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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]

Early obesity predicts initialmodifications in cardiac and vascular autonomic regulation. The aim of this studywas to assess the possible interaction between non-invasivemeasures of autonomic cardiovascular control and peripheral endotheliumregulation in childrenwith overweight and obesity. We involved 114 young subjects (77M/37F, 12.7 ± 2.2 years) with normal weight (NW, n = 46) to overweight or obesity (OB, n = 68). Multivariate statistical techniques utilizing a collection of modern indices of autonomic regulation, adiposity indexes andmetabolic profilewere employed. Resting values showsubstantial equivalence of data. Conversely, blood pressure variance is greater in NW/OB groups. The correlationmatrix betweenmajor autonomic andmetabolic/hemodynamic variables shows a clustered significant correlation between homogeneous indices. A significant correlation betweenmetabolic indices and endothelial and autonomic control, mostly in its vascular end, was recorded. Particularly, the alpha index is significantly correlated with triglycerides (r = -0.261) and endothelial indices (RHI, r = 0.276). Children with obesity show a link between indices of autonomic and endothelial function, fat distribution and metabolic profile. The optimization of autonomic control, for instance by exercise/nutrition interventions, could potentially prevent/delay the occurrence of structural vascular damage leading to reduced cardiovascular health. [ABSTRACT FROM AUTHOR]

Interests about the fine underpinnings of cardiovascular beat-by-beat variability have historical roots. Over the last decades, various aspects of the relationships between arterial pressure and heart period were taken as a proxy of the baroreflex in physiology and medicine, stimulating the interest of investigators in several interconnected scientific fields, in particular, bioengineering, neurophysiology, and clinical medicine. Studies of the overall system facilitated the emergence of a simplified negative (vagal) feedback model of the baroreflex and overshadowed the simultaneous interaction with excitatory, sympathetic positive-feedback mechanisms that would, however, better suit the model of a "paired antagonistic (parasympathetic/sympathetic) innervation of the internal organs." From the bioengineering side, the simplicity of obtaining the series of subsequent RR intervals stimulated the analysis of beat-by-beat variations, providing a multitude of heart rate variability (HRV) indices considered as proxies of the underlying sympatho-vagal balance, and participating to the management of several important clinical conditions, such as hypertension. In this context, advanced statistical methods, used in an integrated manner and controlling for age and gender biases, might help shed new light on the relationship between cardiac baroreflex, assessed by the frequency domain index α, and the HRV indices with the varying of systolic arterial pressure (SAP) levels. The focus is also on a novel unitary Autonomic Nervous System Index (ANSI) built as a synthesis of HRV considering its three most informative proxies [RR, RR variance, and the rest-stand difference in the normalized power of low-frequency (LF) variability component]. Data from a relatively large set of healthy subjects (n = 1154) with a broad range of SAP [from normal (n Nt = 778) to elevated (n Ht = 232)] show that, e.g., α and ANSI significantly correlate overall (r = 0.523, p < 0.001), and that this correlation is lower in hypertensives (r = 0.444, p < 0.001) and higher in pre-hypertensives (r = 0.618, p < 0.001) than in normotensives (r = 0.5, p < 0.001). That suggests the existence of curvilinear "umbrella" patterns that might better describe the effects of the SAP states on the relationships between baroreflex and HRV. By a mix of robust, non-parametric and resampling statistical techniques, we give empirical support to this study hypothesis and show that the pre-hypertensive group results at the apex/bottom in most of the studied trends. [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]

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]

In most sports athletic performance is determined by a combination of hard and soft modifiable components, encompassing physical and psychological elements that can be assessed with modern techniques based respectively on simple friendly methods: analysis of HRV and questionnaires. Specifically a novel % rank Autonomic Nervous System Indicator (ANSI) seems particularly useful also in elite sports. In this investigation we assessed ANSI capacity to detect the expected changes in cardiac autonomic regulation induced in the Italian basketball team by the participation (18 subjects) to the yearly biweekly Alpine training summer camp. We observed that ANSI increased from 58.8 ± 32.5 to 81.7 ± 27.5 (at the end of training camp) and did not change further in the subsequent initial weeks of competition season (overall p < 0.001). Congruent changes were observed in non-linear indices. Concomitantly indices of somatic symptoms were slightly reduced just at the end of the alpine training. We conclude that analysis of HRV and questionnaires might offer a simple, useful technique to monitor changes in cardiac autonomic regulation and psychological state in elite athletes providing a convenient additional element to evaluation of training routines also in the fields. [ABSTRACT FROM AUTHOR]

Lifestyle modification programs (LMP) represent a new approach to cardiometabolic/oncologic risk reduction. Successful LMP in clinical practice must be feasible, cost effective, efficacious and consider home-based exercise. Likewise, multiple mechanisms implied in cardiometabolic risk reduction such as cardiac autonomic regulation (CAR) should be easily evidenced, in spite of the computational complexity involved. This goal could be facilitated by employing novel, friendlier, simpler techniques, such as the Autonomic Nervous System Index (ANSI), which can be treated as a proxy of CAR. In this observational study, we introduce a simple LMP (based on cognitive behavioral strategies and patient-tailored prescription of nutrition and home-based exercise, managed by a single physician) into the currently existing clinical practice of secondary cardiometabolic prevention. In 26 subjects, we assessed CAR (autoregressive spectral analysis of cardiovascular variabilities), body mass composition (bioelectrical impedance analysis) and stress perception (questionnaires). After LMP, ANSI and lipid profile were improved; % of fat mass, waist circumference and stress perception were reduced. We conclude that this preliminary, proof of concept study provides significant evidence in favor of the hypothesis that it is possible to introduce a convenient, cost effective LMP into the currently existing clinical practice of secondary cardiometabolic prevention. Findings suggest a successful comprehensive behavioral change, possibly facilitated by the simplified approach employed in this study, capable of improving cardiac autonomic regulation in addition to body mass composition and stress perception. [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]

Background Chronic non-communicable diseases represent the major drivers of disease burden, being responsible for the majority of health care cost and deaths. Almost half of premature deaths is due to behaviors amenable to change. Accordingly, addressing behavior might represent a strategic change in the health delivery system. Improving lifestyle requires a specific strategy embedding the active collaboration of individuals with a multilevel team-oriented medical practice. With the present study we sought to assess whether the implementation of cognitive-behavioral strategies, following the principles of lifestyle medicine in an outpatient clinic provides better results in weight reduction as compared to simpler strategies as presently executed in General Practitioners' offices. Methods This is an observational study on 173 subjects (age 53.1 ± 11.5), comparing three different groups of preventive practice: a personalized lifestyle medicine, combining cognitive behavioral strategies with patient tailored prescription of exercise and nutrition (Group A); a semi-structured approach with generic counseling (Group B); and an unstructured advice (Group C). Results At the end of the intervention period (17–20 months), group A showed an average weight loss of 5.4 ± 5.1 kg, which was significantly (p < 0.001)more than observed in group B (2.8 ± 5.1 kg) and group C (1.2 ± 4.8 kg). Likewise BMI and waist were progressively more reduced from A to C. Conclusions It is possible to implement preventive cognitive-behavioral lifestyle strategies in outpatient internal medicine clinics. This methodology appears more efficacious in inducing weight reduction after more than a year as compared to usual family medicine approaches. [ABSTRACT FROM AUTHOR]

Introduction: Sleep-related breathing disorders are highly prevalent in patients with ischemic stroke. Among sleep-disordered breathing disorders, obstructive sleep apnea is the most represented one, but central sleep apnea, isolated or in the context of a periodic breathing/Cheyne-Stokes respiration, is frequently reported in these patients. Altered baroreflex responses have been reported in the acute phases of a cerebral event., Methods: We conducted, in a group of patients with ischemic stroke (n=60), a prospective 3-month follow-up physiological study to describe the breathing pattern during sleep and baroreflex sensitivity in the acute phase and in the recovery phase., Results: In the acute phase, within 10 days from the onset of symptoms, 22.4% of patients had a normal breathing pattern, 40.3% had an obstructive pattern, 16.4% had a central pattern, and 29.9% showed a mixed pattern. Smaller variations in the Apnea-Hypopnea Index were found in normal breathing and obstructive groups (ΔAHI 2.1±4.1 and -2.8±11.6, respectively) in comparison with central and mixed patterns (ΔAHI -6.9±15.1 and -12.5±13.1, respectively; ANOVA p =0.01). The obstructive pattern became the most frequent pattern, in 38.3% of patients at baseline and 61.7% of patients at follow-up. Modification of baroreflex sensitivity over time was influenced by the site of the lesion and by the sleep disorder pattern in the acute phase (MANOVA p =0.005)., Conclusion: We suggest that a down-regulation of autonomic activity, possibly related to reduced vagal modulation, may help the recovery after stroke, or a transitory disconnection from the cortical node that participates in the regulation of sympathetic outflow., Competing Interests: Dr Alessia Riglietti reports grants from ABREOC (Scientific Research Advisory Board of the Ente Ospedaliero Cantonale), Doctor PierLuigi Crivelli Foundation and Cecilia Augusta Foundation, during the conduct of the study. Dr Carlo W Cereda is a member of the iSchemaView Medical and Scientific Advisory Board, but this institution played no role in current research . Prof. Dr Marco Pons report grants from ABREOC, Dr Pieruigi Crivelli Foundation and Cecilia Augusta Foundation, during the conduct of the study. The authors have no other financial support or conflicts of interest to declare., (© 2021 Riglietti et al.)

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.

The study proposes an extension of cardiac baroreflex (cBR) sequence analysis, traditionally performed over spontaneous fluctuations of heart period and systolic arterial pressure, to typify peripheral resistance baroreflex (prBR) from spontaneous variations of peripheral resistances and diastolic arterial pressure. The prBR baroreflex sensitivity (BRS prBR ) and percentage of prBR sequences (SEQ% prBR ) were computed along with analogous quantities assessed over cBR (i.e. BRS cBR and SEQ% cBR ). The cBR and prBR were typified in healthy subjects at rest (REST) and during light bicycle ergometer exercise at 10 percent of the maximal effort (EXE). Both cBR and prBR were affected by EXE: indeed, BRS cBR and SEQ% prBR were significantly reduced. Moreover, while BRS cBR and BRS prBR were not significantly associated, SEQ% cBR and SEQ% prBR were, and the correlation coefficient was positive. This study suggests that prBR can be typified from spontaneous variabilities along with the more traditional cBR, thus enlarging the possibility of monitoring human cardiovascular control mechanisms.

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.

Objectives: This study addressed the relationship between spontaneous baroreflex sensitivity and carotid mechanical properties in a clinical setting., Methods: In 191 normal volunteers (age range 20-60 years, mean 44 ± 13), spontaneous indices of baroreflex regulation were obtained noninvasively in the time (baroreflex slope, BRS) and frequency domains (α index and systolic arterial pressure-RR interval transfer gain) as well as using an exogenous autoregressive causal model (A.XAR); carotid mechanical properties were estimated by ultrasound. The link between mechanical measures and spontaneous baroreflex indices was explored by multivariate analysis and linear modeling., Results: Participants were divided into five groups according to age decades. With advancing age we observed a decrease in spontaneous baroreflex indices (BRS from 31.2 to 16.3; α index from 27.4 to 13.6; RR-SAP gain at high frequency from 31 ± 3.0 to 14 ± 3.0 ms/mmHg all P < 0.001) and increase in carotid intima-media thickness (IMT: from 0.53 to 0.69 mm; P < 0.001) and stiffness (local wave speed: from 4.0 to 6.9 m/s; both P < 0.001). A significant correlation was found between spontaneous indices of baroreflex sensitivity and carotid mechanical properties, particularly wave speed (r = -0.328, P < 0.001). After adjusting for age and sex, a significant correlation remained between RR-SAP gain and wave speed and between A.XAR and IMT. Factor analysis and automatic linear modeling confirmed the observation that mechanical carotid properties are strong predictors of the age-related reduction of spontaneous baroreflex., Conclusion: A significant correlation between spontaneous baroreflex indices and local carotid mechanical properties supports the idea that they should be considered in the physiology of baroreflex regulation.

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.

Recent epidemiological evidence indicates that chronic degenerative diseases, notably cardiovascular, represent the major toll in terms of death and of impaired quality of life. Recent estimates indicate that a small increase in financial resources in a number of clinical cases may be sufficient to minimize the consequences of elevated cardiovascular risk per individual. The observation that lifestyle choices, and in particular increased physical exercise, might strongly impact cardiovascular risk, suggests a redesign of preventive strategies, based on the combination of pharmacological and behavioral interventions. Following our recent experience with the INteractive teleConsultation network for worldwide healthcAre Services (INCAS) system, we designed a simpler point-to-point telehealth infrastructure, to be employed in cardiovascular risk reduction programs, predicting a high level of acceptance from the population, at the cost of very limited investment. This model was tested on 181 subjects (ages 18-80 years) in the Italian mountain village of Esino Lario. These subjects underwent a screening test to evaluate arrhythmia and cardiometabolic risks (arrhythmias were found in 14% of subjects, systolic arterial pressure was observed in 43% of subjects above 140 mm Hg, diastolic arterial pressure in 31% above 90 mm Hg). This study demonstrates the feasibility of a scaled-down telehealth application particularly suited to cardiovascular prevention in remote areas, such as in mountain villages.

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.

This paper describes preliminary experience in shared clinical management of patients located in Pointe Noire, Africa, and a referral center, Sacco University Hospital, located in Milan, Italy. The employed infrastructure INteractive TeleConsultation Network for Worldwide HealthcAre Services (INCAS) jointly developed by CEFRIEL (Center of Excellence For Research, Innovation, Education & Industrial Labs partnership) and ENI (Ente Nazionale Idrocarburi) is based on commercial off-the-shelf technology. This minimizes maintenance problems, while permitting a simple and friendly sharing of data using the telephone and e-mail for store-and-forward applications. The critical aspect of the flow of events comprising the exchange of information is discussed. In 60% of cases, only one telemedicine consultation was required. In the remainder 40%, a number of telemedicine consultations were required for appropriate management of clinical cases. The project demonstrated flexibility as documented by the wide range of pathologies that can be dealt with it. Finally the possibility of using shared clinical management as a learning tool is highlighted by the steep and rising learning curve. We conclude, however, that the patient, although handled in a "virtual" manner, should be viewed as very "real," as some of them elected to close the gap physically between Pointe Noire and Milan, and chose to be treated at the referral site.