## 5 Discussion  
An elevated heart rate, serving as a risk factor of mortality and a predictive measurement for various medical conditions such as cardiovascular diseases [1; 2; 3; 4; 5; 6; 7; 8], presents in severe OSA patients [9; 10; 11], and may help patients with several cardiovascular conditions if reduced [2; 7]. In our results of the subgroup of very severe OSA, the non-framework multilevel surgery reduced the mean heart rate from \(68.6\pm 7.3\) to \(62.7\pm 7.5\) beats/min with a mean heart rate reduction of 5.9 beats/min, despite the unfavorable anatomy of the narrow retroglossal space and confined framework. Our sample size of 27 is small and consists of patients treated by a single surgeon, limiting the generalizability of the results. However, the results illustrate an effect size that is big enough to show significance. The heart rate reduction of 5.9 beats/min was inferior to [PERSON]'s 8.7 beats/min 6 months after maxillary-mandibular advancement [45] but better than [PERSON]'s 4.5 beats/min after 3- to 4-day use of nasal CPAP [11], [PERSON]'s 3.4 beats/minute after 6 months of nasal CPAP therapy [37], [PERSON]'s 2.4 beats/min 6 to 9 months after lateral pharyngoplasty [46], and those reporting no change in mean heart rate after their treatments (e.g., see [47; 48; 49], including [PERSON]'s patients after maxillary-mandibular advancement [49]). Because the lack of detailed information in the literature made statistical analysis impossible, this was just the order of the mean heart rate reductions (so as to enable the AHI comparisons below). Care must be taken when interpreting these comparisons due to possible different OSA severities in the databases and the effect size of the treatment (e.g., mean AHI reduction) across studies. The mean AHI reduction in the present study was 40.5 events/h, which was worse than [PERSON]'s 42.2 events/h [44] but better than [PERSON]'s 38.2 events/h [50] and [PERSON]'s 14.4 events/hour [23] in patients with very severe OSA. Mean heart rate in sleep is affected by not only the medical conditions mentioned above, but also other controllable or uncontrollable variables. Mean heart rate in sleep may increase after short-term heavy physical activity, such as in cyclists after a two-week period of intensified training [51]. However, mean heart rate may drop during good-quality sleep of stages 3 and 4 (e.g., see [52]). For each person, studies found an intrinsic night-to-night variation under controlled submaximal physical activity to be about 5-8 beats/min [53; 54; 55; 56]. The difficulty in controlling the intrinsic variation and individual physical activity before each PSG is a limitation of the present study. Apart from treatment effect, this probably contributed to the variation in the mean heart rate reduction in Figure 3.  
OSA is characterized by the recurrent collapse of the upper airway in sleep, leading to chronic intermittent hypoxia. Chronic intermittent hypoxia has been well reported to elevate circulating epinephrine levels [57; 58; 59; 60; 61], which have a strong positive relationship with platelet aggregation [57; 59; 60]. Elevated serum epinephrine levels result in an elevated heart rate in OSA [57; 58; 60; 61]. Studies showed that treatment of OSA by nasal CPAP decreases the epinephrine level and platelet aggregability and restores the physiological periodic pattern of platelet aggregability [57; 62]. Future studies are needed to investigate whether heart rate reduction goes through the same mechanism of decreasing epinephrine level and platelet aggregability following multilevel surgery in very severe OSA patients. An elevated heart rate is associated with a higher risk of developing hypertension and atherosclerosis (e.g., see [2] for a review).