## 4 Discussion  
While key indicators of the cardiovascular feedback regulation are characterized by well-known measures such as BRS, some details could not be revealed by using this single indicator, especially when it comes to the differential diagnostics. Despite of the pronounced discrepancies between the BRS values in patients from Groups 1 and 2 (approximately twofold between their median values for both supine and orthostatic tilt-test phases), blood pressure variability did not exhibit any significant discrepancies between the two patient groups, indicating that there might be another contributing factor that also plays an important role. Such a factor could be revealed and, furthermore, quantified by considering the synchronization coefficient Sync and the time delay stability TDS metrics both indicating the (normalized) total duration of the time fragments when rather synchronous dynamics of blood pressure and pulse intervals could be observed. Our results indicate that in all studied groups under normal conditions both Sync and TDS demonstrate behavior that appears rather _reciprocal_ to BRS. This indicates that in patients with reduced BRS the feedback mechanisms are likely being _activated more frequently_ this way trying to compensate their lower sensitivity and intensity. This compensation seems to be rather a universal phenomenon, as the reciprocal character of Sync and TDS vs. BRS can be clearly observed in the comparison between them in different studied groups in both supine and orthostatic positions (see boxplots in Figures 4-6). The compensation hypothesis is further supported by the fact that during _all_ tilt test phases in both patients from Group 1 and healthy subjects always negative (although not in all cases statistically significant) correlations between BRS and Sync have been observed. Although, qualitatively, a similar effect could also be observed when considering TDS instead of Sync, it appears less pronounced that could be likely attributed to the lower sensitivity of TDS when compared to Sync, as revealed by a recent computer simulations based study [30]. A prominent exception from the above reciprocal relationship as well as from the corresponding negative correlation pattern could be observed only in diabetes patients likely indicating a breakdown of the above compensatory mechanism at least in some of the patients. Notably, this appears generally in line with recent studies of baroreflex control where significant dependence of the orthostatic baroreflex performance on concomitant conditions such as obesity has been reported [21]. Moreover, in the same study a significantly higher number of baroreflex sequences per given time window (that could also serve as another possible substitute to Sync and/or TDS mutual synchronization metrics) likely indicating more frequent activation of the baroreflex loop could be observed in diabetes patients with concomitant obesity compared to control subjects, although differences between diabetes patients and weight-matched control subjects appeared insignificant. Since we have observed similar effect in our study by using the suggested Sync and TDS indicators, also concomitant conditions such as obesity presumably play a key role in the impairment of baroreflex control not only in terms of its low sensitivity, but also in terms of its timely activation in response to blood pressure variations, although more detailed investigations are required to further elucidate the key factors that influence this possible compensation breakdown. Therefore, we believe that proposed additional indicators could be useful for the improvement of the differential diagnostics of blood pressure regulation efficacy and also lead to a deeper insight into the involved concomitant factors this way also aiming at the improvement of the mathematical models representing the underlying feedback control mechanisms.