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Abstract Aging is commonly regarded as a physiological process in which the dynamic complexity of physiological time series and organ systems is gradually lost. This notion is derived from the identification of a decline of nonlinear measures with the advance of aging. However, additional research on cardiovascular control studied through heart rate variability (HRV), i.e., the instantaneous changes in heart rate, shows that despite the constriction of its statistical distribution, the nonlinear organization remains present in advanced age. Here, we used surrogate data testing to investigate the presence of nonlinear information in HRV time series from a publicly available database of 1121 healthy human subjects from 18 to 92 years old. We also studied the influence of basic clinical features, such as sex, body mass index (BMI), and mean heart rate (HR), on such nonlinear information. We found that the percentage of nonlinear time series after 30 years of age diminishes significantly (p

Exploring the presence of nonlinearity through surrogate data testing provides insights into the nature of physical and biological systems like those obtained from heart rate variability (HRV). Short-term HRV time series are of great clinical interest to study autonomic impairments manifested in chronic diseases such as the end stage renal disease (ESRD) and the response of patients to treatment with hemodialysis (HD). In contrast to Iterative Amplitude Adjusted Fourier Transform (IAAFT), the Pinned Wavelet Iterative Amplitude Adjusted Fourier Transform (PWIAAFT) surrogates preserve nonstationary behavior in time series, a common characteristic of HRV. We aimed to test synthetic data and HRV time series for the existence of nonlinearity. Recurrence Quantitative Analysis (RQA) indices were used as discriminative statistics in IAAFT and PWIAAFT surrogates of linear stationary and nonstationary processes. HRV time series of healthy subjects and 29 ESRD patients before and after HD were tested in this setting during an active standing test. Contrary to PWIAAFT, linear nonstationary time series may be erroneously regarded as nonlinear according to the IAAFT surrogates. Here, a lower proportion of HRV time series was classified as nonlinear with PWIAAFT, compared to IAAFT, confirming that the nonstationarity condition influences the testing of nonlinear behavior in HRV. A contribution of nonlinearity was found in the HRV data of healthy individuals. A lower proportion of nonlinear time series was also found in ESRD patients, but statistical significance was not found. Although this proportion tends to be lower in ESRD patients, as much as 60% of time series proved to be nonlinear in healthy subjects. Given the important contribution of nonlinearity in HRV data, a nonlinear point of view is required to achieve a broader understanding of cardiovascular physiology.

Disorders in the child’s neurological development caused by perinatal risks can lead to long-term altered neurological signs that begin at an early age and involve persistent functional disorders. Recent data suggest that tissue dysfunction, not just acute damage, may initiate or perpetuate an inflammatory response. The aim of this study was to find out if any neurological dysfunction in preschool children secondary to damage generated during the perinatal period is associated with the magnitude of perinatal risks and long-term modifications in the serum concentrations of inflammatory molecules. The participants, aged 1–4 years, were on neurodevelopmental follow-up and rehabilitation therapy from the first three months of life and had no acute disease data. We classified the children into three groups according to the importance of their perinatal risks: low, medium, and high. The results show that 1) the magnitude of perinatal risks correlated with the severity of neurological dysfunction; 2) the greatest changes in the concentrations of the molecules of the inflammatory process were associated with the most altered neurological signs. This suggests that persistent nervous system dysfunction keeps inflammatory responses active even in the absence of an acute process of infection or damage.

Objective: To characterize the multifractal behavior of the beat to beat heart-period or RR fluctuations in fibromyalgia patients (FM) in comparison with healthy-matched subjects.Methods: Multifractral detrended fluctuation analysis (MDFA) was used to study multifractality in heartbeat times-series from 30 female healthy subjects and 30 female patients with fibromyalgia during day and night periods.The multifractal changes as derived from the magnitude and sign analysis of these RR fluctuations were also assessed.Results: The RR fluctuations dynamics of healthy subjects showed a broad multifractal spectrum. By contrast, a noticeable decrease in multifractality and non-linearity was observed for patients with fibromyalgia. In addition, the spectra corresponding to FM subjects were located on the average to the right of the spectra of healthy individuals, indicating that the local scaling exponents reflect a smoother behavior compared to healthy dynamics. Moreover, the multifractal analysis as applied to the magnitude and sign heartbeat series confirmed that, in addition to a decreased nonlinearity, fibromyalgia patients presented stronger anticorrelation in directionality, which did not remain invariant for small or rather larger fluctuations as it occurred in healthy subjects.Conclusion: When compared to healthy controls, fibromyalgia patients display decreased nonlinearity and stronger anticorrelations in heart period fluctuations. These findings reinforce the hypothesis of the potential role of the dysfunctional autonomic nervous system in the pathogenesis of fibromyalgia.

Linear heart rate variability (HRV) indices are dependent on the mean heart rate, which has been demonstrated in different models (from sinoatrial cells to humans). The association between nonlinear HRV indices, including those provided by recurrence plot quantitative analysis (RQA), and the mean heart rate (or the mean cardiac period, also called meanNN) has been scarcely studied. For this purpose, we analyzed RQA indices of five minute-long HRV time series obtained in the supine position and during active standing from 30 healthy subjects and 29 end-stage renal disease (ESRD) patients (before and after hemodialysis). In the supine position, ESRD patients showed shorter meanNN (i.e., faster heart rate) and decreased variability compared to healthy subjects. The healthy subjects responded to active standing by shortening the meanNN and decreasing HRV indices to reach similar values of ESRD patients. Bivariate correlations between all RQA indices and meanNN were significant in healthy subjects and ESRD after hemodialysis and for most RQA indices in ESRD patients before hemodialysis. Multiple linear regression analyses showed that RQA indices were also dependent on the position and the ESRD condition. Then, future studies should consider the association among RQA indices, meanNN, and these other factors for a correct interpretation of HRV.

Aortic-valve sclerosis increases cardiovascular mortality risk and precedes aortic-valve stenosis, but its mechanisms are not well understood. The purpose of this study was to compare the cardiac autonomic modulation and inflammation markers between subjects with aortic-valve normal leaflets and subjects with aortic-valve sclerosis. According to 2-D transthoracic echocardiograms, 61 middle-aged volunteers without chronic or acute illnesses were classified in two groups: with no aortic-valve sclerosis (NAVS, N = 16) and with aortic-valve sclerosis (AVS, N = 45). An electrocardiogram at the supine position and active standing was collected to estimate heart rate variability (HRV) indices. A blood sample was obtained to quantify markers of inflammation. Compared to NAVS, AVS subjects showed higher levels of IL-6 (1619 ± 650 vs. 1169 ± 676 pg/mL, p = 0.044) as well as TNFα (370.8 ± 182.0 vs. 247.3 ± 188.2 pg/mL, p = 0.032), and larger low-frequency (LF) to high-frequency (HF) ratio during supine position (Ln(LF/HF) = 0.85 ± 0.85 vs. 0.11 ± 0.69, p = 0.003). Multiple logistic regression analysis showed that AVS was independently associated with LF/HF, TNFα and left ventricle mass index (p < 0.05). In conclusion, a significant reduction of the parasympathetic-driven cardiac modulation and low-grade inflammation occurs in aortic-valve sclerosis.