Assessing the cardiac autonomic response to bicycle exercise in Olympic athletes with different loads of endurance training: new insights from statistical indicators based on multilevel exploratory factor analysis.

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.

Psychological Intervention Based on Mental Relaxation to Manage Stress in Female Junior Elite Soccer Team: Improvement in Cardiac Autonomic Control, Perception of Stress and Overall Health.

Chronic stress may represent one of the most important factors that negatively affects the health and performance of athletes. Finding a way to introduce psychological strategies to manage stress in everyday training routines is challenging, particularly in junior teams. We also must consider that a stress management intervention should be regarded as "efficacious" only if its application results in improvement of the complex underlying pathogenetic substratum, which considers mechanistically interrelated factors, such as immunological, endocrine and autonomic controls further to psychological functioning and behavior. In this study, we investigated the feasibility of implementing, in a standard training routine of the junior team of the Italian major soccer league, a stress management program based on mental relaxation training (MRT). We evaluated its effects on stress perception and cardiac autonomic regulation as assessed by means of ANSI, a single composite percentile-ranked proxy of autonomic balance, which is free of gender and age bias, economical, and simple to apply in a clinical setting. We observed that the simple employed MRT intervention was feasible in a female junior soccer team and was associated with a reduced perception of stress, an improved perception of overall health, and a betterment of cardiac autonomic control. This data may corroborate the scientific literature that indicates psychological intervention based on MRT as an efficacious strategy to improve performance, managing negative stress effects on cardiac autonomic control.

Relationship between Body Composition and Cardiac Autonomic Regulation in a Large Population of Italian Olympic Athletes.

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.

Altered Cardiac Autonomic Regulation in Overweight and Obese Subjects: The Role of Age-and-Gender-Adjusted Statistical Indicators of Heart Rate Variability and Cardiac Baroreflex.

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.

Out-of-hospital cardiac arrest (OHCA) Survey in Lombardy: data analysis through prospective short time period assessment.

BACKGROUND AND AIM OF THE WORK: The results of out-of-hospital cardiac arrests (OHCA) are usually reported through data collected collected via "ad hoc"  registries, but in large populations, samples of short time periods can be used to apply the results to the entire population. We would like to describe the situation of Lombardy to provide evidence on successful procedures, which may be carried out in a larger context. METHODS: Observational, prospective, analytical, single cohort study in Lombardy population. Data of OHCA of cardiac aetiology, according to "Utstein Style", with resuscitation attempts started by the Emergency Medical Service (EMS), were collected for 40 days subdivided in 10-day-periods in all seasons 2014-15 via Operating System "Emergency Management" (EmMa). RESULTS: Of 1219 cases, 536 events of witnessed OHCA of presumed cardiac etiology were analyzed. Outcomes were: sustained Return Of Spontaneous Circulation ROSC (25.6%), Survival Event in Emergency Department (22.8%), Survival after 24 hours (21.2%) and Survival after hospital discharge at home 30 days after (11.2%). Statistically significant results were found in age, rhythm of presentation, and resuscitation by bystanders. Sex, seasonality and rescue timing did not differ statistically. CONCLUSIONS: Overall the thirty-day survival rate was similar to studies with larger databases. Our data are consistent with the concept that all emergency service should provide CPR instructions for every citizen who activate the EMS in the suspect of a SCA; further investigation should clarify how long interval could be useful for ROSC and sustained ROSC in patients resuscitated by lay people using CPR instructions.

Cardiac Baroreflex, HRV, and Statistics: An Interdisciplinary Approach in Hypertension.

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.

Autonomic Differentiation Map: A Novel Statistical Tool for Interpretation of Heart Rate Variability.

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.

May a unitary autonomic index help assess autonomic cardiac regulation in elite athletes? Preliminary observations on the national Italian Olympic committee team.

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.

A composite autonomic index as unitary metric for heart rate variability: a proof of concept.

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.

Reducing the risk of metabolic syndrome at the worksite: preliminary experience with an ecological approach.

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.

May autonomic indices from cardiovascular variability help identify hypertension?

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.

Health promotion in the workplace: assessing stress and lifestyle with an intranet tool.

BACKGROUND: Chronic noncommunicable conditions, particularly cardiovascular and metabolic diseases, are the major causes of death and morbidity in both industrialized and low- to middle-income countries. Recent epidemiological investigations suggest that management of lifestyle factors, such as stress and lack of physical activity, could have an important value in cardiometabolic conditions, while information technology tools could play a significant facilitatory role. OBJECTIVES: The objective of our study was to verify the feasibility of using a private website, directed to the workers of a major Italian company, to describe their health profile and lifestyle and work habits using an ad hoc self-administered questionnaire. METHODS: We administered anonymous multiple choice Web-based questionnaires to 945 participants (683 completed the task) as part of an ongoing health promotion program in a multinational company. Qualitative and quantitative data were synthesized with nonlinear principal component analysis to construct indicators (ie, variables) for stress, control, and lifestyle domains. Considering in addition absenteeism, the Calinski-Harabasz statistic and cluster analysis jointly differentiated seven clusters, which displayed different distributions of standardized classification variables. The final step consisted in assessing the relationship of the resulting seven subject typologies with personal data, illnesses, and metabolic syndrome status, carried out for the most part with descriptive methods. RESULTS: Statistical analyses singled out two not-overlapping domains of stress and control, as well as three not-overlapping domains of physical activity, smoking, and alcohol habits. The centroids of the seven clusters generated by the procedure were significantly (P < .001) different considering all possible 21 comparisons between couples of groups. Percentage distributions of variables describing personal information (gender, age group, work category, illness status, or metabolic syndrome) within participant typologies show some noteworthy findings: females, workers aged 35-44 years, junior white collar workers, and respondents reporting illness were more prevalent in the stress group than in the overall studied population; preclinical metabolic syndrome status was more prevalent in the group with higher alcohol consumption. Absentees reported more illness. CONCLUSIONS: The present Intranet-based study shows the potential of applying diverse statistical techniques to deal jointly with qualitative and quantitative self-reported data. The resulting formal description of subject typologies and their relationship with personal characteristics might provide a convenient tool for supporting health promotion in the work environment.

Complementary medicine for the management of chronic stress: superiority of active versus passive techniques.

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.

Thyroid dysfunction in women with systemic sclerosis.

Hypothyroidism has been frequently reported in systemic sclerosis (SSc), but whether SSc itself increases the risk of thyroid dysfunction is still controversial. The aim of the present study was to determine whether routine thyroid function screening in SSc should be warranted. Serum levels of free triiodothyronine, free thyroxine, and thyroid-stimulating hormone, and the presence of thyroid-specific autoantibodies (antithyroid peroxidase and antithyreoglobulin) were measured in 79 women with SSc and 81 age-matched women with osteoarthritis (OA) serving as controls. Hyperthyroidism was found in 2 of 79 (2.5%) SSc and in 4 of 81 (5%) OA cases. Hypothyroidism was found in 16 of 79 (20%) patients with SSc (subclinical in 14/16 cases) and in 9 of 81 (11%) patients with OA (subclinical in all cases; P = 0.131). Antithyreoglobulin antibodies were present in 14% versus 13% patients (SSc versus OA, P = NS), whereas antithyroid peroxidase antibodies were present in 23% versus 11% patients (SSc versus OA, P = 0.057). The risk of hypothyroidism was significantly higher in antithyroid peroxidase-positive patients (P < 0.0001), irrespective of the primary diagnosis, and greater in women with OA (OR = 24.6, 95% CI 4.3-141.9, P < 0.0001) than SSc (OR = 4.2, 95% CI 1.2-14.3, P = 0.035). SSc is not independently associated with an increased risk of thyroid dysfunction, but antithyroid peroxidase antibodies may identify a subset of patients at risk of developing thyroid dysfunction.