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Cardiovascular regulation and autonomic function change across sleep stages and compared to wake. Little information is present in literature about cardiac control during sleep especially in relation to new information-theoretic quantities such as synergy and redundancy. In the present work we compute synergy and redundancy of baroreflex and non-baroreflex components of the cardiac control according to two information-theoretic approaches, namely predictive information decomposition (PID) and minimal mutual information (MMI) methods. We applied a bivariate approach to heart period (HP) and systolic arterial pressure (SAP) beat-to-beat variability series during sleep in a healthy subject. PID approach computes the net balance between synergy and redundancy, while MMI calculates the two quantities as separate entities. Results suggested that: i) redundancy was dominant over synergy during NREM phases; ii) redundancy increased during NREM phase; iii) synergy did not change across the sleep stages. We interpret this result as a consequence of the vagal enhancement, slowing and deepening of respiration during NREM phases. These preliminary findings support the potential of assessing redundancy/synergy of baroreflex-related and unrelated regulations during sleep to improve our knowledge about physiological mechanisms.

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.

Objective: The optimal protein intake for elderly individuals who exercise regularly has not yet been clearly defined. The aim of this study was to test the hypothesis that protein intake level is associated with muscle strength in elderly elite athletes., Methods: We evaluated 50 elite senior athletes (38 men and 12 women) participating in the European Master Games 2011 in an observational cross-sectional study. Participants were divided into two groups-lower (LPI) or higher (HPI) protein intake-according to the median value of their ratio of urinary urea nitrogen to urinary creatinine (i.e., 8.8 g/L), as a marker of protein intake. A dietary interview confirmed differences in protein consumption between the LPI and HPI groups. We also evaluated body composition (bioimpedance), muscle strength, and hematochemical indices., Results: LPI and HPI groups were homogeneous for age (72 [68-74] and 71 [68-74] y, respectively), fat-free mass index (18.4 [17-19.4] and 18.2 [17-19.1] kg/m 2 ), body fat (18.3% [12.3-20.7%] and 16.6% [13.6-21.2%]), and glomerular filtration rate (57.7 [53.8-64.9] and 62.7 [56.1-69.3] mL/min/1.73 m 2 ). The HPI group showed greater leg and trunk muscle strength (N) compared with the LPI group (left leg extension, 339 [238-369] versus 454 [273-561], respectively, P < 0.05; right leg extension, 319 [249-417] versus 432 [334-635], P ≤ 0.05; trunk extension, 435 [370-467] versus 464 [390-568], P ≤ 0.05)., Conclusions: Higher protein intake in elite senior athletes is associated with a greater muscle strength., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Spectral analysis of Heart Rate Variability (HRV) is a simple, non-invasive technique that is widely used in sport to assess sympatho-vagal regulation of the heart. Its employment is increasing partly due to the rising usage of wearable devices. However data acquisition using these devices may be suboptimal because they cannot discriminate between sinus and non-sinus beats and do not record any data regarding respiratory frequency. This information is mandatory for a correct clinical interpretation., Methods: This study involved 974 elite athletes, all of them underwent a complete autonomic assessment, by way of Autoregressive HRV analysis., Results: In 91 subjects (9% of the total population) we observed criticalities of either cardiac rhythm or respiration. Through perusal of one-lead ECG analysis we observed that 77 subjects had atrial or ventricular ectopy, i.e. conditions which impair stationarity and sinus rhythm. Running anyway autonomic nervous system analysis in this population, we observed that RR variance and raw values of LF and HF regions are significantly higher in arrhythmic subjects. In addition 14 subjects had slow (about 6 breath/min, 0.1Hz) respiration. This condition clouds the separation between LF from HF spectral regions of RR interval variability, respectively markers of the prevalent sympathetic and vagal modulation of SA node and of their synergistic interaction., Conclusions: Caution must be payed when assessing HRV with non-ECG wearable devices. Recording ECG signal and ensuring that respiratory rate is higher than 10 breath/min are both prerequisites for a more reliable analysis of HRV particularly in athletes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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.

Aim: Given the time spent at work, the workplace represents an ideal setting to implement preventive programs for non-communicable diseases, the major cause of mortality and morbidity in Western and developing countries. We sought to verify if an ecological approach based on corporate culture, employees' education and concrete modifications of workplace environment, offering easy opportunity to assume healthy lifestyle, could be associated with reduced cardiometabolic risk., Methods: The study involved 1089 workers in two multinational companies following different workplace health promotion policies. Company A offered to all employees the opportunity to access a web platform dedicated to general information on health and diseases. Company B implemented an ecological model encompassing company culture, employees' education and concrete modifications of workplace environment, giving to all employees the opportunity to adopt healthy solutions throughout daily living at workplace. Participants volunteered self-reported clinical information using an IT tool. Numbers of Metabolic Syndrome components (MetS) were taken as proxy of cardiometabolic risk., Results: MetS probability obtained via statistical modeling was lower in company B as compared to company A, and absenteeism was also lower in company B. Our study shows that a work environment favoring assumption of healthy lifestyle, as in company B, is associated with a lower percentage of employees with MetS components and lower absenteeism. Moreover, statistical modeling shows that individual probabilities of being without MetS elements, controlling for age and gender, is remarkably higher in company B., Conclusions: Our data suggest that ecological approaches might be useful in worksite prevention policies.

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.

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., (Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

The evidence supporting the importance of a healthy lifestyle (active life, healthy diet, not smoking, and low stress) as a part of programs for primary and secondary prevention of cardiometabolic diseases is strong, compelling, and continuously growing. In this study, we test whether a simple web-based healthy lifestyle index, using self-reports, is related to indices of cardiovascular health and metabolic syndrome and could be employed in large wellness programs intended to promote healthy lifestyle. We studied 411 workers in an Italian multinational factory who were enrolled in a voluntary program consisting of a health checkup and an online questionnaire on lifestyle. These domains were combined into a single simple index. Participants were subdivided into three healthy lifestyle index (HI) groups (red, yellow, and green) ranging from poor to good HI quality (HI from red to green: 41.8 ± 14.6; 75.7 ± 8.5; 93.8 ± 2.2; p < 0.05). The groups differed in indicators of cardiovascular and metabolic health (waist circumference females: 82.1 ± 9.56, 78.9 ± 9.3, 72.7 ± 6.6; males: 95.2 ± 11.7, 90.0 ± 9.5, 85.7 ± 6.1 cm; group difference p < 0.05). Moreover, they differed significantly in the likelihood of having more components of the metabolic syndrome and, conversely, fewer components of the ideal cardiovascular health profile (with red having the worst profile). The red group was also characterized by the highest absenteeism. We report for the first time that a web-based self-reported poor health behavior was significantly associated with clinical and laboratory (partial correlation between HI and high-density cholesterol 0.192; body mass index -0.288; systolic blood pressure -0.130; all p < 0.05) results indicating a negative cardiometabolic profile.

Purpose: The dynamics of vagal withdrawal and reactivation during pulses of exercise are described by indices computed from heart period (RR) variations, which may be sensitive to duration and load. We sought to assess the consistency over time of these indices, which is not well established., Methods: We recorded continuous electrocardiogram during series of five successive bouts (2 min) of submaximal exercise (at 40 and 70% of VO(2peak), different days). Autonomic responsiveness was inferred from quantification of onset and offset of RR dynamics of each individual bout. Consistency of results was assessed with intraclass correlation (ICC)., Results: During exercise bouts, indices from tachycardic and bradycardic transients reach lower levels in response to higher exercise loads and progression of exercise. There is a significant effect of load and time (i.e., bout repetition) for all examined variables, with a clear interaction. However, no interaction is observed with the 60 s change in heart rate. ICC analysis demonstrates that various indices are characterized by large differences in stability, which is generally greater within the same day (e.g., tachyspeed ICC at 40% = 0.751, at 70% = 0.704, both days = 0.633; bradyspeed, respectively, = 0.545, 0.666, 0.516)., Conclusions: Intensity and duration of exercise modulate vagal withdrawal and reactivation. Analysis of RR variations, during successive brief exercise bouts at lower and higher intensity, ensures a consistency similar to that reported for autonomic cardiac regulation at rest and might guide the choice among multiple indices that are obtained from the tachogram.

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.

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 © 2011. Published by Elsevier B.V.)

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.

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 alpha- was respectively of 17.5+/-1.5 versus 25.1+/-1.8 msec/mmHg, p<<0.02). These data suggest possible preventive strategies, based on tailored treatments aiming at a betterment of individual autonomic profile.

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.

Spontaneous baroreflex function and vascular changes were assessed in young adults during dynamical mild exercise. Windkessel time constant was assessed by two different methods: two-element windkessel model, and by an autoregressive (AR) model, while the baroreflex sensitivity (BRS, ms/mmHg) was assessed by the sequence method. Results showed a change in the baroreflex control of heart rate (HR) with the severity of exercise, as well as the resetting phenomenon. Methods used to estimate the windkessel time constant were poorly correlated. Subject by subject correlation was found between the BRS and the time constant derived from the AR model within exercise and recovery period. These results may suggest that reflex mechanisms controlling HR may also participate in controlling peripheral circulation or, viceversa, BRS is influenced by vascular tone.

Ten estimates of baroreflex sensitivity (BRS) were compared during progressive graded exercise: they were computed from sequence method, spectral and cross-spectral analysis methods, and parametric model-based methods. Results showed baroreflex control of heart rate (HR) changes as a function of the intensity of exercise, as well as the resetting phenomenon. Sequence, spectral and cross-spectral methods generally provided higher estimates than parametric model-based ones. This bias was particularly evident during exercise, and in the high frequency (HF) respiratory band. Results may suggest that the interaction of respiration and baroreflex function play an important in the cardiovascular adaptation from rest to exercise and from exercise to the recovery period.

Arterial pressure variability is a relatively unexplored topic among the various and detailed studies of cardiovascular variability. A deeper analysis of components and contributions carried by diastolic and pulse pressure may provide a unique insight on the potential systemic effects due to vasomotor activity and response at the level of microcirculation, whose dynamics are either driven by neural and vascular modulations. The aim of the present work is to develop a multivariate parametric model for the identification of the main components of diastolic and pulse pressure in order to investigate all the potential correlations between systemic arterial pressure variability and peripheral sources of oscillations and to analyze their interactions with the most known mechanisms of cardiovascular regulation.