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It is well recognized that regular physical activity may improve cardiac autonomic regulation preventing chronic non-communicable diseases. Accordingly, the assessment of cardiac autonomic regulation (CAR) with non-invasive techniques, such as RR interval Variability (V) might be of practical interest. We studied 56 soccer players (21.2 ± 4.2 years.) and 56 controls (22.2 ± 1.5 years.) and used a ranked Autonomic Nervous System Index (ANSI), resulting from the combination of multivariate statistical methodologies applied to spectral analysis derived indices from RRV. We hypothesized that ANSI would be higher in soccer players as compared to controls ( p < 0.001) and that values would be greatest in defenders and midfielders, who are known to run longer distances during competitions. Conversely in the intrinsically stationary goalkeepers ANSI would be similar to controls. Our data show that it is possible to assess the overall level of autonomic performance in soccer players as compared to the general population, using a ranked composite autonomic proxy (ANSI). This approach suggests as well that CAR is better in those players who during competitions run for a greater distance. We conclude that it is possible to highlight the differences in autonomic profile due to distinct exercise routines, using ANSI, a simple ranked, composite autonomic proxy.

In athletes, spectral analysis of HR variability (HRV) has been shown capable to detect the adaptational changes in sympatho-vagal control attending physical training. So far, studies investigated autonomic nervous system (ANS) changes occurring with endurance training, whereas adaptations to markedly different exercise modes, for example, strength training, have never been investigated. We assessed the changes in cardiac ANS parameters during long-term training in weight lifters of the Italian team preparing for the European Championship, where athletes competed for obtaining the pass for Olympic Games. We investigated nine athletes. Subject trained 3 sessions/day, 6 days a week. The intensity of strength exercises varied from 70% to 95% 1 RM. Training load (TL) was calculated as: volume (min) × intensity (%1RM).All ANS parameters were significantly and highly correlated on an individual basis to the dose of exercise with a second-order regression model (r 2 ranged from 0.96 to 0.99; P < 0.001). The low-frequency (LF) component of HRV and LF/HF ratio showed an initial increase with the progression of TL and then a decrease, resembling a bell-shaped curve with a minimum at the highest TL. The high-frequency (HF) component of HRV and R-R interval showed a reciprocal pattern, with an initial decrease with progression of TL followed by an increase, resembling an U-shaped curve with a maximum at the highest TL. These adaptations were at the opposite to those previously reported in endurance athletes. These results suggest that in Olympic weight lifters, ANS adaptations to training are dose-related on individual basis and that ANS adaptations are mainly sport-specific., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Purpose: Optimal autonomic regulation and stress resilience might be considered critical elements of athletic performance. We hypothesize that a novel unitary autonomic index for sports (ANSIs), together with a somatic stress related symptom score (4SQ) might help characterize athletes who were eventually selected for the Rio 2016 Olympic Games Italian team (Rio +)., Methods: In this retrospective study we examined 778 athletes (age 24.4 ± 6.7 yrs) who underwent a planned yearly pre-participation screening. All athletes underwent clinical, autonomic and exercise ECG evaluation. The combination of vagal and sympathetic indices from RR variability into ANSIs was performed by radar plot and percent ranking of index variables. We assessed (Rio +) versus (Rio -) athletes also after subdivision into three sport intensity groups (low, mid and high intensity)., Results: Overall there were no significant differences between (Rio +) and (Rio -) athletes when considering individual spectral derived variables. Conversely, the unitary Index ANSIs was significantly higher in (Rio +) compared to (Rio -) athletes (respectively 54.5 ± 29.5 and 47.9 ± 28.4 p = 0.014). This difference was particularly evident (p = 0.017) in the group of athletes characterized by both high static and dynamic components. 4SQ was smaller in the (Rio +) group, particularly in the groups of athletes characterized by both low-medium static and dynamic components., Conclusions: ANSIs, a proxy of integrated cardiac autonomic regulation and simple assessment of resilience to stress, may differentiate Italian athletes who were eventually selected for participation in the 2016 Rio Olympic Games from those who were not, suggesting the possibility of a "winning functional phenotype".

Since the seminal studies by Sayers (Ergonomics 16:17-32, 1973) and Akselrod et al. (Science 213:220-222, 1981) a few decades ago, it became clear that beat-by-beat oscillations in RR interval length (i.e. heart-rate variability [HRV]) contain information on underlying neural-control mechanisms based on the instantaneous balance between parasympathetic and sympathetic innervation. Over the years, the number of studies addressing HRV has increased markedly and now outnumbers 23,000. Despite such a large interest, there is still a continuing debate about interpretation of indices produced by computer analysis of HRV.The main part of studies relies on spectral techniques to extract parameters that are linked to hidden information. The general idea is that these proxies of autonomic regulation can be useful to clinical applications in various conditions in which autonomic dysregulation may play a role. There are, however, serious shortcomings related to algorithms, interpretation, and the hidden value of individual indices. In particular, it appears that specific training is necessary to interpret the hidden informational value of HRV. This technical complexity represents a severe barrier to large-scale clinical applications. Moreover, important differences in HRV separate the sexes, and age plays an additional confounding role.We present here a preliminary application of a novel unitary index of RR variability (Autonomic Nervous System Index of cardiac regulation) capable of providing information on the performance of autonomic regulation using a percentile rank position as projected on a large benchmark population. A summary of the underlying sympatho-vagal model is also presented.

Background: Long term endurance training, as occurring in elite athletes, is associated to cardiac neural remodeling in favor of cardioprotective vagal mechanisms, resulting in resting bradycardia and augmented contribution of cardiac parasympathetic nerve activity. Autonomic assessment can be performed by way of heart rate variability. This technique however provides multiple indices, and there is not yet complete agreement on their specific significance. Purpose of the study was to assess whether a rank transformation and radar plot could provide a unitary autonomic index, capable to show a correlation between intensity of individual work and quality of autonomic regulation., Methods: We studied 711 (23.6±6.2 years) elite athletes that took part in the selection procedure for the 2016 Rio Olympic Games for the National Italian Olympic Committee (CONI). Indices from Heart Rate Variability HRV obtained at rest, during standing up and during recovery from an exercise test were used to compute a percent ranked unitary autonomic index for sport (ANSIs), taken as proxy of quality of autonomic regulation., Results: Within the observed wide range of energy expenditure, the unitary autonomic index ANSIs appears significantly correlated to individual and discipline specific training workloads (r=0.25, P<0.001 and r=0.78, P<0.001, respectively), correcting for possible age and gender bias. ANSIs also positively correlates to lipid profile., Conclusions: Estimated intensity of physical activity correlates with quality of cardiac autonomic regulation, as expressed by a novel unitary index of cardiac autonomic regulation. ANSIs could provide a novel and convenient approach to individual autonomic evaluation in athletes.

Background: This study addresses whether a unitary cardiac autonomic nervous system index (ANSI), obtained combining multiple metrics from heart rate variability (HRV) into a radar plot could provide an easy appreciation of autonomic performance in a clinical setting., Materials and Methods: Data are standardized using percentile ranking of autonomic proxies from a relatively large reference population (n = 1593, age 39 ± 13 years). Autonomic indices are obtained from autoregressive spectral analysis of (ECG derived) HRV at rest and during standing up. A reduced ANSI (using RR, RR variance and rest-stand difference of LFnu) is then constructed as a radar plot, quantified according to its combined area and tested against different risk subgroups., Results: With growing risk profile, there is a marked reduction of the rank value of ANSI, quantified individually by the radar plot area. The practical usefulness of the approach was tested in small groups of additional subjects putatively characterized by elevated or poor autonomic performance. Data show that elite endurance athletes are characterized by elevated values of ANSI (80·6 ± 14·9, P < 0·001) while subjects with either Type 1 or Type 2 diabetes show lower values (DM1 = 37·0 ± 18·9 and DM2 = 26·8 ± 23·3, P = 0·002), and patients with coronary artery disease (CAD) represent a nadir (17 ± 20, P < 0·001)., Conclusions: This observational study shows the feasibility of testing simpler metrics of cardiac autonomic regulation based on a multivariate unitary index in a preventive setting. This simple approach might foster a wider application of HRV in the clinical arena, and permit an easier appreciation of autonomic performance., (© 2017 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: In the general population higher levels of exercise capacity seem to protect the cardiovascular system with effects well beyond traditional risk factors. We hypothesize that this phenomenon, called "risk factor gap", could be ascribed to functional components, such as autonomic adaptation to aerobic training., Methods: In 257 subjects (age 36.2±0.8 years) we measured VO2peak (incremental cycling exercise), together with arterial pressure and autonomic proxies (baroreflex gain, R-R variance and standing induced increase in marker of excitatory oscillatory regulation of the SA node, ∆LFRRnu)., Results: Autonomic proxies appeared significantly correlated with indicators of aerobic fitness (age and gender corrected correlation between VO2peak, baroreflex gain: r=0.277, P<0.001, and DAP r=-0.228, P<0.001). Subsequently, subjects were subdivided in three age and gender adjusted categories of VO2peak (poor, medium and good). Autonomic indices and arterial pressure appeared significantly ordered with categories of VO2peak (P<0.006). In addition, within these categories the proportion of subjects with a desirable autonomic and pressure profile becomes significantly greater with better fitness levels., Conclusions: The strong ordered relationship between categories of aerobic fitness and autonomic proxies speaks in favor of a complementary role of the autonomic nervous system in the management of cardiovascular risk factor gap at a population level.

Purpose: Autonomic assessment might be useful in training management. We planned to assess whether oscillatory metrics of RR variability (such as LFnu) would be more efficient than static indices from low order statistics (RR variance) at discriminating laying rest from stand posture, as an analog of a shift to sympathetic dominance., Methods: We studied a large population of elite Olympic athletes: a total of 406 athletes (162 females and 244 males, of similar age 21.7 and 24.4 years) participating to the selection for the upcoming 2016 Olympic games. We employed various methods to extract autonomic indices from RR variability and employed a stepwise statistical approach combining factor and discriminant analysis., Results: We observed that that relative power of oscillatory components from spectral analysis of RR variability (such as LF or HF in nu) and indices from symbolic analysis (particularly 0V) clearly outperform RR variance in discriminating between two physiological conditions (laying rest and stand) related to posture and autonomic activation., Conclusions: In world class Olympic athletes we have shown that a small subset of RR variability indices, related to sympathovagal balance, may be more appropriate than RR variance to assess excitatory sympathetic autonomic responsiveness of the SA node. These findings may have practical implications for the use of RR variability in guiding training and predicting success in competitions.

Purpose: Surgery and adjuvant therapy improved prognosis of breast cancer survivors. This improvement risks being offset by potential late-occurring cardiovascular toxicity of oncologic treatment and increased cardiometabolic risk profile associated with lifestyle changes. We address the hypothesis that in breast cancer survivors, multiple functional alterations might define a phenotype, characterized by vagal impairment, diminished aerobic fitness, increased metabolic risk, and reduced wellbeing., Methods: We studied 171 sedentary asymptomatic women (106 cancer survivor-65 controls) of similar age (53 ± 8.6; 51 ± 8.1 years). Autonomic regulation was evaluated by autoregressive spectral analysis of R wave to R wave (RR) interval and systolic arterial pressure variability. Aerobic fitness was directly assessed by cardiopulmonary exercise test. Body mass index (BMI) and waist circumference served as proxies of metabolism. Fatigue and stress-related symptoms were evaluated with validated questionnaire., Results: Patients showed significantly smaller total RR variance (1644 ± 2363 vs. 2302 ± 1561 msec2), smaller absolute power of low frequency (LF) (386 ± 745 vs. 810 ± 1300 msec2) and high frequency (HF) (485 ± 1202 vs. 582 ± 555 msec2) of RR interval variability and smaller spontaneous baroreflex sensitivity (15.0 ± 8.9 vs. 21.9 ± 10 msec/mmHg), suggesting vagal impairment. VO2 peak and O2 pulse were lower in cancer survivors than in controls. Fatigue and stress-related somatic symptoms scores were higher, as was BMI and waist circumference., Conclusion: Breast cancer survivors show multiple dysfunctions: vagal impairment, lower aerobic fitness, signs of altered metabolism, and higher perception of fatigue., Implications for Cancer Survivors: We propose that the concept of clinical phenotype, which may accommodate multiple functional disturbances, might be useful in long-term personalized prevention programs for breast cancer survivors.

Introduction: Altered profile of RR variability and reduced baroreflex gain, as autonomic proxies, are observed in hypertensive individuals., Aim: To assess whether using logistic models and cross-validation techniques autonomic proxies can be used to identify clinical hypertensive and normotensive groups., Methods: An observational study on 405 individuals (155 mild hypertensive and 250 controls). We used four steps for statistical analysis: preliminary descriptive statistics; logistic regression modelling; detection of best parsimonious set of variables; and concordance analysis between clinical and autonomic hypertension profile., Results: Accuracy index (rate of correct identifications of normotensive and hypertensive states), computed on each of the four gradually more complex logistic models (from A to D), reached its highest value (82.7%), in the most complete model D, including autonomic nervous system indices (RR variability and baroreflex gain), age and sex. Measures of predictive performance increased from the simplest model to the most complex one [model D, positive predictive value (PPV) = 0.767, negative predictive value (NPV) = 0.866], with higher specificity than sensitivity. A parsimonious set of autonomic proxies (Mean RR, ΔRRLFnu - i.e. change from rest to standing up - baroreflex gain combined with age and sex) led to an accuracy index of 80.5%, thus proving to have discriminant and predictive powers in detecting hypertension very similar to the whole set of the explicative variables comprised in the complete model D., Conclusion: The clinical value of the observation that the information collectively carried by a small subset of indirect autonomic proxies may identify either hypertensive or normotensive groups needs to be further investigated.

Considering that changes in exercise routines might have relevance in treatment of adolescents with type 1 diabetes mellitus, we sought to assess whether spontaneous modifications to weekly exercise habits might occur in these patients and whether such variations would be accompanied by alterations in autonomic profile. In this observational study, we examined 77 patients (age 15.0 ± 0.6 years.) who in addition to a tailored optimal insulin treatment were invited to perform at least 1 h a day of moderate, aerobic exercise, as suggested by recent guidelines. Patients were studied at baseline (T0) and after 15.8 ± 0.7 months (T1). They were divided into three subgroups according to increased, unchanged and diminished total estimated weekly METs between T0 and T1. Autonomic profile was evaluated by assessing spontaneous baroreflex gain and low-frequency oscillation in arterial pressure, using spectral analysis of RR and systolic arterial pressure time series. Insulin therapy and biochemical data were similar among the 3 groups at T0 and T1, while body mass index standard deviation score was slightly reduced (p < 0.04) and markers of autonomic performance were improved (alpha index, from 17 ± 1 to 20 ± 2 ms/mmHg, p < 0.002) in the group who increased the amount of exercise (from 1627 ± 250 to 3582 ± 448 METs min wt(-1), p < 0.001). Furthermore, the change in total weekly METs significantly correlates with changes of key indices of autonomic regulation. The favourable autonomic effects of moderate increase in spontaneous exercise load suggest testing more formally this intervention in adolescents with type 1 diabetes.

Overweight (OW) and obesity in children are important forerunners of cardiovascular risk, possibly through autonomic nervous system (ANS) dysregulation, while physical exercise exerts a beneficial influence. In this observational study we hypothesise that OW might influence ANS profile even in a population performing high volume of supervised exercise. We study 103 young soccer players, homogeneous in terms of gender (all male), cultural background, school, age (11.2 ± 1 years) and exercise routine, since they all belong to the same soccer club, thus guaranteeing equality of supervised training and similar levels of competitiveness. ANS is evaluated by autoregressive spectral analysis of heart rate and systolic arterial pressure (SAP) variabilities. We estimate also the accumulated weekly Metabolic Equivalents and time spent in sedentary activities. We subdivide the entire population in two subgroups (normal weight and OW) based on the International Obesity Task Force criteria. In OW soccer players (10.7% of total group) we observe an altered profile of autonomic cardiovascular regulation, characterised by higher values of SAP (113 ± 4 vs 100 ± 1 mm Hg, 39.7 ± 3 vs 66.2 ± 10%), higher Low Frequency variability power of SAP (an index of vasomotor sympathetic regulation) (12 ± 3 vs 4.5 mm Hg(2)) and smaller spontaneous baroreflex gain (an index of cardiac vagal regulation) (19 ± 3 vs 33 ± 3 ms/mm Hg) (all (p < 0.02)). Moreover Correlation analysis on the entire study population shows a significant link between anthropometric and autonomic indices. These data show that OW is associated to a clear autonomic impairment even in children subjected to an intense aerobic training.

Background: Recent epidemiological data indicate that chronic stress is an important component of cardiovascular risk, implicitly suggesting that stress management might offer a useful complement to orthodox medical treatment and prevention of hypertension. In this context, information on mechanisms, such as subclinical increases in arterial pressure and sympathetic drive, is well documented. Conversely, evidence on methodologies and comparative efficacy needs to be improved. Accordingly, this study was planned to test the autonomic and subjective effects of two popular modalities of stress management., Methods: We studied 70 patients complaining of stress-related symptoms, avoiding any potential autonomic confounder, such as established hypertension or drug treatment. Patients were divided in three groups: group I (n = 30) followed a breathing-guided relaxation training (active); group II (n = 15) an oriental massage, shiatsu (passive); and group III (n = 25) followed a sham intervention. Subjective effects of stress were assessed by validated questionnaires and autonomic nervous system regulation by spectral analysis of RR interval variability. Factor analysis was used to extract information simultaneously embedded in subjective and functional data., Results: Although the problem of a greater quantity of treatment procedure in the active group than in the passive group existed, results showed that active relaxation, further to slightly reducing arterial pressure, might be more effective in relieving symptoms of stress and inducing an improved profile of autonomic cardiovascular regulation, as compared with passive massage or sham intervention., Conclusion: This active technique seems capable of beneficially addressing simultaneously the individual psychological and physiopathological dimensions of stress in clinical settings, with potentially beneficial effects on cardiovascular risk profile.

Background: Physical inactivity represents a major risk for cardiovascular disorders, such as hypertension, myocardial infarction or sudden death; however, underlying mechanisms are not clearly elucidated. Clinical and epidemiological investigations suggest, beyond molecular changes, the possibility of an induced impairment in autonomic cardiovascular regulation. However, this hypothesis has not been tested directly., Methods: Accordingly, we planned a study with noninvasive, minimally intrusive, techniques on healthy volunteers. Participants were maintained for 90 days strictly in bed, 24 h a day, in head-down (-6 degrees ) position (HDBR). Physical activity was thus virtually abolished for the entire period of HDBR. We examined efferent muscle sympathetic nerve activity, as a measure of vascular sympathetic control, baroreceptor reflex sensitivity, heart rate variability (assessing cardiovagal regulation), RR and systolic arterial pressure and low-frequency and high-frequency normalized components (as a window on central oscillatory regulation). Measures were obtained at rest and during simple maneuvers (moderate handgrip, lower body negative pressure and active standing) to assess potential changes in autonomic cardiovascular responsiveness to standard stimuli and the related oscillatory profiles., Results: HDBR transiently reduced muscle sympathetic nerve activity, RR, heart rate variability and baroreceptor reflex sensitivity late during HDBR or early during the recovery phase. Conversely, oscillatory profiles of RR and systolic arterial pressure variability were maintained throughout. Responsiveness to test stimuli was also largely maintained., Conclusion: Prolonged inactivity as induced by HDBR in healthy volunteers reduces both cardiovagal and vascular sympathetic regulation, while largely maintaining peripheral responsiveness to standardized stimuli and sparing the functional structure of central oscillatory cardiovascular regulation.

Background: Sleep disorders are associated to a number of cardiovascular disturbances that might increase cardiovascular risk. Sleep deprivation, in particular, might, by inducing autonomic dysregulation, raise arterial pressure and hypertensive risk. Available evidence however is contradictory., Methods: We tested the main hypothesis that one night sleep deprivation in 24 volunteers might alter hemodynamics (heart rate and Arterial Pressure - AP), autonomic regulation (mono and bivariate spectral analysis of RR and non invasive AP variability) and baroreflex control (spectral index alpha and spontaneous baroreflex slope), performance indices (reaction time) and subjective stress (questionnaires and salivary cortisol). Volunteers were studied in normal living conditions and while kept in isolation and confinement, to test the presence of possible bias related to environmental stress., Results: Results indicate that there were no differences between normal living conditions and isolation and confinement (Intraclass Correlation Coefficient >0.75 for most variables). Conversely, after one night sleep deprivation subjects felt tired (p<0.05), and performance deteriorated (p<0.05), while cortisol profile was substantially maintained, hemodynamic parameters did not change and HRV and index alpha increased slightly., Conclusions: Findings support the contention that one night sleep deprivation, in absence of significant additional stress or disturbances, does not lead to increased arterial pressure values or to changes in autonomic or baroreflex profiles that could conceivably favor hypertension development, but induces the expected increase in tiredness and reduction in performance.

Alterations in lipid metabolism are a possible consequence of highly active antiretroviral therapies (HAART) for human immunodeficiency virus (HIV)-positive patients with consequent increase of cardiovascular risk. In this context we hypothesized that both acquired immunodeficiency syndrome (AIDS) and HAART might be associated to alterations in autonomic cardiovascular regulation. In this preliminary investigation we enrolled a total of 66 men, subdivided in two groups, 33 HIV-positive patients, and 33 healthy controls, and we tested the hypothesis that heart rate variability (HRV) of HIV positive patients can be assessed with a transtelephonic approach from the HIV clinic: 100% of the total of electrocardiograms (ECG) recordings that were sent from the distant site were successfully received and analyzed. Evaluation of the signal was subsequently performed in the centralized laboratory, and consisted in extracting the RR interval variability (RRV) series and afterward subjecting it to autoregressive spectral analysis. This study shows the feasibility of obtaining, from personnel without specific training, adequate RR variability data for further spectral analysis form a distant specialized autonomic laboratory. This feature is of critical importance in the context of possible large-scale application of this simple telemedicine approach.

Work stress may increase cardiovascular risk either indirectly, by inducing unhealthy life styles, or directly, by affecting the autonomic nervous system and arterial pressure. We hypothesized that, before any apparent sign of disease, work-related stress is already accompanied by alterations of RR variability profile and that a simple onsite stress management program based on cognitive restructuring and relaxation training could reduce the level of stress symptoms, revert stress-related autonomic nervous system dysregulation, and lower arterial pressure. We compared 91 white-collar workers, enrolled at a time of work downsizing (hence, in a stress condition), with 79 healthy control subjects. Psychological profiles were assessed by questionnaires and autonomic nervous system regulation by spectral analysis of RR variability. We also tested a simple onsite stress management program (cognitive restructuring and relaxation training) in a subgroup of workers compared with a sham subgroup (sham program). Workers presented an elevated level of stress-related symptoms and an altered variability profile as compared with control subjects (low-frequency component of RR variability was, respectively, 65.2+/-2 versus 55.3+/-2 normalized units; P<0.001; opposite changes were observed for the high-frequency component). These alterations were largely reverted (low-frequency component of RR variability from 63.6+/-3.9 to 49.3+/-3 normalized units; P<0.001) by the stress management program, which also slightly lowered systolic arterial pressure. No changes were observed in the sham program group. This noninvasive study indicates that work stress is associated with unpleasant symptoms and with an altered autonomic profile and suggests that a stress management program could be implemented at the worksite, with possible preventive advantages for hypertension.

Elevated psychosocial stress might favor the occurrence of cardiovascular disease; however, mechanisms are incompletely understood. We hypothesized that patients (n=126; 44+/-1 years of age) referred to an internal medicine clinic because of symptoms related to chronic psychosocial stress would demonstrate signs of autonomic dysregulation compared with controls (n=132; 42+/-1 years of age). We used autoregressive spectral analysis of RR interval variability to obtain indirect markers of sympathetic and of vagal (respectively, low-frequency and high-frequency components, both expressed in normalized units) oscillatory modulation of sinoatrial node, as well as of sympathetic vasomotor regulation (low-frequency component of systolic arterial pressure variability) and of cardiac baroreflex sensitivity (alpha-index). Higher values of systolic and diastolic arterial pressure (respectively, 124+/-1 versus 117+/-1 mm Hg and 80+/-1 versus 75+/-1 mm Hg; both P<0.001), altered markers of autonomic regulation (increased normalized low-frequency and reduced high-frequency component of RR variability, P<0.005; increased-low frequency component of systolic arterial pressure variability, P<0.002), and reduced baroreflex sensitivity (19.3+/-1.4 versus 23.0+/-2.0 ms/mm Hg; P<0.05) were observed in patients compared with controls. Autonomic responses to active standing were also blunted in stressed patients. Autonomic markers were significantly correlated to stress perception score and were capable of discriminating between controls and patients with a high degree of accuracy. Chronic real-life stress in humans appears associated to increased arterial pressure and to impaired autonomic regulation of cardiovascular functions. The combination of sympathetic predominance, vagal withdrawal, and blunted baroreflex sensitivity might represent a treatable mechanistic link between psychosocial factors and future incidence of hypertension.

Background: Chronic orthostatic intolerance (COI) is a common and disabling autonomic syndrome of unclear pathophysiology. We tested the hypothesis that baroreflex and autonomic responses to graded lower body suction (LBNP, up to -40 mmHg) could be altered in COI patients., Methods: Electrocardiogram (ECG), non-invasive arterial blood pressure and respiratory activity were measured during progressive LBNP (seven patients and seven volunteers). Lumped arterial baroreflex sensitivity (alpha index), and its arterial and cardiopulmonary components, were assessed by multivariate closed-loop analysis of RR interval and systolic arterial pressure (SAP) spontaneous variabilities and respiration. Monovariate spectral analysis of RR interval and SAP variability provided markers of autonomic regulation of the sinoatrial (SA) node and of vascular sympathetic modulation., Results: Similar reductions in overall and cardiopulmonary baroreflex gain were observed in both groups in response to graded LBNP. In contrast, only controls demonstrated a selective increase in arterial baroreflex sensitivity, at low-grade LBNP. Clear increases in the low-frequency component of RR interval variability (LFRR) [and decreases in the high-frequency component of RR interval variability (HFRR), both in normalized units] were observed in controls with graded LBNP, while insignificant changes occurred in COI patients, who showed, conversely, exaggerated sympathetic vasomotor responses [as assessed by the low frequency component of SAP variability (LFSAP)]., Conclusions: Patients with chronic orthostatic intolerance show distinct signs of altered baroreflex and autonomic regulation of the SA node and of the vasculature in response to graded LBNP.

We examined on 56 (age 38+/-2 [range: 16-60] years) healthy subjects the effects of aging on cardiovascular autonomic responses to progressive supine bicycle exercise of light intensity. Autoregressive spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided measures of the exercise-induced changes in baroreflex gain (by index alpha) and in sympathetic and vagal modulation of the SA node (by the normalized low [LF] and high frequency [HF] component of RR interval variability, respectively), as well as of changes in sympathetic vasomotor control (LF(SAP)). For each hemodynamic and autonomic variable, the gain of the response was expressed both as individual step increments, and as the slope of the linear regression of the sequential data points from rest and during the three steps of exercise. Age resulted significantly correlated to changes in spectral derived markers of SA modulation (LF(RR), HF(RR) and index alpha). Conversely, no significant relationships were found with changes in RR interval, in SAP and indices of vascular regulation (LF(SAP)). In addition, exercise-induced changes in indices of SA node regulation were more evident in the youngest tertile (age 25+/-1 years), compared to the oldest tertile (age 52+/-1 years). In conclusion, we have observed that aging progressively and selectively reduces the cardiac autonomic excitatory response to light exercise, while hemodynamic and vascular responsiveness are maintained.

Background: Subjects in the upper-normal range of arterial pressure have an excess cardiovascular risk, which suggests that other factors, such as impaired autonomic regulation, might be implicated. This study was designed to assess whether noninvasive markers of cardiac and vascular autonomic regulation might already be altered in subjects with high-normal arterial pressure levels., Methods and Results: We performed an observational study on a population comprising 300 subjects of both sexes with arterial pressure ranging from 90/60 to 210/120 mm Hg, who were divided into 3 groups (each n=100) with average systolic pressures of 103, 133, and 163 mm Hg. Autonomic regulation was inferred from spectral analysis of RR interval and systolic arterial pressure variability, considering rest and stand-induced changes, to account for sympathetic excitatory components. Significant alterations in markers of sinoatrial regulation (increased low-frequency normalized units, reduced high-frequency normalized units, and alpha-index) were already apparent in subjects in the second tertile, ie, those with arterial pressure within normal limits. Markers of vascular regulation instead showed significant alterations in the third (hypertensive) tertile. In response to standing, changes in markers of sinoatrial modulations were gradually reduced, whereas those of vascular regulation were increased. A tight link between progression of arterial pressure and the continuum of changes in autonomic markers as shown by simple correlation analysis appeared strongly affected by age and was spread across many spectral analysis-derived variables. Hypertensive autonomic dysregulation was particularly apparent in the youngest group., Conclusions: RR-variability parameters might prove useful to assess, with longitudinal studies, the mechanistic role of autonomic impairment in the increased risk of prehypertensive conditions.

Background: Although cardiovascular rehabilitation and exercise training have substantial benefits in various ischemic heart disease (IHD) risk factors and subsequent prognosis after major IHD events, there is a paucity of information about its effects on autonomic regulation (such as heart rate variability [HRV] and baroreflex gain), particularly considering its arterial and cardiopulmonary components., Methods: We studied 40 patients (aged 60 +/- 6 y) after major IHD events, including 29 who underwent a comprehensive phase II cardiac rehabilitation and exercise training program and 11 controls who did not attend cardiac rehabilitation. Specifically, we determined whether active training improves prognostic indices of autonomic regulation of the SA node and whether changes in baroreflex gain could be ascribed to the arterial or to the cardiopulmonary component of the overall arterial pressure/heart period baroreflex., Results: Only patients with IHD undergoing active rehabilitation demonstrated a significant increase in R-R interval, in its variance, in overall gain of arterial pressure/heart period baroreflex (7.44 +/- 1.20 ms/mm Hg to 12.12 +/- 1.48 ms/mm Hg, P <.001) and in peak oxygen consumption (Delta = 2.45 mL/kg/min, P <.001). Separate examination of the selective arterial and cardiopulmonary components showed that only the latter increased significantly (6.17 +/- 1.09 ms/mm Hg to 10.62 +/- 1.56 ms/mm Hg; P <.01)., Conclusions: Cardiac rehabilitation is associated with significant improvements in autonomic markers of neural regulation of the SA node, such as increases in R-R variance and the gain of the overall spontaneous baroreflex, with specific improvements in the cardiopulmonary component as opposed to the arterial baroreflex component of this system. These improvements may further explain the reduction in morbidity and mortality noted after formal cardiac rehabilitation and exercise training programs.

Psychological stress represents a risk factor for hypertension, but mechanisms are not known in detail. In this investigation we tested the hypothesis that real-life stress conditions produce changes in autonomic cardiac and vascular regulation that might differ in magnitude. University students, a well-established model of mild real-life stress, were examined shortly before a university examination, and a second time 3 months afterward, during holiday. Autonomic cardiovascular regulation was assessed by a noninvasive approach, based on autoregressive analysis of RR interval variability (V) and of systolic arterial pressure (SAP) V. The overall level of stress in the two sessions was gauged from the elevated salivary cortisol (5.6+/-0.5 versus 2.4+/-0.2 ng/mL, P<0.05) and altered cytokine profile (P<0.05). During the stress day, the RR interval was reduced and arterial pressure increased significantly; simultaneously, the normalized low frequency component of RRV (a marker of sympathetic modulation of the sinoatrial node) was increased and the index alpha (a measure of baroreflex gain) reduced. Concomitantly, the autonomic response to the sympathetic excitation produced by standing was altered: cardiac response was impaired and vascular responsiveness increased. Markers of autonomic regulation of the sinoatrial node correlated significantly with cortisol levels, both at rest and also considering standing induced changes, suggesting a gradual range of effects. The data support the concept that mild real-life stress increases arterial pressure and impairs cardiovascular homeostasis. These changes, assessable with spectral analysis of cardiovascular variability, might contribute, in susceptible individuals, to the link between psychological stress and increased cardiovascular risk of hypertension.

Background: Metabolic syndrome (MetS) is associated with an increased risk of cardiovascular diseases. Compelling evidence supports the key role of dysfunction in the autonomic nervous system in that association, as well as mutual correlation among the components of MetS. The autonomic nervous system index (ANSI) is a percentile-ranked unitary proxy of cardiac autonomic regulation (CAR) that is designed to be free of age and sex bias, with higher values indicating better autonomic control. This study investigates CAR using the ANSI in patients with MetS. Methods: A total of 133 patients referred to the Exercise Medicine Clinic of Istituto Auxologico Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) underwent CAR assessment using the ANSI and answered lifestyle questions in ad hoc questionnaires. The participants were retrospectively subdivided into two groups according to the presence or absence of MetS criteria. Results: Of the subjects, 58 were diagnosed with MetS, and 75 were not (no MetS). The ANSI was significantly impaired (32.9 vs. 44.8, P<0.01) in the MetS group, and ANSI scores showed a decreasing trend (P=0.004) as the number of MetS components increased. No significant lifestyle differences were found between the groups. Conclusion: The ANSI was significantly reduced in subjects with MetS, and, net of age and sex effects, CAR impairment became progressively more apparent as the number of MetS components increased. [ABSTRACT FROM AUTHOR]

Aim: The mechanisms governing the organism's response to exercise are complex and difficult to study. Spectral analysis of heart rate variability (HRV) could represent a convenient methodology for studying humans' autonomic nervous system (ANS). However, difficulties in interpreting the multitude of correlated HRV-derived indices, mainly when computed over different time segments, may represent a barrier to its usage. This preliminary investigation addressed to elite athletes proposes a novel method describing the cardiac autonomic response to exercise based on multilevel exploratory factor analysis (MEFA), which reduces the multitude of HRV-derived indices to fewer uncorrelated ANS indicators capable of accounting for their interrelationships and overcoming the above difficulties. Methods: The study involved 30 Italian Olympic athletes, divided into 15 cyclists (prevalent high-intensity endurance training) and 15 shooters (prevalent technical training with low-intensity endurance component). All athletes underwent a complete test of a dynamic protocol, constituted by a rest-stand test followed by a stepwise bicycle stress test subdivided into a single bout of progressive endurance (from aerobic to anaerobic) exercise and recovery. Then, by spectral analysis, values of 12 ANS proxies were computed at each time segment (9 epochs in all) of the complete test. Results: We obtained two global ANS indicators (amplitude and frequency), expressing the athletes' overall autonomic response to the complete test, and three dynamic ANS indicators (amplitude, signal self-similarity, and oscillatory), describing the principal dynamics over time of the variability of RR interval (RRV). Globally, cyclists have significantly higher amplitude levels (median ± MAD: cyclists 69.9 ± 20.5; shooters 37.2 ± 19.4) and lower frequency levels (median ± MAD: cyclists 37.4 ± 14.8; shooters 78.2 ± 10.2) than shooters, i.e., a parasympathetic predominance compared to shooters. Regarding the RRV dynamics, the signal self-similarity and oscillatory indicators have the strongest sensitivity in detecting the rest-stand change; the amplitude indicator is highly effective in detecting the athletes' autonomic changes in the exercise fraction; the amplitude and oscillatory indicators present significant differences between cyclists and shooters in specific test epochs. Conclusion: This MEFA application permits a more straightforward representation of the complexity characterizing ANS modulation during exercise, simplifying the interpretation of the HRV-derived indices and facilitating the possible real-life use of this non-invasive methodology. [ABSTRACT FROM AUTHOR]

Physical inactivity increases cardiometabolic risk through a variety of mechanisms, among which alterations of immunological, metabolic, and autonomic control systems may play a pivotal role. Physical inactivity is frequently associated with other factors that may further worsen prognosis. The association between physical inactivity and hypoxia is particularly interesting and characterizes several conditions—whether physiological (e.g., residing or trekking at high altitude and space flights) or pathological (e.g., chronic cardiopulmonary diseases and COVID-19). In this randomized intervention study, we investigated the combined effects of physical inactivity and hypoxia on autonomic control in eleven healthy and physically active male volunteers, both at baseline (ambulatory) conditions and, in a randomized order, hypoxic ambulatory, hypoxic bedrest, and normoxic bedrest (i.e., a simple experimental model of physical inactivity). Autoregressive spectral analysis of cardiovascular variabilities was employed to assess cardiac autonomic control. Notably, we found hypoxia to be associated with an impairment of cardiac autonomic control, especially when combined with bedrest. In particular, we observed an impairment of indices of baroreflex control, a reduction in the marker of prevalent vagal control to the SA node, and an increase in the marker of sympathetic control to vasculature. [ABSTRACT FROM AUTHOR]

Exercise is one of the major determinants of a healthy lifestyle, which is particularly important in childhood and serves as a powerful preventive tool. On the other hand, obesity and arterial hypertension rates are increasing in children, representing a huge risk for developing major cardiovascular and metabolic diseases in adult life. Of fundamental importance is the modality and volume of exercise required to obtain benefits. In this feasibility study, we considered a group of obese children, studied before and after a 12-week online exercise training program, and subdivided the participants into two groups considering the volume of exercise performed (above or below 1200 MET·min/week). This threshold level was applied in two different ways: subdivision A considered the total weekly physical activity volume (considering both time spent walking for at least 10 min consecutively and time spent performing structured exercise) and subdivision B considered only the weekly volume of structured exercise. We assessed autonomic and metabolic control and auxological and lifestyle parameters. We observed that the improved volume of structured exercise was associated with reduced arterial pressure percentile only in subdivision B and an improvement in markers of vagal and metabolic control was evident. Moreover, the 12-week online exercise training program, defined considering individual fitness level and progressively adapted as the goal was reached, proved to be sustainable from an economical and organizational point of view. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study on Spinal Cord Injury (SCI) patients with cervical or thoracic lesion was to assess whether disturbances of ANS control, according to location, might differently affect vagal and sympatho-vagal markers during sleep and orthostatic challenge. We analyzed with linear and nonlinear techniques beat-by-beat RR and arterial pressure (and respiration) variability signals, extracted from a polysomnographic study and a rest–tilt test. We considered spontaneous or induced sympathetic excitation, as obtained shifting from non-REM to REM sleep or from rest to passive tilt. We obtained evidence of ANS cardiac (dys)regulation, of greater importance for gradually proximal location (i.e., cervical) SCI, compatible with a progressive loss of modulatory role of sympathetic afferents to the spinal cord. Furthermore, in accordance with the dual, vagal and sympathetic bidirectional innervation, the results suggest that vagally mediated negative feedback baroreflexes were substantially maintained in all cases. Conversely, the LF and HF balance (expressed specifically by normalized units) appeared to be negatively affected by SCI, particularly in the case of cervical lesion (group p = 0.006, interaction p = 0.011). Multivariate analysis of cardiovascular variability may be a convenient technique to assess autonomic responsiveness and alteration of functionality in patients with SCI addressing selectively vagal or sympathetic alterations and injury location. This contention requires confirmatory studies with a larger population. [ABSTRACT FROM AUTHOR]

Athletic performance is determined by many factors, such as cardiorespiratory fitness, muscular strength and psychological features, which all interact simultaneously. The large Italian National Olympic Committee database of Olympic athletes offers a unique healthy population to verify the strength of the interplay among a number of major elements of training, including autonomic nervous system (ANS) modulation, biochemical indicators and body composition, in a system medicine approach. This observational, retrospective study involved 583 individuals. As part of the yearly precompetitive examination, cardiac autonomic (heart rate variability), psychological, physical (cycloergometer stress test), biochemical and body composition (BOD POD) evaluations were performed. In subsequent analysis, we first considered the relationship between body composition and single individual variables in a simple correlation matrix, including a multitude of variables; then, Exploratory Factor Analysis (EFA) restricted the information to six latent domains, each combining congruent information in relation to body composition. Finally, we employed a multiple quantile regression model to evaluate possible relationships between ANSIs (index capable of synthetizing ANS regulation) and the latent domains indicated by EFA reflecting body composition. We observed a clear relationship between ANS and body mass composition parameters, as indicated by both bivariate correlations and the quantile regression result of ANSIs versus the latent domain aggregating mainly body composition data expressed in % (p = 0.002). In conclusion, these results suggest that specific training may elicit parallel adaptation of ANS control and body composition. The analysis of Olympic athletes' data allowed us to obtain a better understanding of the complex, multidimensional factors involved in determining sport performance. The latter appears to be determined by the simultaneous interaction not only of cardiorespiratory fitness, muscular strength and psychological features, but also of ANS cardiovascular modulation and body composition. [ABSTRACT FROM AUTHOR]

Obesity is associated with an increased risk of several chronic comorbidities, which may also be determined by dysfunctional autonomic nervous system (ANS). The influence of bariatric surgery (BS) on ANS balance was explored in previous studies, but with high heterogeneity in both the assessment timing and methods employed. In the present observational study, we applied a clinical protocol which considers two subsequent phases. Twenty-nine non-diabetic obese subjects were studied at baseline (T0), after one month of lifestyle modification (prehabilitation) (phase 1-T1), and after eight months following BS (phase 2-T2). ANS regulation was assessed across the three study epochs by means of ANSI, a single composite percent-ranked proxy of autonomic balance, being free of gender and age bias, economical and simple to apply in a clinical setting. The aim of the present study was to investigate the effects of the clinical protocol based on prehabilitation and subsequent BS on the ANS regulation by means of ANSI. Potential intertwined correlations with metabolic parameters were also investigated. Notably, we observed a progressive improvement in ANS control, even by employing ANSI. Moreover, the reduction in the markers of sympathetic overactivity was found to significantly correlate with the amelioration in some metabolic parameters (fasting glucose, insulin levels, and waist circumference), as well as in stress and tiredness perception. In conclusion, this study provides convincing evidence that a unitary proxy of cardiac autonomic regulation (CAR) may reflect the progressive improvement in autonomic regulation following behavioral and surgical interventions in obese patients. Intriguingly, this might contribute to reducing cardiovascular and metabolic risk. [ABSTRACT FROM AUTHOR]

QT interval (QT) variability analysis provides pathophysiological and prognostic information utilized in cardiac and non-cardiac diseases, complementary to those obtained from the analysis of heart period (HP) variability. An increased QT variability has been associated to a higher risk for cardiac events and poorest prognosis. Autonomic cardiovascular adaptation to internal and external challenges, such those occurring in athletes exposed to high levels of physical stress and in ageing could also be deepen by analyzing QT variability, searching for early prognostic signatures. The aim of the study was to analyze the QT variability and cardiac control complexity in a group of middle-aged half-marathon runners at baseline (B) and at a 10-year follow-up (FU). We found that the overall QT variability decreased at FU, despite the inescapable increase in age (52.3 ± 8.0 years at FU). This change was accompanied by an increase of the HP variability complexity without changes of the QT variability complexity. Of notice, over the years, the group of athletes maintained their regular physical activity by switching to a moderate intensity rather than strenuous. In conclusion, regular and moderate exercise over the years was beneficial for this group of athletes, as reflected by the decreased overall QT variability that is known to be associated to lower cardiovascular risk. The concomitant enhanced cardiac control complexity also suggests a trend opposite to what usually occurs with ageing, resulting in a more flexible cardiac control, typical of younger people. [ABSTRACT FROM AUTHOR]

In the context of functional determinants of cardiovascular risk, a simple excess in body weight, as indexed by a rise in body mass index (BMI), plays a significant, well-recognized causal role. Conversely, BMI reductions toward normal result in an improvement of risk. Obesity is associated with impaired cardiac autonomic regulation (CAR), through either vagal or sympathetic mechanisms, which could favor the tendency to foster hypertension. Here we study the changing properties of the relationship between increasing grades of BMI and CAR in a population of 756 healthy subjects (age 35.9 ± 12.41 years, 37.4% males, 21.6% overweight, and 16% obese). Evaluation of CAR is based on autoregressive spectral analysis of short-term RR interval and systolic arterial pressure variability, from which a multitude of indices, treated overall as autonomic nervous system (ANS) proxies, is derived. Inspection of the study hypothesis that elevated BMI conditions associate significantly with alterations of CAR, independently of age and gender, is carried out using a mix of statistical transformations, exploratory factor analysis, non-parametric testing procedures, and graphical tools particularly well suited to address alterations of CAR as a disturbed process. In particular, to remove the effects of the inter-individual variability, deriving from components like age, gender or ethnicity, and to reduce the number of ANS proxies, we set up six age-and-gender-adjusted CAR indicators, corresponding to four ANS latent domains (oscillatory, amplitude, pressure, and pulse), cardiac baroreflex regulation, and autonomic nervous system index (ANSI). An impairment of the CAR indicators is overall evident in the overweight group and more marked in the obesity group. Empirical evidence is strong (9/9 concordant non-parametric test results) for pressure domain, almost strong (8/9) for ANSI, medium-strong for baroreflex (6/9) and pulse (7/9), weak for oscillatory (2/9) and amplitude (1/9) domains. In addition, the distribution of the CAR indicators corresponding to pressure, pulse, baroreflex, and ANSI is skewed toward the unfavorable abscissa extremity, particularly in the obese group. The significant association of increased BMI with progressive impairments of CAR regarding specifically the pressure domain and the overall ANS performance might underscore the strong hypertensive tendency observed in obesity. [ABSTRACT FROM AUTHOR]

Objective: Traditional definition of sample entropy (SampEn), here referred to as global SampEn (GSampEn), provides a conditional entropy estimate that blurs the local statistical properties of the time series. We hypothesized that a local version of SampEn (LSampEn) might be more powerful in the presence of determinism than GSampEn. Methods: LSampEn was computed by calculating the probability of the current sample conditioned on each reference pattern and averaging it over all reference patterns. The improved ability of LSampEn compared to GSampEn was demonstrated by simulating deterministic periodic, deterministic chaotic, and linear stochastic dynamics corrupted by additive noise and over real cardiovascular variability series recorded from 16 healthy subjects (max–min age range: 22–58 years) during incremental bicycle ergometer exercise. Results: We found that: i) LSampEn is more robust in describing deterministic periodic or nonlinear features in the presence of additive noise than GSampEn, ii) in association with a surrogate approach, LSampEn is more powerful in detecting nonlinear dynamics than GSampEn, iii) LSampEn and GSampEn are equivalent in the presence of stochastic linear dynamics, and iv) only LSampEn can detect the decrease of complexity of heart period variability during bicycle exercise being a likely hallmark of sympathetic activation. Conclusion: LSampEn preserves the GSampEn capability in characterizing the complexity of short sequences but improves its reliability in the presence of deterministic patterns featuring sharp state transitions and nonlinear dynamics. Significance: Variations of complexity can be measured with a greater statistical power over short series using LSampEn, especially when nonlinear features are present. [ABSTRACT FROM AUTHOR]

The arm of the baroreflex (BR) controlling peripheral resistances (PR), labeled as BR of PR (prBR), was characterized through an extension of the cardiac BR (cBR) sequence analysis. The method exploits recordings of skin blood flow (SBF) from the palm of the non-dominant hand via a laser Doppler flowmeter and of arterial pressure (AP) from the middle finger of the same hand via a plethysmographic device. PR was estimated beat-by-beat as the ratio of mean AP to mean SBF computed over the same heart period (HP). Peripheral resistances-diastolic arterial pressure (PR-DAP) sequences featuring simultaneous increases of PR and decreases of diastolic AP (DAP) or vice versa were identified and the slope of the regression line in the (DAP, PR) plane was taken as an estimate of prBR sensitivity (BRSprBR). The percentage of prBR sequences (SEQ%prBR) was taken as a measure of prBR involvement and the prBR effectiveness index (EIprBR) was computed as the fraction of DAP sequences capable to drive antiparallel PR variations. Analogous markers were computed over cBR from HP and systolic AP (SAP) variability [i.e., cBR sensitivity (BRScBR), percentage of cBR sequences (SEQ%cBR); and effectiveness index of the cBR (EIcBR)]. prBR and cBR were typified during incremental light-to-moderate bicycle ergometer exercise at 10, 20, and 30% of the maximum effort in 16 healthy subjects (aged from 22 to 58 years, six males). We found that: (i) BRScBR decreased gradually with the challenge, while BRSprBR declined only at the heaviest workload; (ii) SEQ%cBR decreased solely at the lightest workload, while the decline of SEQ%prBR was significant regardless of the intensity of the challenge; (iii) EIprBR and EIcBR were not affected by exercise; (iv) after pooling together all the data regardless of the experimental conditions, BRSprBR and BRScBR were uncorrelated, while SEQ%cBR and SEQ%prBR as well as EIcBR and EIprBR, were significantly and positively correlated; (v) when the correlation between SEQ%cBR and SEQ%prBR and between EIcBR and EIprBR was assessed separately in each experimental condition, it was not systematically detected. This study suggests that prBR characterization provides information complementary to cBR that might be fruitfully exploited to improve patients' risk stratification. [ABSTRACT FROM AUTHOR]

Purpose: Optimal autonomic regulation and stress resilience might be considered critical elements of athletic performance. We hypothesize that a novel unitary autonomic index for sports (ANSIs), together with a somatic stress related symptom score (4SQ) might help characterize athletes who were eventually selected for the Rio 2016 Olympic Games Italian team (Rio +).Methods: In this retrospective study we examined 778 athletes (age 24.4 ± 6.7 yrs) who underwent a planned yearly pre-participation screening. All athletes underwent clinical, autonomic and exercise ECG evaluation. The combination of vagal and sympathetic indices from RR variability into ANSIs was performed by radar plot and percent ranking of index variables. We assessed (Rio +) versus (Rio -) athletes also after subdivision into three sport intensity groups (low, mid and high intensity).Results: Overall there were no significant differences between (Rio +) and (Rio -) athletes when considering individual spectral derived variables. Conversely, the unitary Index ANSIs was significantly higher in (Rio +) compared to (Rio -) athletes (respectively 54.5 ± 29.5 and 47.9 ± 28.4 p = 0.014). This difference was particularly evident (p = 0.017) in the group of athletes characterized by both high static and dynamic components. 4SQ was smaller in the (Rio +) group, particularly in the groups of athletes characterized by both low-medium static and dynamic components.Conclusions: ANSIs, a proxy of integrated cardiac autonomic regulation and simple assessment of resilience to stress, may differentiate Italian athletes who were eventually selected for participation in the 2016 Rio Olympic Games from those who were not, suggesting the possibility of a "winning functional phenotype". [ABSTRACT FROM AUTHOR]

In spite of the large body of evidence suggesting Heart Rate Variability (HRV) alone or combined with blood pressure variability (providing an estimate of baroreflex gain) as a useful technique to assess the autonomic regulation of the cardiovascular system, there is still an ongoing debate about methodology, interpretation, and clinical applications. In the present investigation, we hypothesize that non-parametric and multivariate exploratory statistical manipulation of HRV data could provide a novel informational tool useful to differentiate normal controls from clinical groups, such as athletes, or subjects affected by obesity, hypertension, or stress. With a data-driven protocol in 1,352 ambulant subjects, we compute HRV and baroreflex indices from short-term data series as proxies of autonomic (ANS) regulation. We apply a three-step statistical procedure, by first removing age and gender effects. Subsequently, by factor analysis, we extract four ANS latent domains that detain the large majority of information (86.94%), subdivided in oscillatory (40.84%), amplitude (18.04%), pressure (16.48%), and pulse domains (11.58%). Finally, we test the overall capacity to differentiate clinical groups vs. control. To give more practical value and improve readability, statistical results concerning individual discriminant ANS proxies and ANS differentiation profiles are displayed through peculiar graphical tools, i.e., significance diagram and ANS differentiation map, respectively. This approach, which simultaneously uses all available information about the system, shows what domains make up the difference in ANS discrimination. e.g., athletes differ from controls in all domains, but with a graded strength: maximal in the (normalized) oscillatory and in the pulse domains, slightly less in the pressure domain and minimal in the amplitude domain. The application of multiple (non-parametric and exploratory) statistical and graphical tools to ANS proxies defines differentiation profiles that could provide a better understanding of autonomic differences between clinical groups and controls. ANS differentiation map permits to rapidly and simply synthesize the possible difference between clinical groups and controls, evidencing the ANS latent domains that have at least a medium strength of discrimination, while the significance diagram permits to identify the single ANS proxies inside each ANS latent domain that resulted in significant comparisons according to statistical tests. [ABSTRACT FROM AUTHOR]

Abstract: In this brief review we address schematically the relationship between two emerging issues in clinical medicine: stress and functional syndromes. It is becoming increasingly clear that they demand a multidimensional approach, considering simultaneously elements of behavioral therapy with traditional pharmacological treatment, guided by a better physiopathological understanding including autonomic assessment. New techniques, based on innovative analysis of continuous segments of electrocardiogram and non invasive arterial pressure recordings capable to extract hidden oscillations, provide quantitative indices of sympathetic and vagal modulation of the cardiovascular system. This more complete diagnostic process facilitates explanation of symptoms and reassurance of patients, based on functional evidence. The described clinical approach implies in addition an active collaboration of patients requiring the implementation of a creative alliance. Physical exercise, eating habits and muscular–mental relaxation are combined with pharmacological tools as needed. [Copyright &y& Elsevier]

To focus on early cardiac and vascular autonomic dysfunction that might complicate type 1 diabetes mellitus in children, we planned an observational, cross-sectional study in a population of 93 young patients, under insulin treatment, subdivided in 2 age subgroups (children: 11.5+/-0.4 years; adolescents: 19.3+/-0.2 years). Time and frequency domain analysis of RR interval and systolic arterial pressure variability provided quantitative indices of the sympatho-vagal balance regulating the heart period, of the gain of cardiac baroreflex, and of the sympathetic vasomotor control. Sixty-eight children of comparable age served as a reference group. At rest, systolic arterial pressure and the power of its low-frequency component were greater in patients than in controls, particularly in children (14.0+/-2.3 versus 3.1+/-0.3 mm Hg2). Moreover, baroreflex gain was significantly reduced in both subgroups of patients. Standing induced similar changes in the autonomic profiles of controls and patients. A repeat study after 1 year showed a progression in low-frequency oscillations of arterial pressure and a shift toward low frequency in RR variability. Data in young patients with type 1 diabetes mellitus show a significant increase in arterial pressure, a reduced gain of the baroreflex regulation of the heart period, and an increase of the low-frequency component of systolic arterial pressure variability, suggestive of simultaneous impairment of vagal cardiac control and increases of sympathetic vasomotor regulation. A repeat study after 1 year shows a further increase of sympathetic cardiac and vascular modulation, suggesting early progression of the autonomic dysfunction. [ABSTRACT FROM AUTHOR]

The increased cardiometabolic risk observed in breast cancer survivors (BCS) is due to multiple mechanisms: Hormonal and immunological dysfunction are well-identified ones, while cardiac autonomic regulation (CAR) is less recognized but may play a new complementary role particularly relevant when considering conditions and behaviors associated with a better prognosis in BCS, such as physical training. This observational study investigated a group of consecutive (172) BCS subdivided in two groups: those who reached the physical activity goals above 600 (MET·min/week) and those who did not. We assessed CAR by autoregressive spectral analysis of cardiovascular variabilities (considering in particular the unitary autonomic nervous system index—ANSI), body mass composition, stress perception and lifestyle in order to verify possible differences due to execution of physical activity. Subjects who spontaneously met physical activity recommendations presented a better autonomic, metabolic and psychological profile compared to those who did not. Lower physical activity volume, poor metabolic parameters, increased stress and fatigue perception may cluster together, leading to worsened CAR. This control mechanism may play a complementary role in determining the increased cardiometabolic risk observed in BCS. Furthermore, it may also explain, albeit in part, the better prognosis observed in patients following interventions aiming to improve the sympathetic–parasympathetic balance, such as physical training, using a personalized medicine approach. [ABSTRACT FROM AUTHOR]

Abstract: Caregiving, an important component of cancer patient treatment, may set forth a cascade of stress responses such as sympatho-adrenal activation, immuno-humoral changes and an unhealthy lifestyle, which could be hazardous to caregivers’ health. In this observational study, we addressed whether autonomic nervous system (ANS) regulation and perception of stress would be altered in a group of 58 health cancer caregivers as compared to 60 controls. We employed non invasive autoregressive spectral analysis of cardiovascular variabilities and ad hoc questionnaires. Caregivers show, in addition to signs of psychological involvement, a clear autonomic imbalance, suggestive of sympathetic predominance at rest and of a reduction of vagal cardiac regulation (overall gain of baroreflex -index α- was respectively of 17.5±1.5 versus 25.1±1.8msec/mmHg, p<<0.02). These data suggest possible preventive strategies, based on tailored treatments aiming at a betterment of individual autonomic profile. [Copyright &y& Elsevier]

In adults, initial stages of hypertension are associated with elevated sympathetic drive and significant alterations in indirect autonomic markers. There is growing evidence that children in the highest-pressure percentiles will be more likely to develop hypertension in adulthood, although mechanisms are not understood. We assessed whether computer analysis of RR interval and arterial blood pressure variability could detect early autonomic alterations in childhood hypertension, as assessed by noninvasive time and frequency domain measures of baroreflex regulation. We studied 75 children, subdivided in 3 subgroups of similar age (9.7+/-0.2 years): control subjects, prehypertensive children (ie, children with arterial pressure values >90th and <95th percentile for age, gender, and height), and children in the hypertensive range (ie, >95th percentile; systolic arterial pressure: 97+/-3/57+/-2, 121+/-5/70+/-1, and 128+/-2/80+/-2 mm Hg, respectively). We observed that hypertensive children demonstrate a significant impairment of the baroreflex as compared with control subjects (index alpha: 20+/-2 and 40+/-4 ms/mm Hg; spontaneous baroreflex slope: 20+/-2 and 37+/-5; ms/mm Hg; P<0.05 in both cases) and reduced RR variance. A similar baroreflex impairment is also observed in children whose arterial pressure falls short of this limit, ie, in the prehypertensive range. In conclusion, hypertensive children display a marked baroreflex impairment. A similar baroreflex impairment is also observed in the prehypertensive state. Baroreflex assessment could furnish additional information in the clinical assessment of pediatric hypertension. [ABSTRACT FROM AUTHOR]

Objectives: An increased sympathetic drive, in view of its proarrhythmic, proatherosclerotic, and prothrombotic actions, could contribute to the elevated cardiovascular risk of habitual smokers. However, the underlying mechanisms are still debated. In this study we address the hypothesis that spectral analysis of RR interval and systolic arterial pressure short-term variabilities may be used to assess the complex autonomic changes produced by habitual cigarette smoking. Methods: A cross-sectional design compared heavy (> 20 cigarettes/day) habitual smokers (n = 20; 40 ± 3 years), with similar age controls. Spectral analysis of RR interval variability provided markers of the sympatho-vagal balance modulating the SA node, by way of the normalised low frequency (LF ≅ 0.10 Hz) and high frequency (HF ≅ 0.25 Hz) components. The LF component of systolic arterial pressure (SAP) variability assessed the sympathetic vasomotor modulation. The frequency domain index (α) measured the baroreflex gain of the SA node. Subjects were studied at rest, and during the sympathetic excitation produced by active standing. Results: In smokers LFRR was, at rest, greater than in controls (70.6 ± 3.8 vs 46.0 ± 2.5 normalised units, nu); concurrently HFRR was reduced (22.1 ± 3.2 vs 42.0 ± 2.8 nu). Baroreflex gain and RR variance were also smaller in smokers. LFSAP was, instead, similar in the smokers and control groups. The standing induced increase in LFRR was blunted (P < 0.001) in smokers. Conclusions: Spectral analysis of RR interval and systolic arterial pressure variability indicates that habitual cigarette smoking induces selective alterations in neural control of the SA node. An increase at rest in markers of sympathetic modulation is accompanied by signs of reduced vagal drive and depressed baroreflex gain; while sympathetic vasomotor modulation appears similar in controls and smokers. Data are consistent with the hypothesis that autonomic alterations may contribute to the increased cardiovascular risk present in smokers. [ABSTRACT FROM PUBLISHER]