Screening Sportsmen and Sportswomen Over Age 35: The Relevance of an Exercise Electrocardiogram. Data From the SEEPRED Study.

INTRODUCTION: The importance of exercise electrocardiogram (ECG) is still controversial in the prevention of cardiovascular events among sportsmen and sportswomen. The aim of this study was to assess the relevance of exercise ECG as a screening tool to prevent cardiovascular events when any cardiovascular disease (CVD) risk factors are present. METHODS: The study included leisure time asymptomatic sportsmen and sportswomen over age 35 evaluated from 2011 to 2016 at the University Hospital of Saint-Etienne (France). Major adverse cardiovascular events (MACE) and atrial fibrillation were collected at 3 years. RESULTS: Of the cohort of 2457 sportsmen and sportswomen (mean age 50.2 ± 9.4 years), 50 (2%) had a high-risk SCORE2. A total of 256 exercise ECGs (10%) were defined as positive, most of them due to silent myocardial ischemia (SMI) (n = 196; 8%). These 196 SMI cases led to 33 coronary angiograms (1%), which revealed 23 significant coronary stenoses requiring revascularization. In multivariate logistic regression analysis, having at least two CVD risk factors was independently associated with (1) positive exercise ECG (OR = 1.80 [95% CI: 1.29-2.52], p = 0.0006), with (2) suspected SMI (OR = 2.57 [95% CI: 1.10-6.02], p = 0.0304), with (3) confirmed SMI (OR = 8.20 [95% CI: 3.46-19.46], p < 0.0001) and with (4) cardiovascular events (MACE or atrial fibrillation) (OR = 6.95 [95% CI: 3.49-13.81], p < 0.0001) at 3 years (median). CONCLUSIONS: The study supports the European recommendations for the use of exercise ECG in evaluation of asymptomatic leisure time sportsmen over age 35. Having at least two CVD risk factors was the best predictor for presence of coronary artery stenosis that may increase the risk for adverse events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06024863.

Early Increase in Blood-Brain Barrier Permeability in a Murine Model Exposed to Fifteen Days of Intermittent Hypoxia.

Obstructive sleep apnea (OSA) is characterized by intermittent repeated episodes of hypoxia-reoxygenation. OSA is associated with cerebrovascular consequences. An enhanced blood-brain barrier (BBB) permeability has been proposed as a marker of those disorders. We studied in mice the effects of 1 day and 15 days intermittent hypoxia (IH) exposure on BBB function. We focused on the dorsal part of the hippocampus and attempted to identify the molecular mechanisms by combining in vivo BBB permeability (Evans blue tests) and mRNA expression of several junction proteins (zona occludens (ZO-1,2,3), VE-cadherin, claudins (1,5,12), cingulin) and of aquaporins (1,4,9) on hippocampal brain tissues. After 15 days of IH exposure we observed an increase in BBB permeability, associated with increased mRNA expressions of claudins 1 and 12, aquaporins 1 and 9. IH seemed to increase early for claudin-1 mRNA expression as it doubled with 1 day of exposure and returned near to its base level after 15 days. Claudin-1 overexpression may represent an immediate response to IH exposure. Then, after 15 days of exposure, an increase in functional BBB permeability was associated with enhanced expression of aquaporin. These BBB alterations are possibly associated with a vasogenic oedema that may affect brain functions and accelerate neurodegenerative processes.

Monitoring of Both Humoral and Cellular Immunities Could Early Predict COVID-19 Vaccine Efficacy Against the Different SARS-CoV2 Variants.

Reliable immunoassays are essential to early predict and monitor vaccine efficacy against SARS-CoV-2. The performance of an Interferon Gamma Release Assay (IGRA, QuantiFERON® SARS-CoV-2), and a current anti-spike serological test, compared to a plaque reduction neutralization test (PRNT) taken as gold standard were compared. Eighty vaccinated individuals, whose 16% had a previous history of COVID-19, were included in a longitudinal prospective study and sampled before and two to four weeks after each dose of vaccine. In non-infected patients, 2 doses were required for obtaining both positive IGRA and PRNT assays, while serology was positive after one dose. Each dose of vaccine significantly increased the humoral and cellular response. By contrast, convalescent subjects needed a single dose of vaccine to be positive on all 3 tests. Both IGRA and current serology assay were found predictive of a positive titer of neutralizing antibodies that is correlated with vaccine protection. Patients over 65 or 80 years old had a significantly reduced response. The response tended to be better with the heterologous scheme (vs. homologous) and with the mRNA-1273 vaccine (vs. BNT162b2) in the homologous group, in patients under 55 and under 65 years old, respectively. Finally, decrease intensity or absence of IGRA response and to a less extent of anti-spike serology were also correlated to reinfection which has occurred during the follow up. In conclusion, both IGRA and current anti-spike serology assays could be used at defined thresholds to monitor the vaccine response against SARS-CoV-2 and to simply identify non-responding individuals after a complete vaccination scheme. Two available specific tests (IGRA and anti-spike antibodies) could early assess the vaccine-induced immunity against SARS-CoV-2 at the individual scale, to potentially adapt the vaccination scheme in non-responder patients.

Loss of Blood-Brain Barrier Integrity in an In Vitro Model Subjected to Intermittent Hypoxia: Is Reversion Possible with a HIF-1α Pathway Inhibitor?

Several sleep-related breathing disorders provoke repeated hypoxia stresses, which potentially lead to neurological diseases, such as cognitive impairment. Nevertheless, consequences of repeated intermittent hypoxia on the blood-brain barrier (BBB) are less recognized. This study compared two methods of intermittent hypoxia induction on the cerebral endothelium of the BBB: one using hydralazine and the other using a hypoxia chamber. These cycles were performed on an endothelial cell and astrocyte coculture model. Na-Fl permeability, tight junction protein, and ABC transporters (P-gp and MRP-1) content were evaluated with or without HIF-1 inhibitors YC-1. Our results demonstrated that hydralazine as well as intermittent physical hypoxia progressively altered BBB integrity, as shown by an increase in Na-Fl permeability. This alteration was accompanied by a decrease in concentration of tight junction proteins ZO-1 and claudin-5. In turn, microvascular endothelial cells up-regulated the expression of P-gp and MRP-1. An alteration was also found under hydralazine after the third cycle. On the other hand, the third intermittent hypoxia exposure showed a preservation of BBB characteristics. Furthermore, inhibition of HIF-1α with YC-1 prevented BBB dysfunction after hydralazine treatment. In the case of physical intermittent hypoxia, we observed an incomplete reversion suggesting that other biological mechanisms may be involved in BBB dysfunction. In conclusion, intermittent hypoxia led to an alteration of the BBB model with an adaptation observed after the third cycle.

Using 99mTc-(V)-DMSA to follow the vascular calcification process in vascular smooth muscle cells based on pit-1 expression.

BACKGROUND: Vascular calcification is an established feature of atherosclerosis process. The sodium/phosphate transporter PiT-1 acts as a biosensor in vascular calcification of VSMCs. [99mTc]-Pentavalent dimercaptosuccinic acid (99mTc-(V)-DMSA) was mediated by PiT-1 transporter in tumoral cells and we propose its evaluation in a vascular calcification in vitro model. The aim of this study was to determine if 99mTc-(V)-DMSA can follow the vascular calcification process in vascular smooth muscle cells (VSMCs) based on PiT-1 expression. METHODS: From a rat aortic VSMC cell line (A7r5), we set up a model of calcification within 7 days using a calcifying medium containing a high inorganic phosphate concentration. Phosphocalcic deposits were monitored with Alizarin red and Von Kossa staining and with phase contrast microscopy. PiT-1 expression was evaluated with an immunofluorescence assay and osteopontin expression, with whole cell ELISA assay. 99mTc-(V)-DMSA uptake was measured in control and calcifying conditions and compared with optical microscopy evaluation. RESULTS: Under hyperphosphatemia conditions, the VSMC cells progressively overexpressed osteopontin protein, PiT-1 transporter, and synthetized mineralized matrix with phosphocalcic deposition. 99mTc-(V)-DMSA uptake was to 2.8±2.08%DA/mg-protein in control cells and 42±24%DA/mg-protein in calcified cells (P<0.001). PiT-1 inhibition with phosphonoformic acid completely reverse the calcium deposition as well as the 99mTc-(V)-DMSA uptake. These results demonstrated that 99mTc-(V)-DMSA in-vitro uptake is mediated by PiT-1 transporter and follow the VSMC calcification process. CONCLUSIONS: These preliminary in-vitro results showed 99mTc-(V)-DMSA uptake follow the phospho-calcic deposition mediated by PiT-1 transporter. This radiotracer may have some potential to detect changes of VSMC metabolism occurring in the atherosclerosis process.

Longer-term effects of supervised physical activity on obstructive sleep apnea and subsequent health consequences.

Although recent trials have shown promising benefits of exercise on obstructive sleep apnea (OSA) severity, the long-term effect of these interventions remains unknown. The aim of this study was to assess the effect of a 9-month community physical activity program on OSA severity one year later in free-living conditions. OSA patients, previously included in a 9-month randomized controlled trial (EXESAS study) evaluating the effects of supervised community physical activity on OSA severity, were invited to participate in an extra one-year observational study. Twenty-eight patients completed the study. Although OSA severity did not significantly worsen over the real-life period (9 to 21 months of follow-up), reductions in apnea-hypopnea index (AHI) and oxygen desaturation index were no longer significant after 21 months of follow-up compared to baseline (baseline AHI: 22.2 ± 6.3 /h; 9 months: 16.3 ± 6.4 /h; 21 months: 18.7 ± 8.9 /h). Benefits observed at 9 months on daytime sleepiness and mental health were preserved at 21 months, whereas cardiorespiratory fitness slightly decreased. Per-protocol analysis revealed that patients who stopped exercise at 9 months had worsened OSA severity compared to those who continued exercise during the real-life period (AHI: +9.0 ± 8.8 vs. -1.3 ± 5.3 /h; p < .01). In conclusion, our study suggested that improvements in OSA severity remain transient and is dependent on long-term adherence to regular physical activity practice.

Muscle Proteomic and Transcriptomic Profiling of Healthy Aging and Metabolic Syndrome in Men.

(1) Background: Aging is associated with a progressive decline in muscle mass and function. Aging is also a primary risk factor for metabolic syndrome, which further alters muscle metabolism. However, the molecular mechanisms involved remain to be clarified. Herein we performed omic profiling to decipher in muscle which dominating processes are associated with healthy aging and metabolic syndrome in old men. (2) Methods: This study included 15 healthy young, 15 healthy old, and 9 old men with metabolic syndrome. Old men were selected from a well-characterized cohort, and each vastus lateralis biopsy was used to combine global transcriptomic and proteomic analyses. (3) Results: Over-representation analysis of differentially expressed genes (ORA) and functional class scoring of pathways (FCS) indicated that healthy aging was mainly associated with upregulations of apoptosis and immune function and downregulations of glycolysis and protein catabolism. ORA and FCS indicated that with metabolic syndrome the dominating biological processes were upregulation of proteolysis and downregulation of oxidative phosphorylation. Proteomic profiling matched 586 muscle proteins between individuals. The proteome of healthy aging revealed modifications consistent with a fast-to-slow transition and downregulation of glycolysis. These transitions were reduced with metabolic syndrome, which was more associated with alterations in NADH/NAD+ shuttle and ß-oxidation. Proteomic profiling further showed that all old muscles overexpressed protein chaperones to preserve proteostasis and myofiber integrity. There was also evidence of aging-related increases in reactive oxygen species but better detoxifications of cytotoxic aldehydes and membrane protection in healthy than in metabolic syndrome muscles. (4) Conclusions: Most candidate proteins and mRNAs identified herein constitute putative muscle biomarkers of healthy aging and metabolic syndrome in old men.

Vigilance and sleepiness in nurses working 12-hr shifts and their coping strategies.

AIM: To describe the progression of vigilance and sleepiness over the shift and the coping strategies of nurses working 12-hr day or night shifts. BACKGROUND: The spread of 12-hr shift work in nursing raises the question of whether sufficient vigilance can be maintained to ensure quality of care. METHOD: 18 nurses working 12-hr shifts filled out a Karolinska Sleepiness Scale questionnaire and a Brief Psychomotor Vigilance Test, at the beginning of the shift and then every 3 hr. Coping strategies and quality of care were assessed on self-administered questionnaires, filled out at 3 hr, 6 hr, 9 hr and 12 hr after the start of the shift. RESULTS: The present investigation did not show significantly excessive sleepiness or vigilance impairment or poor self-perception of quality of work during 12-hr nursing work shifts, although Psychomotor Vigilance Test results gradually deteriorated slightly over duty time (from start to end of shift). Certain coping strategies were preferred such as 'having a nap' later in the night shift. CONCLUSION: Attention needs to be paid to the health status of nurses working 12-hr shifts, with regular medical monitoring by the occupational health service. IMPLICATIONS FOR NURSING MANAGEMENT: Coping strategies to maintain sufficient vigilance to ensure quality of care should be facilitated.

Intermittent Hypoxia and Its Impact on Nrf2/HIF-1α Expression and ABC Transporters: An in Vitro Human Blood-Brain Barrier Model Study.

BACKGROUND/AIMS: Obstructive sleep apnea (OSA) is characterized by repeated episodes of complete or partial obstruction of the upper airways, leading to chronic intermittent hypoxia (IH). OSA patients are considered at high cerebrovascular risk and may also present cognitive impairment. One hypothesis explored is that disturbances may be linked to blood-brain barrier (BBB) dysfunction. The BBB is a protective barrier separating the brain from blood flow. The BBB limits the paracellular pathway through tight and adherens junctions, and the transcellular passage by efflux pumps (ABC transporters). The aims of this study were to evaluate the impact of IH and sustained hypoxia (SH) on a validated in vitro BBB model and to investigate the factors expressed under both conditions. METHODS: Exposure of endothelial cells (HBEC-5i) in our in vitro model of BBB to hypoxia was performed using IH cycles: 1% O2-35 min/18% O2-25 min for 6 cycles or 6 h of SH at 1% O2. After exposure, we studied the cytotoxicity and the level of ROS in our cells. We measured the apparent BBB permeability using sodium fluorescein, FITC-dextran and TEER measurement. Whole cell ELISA were performed to evaluate the expression of tight junctions, ABC transporters, HIF-1α and Nrf2. The functionality of ABC transporters was evaluated with accumulation studies. Immunofluorescence assays were also conducted to illustrate the whole cell ELISAs. RESULTS: Our study showed that 6 h of IH or SH induced a BBB disruption marked by a significant decrease in junction protein expressions (claudin-5, VE-cadherin, ZO-1) and an increase in permeability. We also observed an upregulation in P-gp protein expression and functionality and a downregulation in BCRP. Hypoxia induced production of ROS, Nrf2 and HIF-1α. They were expressed in both sustained and intermittent conditions, but the expression and the activity of P-gp and BCRP were different. CONCLUSION: Understanding these mechanisms seems essential in order to propose new therapeutic strategies for patients with OSA.

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.

Physical activity types and risk of dementia in community-dwelling older people: the Three-City cohort.

BACKGROUND: Physical activity may decrease the risk of dementia; however, previous cohort studies seldom investigated the different types of physical activity and household activities. Our objective was to analyze the links between two physical activity types and dementia in older people. METHODS: The study used data from the prospective observational Three-city cohort and included 1550 community-dwelling individuals aged 72 to 87 without dementia at baseline. Physical activity was assessed with the Voorrips questionnaire. Two sub-scores were calculated to assess household/transportation activities and leisure/sport activities. Restricted cubic spline and proportional hazard Cox models were used to estimate the non-linear exposure-response curve for the dementia risk and the appropriate activity level thresholds. Models were adjusted for possible confounders, including socio-demographic variables, comorbidities, depressive symptoms and APOE genotype. RESULTS: The median age was 80 years, and 63.6% of participants were women. After a median follow-up of 4.6 years, dementia was diagnosed in 117 participants (7.6%). An inverse J-shaped association was found between household/transportation physical activity sub-score and dementia risk, which means that the risk is lowest for the moderately high values and then re-increases slightly for the highest values. The results remained significant when this sub-score was categorized in three classes (low, moderate, and high), with hazard ratios (95% confidence interval) of 0.55 (0.35-0.87) and 0.62 (0.38-1.01) for moderate and high activity levels, respectively. No significant effect was found for leisure/sport activities. CONCLUSIONS: The 5-year risk of dementia was significantly and negatively associated with the household/transportation activity level, but not with the leisure and sport activity sub-score. This highlights the importance of considering all physical activity types in 72 years or older people.

Social marketing interventions to promote physical activity among 60 years and older: a systematic review of the literature.

BACKGROUND: Falls are a significant source of morbidity in people aged 65 and over, affecting one in three people in this age group. The scientific evidence indicates that physical activity is the most effective method for preventing falls among seniors. Although public health professionals often use social marketing to design and plan successful interventions, its use to promote physical activity and prevent falls among older people remains low. This article aims to provide a new systematic literature review of social marketing interventions promoting physical activity and targeting people aged 60 and over. METHODS: Following CRD's guidance and PRISMA guidelines, we searched between January 2008 and July 2019 for relevant articles in five primary databases using predefined search and inclusion criteria. Two independent reviewers analysed the selected articles to identify evidence of the seven social marketing benchmark criteria, defined by experts in the field as the common elements that contribute to social marketing success. RESULTS: The final review included nine studies. Of the studies selected, three specifically targeted over 60-year-olds, whereas the others segmented the population into several age-based subcategories, including over 60-year-olds. Eight studies highlighted positive results for the participants with an increase in participation or an increase in physical activity level. None of the nine studies selected for this systematic review implemented the entire social marketing approach. CONCLUSION: Few published interventions use the seven social marketing criteria. Further research is required to encourage uptake and inclusion in successful social marketing interventions to increase program effectiveness in this target population.

Correction to: Social marketing interventions to promote physical activity among 60 years and older: a systematic review of the literature.

An amendment to this paper has been published and can be accessed via the original article.

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.

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.

Arterial stiffness alteration and obstructive sleep apnea in an elderly cohort free of cardiovascular event history: the PROOF cohort study.

INTRODUCTION: Several studies suggest in middle-aged subjects a relationship between arterial stiffness, a cardiovascular risk marker, and moderate to severe obstructive sleep apnea (OSA). No extensive data are present in older subjects. This study explores this association in a sample of healthy older subjects suffering OSA. METHODS: A total of 101 volunteers aged 75.3 ± 0.7 years were examined at the hospital sleep center. Each subject was assessed for medical history, body mass index and 24-h blood pressure measures, biological blood samples, and home polygraphy in 2002-2003 (P2) as well as in 2009-2010 (P4). Arterial stiffness was also assessed using carotid-femoral and carotid-radial pulse wave velocity (cfPWV and crPWV) during P4 examination. RESULTS: The total group consisted of 59 women and 42 men with a mean apnea-hypopnea index (AHI) of 17.8 ± 12.1 and a mean oxygen desaturation index (ODI) of 9.8 ± 8.9. No-OSA (AHI < 15) represented 50% of the sample, and severe cases (AHI > 30) 17%. No significant differences had been founded between men and women for blood pressure, cfPWV, and crPWV. Considering the severity of the AHI, no significant differences between groups were present for PWV and blood pressure values. No difference for PWV was present for subjects with and without hypertension. No correlation was found between PWV value and AHI and ODI values at P2 or between P2 and P4 visits. cfPWV was higher in patients demonstrating incident hypertension during the follow-up. CONCLUSIONS: In this sample of older subjects, PWV is not affected by AHI and ODI but was associated with incident hypertension. These results may suggest potential protective and adaptive mechanisms in older sleep apnea patients. CLINICAL TRIAL REGISTRATIONS: NCT 00759304 and NCT 00766584 .

Sleep apnoea in the asymptomatic elderly: a real issue for the brain?

The link between sleep apnoea and brain structure is unclear; although dysfunction of the hippocampus, middle temporal gyrus and brainstem/cerebellum have been observed previously. However, this link has been little explored in elderly subjects. The aim of this study was to explore the link between sleep apnoea and the brain in an elderly population.226 asymptomatic elderly subjects (age mean±sd 75.3±0.9 years, range 72.3-77.8 years) from the PROOF (Evaluation of Ageing, Autonomic Nervous System Activity and Cardiovascular Events) cohort study were explored using linear voxel-based or cortical thickness with apnoea/hypopnoea index (AHI; mean±sd 15.9±11.5 events·h-1, range 6-63.6 events·h-1) as a covariate of main interest. The brain volumes of 20 control subjects, 18 apnoeic (AHI >29 events·h-1) treated patients and 20 apnoeic untreated patients from this population were compared using voxel-based morphometry, cortical thickness or surface-based analyses.AHI was not associated with any change in local brain volume, cortical thickness or cortex surface. Control subjects, apnoeic treated and untreated patients were not different in terms of local brain volume, cortical thickness or surface.In a specific population of asymptomatic elderly healthy subjects, sleep apnoea does not seem to be associated with a change in local brain volume or in cortical thickness.

Use of Vitamin K Antagonists and Brain Morphological Changes in Older Adults: An Exposed/Unexposed Voxel-Based Morphometric Study.

BACKGROUND: Vitamin K antagonists (VKAs) are commonly used for their role in haemostasis by interfering with the vitamin K cycle. Since vitamin K also participates in brain physiology, this voxel-based morphometric study aimed to determine whether the duration of exposure to VKAs correlated with focal brain volume reduction in older adults. METHODS: In this exposed/unexposed (1: 2) study nested within the GAIT (Gait and Alzheimer Interactions Tracking) cohort, 18 participants exposed to VKA (mean age 75 ± 5 years; 33.3% female; mean exposure 2,122 ± 1,799 days) and 36 matched participants using no VKA (mean age 75 ± 5 years; 33.3% female) underwent MRI scanning of the brain. Cortical grey and white matter volumes were automatically segmented using statistical parametric mapping. Age, gender, educational level, history of atrial fibrillation, type of MRI, and total intracranial volume were included as covariables. RESULTS: The duration of exposure to VKA correlated inversely across the whole brain with the subvolumes of two clusters in the grey matter (right frontal inferior operculum and right precuneus) and one cluster in the white matter (left middle frontal gyrus). In contrast, the grade of white matter hyperintensities did not differ according to the use of VKA. CONCLUSION: We found focal atrophies in older adults exposed to VKA. These findings provide new insights elucidating the effects of VKAs on brain health and function in older adults.

Hydralazine is a Suitable Mimetic Agent of Hypoxia to Study the Impact of Hypoxic Stress on In Vitro Blood-Brain Barrier Model.

BACKGROUND/AIMS: Understanding cellular mechanisms induced by hypoxia is fundamental to reduce blood-brain barrier (BBB) disruption. Nevertheless, the investigation of hypoxia on cellular pathways is complex with true hypoxia because HIF-1α has a short lifetime and rapidly reverts back to a normoxic state. To overcome this difficulty, mimetic agents of the hypoxia pathway have been developed, including the gold standard CoCl2. In this study, we proposed to compare CoCl2 and hydralazine in order to determine a suitable mimetic agent of hypoxia for the study on the BBB. METHODS: We studied the cytotoxicity and the impact of these molecules on the integrity of an in vitro BBB model by comparing them to hypoxia controls. RESULTS: We showed that the impact of hypoxic stress in our in vitro BBB model is rather similar between hydralazine and CoCl2. Chemical hypoxic stress led to an increase of BBB permeability either with CoCl2 or hydralazine. Tight junction protein expressions showed that this chemical hypoxic stress decreased ZO-1 but not occluding expressions, and cells had set up a defence mechanism by increasing expression and activity of their efflux transporters. CONCLUSION: Our results demonstrated that hydralazine is a better mimetic agent and more suitable than CoCl2 because it had the same effect but without the cytotoxic effect on in vitro BBB cells.