) that provides the variables PWV and Augmentation Index adjusted for a Heart Rate (HR) of 75 beats per minute (Alx@75) to estimate arterial stiffness. PWV was determined by a mathematical model considering pulse wave parameters and wave separation analysis . AIx@75 was calculated from the difference between the peak of the reflection wave (P2) and the peak of the incident wave (P1) and was expressed as a percentage of the central pulse pressure (cPP), corrected for a heart rate of 75 bpm [AIx@75 = 100 × (P2 - P1) / cPP] . The monitor also provided the measurements of HR, Systolic (SBP) and Diastolic (DBP) Blood Pressure, and peripheral and central Pulse Pressure (PP). These factors have been recently proposed to estimate cardiovascular risk in many populations . To obtain reliable data, participants were instructed to remain seated with their feet and arms supported. The examination was performed after 10 min of rest . Three consecutive measurements of all parameters were performed, and their mean, when acceptable, was considered for analysis. Participants received prior instructions to abstain from stimulating foods (coffee, cola-based soft drinks, chocolate, etc.), alcoholic beverages, and nicotine as well as to avoid physical activity for a minimum of 24 h before the exam . 

The data were presented in frequency tables with absolute frequencies and their respective percentages, as well as descriptive measures (mean, standard deviation, and 25th and 75th percentiles) for quantitative data. Quantitative variables were tested for Normality using the Shapiro-Wilk test. ANOVA was used to compare means between groups, followed by Bonferroni tests for multiple comparison analyses. The Kruskal-Wallis test was used to compare non-parametric data, followed by Mann-Whitney tests for two-by-two comparisons. The Chi-Square test with Monte Carlo simulations was applied to evaluate the association between the presence of comorbidities and the groups. A significance level of 0.05 ( p < 0.05) was adopted for all statistical analyses. All analyses were performed using SPSS statistical software. 

Table shows that the groups are homogeneous in terms of age, gender, height, weight, education background, marital styatus, comorbidities and madications in use. On the other hand, there is a significant difference between the CPAP, Control, and MAA groups for BMI ( p < 0.001). BMI was significantly higher in MAA group than CPAP Group. The groups showed no difference between the comorbidities described. Comparative PSG analysis between groups (Table ) revealed some differences in some sleep-related parameters. The initial AHI (obtained prior treatment and used to diagnose the condition) demonstrated significant differences between CPAP and MAA groups, but not between these apnea-treated groups compared to the Control Group. Minimum SpO 2 revealed significant differences between CPAP and MAA Group. The analysis of the total time of SpO 2 below 90% and mean SpO 2 showed no significant difference between the groups. Regarding sleep efficiency, REM sleep latency, and percentages of N1, N2, N3, and REM, no statistically significant differences were observed between the groups. CPAP and MMA groups showed similar treatment time prior evaluation. The assessment of quality of life between the groups revealed significant differences in several dimensions. The results presented in Fig. indicate that patients treated with both CPAP and MAA had significantly less daytime sleepiness, daytime and nighttime symptoms, and a more positive emotional experience compared to Control Group. Furthermore, the MAA Group had less daytime sleepiness than CPAP Group. Although the analysis showed significant differences in these dimensions, no significant variations were observed in social interactions between the groups. The results showed in Table reveal that for the vascular and hemodynamic parameters and arterial stiffness indices evaluated by the Mobil-O-Graph device, there was no significant difference between the groups for any variable studied. 

To the best of our knowledge, this was the first study that compared the QoL and hemodynamic parameters and arterial stiffness in patients with OSA treated with CPAP, MAA, and untreated. Our results point to a significant improvement in the quality of life of patients with OSA treated, especially with MAA. The hemodynamic and arterial stiffness parameters, which are used as predictors of cardiovascular diseases, however, were not different between the different groups. Demographic and polysomnographic parameters. We only evaluated patients diagnosed with moderate to severe OSA and the groups were homogeneous in terms of demographic characteristics, except for the BMI, which was higher in the CPAP group in relation to the MAA group, but not to the control group. Likewise, when we evaluated the polysomnographic characteristics, we also noticed that the CPAP group showed a higher AHI and lower minimum SpO 2 when compared to the MAA group. These are parameters that are related to a greater severity of OSA and these findings most likely reflect a tendency to prescribe CPAP therapy for more obese patients with higher AHI and lower minimum SpO 2 . As CPAP therapy is already clinically established as the most effective method for treating the condition, it would be ideal for this patient profile, which has an increased risk of complications related to apnea . Other studies aiming to evaluate the QoL or effectiveness comparatively between these two therapies for the treatment of OSA also show a tendency to find differences in these polysomnographic parameters and BMI when trying to homogenize the groups at baseline, as seen in Vires et al.., (2019) . Despite these differences observed when comparing the CPAP and MAA groups, none of these treated groups were different from the untreated control. This homogenization is important for comparisons of possible improvements in quality of life and hemodynamic parameters from the treatment with each of these therapies. Quality of life When we compared patients using CPAP with patients in the Control group, we noticed an increase in scores for all QoL domains assessed by the QSQ. However, the improvement in QoL was only statistically confirmed for the nocturnal symptoms domain. Our results corroborate the study by Martinez Deltoro et al. (2023) which also shows an increase in all domains but only significant results for the domains of nocturnal symptoms and social interactions in a sample of 192 patients adhering to CPAP therapy evaluated for 3 months after the start of therapy . Another similar study that assessed quality of life using the same instrument in elderly people over 70 years of age also showed improvement in the domains of nocturnal symptoms and social interactions, but not in the other domains . It was already expected to find changes in the domain of nocturnal symptoms, which are mainly related to snoring, suffocation, and dry or sore throat, which are clinical symptoms that normally disappear with the use of CPAP . For the MAA, we observed statistically higher scores in all domains of the QSQ when compared to the control group, except for social interactions. A study that also adopted the assessment of QoL using the same inventory in patients treated with MAA, followed up for 5 years, also showed improvement in all domains, regardless of the initial severity of apnea before treatment and the evaluation period . Although the literature shows a more moderate reduction in AHI for MAA in relation to CPAP in patients with OSA, there is already a consensus on an improvement as significant or even greater for MAA than CPAP in QoL and also in daytime sleepiness . It is already widely discussed that these parameters should be considered as markers of the success of MAA therapy and not only the polysomnographic parameters . The literature shows that daytime sleepiness assessed by both the QSQ and the Epworth Sleepiness Scale, another more targeted instrument to assess daytime sleepiness, is lower both after the implementation of OSA treatment using MAA and CPAP . In our study we observed a much more significant improvement in this parameter for the group treated with MAA and a smaller improvement for CPAP, causing a statistically significant difference between parameters when comparing the MAA and CPAP groups. We did not find any other work in the literature that pointed to a significant superiority of MAA in reducing daytime drowsiness in relation to CPAP and, although MAA has shown a great improvement in QoL, we believe that new studies in larger populations are necessary to confirm this finding. Arterial stiffness and hemodynamic parameters No difference was observed between any variable related to arterial stiffness or other important hemodynamic parameters among the groups evaluated in our study. Despite the improvement in polysomnographic parameters and QoL, there is no consensus in the literature between the use of CPAP and MAA in improving cardiovascular outcomes, and it is still a very controversial subject . Some studies have demonstrated the beneficial effects of CPAP on the cardiovascular system, but these effects seem to be time-dependent and require a high level of adherence, especially in patients without excessive daytime sleepiness and with advanced cardiovascular diseases . Although some studies have shown reduced arterial stiffness and cardiovascular risk associated with CPAP adherence in individuals with OSA, the data in the literature remain contradictory . Most recent randomized clinical trials have not demonstrated a benefit for CPAP treatment on cardiovascular outcomes except in hypertensive patients in whom CPAP therapy induced protective effects on coronary artery disease and cardiovascular mortality . For MAA, little is known about the real impact of this therapy on cardiovascular improvement, and the few trials in the area evaluating arterial stiffness in OSA treated with MAA suggest an improvement in parameters related to arterial stiffness with continued use . Although we evaluated the CPAP and MAA Groups at similar treatment times, our work did not focus on the patient adherence level to these therapies. Even so, all patients in these two treated groups reported using MAA or CPAP for at least 4 h per night for at least 5 days per week. Although we did not observe a statistically significant difference, we can notice a trend towards a decrease in PWV, which is the main marker of arterial stiffness in the adult population, for CPAP and mainly MAA in relation to the Control Group. Perhaps in studies with larger populations, this difference can be better visualized and help to fill the gap between the treatment of OSA by different methods and the predictability of cardiovascular outcomes. Our findings cannot be generalized to younger populations, as we did not include patients under the age of 50 due to the low prevalence of moderate to severe OSA within this demographic . Including younger patients would have complicated age standardization across groups, introducing substantial bias, given that arterial stiffness varies significantly with age. It is recognized that many younger individuals remain undiagnosed with OSA. Screening for OSA in this patient profile is essential, and such diagnoses would facilitate additional studies to better understand the impact of OSA across different age groups, particularly among younger patients. Study strengths and limitations Our study has some strengths and limitations that should be acknowledged. All patients in the three groups evaluated were diagnosed with severe-to-moderate OSA through Type I PSG, which is considered the gold standard method for diagnosing OSA. Furthemore, all the patients in the treated groups reported good adherence to both CPAP and MAA therapies, in accordance with what is recommended by the American Academy of Sleep Medicine . The limitations of this study are: first, our groups were not homogeneous in relation to BMI, AIH, and minimum SpO 2 ; second, the number of individuals was limited; and correlated to our findings; third, the PSG parameters were not evaluated after treatment with CPAP or MAA to assure the effectiveness of the therapy; fourth, patients in the CPAP and MAA groups came from different institutions: a military hospital and a private clinic. Patients in these settings may differ in terms of social status and perhaps lifestyle, which may contribute to bias in the study results; fifth, we did not use an effective method to ensure the adequate use of oral devices or CPAP for the necessary time according to the inclusion criteria. Although most CPAPs have remote monitoring of usage time, MAA does not, and therefore, we would not be able to ensure the use for the appropriate time. To avoid creating a confounding factor between the groups, we chose to use self-reported usage time in both groups. It is important to emphasize the development of monitoring methods for oral devices as well, as this must be the only way to attribute the success of this therapy in the treatment of OSA to the time the device is used. 

When we compared patients using CPAP with patients in the Control group, we noticed an increase in scores for all QoL domains assessed by the QSQ. However, the improvement in QoL was only statistically confirmed for the nocturnal symptoms domain. Our results corroborate the study by Martinez Deltoro et al. (2023) which also shows an increase in all domains but only significant results for the domains of nocturnal symptoms and social interactions in a sample of 192 patients adhering to CPAP therapy evaluated for 3 months after the start of therapy . Another similar study that assessed quality of life using the same instrument in elderly people over 70 years of age also showed improvement in the domains of nocturnal symptoms and social interactions, but not in the other domains . It was already expected to find changes in the domain of nocturnal symptoms, which are mainly related to snoring, suffocation, and dry or sore throat, which are clinical symptoms that normally disappear with the use of CPAP . For the MAA, we observed statistically higher scores in all domains of the QSQ when compared to the control group, except for social interactions. A study that also adopted the assessment of QoL using the same inventory in patients treated with MAA, followed up for 5 years, also showed improvement in all domains, regardless of the initial severity of apnea before treatment and the evaluation period . Although the literature shows a more moderate reduction in AHI for MAA in relation to CPAP in patients with OSA, there is already a consensus on an improvement as significant or even greater for MAA than CPAP in QoL and also in daytime sleepiness . It is already widely discussed that these parameters should be considered as markers of the success of MAA therapy and not only the polysomnographic parameters . The literature shows that daytime sleepiness assessed by both the QSQ and the Epworth Sleepiness Scale, another more targeted instrument to assess daytime sleepiness, is lower both after the implementation of OSA treatment using MAA and CPAP . In our study we observed a much more significant improvement in this parameter for the group treated with MAA and a smaller improvement for CPAP, causing a statistically significant difference between parameters when comparing the MAA and CPAP groups. We did not find any other work in the literature that pointed to a significant superiority of MAA in reducing daytime drowsiness in relation to CPAP and, although MAA has shown a great improvement in QoL, we believe that new studies in larger populations are necessary to confirm this finding. 

No difference was observed between any variable related to arterial stiffness or other important hemodynamic parameters among the groups evaluated in our study. Despite the improvement in polysomnographic parameters and QoL, there is no consensus in the literature between the use of CPAP and MAA in improving cardiovascular outcomes, and it is still a very controversial subject . Some studies have demonstrated the beneficial effects of CPAP on the cardiovascular system, but these effects seem to be time-dependent and require a high level of adherence, especially in patients without excessive daytime sleepiness and with advanced cardiovascular diseases . Although some studies have shown reduced arterial stiffness and cardiovascular risk associated with CPAP adherence in individuals with OSA, the data in the literature remain contradictory . Most recent randomized clinical trials have not demonstrated a benefit for CPAP treatment on cardiovascular outcomes except in hypertensive patients in whom CPAP therapy induced protective effects on coronary artery disease and cardiovascular mortality . For MAA, little is known about the real impact of this therapy on cardiovascular improvement, and the few trials in the area evaluating arterial stiffness in OSA treated with MAA suggest an improvement in parameters related to arterial stiffness with continued use . Although we evaluated the CPAP and MAA Groups at similar treatment times, our work did not focus on the patient adherence level to these therapies. Even so, all patients in these two treated groups reported using MAA or CPAP for at least 4 h per night for at least 5 days per week. Although we did not observe a statistically significant difference, we can notice a trend towards a decrease in PWV, which is the main marker of arterial stiffness in the adult population, for CPAP and mainly MAA in relation to the Control Group. Perhaps in studies with larger populations, this difference can be better visualized and help to fill the gap between the treatment of OSA by different methods and the predictability of cardiovascular outcomes. Our findings cannot be generalized to younger populations, as we did not include patients under the age of 50 due to the low prevalence of moderate to severe OSA within this demographic . Including younger patients would have complicated age standardization across groups, introducing substantial bias, given that arterial stiffness varies significantly with age. It is recognized that many younger individuals remain undiagnosed with OSA. Screening for OSA in this patient profile is essential, and such diagnoses would facilitate additional studies to better understand the impact of OSA across different age groups, particularly among younger patients. 

Our study has some strengths and limitations that should be acknowledged. All patients in the three groups evaluated were diagnosed with severe-to-moderate OSA through Type I PSG, which is considered the gold standard method for diagnosing OSA. Furthemore, all the patients in the treated groups reported good adherence to both CPAP and MAA therapies, in accordance with what is recommended by the American Academy of Sleep Medicine . The limitations of this study are: first, our groups were not homogeneous in relation to BMI, AIH, and minimum SpO 2 ; second, the number of individuals was limited; and correlated to our findings; third, the PSG parameters were not evaluated after treatment with CPAP or MAA to assure the effectiveness of the therapy; fourth, patients in the CPAP and MAA groups came from different institutions: a military hospital and a private clinic. Patients in these settings may differ in terms of social status and perhaps lifestyle, which may contribute to bias in the study results; fifth, we did not use an effective method to ensure the adequate use of oral devices or CPAP for the necessary time according to the inclusion criteria. Although most CPAPs have remote monitoring of usage time, MAA does not, and therefore, we would not be able to ensure the use for the appropriate time. To avoid creating a confounding factor between the groups, we chose to use self-reported usage time in both groups. It is important to emphasize the development of monitoring methods for oral devices as well, as this must be the only way to attribute the success of this therapy in the treatment of OSA to the time the device is used. 

Our results indicate a significant improvement in QoL for patients with OSA treated with CPAP and primarily MAA. However, it is important to note that there were no significant differences in arterial stiffness or hemodynamic parameters measured by the Mobil-O-Graph device between the treated groups and untreated OSA patients. This finding underscores the distinction between subjective improvements in QoL and objective cardiovascular measures. While the treatments effectively enhance QoL, they do not appear to lead to cardiovascular improvements, as indicated by the stable arterial stiffness. Thus, our study highlights the need for further research to understand the long-term cardiovascular implications of OSA treatment, even when QoL shows marked enhancement. 

