Causal analyses to study autonomic regulation during acute head-out water immersion, head-down tilt and supine position.

NEW FINDINGS: What is the central question of this study? Can Granger causality analysis of R-R intervals, systolic blood pressure and respiration provide evidence for the different physiological mechanisms induced during thermoneutral water immersion, 6 deg head-down tilt and supine position tests that are not accessible using traditional heart rate variability and baroreflex methods? What is the main finding and its importance? The Granger analysis demonstrated a significant difference in the causal link from R-R intervals to respiration between water immersion and head-down tilt. The underlying physiological mechanism explaining this difference could be the variation in peripheral resistances. ABSTRACT: Thermoneutral head-out water immersion (WI) and 6 deg head-down tilt (HDT) are used to simulate SCUBA diving, swimming and microgravity, because these models induce an increase in central blood volume. Standard methods to analyse autonomic regulation have demonstrated an increase in parasympathetic activity and baroreflex sensitivity during these experimental conditions. However, such methods are not adapted to quantify all closed-loop interactions involved in respiratory and cardiovascular regulation. To overcome this limitation, we used Granger causality analysis between R-R intervals (RR), systolic blood pressure (SBP) and respiration (RE) in eight young, healthy subjects, recorded during 30 min periods in the supine position, WI and HDT. For all experimental conditions, we found a bidirectional causal relationship between RE and RR and between RR and SBP, with a dominant direction from RR to SBP, and a unidirectional causality from RE to SBP. These causal relationships remained unchanged for the three experimental tests. Interestingly, there was a lower causal relationship from RR to RE during WI compared with HDT. This causal link from RR to RE could be modulated by peripheral resistances. These results highlight differences in cardiovascular regulation during WI and HDT and confirm that Granger causality might reveal physiological mechanisms not accessible with standard methods.

Autonomic cardiovascular adaptations to acute head-out water immersion, head-down tilt and supine position.

PURPOSE: Thermoneutral head-out water immersion (WI) and 6° head-down tilt (HDT) have been considered as suitable models to increase central blood volume and simulate autonomic cardiovascular adaptations to microgravity, swimming or scuba diving. However, any differences in autonomic cardiovascular adaptations are still unclear. In this study, we hypothesized that WI induces a higher activation of arterial baroreceptors and the parasympathetic system. METHODS: Ten healthy men underwent 30 min of WI, HDT, and a supine position (SP). RR intervals (RRI) and blood pressure (BP) were continuously monitored. High frequency power (HF), low frequency power (LF) and LF/HF ratio were calculated to study sympathetic and parasympathetic activities, and a spontaneous baroreflex method was used to study arterial baroreflex sensitivity (aBRS). Lung transfer of nitric oxide and carbon monoxide (TLNO/TLCO), vital capacity and alveolar volume (Vc/VA) were measured to study central blood redistribution. RESULTS: We observed (1) a similar increase in RRI and decrease in BP; (2) a similar increase in HF power during all experimental conditions, whereas LF increased after; (3) a similar rise in aBRS; (4) a similar increase in Vc/VA and decrease in TLNO/TLCO in all experimental conditions. CONCLUSIONS: These results showed a cardiac parasympathetic dominance to the same extent, underpinned by a similar arterial baroreflex activation during WI and HDT as well as control SP. Future studies may address their association with cold or hyperoxia to assess their ability to replicate autonomic cardiovascular adaptations to microgravity, swimming or scuba diving.

How the insula speaks to the heart: Cardiac responses to insular stimulation in humans.

Despite numerous studies suggesting the role of insular cortex in the control of autonomic activity, the exact location of cardiac motor regions remains controversial. We provide here a functional mapping of autonomic cardiac responses to intracortical stimulations of the human insula. The cardiac effects of 100 insular electrical stimulations into 47 epileptic patients were divided into tachycardia, bradycardia, and no cardiac response according to the magnitude of RR interval (RRI) reactivity. Sympathetic (low frequency, LF, and low to high frequency powers ratio, LF/HF ratio) and parasympathetic (high frequency power, HF) reactivity were studied using RRI analysis. Bradycardia was induced by 26 stimulations (26%) and tachycardia by 21 stimulations (21%). Right and left insular stimulations induced as often a bradycardia as a tachycardia. Tachycardia was accompanied by an increase in LF/HF ratio, suggesting an increase in sympathetic tone; while bradycardia seemed accompanied by an increase of parasympathetic tone reflected by an increase in HF. There was some left/right asymmetry in insular subregions where increased or decreased heart rates were produced after stimulation. However, spatial distribution of tachycardia responses predominated in the posterior insula, whereas bradycardia sites were more anterior in the median part of the insula. These findings seemed to indicate a posterior predominance of sympathetic control in the insula, whichever the side; whereas the parasympathetic control seemed more anterior. Dysfunction of these regions should be considered when modifications of cardiac activity occur during epileptic seizures and in cardiovascular diseases.

Assessing pain in the postoperative period: Analgesia Nociception IndexTMversus pupillometry.

BACKGROUND: Potential methods for objective assessment of postoperative pain include the Analgesia Nociception Index™ (ANI), a real-time index of the parasympathetic tone, the pupillary light reflex (PLR), and the variation coefficient of pupillary diameter (VCPD), a measure of pupillary diameter (PD) fluctuations. Until now, the literature is divided as to their respective accuracy magnitudes for assessing a patient's pain. The VCPD has been demonstrated to strongly correlate with pain in an obstetrical population. However, the pain induced by obstetrical labour is different, given its intermittent nature, than the pain observed during the postoperative period. The aim of the current study was to compare the respective values of these variables at VAS scores ≥4. METHODS: After approval by the Ethics Committee, 345 patients aged on average 50 (SD 17) yr (range: 18-91 yr) of age were included. The protocols of general anaesthesia and postoperative analgesia were left to the anaesthetist's discretion. Some 40 min after tracheal intubation, VAS, ANI, PD, PLR, and VCPD values were recorded. RESULTS: VCPD correlates more strongly (r=0.78) with pain as assessed with the VAS than ANI (r=-0.15). PD and PLR are not statistically correlated with VAS. The ability of VCPD to assess the pain of patients (VAS≥4) is strong [area under the curve (AUC): 0.92, confidence interval (CI): 0.89-0.95], and better than for ANI (AUC: 0.39, CI: 0.33-0.45). CONCLUSIONS: Our study suggests that VCPD could be a useful tool for monitoring pain in conscious patients during the postoperative period. CLINICAL TRIAL REGISTRATION: NCT03267979.

Effect of exercise training on heart rate variability in patients with obstructive sleep apnea: A randomized controlled trial.

While obstructive sleep apnea (OSA) increases chemoreflex, leading to an autonomic dysfunction in the long term, no studies have yet assessed the potential benefit of exercise on cardiac autonomic activity in these patients. The aim of this study was to evaluate potential improvement in cardiac autonomic function (CAF) measured through heart rate variability (HRV) after a 9-month physical activity program in patients with OSA. Seventy-four patients with moderate OSA, aged 40-80 years, were randomly assigned to an exercise group (n = 36, 3 × 1 h/wk) or a control group (n = 38) during 9 months. Linear and nonlinear HRV parameters were measured during night using a Holter ECG. After 9 months, mean R-R intervals increased in the exercise group without any changes in HRV parameters, while controls decreased global (standard deviation of normal-to-normal intervals, total power) and parasympathetic (root mean square successive difference of N-Ns, very low frequency, high frequency, and standard deviation of the instantaneous beat-to-beat variability) indices of HRV (P < 0.05 for all). Significant correlations with moderate effect size were found between changes in apnea severity and changes in R-R intervals (P < 0.05). Improvement in moderate-to-vigorous physical activity was also correlated to improvement in nocturnal oxygen parameters (P < 0.05). In conclusion, supervised community physical activity may prevent a decline in nighttime CAF observed in nontreated community-dwelling patients with moderate OSA over a 9-month period. Thus, beyond apnea-hypopnea index improvement, exercise may be cardioprotective in OSA patients through bradycardia, CAF preservation, and VO2peak increase.

Autonomic cardiac regulation after general anesthesia in children.

BACKGROUND: General anesthesia dramatically decreases the activity of the autonomic nervous system. Most of the hypnotic agents used to induce anesthesia inhibit sympathetic cardiovascular regulation and baroreflex control in a dose-dependent manner, lowering cardiac adaptability during the operation. The consequence of this effect in children during and after surgery has never been studied to date. AIM: The aim of this study was to follow the variations in autonomic cardiac indices in children younger than 8 years old after general anesthesia (6-24 hours) in programmed surgery. METHOD: A prospective descriptive monocentric study of 44 children under 8 years old who underwent scheduled surgery at our hospital center (Saint-Étienne University Hospital, France) was performed between June 1, 2016 and November 1, 2016. Heart rate variability was monitored for 24 hours using Holter-ECG devices and the resulting data were interpreted using linear and nonlinear analyses. RESULTS: Compared to baseline thresholds before surgery, all heart rate variability indices decreased dramatically during general anesthesia. After awakening, a slight reduction in sympathetic activity persisted 6 hours after surgery, but all measurements of sympathetic and parasympathetic activity had returned to baseline thresholds 12 hours after the operation. Twenty-four hours after surgery, some parameters had increased above the corresponding baseline levels. CONCLUSION: Autonomic nervous function normalizes rapidly (within 12 hours) in prepubertal children. This study indicates that general anesthesia does not seem to increase the long-term risk of autonomic dysfunction in these patients.

High-resolution Raman Spectroscopy for the Nanostructural Characterization of Explosive Nanodiamond Precursors.

The specific attributes of nanodiamonds have attracted increasing interest for electronics or biomedical applications. An efficient synthetic route towards nanodiamonds is via detonation of hexolite (i.e. a mixture of TNT [2,4,6-trinitrotoluene] and RDX [1,3,5-trinitro-1,3,5-triazine]). In particular, detonation of hexolite crystallized by spray flash evaporation (SFE) yields extremely small diamonds (<4 nm). To unravel the detonation mechanism, a structural characterization of the explosives is required but is challenging due to their thermal instability. We demonstrate a combination of conventional Raman spectroscopy and tip-enhanced Raman spectroscopy (TERS) for resolving morphological and structural differences of differently prepared hexolite nanocomposites. The experiments allow for the first time a structural differentiation of individual TNT and RDX crystals and 15-20 nm sized core-shell structures, consequently providing a general approach to investigate the actual composition of mixtures on the nanometer scale.

A 7-year follow-up study of obstructive sleep apnoea in healthy elderly: The PROOF cohort study.

BACKGROUND AND OBJECTIVE: Clinical and epidemiological cohort studies have shown that obstructive sleep apnoea (OSA) is a common but largely undiagnosed disorder in senior subjects, where progressive deterioration of the pathology would be expected as a consequence of the ageing processes. Our study examines the longitudinal progression of OSA over a 7-year period in a community-based sample of healthy subjects. METHODS: The sample consisted of 284 volunteers, aged >65 years (52% women, 48% men) accepting clinical and instrumental follow-up at 7 years. OSA was defined as an apnoea-hypopnoea index (AHI) of ≥15. RESULTS: Between evaluations in the total sample, AHI slightly decreased from 17.8 ± 14 to 16.7 ± 11 with a decrease affecting more the hypopnoea index (P < 0.001) and associated with significant changes (P < 0.001) in all indices of hypoxaemia. While in the non-OSA group there was a slight but significant increase of AHI, a significant AHI decrease was noted in mild-moderate patients (P < 0.01) and a significant rise of nocturnal hypoxaemia in severe OSA patients (P < 0.001). The AHI decrease was not associated with clinical, weight, metabolic and blood pressure changes between the two evaluations; the baseline AHI value being the only factor correlated to the degree of AHI decline. CONCLUSIONS: In elderlies, the severity and prevalence of OSA decrease progressively with ageing without effect of factors commonly influencing OSA severity. This trend may support the hypothesis that in healthy elderly, OSA is a phenomenon related to ageing.

Sleep-related autonomic overactivity in a general elderly population and its relationship to cardiovascular regulation.

Alteration in cardiac autonomic activity during sleep is a common feature of sleep disorders. Diurnal sympathetic overactivity is a possible consequence and could contribute to future cardiovascular complications. The aim of this study is to assess the relationship between cardiac autonomic activity during sleep and diurnal autonomic cardiovascular control. In a large cohort (n = 1011) of subjects aged 65 years old (± 0.4) free of cardiac and cerebrovascular events and of sleep-related breathing disorders, we evaluated (cross-sectional study) the prevalence of unexpected alteration in sleep-related autonomic overactivity according to the presence of a cyclical nocturnal heart rate variability [quantified using the relative power spectral density of the very low-frequency band of the heart rate increment (VLFi%) from ECG Holter monitoring]. We tested its relationship with diurnal ambulatory blood pressure and spontaneous baroreflex sensitivity (sBRS). An abnormal cardiac autonomic activity during sleep was retained in 34.4% of this population according to a VLFi% >4. Using multiple logistic regression analysis, the severity of the autonomic alteration was mainly correlated after adjustment with lower sBRS (p = 0.01; OR: 0.94; 95% CI: 0.90-0.98). Diurnal baroreflex control alteration is associated with sleep-related autonomic overactivity elderly. Such alteration may contribute to the increased incidence of cardiovascular complications in sleep disorders.

Nonlinear optical behavior of porphyrin functionalized nanodiamonds: an efficient material for optical power limiting.

The nonlinear optical mechanisms and the optical limiting behavior of porphyrin functionalized detonation nanodiamonds are investigated and compared to the conventional detonation nanodiamonds (DNDs). The optical limiting behavior is characterized by means of nonlinear transmittance, Z-scan, and scattered intensity measurements when submitted to a nanosecond pulsed Nd:YAG laser operating at the second harmonic wavelength. We found that the largest nonlinear attenuation was observed on the 4,4',4'',4'''-(porphyrin-5, 10, 15, 20-tetrayl) tetrakis benzoic acid (PCOOH) suspension. Using Z-scan experiments, it is shown that nonlinear refraction predominates in the unfunctionalized DND suspension, while nonlinear absorption is the most relevant mechanism in the porphyrin functionalized DNDs. Furthermore, a stronger backscattered intensity signal is highlighted for the unfunctionalized DNDs through nonlinear scattering measurements.

Modeling of performance and ANS activity for predicting future responses to training.

PURPOSE: Our aim was to assess whether we can predict satisfactorily performance in swimming and high frequency power (HF power) of heart rate variability from the responses to previous training. We have tested predictions using the model of Banister and the variable dose-response model. METHODS: Data came from ten swimmers followed during 30 weeks of training with performance and HF power measured each week. The first 15-week training period was used to estimate the parameters of each model for both performance and HF power. Both were then predicted in response to the training done during the second 15-week training period. The bias and precision were estimated from the mean and SD of the difference between prediction and actual value expressed as a percentage of performance or HF power at the first week. RESULTS: With the variable-dose response model, the bias for performance prediction was -0.24 ± 0.06 and the precision 0.69 ± 0.24% (mean ± between-subject SD). For HF power, the bias was 0 ± 21 and the precision 22 ± 8%. When HF power was transformed into performance using a quadratic relation in each swimmer established from the first 15-week period, the bias was 0.18 ± 0.74 and the precision 0.80 ± 0.30%. No clear trend in the error was observed during the second period. CONCLUSIONS: This study showed that the modeling of training effects on performance allowed accurate performance prediction supporting its relevance to control and predict week after week the responses to future training.

Effects of gravitational acceleration on cardiovascular autonomic control in resting humans.

PURPOSE: Previous studies of cardiovascular responses in hypergravity suggest increased sympathetic regulation. The analysis of spontaneous heart rate variability (HRV) parameters and spontaneous baroreflex sensitivity (BRS) informs on the reciprocal balance of parasympathetic and sympathetic regulations at rest. This paper was aimed at determining the effects of gravitational acceleration (a g) on HRV and BRS. METHODS: Eleven healthy subjects (age 26.6 ± 6.1) were studied in a human centrifuge at four a g levels (1, 1.5, 2 and 2.5 g) during 5-min sessions at rest. We evaluated spontaneous variability of R-R interval (RR), and of systolic and diastolic blood pressure (SAP and DAP, respectively), by power spectral analysis, and BRS by the sequence method, using the BRSanalysis(®) software. RESULTS: At 2.5 g, compared to 1 g, (1) the total power (P TOT) and the powers of LF and HF components of HRV were lower, while the LF/HF ratio was higher; (2) normalized units for LF and HF did not changed significantly; (3) the P TOT, LF and HF powers of SAP were higher; (4) the P TOT and LF power of DAP were higher; and (5) BRS was decreased. CONCLUSIONS: These results do not agree with the notion of sympathetic up-regulation supported by the increase in HR and DAP (tonic indices), and of SAP and DAP LF powers (oscillatory indices). The P TOT reduction leads to speculate that only the sympathetic branch of the ANS might have been active during elevated a g exposure. The vascular response occurred in a condition of massive baroreceptive unloading.

Bradycardia and asystole during generalised interictal EEG discharges.

Few studies have investigated the effects of interictal epileptic discharges on the cardiac autonomic system. This study reports the case of a 37-year-old man with refractory generalised epilepsy, who recently reported an increase in frequency of nocturnal tonic-clonic seizures, not responding to treatment. During the nocturnal video study, in non-rapid eye movements sleep, we recorded 106 generalised sharp- and polyspike-waves lasting for 3 to 7 seconds, associated with bradycardia and asystole, without behavioural changes and without increase in deltoid muscle activity. The asystole had a duration of between 3 and 8 seconds. In one case, a 7 second asystole was associated with a tonic-clonic generalised seizure. A 24-hour electrocardiographic study revealed a bradycardia and a Wenckebach atrioventricular block. Heart rate analysis at the time of the interictal epileptic discharges revealed an abrupt increase in the RR interval, occurring simultaneously with the onset of interictal epileptic discharges and followed by a return to values below baseline value. A cardiac pacemaker was installed with a reduction of asystole length during the interictal epileptic discharges. Our findings indicate, for the first time, the role of interictal generalised discharges in EEG-related asystole and bradycardia. These data support the hypothesis that some patients with epilepsy may be predisposed to disturbances of the autonomic cardiac system.

Local detection of nitrogen-vacancy centers in a nanodiamond monolayer.

Nitrogen-vacancy defect centers (NV) contained in nanodiamonds (NDs) are a promising candidate in quantum information processing and single photon sources due to the capability of controlling their assembly on various surfaces. However, their detection with traditional optical techniques becomes challenging when probing high NV densities at the nanometer scale. Here, we combine scanning probe techniques to characterize in a monolayer the structural and electronic properties of bucky-diamonds with sizes below 10 nm. We further observe by light-assisted Kelvin- and scanning tunneling spectroscopy a clear signature of negatively charged subsurface NV centers in NDs at the nanoscale where conventional techniques are limited.

Impact of spa therapy on physical activity, sleep and heart rate variability among individuals with fibromyalgia: Results of an ancillary study.

Spa therapy is recommended to manage symptoms of fibromyalgia, but the physiological mechanisms underlying this improvement have been poorly studied. In an original study, we explored the effect of a 3-week rheumatology spa treatment for fibromyalgia patients on quality of life and with a symptom severity questionnaire. We present here the results of an ancillary study which explored three secondary criteria using objective measurement methods: diurnal actimetry for physical activity analysis, nocturnal actimetry for sleep analysis and heart rate variability. Eighty-three fibromyalgia patients were randomized to participate in an immediate 3-week rheumatological spa therapy, either a start within 6 weeks after inclusion (interventional group, n = 39) or a delayed, start 6 months after inclusion (control group, n = 44). Patients were asked to wear an actimeter (n = 56) to assess diurnal physical activity and sleep quality and a 24-h Holter ECG (n = 60) to assess nocturnal heart rate variability at baseline, 3 months and 6 months after inclusion. Time spent in sedentary and light physical activity was reduced to ∼30 min at 6 months in the interventional group (P = 0.027). Sleep quality and heart rate variability were not improved. Spa therapy made it possible to reduce sedentary activities in patients' daily life for up to 6 months afterwards, concomitant with the improvement in quality of life, pain and fatigue as highlighted in the original Thermalgi study.

Impaired post-sleep apnea autonomic arousals in patients with drug-resistant epilepsy.

OBJECTIVE: Sudden and unexpected deaths in epilepsy (SUDEP) pathophysiology may involve an interaction between respiratory dysfunction and sleep/wake state regulation. We investigated whether patients with epilepsy exhibit impaired sleep apnea-related arousals. METHODS: Patients with drug-resistant (N = 20) or drug-sensitive (N = 20) epilepsy and obstructive sleep apnea, as well as patients with sleep apnea but without epilepsy (controls, N = 20) were included. We explored (1) the respiratory arousal threshold based on nadir oxygen saturation, apnea-hypopnea index, and fraction of hypopnea among respiratory events; (2) the cardiac autonomic response to apnea/hypopnea quantified as percentages of changes from the baseline in RR intervals (RRI), high (HF) and low (LF) frequency powers, and LF/HF. RESULTS: The respiratory arousal threshold did not differ between groups. At arousal onset, RRI decreased (-9.42%) and LF power (179%) and LF/HF ratio (190%) increased. This was followed by an increase in HF power (118%), p < 0.05. The RRI decrease was lower in drug-resistant (-7.40%) than in drug-sensitive patients (-9.94%) and controls (-10.91%), p < 0.05. LF and HF power increases were higher in drug-resistant (188%/126%) than in drug-sensitive patients (172%/126%) and controls (177%/115%), p < 0.05. CONCLUSIONS: Cardiac reactivity following sleep apnea is impaired in drug-resistant epilepsy. SIGNIFICANCE: This autonomic dysfunction might contribute to SUDEP pathophysiology.

Why, when and how to assess autonomic nervous system maturation in neonatal care units: A practical overview.

The evaluation of the autonomic reactivity of newborns by heart rate variability (HRV) analysis is a simple and essential aid to identifying pathological situations of dysautonomia. Thanks to this relatively simple and reproducible analytic tool, the pediatrician can identify and target children at high risk of life-threatening events, i.e., those with insufficient intrinsic capacity for cardiorespiratory self-regulation, who should benefit from close cardiorespiratory monitoring. Different mathematical algorithms integrate delayed or real-time variations in the length of the RR interval to better understand the state of autonomic maturation of the newborn. HRV analysis, as a non-invasive tool for assessing autonomic balance, is essential to assess the functioning of the autonomic nervous system and, more specifically, parasympathetic/sympathetic balance. Despite many recognized diagnostic and therapeutic implications, its application to neonatal medicine is not yet well understood.

CVRanalysis: a free software for analyzing cardiac, vascular and respiratory interactions.

Introduction: Simultaneous beat-to-beat R-R intervals, blood pressure and respiration signals are routinely analyzed for the evaluation of autonomic cardiovascular and cardiorespiratory regulations for research or clinical purposes. The more recognized analyses are i) heart rate variability and cardiac coherence, which provides an evaluation of autonomic nervous system activity and more particularly parasympathetic and sympathetic autonomic arms; ii) blood pressure variability which is mainly linked to sympathetic modulation and myogenic vascular function; iii) baroreflex sensitivity; iv) time-frequency analyses to identify fast modifications of autonomic activity; and more recently, v) time and frequency domain Granger causality analyses were introduced for assessing bidirectional causal links between each considered signal, thus allowing the scrutiny of many physiological regulatory mechanisms. Methods: These analyses are commonly applied in various populations and conditions, including mortality and morbidity predictions, cardiac and respiratory rehabilitation, training and overtraining, diabetes, autonomic status of newborns, anesthesia, or neurophysiological studies. Results: We developed CVRanalysis, a free software to analyze cardiac, vascular and respiratory interactions, with a friendly graphical interface designed to meet laboratory requirements. The main strength of CVRanalysis resides in its wide scope of applications: recordings can arise from beat-to-beat preprocessed data (R-R, systolic, diastolic and mean blood pressure, respiration) or raw data (ECG, continuous blood pressure and respiratory waveforms). It has several tools for beat detection and correction, as well as setting of specific areas or events. In addition to the wide possibility of analyses cited above, the interface is also designed for easy study of large cohorts, including batch mode signal processing to avoid running repetitive operations. Results are displayed as figures or saved in text files that are easily employable in statistical softwares. Conclusion: CVRanalysis is freely available at this website: anslabtools.univ-st-etienne.fr. It has been developed using MATLAB® and works on Windows 64-bit operating systems. The software is a standalone application avoiding to have programming skills and to install MATLAB. The aims of this paper area are to describe the physiological, research and clinical contexts of CVRanalysis, to introduce the methodological approach of the different techniques used, and to show an overview of the software with the aid of screenshots.

Obesity related to metabolic syndrome: comparison of obesity indicators in an older french population.

OBJECTIVES: Metabolic syndrome (MS) represents a cluster of metabolic abnormalities. Insulin resistance is a major component of the syndrome. We analyze in this study the relationship between body fat composition and MS in comparison to usual obesity indicators in an older adult population. DESIGN: The PROgnostic indicator OF cardiovascular and cerebrovascular events (PROOF) study is a prospective longitudinal community cohort study among the inhabitants of Saint-Etienne, France. METHODS: The study is a cohort study of 1011 subjects, mean age 65.6 ± 0.8 years old at inclusion, recruited from the electoral list of the town in 2000. Among them, 806 subjects realized a Dual-energy X-ray absorptiometry (DXA) used to evaluate body fat and lean mass repartition. We evaluate biological metabolic parameters according to usual techniques. The indices of obesity were calculated according to standard formula. MS presence and its components were simultaneously evaluated. RESULTS: All obesity parameters were significantly higher (p < 0.0001) in subjects suffering metabolic syndrome as compared to those without. Body fat index (BFI) presented a stronger correlation to total fat mass, trunk fat mass and body adiposity index (BAI). The correlations between body indices and metabolic components showed that body mass index (BMI) and waist circumference were more strongly associated with BFI as compared to BAI and total fat mass. According to logistic regression analysis, only the waist-hip ratio (WHR) demonstrated a significant association with MS severity (p < 0.0001). CONCLUSIONS: Among the obesity indices, BFI and BAI represented the best indicators to characterize global obesity while WHR only is highly predictive of metabolic syndrome presence and severity. The BAI indicator is an alternative for measuring obesity. Comparison of long-term impact of such markers on cardiovascular morbidity and mortality is now questioned.

Relationship between moderate-to-vigorous, light intensity physical activity and sedentary behavior in a prospective cohort of older French adults: a 18-year follow-up of mortality and cardiovascular events ─ the PROOF cohort study.

Background: It is well documented that moderate-to-vigorous intensity physical activity (MVPA) is effective in the prevention of major chronic diseases. Even though the current international physical activity (PA) guidelines still mainly focus on MVPA, the topic of the most recent epidemiological studies has shifted from MVPA to light intensity physical activity (LPA), owing to the necessity of promoting all activities vs. sedentary behavior (SB). However, the evidence remains currently limited. Thus, the clarification of the effects of LPA and the close relationship with SB is crucial to promote public health. Method: PA and SB were assessed by a validated self-administered questionnaire (POPAQ) investigating 5 different types of PA during the 7 previous days. PA was measured in metabolic equivalent of task (MET)-h, which refers to the amount of energy (calories) expended per hour of PA. SB was measured in hour/day. Medical histories and examinations were taken during each clinical visit to determine clinical events. All-cause mortality was established using the same procedure and by checking local death registries. The relationships between the intensity of PA (light, moderate to vigorous) and mortality and between the periods of SB and mortality or CV events were analyzed by splines and COX models, adjusted for sex and year of birth. Results: From the 1011 65-year-old subjects initially included in 2001 (60% women), the last 18-year follow-up has been currently completed since 2019. A total of 197 deaths (19.2%, including 77 CV deaths) and 195 CV events (19.3%) were reported. Averages (standard deviation) of MVPA, LPA and SB were, respectively, 1.2 h/d (0.3), 5.8 h/d (1.1), and 6.6 h/d (2.3). For all-cause deaths, as well as CV deaths, the splines were significant for LPA (p = 0.04 and p = 0.01), and MVPA (p < 0.001 and p < 0.001), but not for SB (p = 0.24 and p = 0.90). There was a significant reduction in CV events when SB was decreasing from 10.9 to 3.3 h/d. Conclusion: The PROOF cohort study shows a clear dose-response between the dose of LPA, MVPA, SB and risk of mortality. These findings provide additional evidence to support the inclusion of LPA in future PA guidelines.