The proposed approach evaluates complexity of the cardiovascular control and causality among cardiovascular regulatory mechanisms from spontaneous variability of heart period (HP), systolic arterial pressure (SAP) and respiration (RESP). It relies on construction of a multivariate embedding space, optimization of the embedding dimension and a procedure allowing the selection of the components most suitable to form the multivariate embedding space. Moreover, it allows the comparison between linear model-based (MB) and nonlinear model-free (MF) techniques and between MF approaches exploiting local predictability (LP) and conditional entropy (CE). The framework was applied to study age-related modifications of complexity and causality in healthy humans in supine resting (REST) and during standing (STAND). We found that: 1) MF approaches are more efficient than the MB method when nonlinear components are present, while the reverse situation holds in presence of high dimensional embedding spaces; 2) the CE method is the least powerful in detecting age-related trends; 3) the association of HP complexity on age suggests an impairment of cardiac regulation and response to STAND; 4) the relation of SAP complexity on age indicates a gradual increase of sympathetic activity and a reduced responsiveness of vasomotor control to STAND; 5) the association from SAP to HP on age during STAND reveals a progressive inefficiency of baroreflex; 6) the reduced connection from HP to SAP with age might be linked to the progressive exploitation of Frank-Starling mechanism at REST and to the progressive increase of peripheral resistances during STAND; 7) at REST the diminished association from RESP to HP with age suggests a vagal withdrawal and a gradual uncoupling between respiratory activity and heart; 8) the weakened connection from RESP to SAP with age might be related to the progressive increase of left ventricular thickness and vascular stiffness and to the gradual decrease of respiratory sinus arrhythmia.

The term inflammaging is now widely used to designate the inflammatory process of natural aging. During this process, cytokine balance is altered, presumably due to the loss of homeostasis, thus contributing to a greater predisposition to disease and exacerbation of chronic diseases. The aim of the study was to analyze the relationship between pro-inflammatory markers and age in the natural aging process of healthy individuals. One hundred and ten subjects were divided into 5 groups according to age (22 subjects/group). Interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were quantified using the ELISA method. High-sensitivity C-reactive protein (hsCRP) was analyzed by turbidimetry according to laboratory procedures. The main findings of this study were: a positive correlation between hsCRP and IL-6 as a function of age (110 subjects); women showed stronger correlations; the 51–60 age group had the highest values for hsCRP and IL-6; women presented higher values for hsCRP in the 51–60 age group and higher values for IL-6 in the 61–70 age group; and men showed higher values in the 51–60 age group for hsCRP and IL-6. In conclusion, the natural aging process increased IL-6 and hsCRP levels, which is consistent with the inflammaging theory; however, women presented stronger correlations compared to men (IL-6 and hsCRP) and the 51–60 age range seems to be a key point for these increases. These findings are important because they indicate that early preventive measures may minimize the increase in these inflammatory markers in natural human aging.

Short-term complexity of heart period (HP) and systolic arterial pressure (SAP) was computed to detect age and gender influences over cardiovascular control in resting supine condition (REST) and during standing (STAND). Healthy subjects (n = 110, men = 55) were equally divided into five groups (21-30; 31-40; 41-50; 51-60; and 61-70 years of age). HP and SAP series were recorded for 15 min at REST and during STAND. A normalized complexity index (NCI) based on conditional entropy was assessed. At REST we found that both NCIHP and NCISAP decreased with age in the overall population, but only women were OPEN ACCESSEntropy 2014, 16 6687 responsible for this trend. During STAND we observed that both NCIHP and NCISAP were unrelated to age in the overall population, even when divided by gender. When the variation of NCI in response to STAND (ΔNCI = NCI at REST-NCI during STAND) was computed individually, we found that ΔNCIHP progressively decreased with age in the overall population, and women were again responsible for this trend. Conversely, ΔNCISAP was unrelated to age and gender. This study stresses that the complexity of cardiovascular control and its ability to respond to stressors are more importantly lost with age in women than in men.

Aging affects baroreflex regulation. The effect of senescence on baroreflex control was assessed from spontaneous fluctuations of heart period (HP) and systolic arterial pressure (SAP) through the HP-SAP gain, while the HP-SAP phase and strength are usually disregarded. This study checks whether the HP-SAP phase and strength, as estimated, respectively, via the phase of the HP-SAP cross spectrum (Ph) and squared coherence function (K), vary with age in healthy individuals and trends are gender-dependent. We evaluated 110 healthy volunteers (55 males) divided into five age subgroups (21-30, 31-40, 41-50, 51-60, and 61-70 yr). Each subgroup was formed by 22 subjects (11 males). HP series was extracted from electrocardiogram and SAP from finger arterial pressure at supine resting (REST) and during active standing (STAND). Ph and K functions were sampled in low-frequency (LF, from 0.04 to 0.15 Hz) and in high-frequency (HF, above 0.15 Hz) bands. Both at REST and during STAND Ph(LF) showed a negative correlation with age regardless of gender even though values were more negative in women. This trend was shown to be compatible with a progressive increase of the baroreflex latency with age. At REST K(LF) decreased with age regardless of gender, but during STAND the high values of K(LF) were more preserved in men than women. At REST and during STAND the association of Ph(HF) and K(HF) with age was absent. The findings points to a greater instability of baroreflex control with age that seems to affect to a greater extent women than men. NEW & NOTEWORTHY Aging increases cardiac baroreflex latency and decreases the degree of cardiac baroreflex involvement in regulating cardiovascular variables. These trends are gender independent but lead to longer delays and asmaller degree of cardiac baroreflex involvement in women than in men, especially during active standing, with important implications on the tolerance to an orthostatic stressor.

In heart period (HP) variability (HPV) recordings the percentage of negative HP variations tends to be greater than that of positive ones and this pattern is referred to as HPV asymmetry (HPVA). HPVA has been studied in several experimental conditions in healthy and pathological populations, but its origin is unclear. The baroreflex (BR) exhibits an asymmetric behavior as well given that it reacts more importantly to positive than negative arterial pressure (AP) variations. We tested the hypothesis that the BR asymmetry (BRA) is a HPVA determinant over spontaneous fluctuations of HP and systolic AP (SAP). We studied 100 healthy subjects (age from 21 to 70 yr, 54 men) comprising 20 subjects in each age decade. Electrocardiogram and noninvasive AP were recorded for 15 min at rest in supine position (REST) and during active standing (STAND). The HPVA was evaluated via Porta’s index and Guzik’s index, while the BRA was assessed as the difference, and normalized difference, between BR sensitivities computed over positive and negative SAP variations via the sequence method applied to HP and SAP variability. HPVA significantly increased during STAND and decreased progressively with age. BRA was not significantly detected both at REST and during STAND. However, we found a significant positive association between BRA and HPVA markers during STAND persisting even within the age groups. This study supports the use of HPVA indexes as descriptors of BRA and identified a challenge soliciting the BR response like STAND to maximize the association between HPVA and BRA markers.

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The aim of the present study was to compare hemodynamic responses between blood flow-restricted resistance exercise (BFR-RE), high-intensity resistance exercise (HI-RE) and low-intensity resistance exercise (LI-RE) performed to muscular failure. 12 men (age: 20±3 years; body mass: 73.5±9 kg; height: 174±6 cm) performed 4 sets of leg press exercises using BFR-RE (30% of 1-RM), HI-RE (80% of 1-RM) and LI-RE (30% of 1-RM) protocols. Systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), stroke volume (SV), cardiac output (CO) and total peripheral vascular resistance (TPR) were measured on a beat-to-beat continuous basis by a noninvasive photoplethysmographic arterial pressure device. The HI-RE and LI-RE showed higher values (<0.05) in all of the sets than the BFR-RE for SBP, DBP, HR. Additionally, HI-RE showed higher SBP (4 set) and DBP (all sets) (<0.05) values than the LI-RE. However, the SV, CO and TPR showed significantly greater values for LI-RE compared to HI-RE and BFR-RE (<0.05). In conclusion, the results of this study indicate that the BFR-RE promotes a lower hemodynamic response compared to the HI-RE and LI-RE performed to muscular failure.

BackgroundCirculatory power (CP) and ventilatory power (VP) are indices that have been used for the clinical evaluation of patients with heart failure; however, no study has evaluated these indices in patients with coronary artery disease (CAD) without heart failure.ObjectiveTo characterize both indices in patients with CAD compared with healthy controls.MethodsEighty-seven men [CAD group = 42 subjects and healthy control group (CG) = 45 subjects] aged 40–65 years were included. Cardiopulmonary exercise testing was performed on a treadmill and the following parameters were measured: 1) peak oxygen consumption (VO2), 2) peak heart rate (HR), 3) peak blood pressure (BP), 4) peak rate-pressure product (peak systolic HR x peak BP), 5) peak oxygen pulse (peak VO2/peak HR), 6) oxygen uptake efficiency (OUES), 7) carbon dioxide production efficiency (minute ventilation/carbon dioxide production slope), 8) CP (peak VO2 x peak systolic BP) and 9) VP (peak systolic BP/carbon dioxide production efficiency).ResultsThe CAD group had significantly lower values for peak VO2 (p < 0.001), peak HR (p < 0.001), peak systolic BP (p < 0.001), peak rate-pressure product (p < 0.001), peak oxygen pulse (p = 0.008), OUES (p < 0.001), CP (p < 0.001), and VP (p < 0.001) and significantly higher values for peak diastolic BP (p = 0.004) and carbon dioxide production efficiency (p < 0.001) compared with CG. Stepwise regression analysis showed that CP was influenced by group (R2 = 0.44, p < 0.001) and VP was influenced by both group and number of vessels with stenosis after treatment (interaction effects: R2 = 0.46, p < 0.001).ConclusionThe indices CP and VP were lower in men with CAD than healthy controls.