Normative Data for a Neuropsychological Test Battery in the French Aging Population: 20-Year Follow-Up From the "PROgnostic OF Cardiovascular and Cerebrovascular Events" Study.

OBJECTIVE: The study aimed to present relevant norms for the evaluation of pathological aging in the French population over a 20-year period, utilizing the "PROgnostic OF cardiovascular and cerebrovascular events" test and questionnaire. METHODS: Three neuropsychological evaluations were administered over 20 years with 929 participants at the first cognitive evaluation (62-69 years old), 631 at the second (71-78 years old), and 293 at the third (81-88 years old). The tests and questionnaires were administered in the following order: McNair's Cognitive Complaints Questionnaire, Depression Questionnaire of Pichot, Mini Mental State Examination, Free and Cued Selective Reminding test, Benton Visual Retention Test, Digit-Symbol Substitution Test of the WAIS-III, Trail Making Test, Stroop Test, Verbal Fluency, and the Similarities subtest of the WAIS-III. RESULTS: Normative data were presented at three time points of the repeated evaluation over 20 years (62-69 years, 71-78 years, and 81-88 years) and four educational levels (no diploma, primary school certificate, certificate of professional aptitude, and baccalaureate and above). The data showed a significant effect of educational level in all neuropsychological tests regardless of age. Gender primarily affected memory, Stroop scores, and Similarities scores. CONCLUSION: This study highlights the importance of educational level and gender in the evaluation of the memory and executive function of elderly persons. Furthermore, the presented norms consider the self-report cognitive complaints and depression symptoms over a long period of life.

Brain alterations associated with overweight evaluated by body mass index or body fat index in an elderly population: the PROOF study.

Background/objectives: Obesity is a complex health issue in which the brain plays a role yet to be determined, especially in the elderly. Indeed, in the ageing population, the balance between fat and lean mass is different; thus, the co-influence between the brain and obesity may differ between the elderly and younger subjects. Our main goal is thus to explore the relationship between the brain and obesity using two different approaches to measure obesity: body mass index (BMI) and an index centred on fat mass, the body fat index (BFI). Subjects/methods: Among the 1,011 subjects of the PROOF population, 273 subjects aged 75 years underwent 3D magnetic resonance imaging as well as dual-energy X-ray absorptiometry to assess fat mass. Voxel-based morphometry was used to explore the local differences in brain volume with obesity. Results: Higher BMI and BFI were associated with higher grey matter (GM) volume in the left cerebellum. Higher BMI and BFI were mainly associated with higher white matter volume in the left and right cerebellum and near the right medial orbital gyrus. Higher BMI was also associated with higher GM volume in the brainstem, whereas higher BFI was associated with higher GM volume in the left middle temporal gyrus. No decrease in white matter was associated with BMI or BFI. Conclusion: In the elderly, the relationship between the brain and obesity does not depend on the marker of obesity. Supra-tentorial brain structures seem to be slightly associated with obesity, whereas the cerebellum seems to be one of the key structures related to obesity.

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.

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.

Sex-related differences in endothelial function and blood viscosity in the elderly population.

Elderly represents a growing population and cardiovascular diseases (CVD) is one of the leading causes of mortality in this population. Sex differences are involved in CVD with middle-aged males being at higher risk than females. After menopause, females are no longer protected by hormones and the role of sex on cardiovascular parameters involved in CVD, such as endothelial function and blood viscosity, is still unclear. The purpose of this study was to investigate the effect of sex on endothelial function, blood viscosity and CVD in elderly. Clinical investigation and blood analyses were performed on 182 (93 females and 89 males) elderly participants (mean age: 75.83 ± 1.22). Health status of participants were classified. Sex differences in endothelial function, blood viscosity, high density lipoprotein (HDL), hematocrit, and red blood cell (RBC) aggregation were assessed. CVD prevalence was higher in males (27.0%) than in females (5.4%) (p < 0.001). Females had higher vasoreactivity (p = 0.014) and HDL (p < 0.001) level than males. Blood viscosity was higher in males than in females at any shear rate (p < 0.001). Hematocrit was greater in males than in females (p < 0.001) while RBC aggregation did not differ between the two populations. To conclude, females have less CVD than age-matched males that might be due to their greater vascular function and lower blood viscosity.

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.

The effect of a pressure ventilatory support on quadriceps endurance is maintained after exercise training in severe COPD patients. A longitudinal randomized, cross over study.

Purpose: In severe chronic obstructive pulmonary disease (COPD) patients, the application of an inspiratory pressure support (IPS) during exercise increases exercise tolerance and the benefit of exercise training during pulmonary rehabilitation (PR). Moreover, it improves quadriceps endurance after a session of cycling exercise suggesting a reduced muscle fatigue. We looked for the persistence of this effect after PR and sought an association between the improved quadriceps endurance with IPS and the training load during PR. Patients and methods: We studied 20 patients with severe COPD (6 in stage 3and 14 in stage 4 of GOLD) before and after PR. As part of a PR program, patients completed 16 cycling sessions over 6 weeks with the addition of IPS during exercise. As a surrogate of muscular fatigue, quadriceps endurance was measured at 70% of maximal strength in a control condition, after a constant work rate exercise test (CWR) with IPS (TlimQ IPS) or with a sham ventilation (TlimQsham), in a random order. These tests were repeated similarly at the end of PR. Results: PR was associated with a significant increase in maximal power output, cycling endurance, quadriceps strength and endurance. Session training load (power output x duration of the session) increased by 142% during the course of the program. Before PR, CWR duration increases with IPS compared to sham ventilation (Δtime = +244s, p = 0.001). Compared to control condition, post-exercise TlimQ reduction was lower with IPS at isotime than at the end of CWR or than with sham ventilation (-9 ± 21%, -18 ± 16% and -23 ± 18%, respectively, p = 0.09, p < 0.0001 and p < 0.0001). After PR, the post-exercise decrease of TlimQ was reduced after IPS compared to sham (-9 ± 18% vs. -21 ± 17%, respectively, p = 0.004). No relationship was found between the prevention of quadriceps fatigue and the training load. Conclusion: In severe COPD patients, the beneficial effect of a ventilator support on quadriceps endurance persisted after PR with IPS. However, it was not related to the increase in training load, and could not predict the training response to non-invasive ventilation during exercise.

Targeting autonomic nervous system as a biomarker of well-ageing in the prevention of stroke.

Stroke prediction is a key health issue for preventive medicine. Atrial fibrillation (AF) detection is well established and the importance of obstructive sleep apneas (OSA) has emerged in recent years. Although autonomic nervous system (ANS) appears strongly implicated in stroke occurrence, this factor is more rarely considered. However, the consequences of decreased parasympathetic activity explored in large cohort studies through measurement of ANS activity indicate that an ability to improve its activity level and equilibrium may prevent stroke. In support of these observations, a compensatory neurostimulation has already proved beneficial on endothelium function. The available data on stroke predictions from ANS is based on many long-term stroke cohorts. These data underline the need of repeated ANS evaluation for the general population, in a medical environment, and remotely by emerging telemedicine digital tools. This would help uncovering the reasons behind the ANS imbalance that would need to be medically adjusted to decrease the risk of stroke. This ANS unbalance help to draw attention on clinical or non-clinical evidence, disclosing the vascular risk, as ANS activity integrates the cumulated risk from many factors of which most are modifiable, such as metabolic inadaptation in diabetes and obesity, sleep ventilatory disorders, hypertension, inflammation, and lack of physical activity. Treating these factors may determine ANS recovery through the appropriate management of these conditions. Natural aging also decreases ANS activity. ANS recovery will decrease global circulating inflammation, which will reinforce endothelial function and thus protect the vessels and the associated organs. ANS is the whistle-blower of vascular risk and the actor of vascular health. Such as, ANS should be regularly checked to help draw attention on vascular risk and help follow the improvements in response to our interventions. While today prediction of stroke relies on classical cardiovascular risk factors, adding autonomic biomarkers as HRV parameters may significantly increase the prediction of stroke.

Resistance Training of Inspiratory Muscles After Coronary Artery Disease May Improve Obstructive Sleep Apnea in Outpatient Cardiac Rehabilitation: RICAOS Study.

Background: Obstructive sleep apnea (OSA) affects 5% of the adult population and its prevalence is up to 13 times higher in coronary artery disease (CAD) patients. However, OSA in this population is less symptomatic, leading to lower adherence to positive airway pressure (CPAP). While oropharyngeal exercise showed a significant decrease in apnea-hypopnea index (AHI) in patients with moderate OSA, there have been no studies testing the impact of specific inspiratory muscle training (IMT) for these patients. The aim of our study was to assess the effectiveness of IMT on AHI reduction in CAD patients with moderate OSA. Methods: We included patients with CAD involved in a cardiac rehabilitation program and presenting an AHI between 15 and 30. Patients were randomized in a 1:1 allocation to a control group (CTL - classic training) or an IMT group (classic training + IMT). IMT consisted in 60 deep inspirations a day, 6 days a week, into a resistive load device set at 70% of the maximum inspiratory pressure (MIP). After 6 weeks, we compared AHI, neck circumference, Epworth Sleepiness Scale, Pittsburgh Sleep Quality index, and quality of life with the 12-item Short Form Survey before and after rehabilitation. Results: We studied 45 patient (60 ± 9 y, BMI = 27 ± 6 kg.m-2). The IMT group (n = 22) significantly improved MIP ( p < 0.05) and had a significant decrease in AHI by 25% (-6.5 ± 9.5, p = 0.02). In the CTL group (n = 23), AHI decreased only by 3.5% (-0.7 ± 13.1; p = 0.29). Between groups, we found a significant improvement in MIP ( p = 0.003) and neck circumference ( p = 0.01) in favor of the IMT group. However, we did not find any significant improvement of AHI in the IMT group compared to CTL ( p = 0.09). Conclusion: A specific IMT during cardiac rehabilitation contributes to reduce significantly AHI in CAD patients with moderate OSA. Magnitude of the decrease in OSA severity could be enhanced according to implementation of specific IMT in this population.

Prevention of Atrial Fibrillation After Atrial Flutter Ablation With Ramipril (from the PREFACE Study).

The clinical efficacy of the inhibitors of the renin-angiotensin-aldosterone system (RAAS) as an upstream therapy for atrial fibrillation (AF) prevention is controversial. No study has itemized so far the role of RAAS inhibitors in AF prevention after atrial flutter (AFL) ablation. This trial aims to investigate the effect of ramipril compared with placebo on AF occurrence in patients hospitalized for AFL ablation without structural heart disease. The Prevention of Atrial Fibrillation by Inhibition Conversion Enzyme (ICE) After Radiofrequency Ablation of Atrial Flutter (PREFACE) trial was a prospective, multicenter, randomized, double-blind, double-dummy trial depicting the AF occurrence during a 12-month follow-up as the primary end point. A total of 198 patients hospitalized for AFL ablation were enrolled in the trial and randomized to placebo or ramipril 5 mg/day. Patients were followed up during 1 year after AFL ablation using 1-week Holter electrocardiogram at 3, 6, 9, and 12 months. The intention-to-treat population encompassed 97 patients in the ramipril group and 101 patients in the placebo group. The primary end point, such as AF occurrence during the 1-year follow-up, was not different between the 2 groups (p = 0.96). Secondary end points, including the occurrence of supraventricular arrhythmia (p = 0.50), heart failure, stroke, and death, were not different between the 2 groups. Safety outcome parameters, including serious adverse events leading to treatment disruption (p = 0.10), hypotension, impairment of renal function, and elevated serum potassium level, also were not different between the 2 groups. In conclusion, RAAS inhibition using ramipril does not reduce AF occurrence in patients facing AFL ablation during the 1-year follow-up.

Association Between Physical Activity, Quadriceps Muscle Performance, and Biological Characteristics of Very Old Men and Women.

The aim of the study was to evaluate the association between physical activity, knee extensors (KE) performance (ie, isometric strength and fatigability), and biological parameters (ie, muscle structural, microvascular, and metabolic properties) in healthy very old men and women. Thirty very old adults (82 ± 1 years, 15 women) performed an isometric Quadriceps Intermittent Fatigue (QIF) test for the assessment of KE maximal force, total work (index of absolute performance), and fatigability. Muscle biopsies from the vastus lateralis muscle were collected to assess muscle fibers type and morphology, microvasculature, and enzymes activity. Correlation analyses were used to investigate the relationships between physical activity (steps/day, actimetry), KE performance, and biological data for each sex separately. Men, compared to women, showed greater total work at the QIF test (44 497 ± 8 629 Ns vs 26 946 ± 4 707 Ns; p < .001). Steps per day were correlated with total work only for women (r = 0.73, p = .011). In men, steps per day were correlated with the percentage (r = 0.57, p = .033), shape factor (r = 0.75, p = .002), and capillary tortuosity of type IIX fibers (r = 0.59, p = .035). No other relevant correlations were observed for men or women between steps per day and biological parameters. Physical activity level was positively associated with the capacity of very old women to perform a fatiguing test, but not maximal force production capacity of the KE. Physical activity of very old men was not correlated with muscle performance. We suggest that very old women could be at higher risk of autonomy loss and increasing the steps per day count could provide a sufficient stimulus for adaptations in less active women.

Association between nocturnal heart rate variability and incident cardiovascular disease events: The HypnoLaus population-based study.

BACKGROUND: Although heart rate variability (HRV) is widely used to assess cardiac autonomic function, few studies have specifically investigated nocturnal HRV. OBJECTIVE: The purpose of this study was to assess the association between nocturnal HRV and cardiovascular disease (CVD) incidence over 4 years in a population-based sample. METHODS: A total of 1784 participants (48.2% men; 58 ± 11 years) from the HypnoLaus population-based cohort free of CVD at baseline were included. Polysomnography-based electrocardiograms were exported to analyze time- and frequency-domain HRV, Poincaré plots indices, detrended fluctuation analysis, acceleration capacity (AC) and deceleration capacity (DC), entropy, heart rate fragmentation (HRF), and heart rate turbulence. Multivariable-adjusted Cox regression analysis was used to assess the association between HRV indices and incident CVD events. RESULTS: Sixty-seven participants (3.8%) developed CVD over mean follow-up of 4.1 ± 1.1 years. In a fully adjusted model, AC (hazard ratio per 1-SD increase; 95% confidence interval: 1.59; 1.17-2.16; P = .004), DC (0.63; 0.47-0.84; P = .002), and HRF (1.41; 1.11-1.78; P = .005) were the only HRV metrics significantly associated with incident CVD events after controlling for false discovery rate. CONCLUSION: Nocturnal novel HRV parameters such as AC, DC, and HRF are better predictors of CVD events than time and frequency traditional HRV parameters. These findings suggest a form of dysautonomia and fragmented rhythms, but further experimental studies are needed to delineate the underlying physiological mechanisms of these novel HRV parameters.

Insulin Resistance and Type 2 Diabetes in Asymptomatic Obstructive Sleep Apnea: Results of the PROOF Cohort Study After 7 Years of Follow-Up.

The aim of the study was to assess potential associations between obstructive sleep apnea (OSA) and the occurrence of diabetes mellitus and insulin resistance in the elderly. Nondiabetic volunteers (n = 549) with undiagnosed or untreated asymptomatic OSA (66.2+/-1 years at the inclusion) were evaluated as an ancillary study of the PROOF cohort study (n = 1,011). After 7 years follow-up, 494 subjects underwent assessment of fasting insulin and glucose levels. OSA was defined by an apnea-hypopnea index (AHI) of ≥15/h using polygraphy. Diabetes mellitus was defined by a fasting glucose ≥ 1.26 g/L and/or when requiring pharmacological treatment, while insulin resistance corresponded to HOMA-IR ≥ 2. Asymptomatic OSA subjects (men or women) did not display increased risk of incident diabetes (2.8 vs. 3.9%, p = 0.51). However, there was a greater frequency of insulin resistance in subjects with severe OSA (AHI > 30) [OR 2.21; 95% CI (1.22-4.02); p = 0.009]. Furthermore, multiple logistic regression showed that triglycerides levels [OR 1.61; 95% CI (1.10-2.36); p = 0.01] and fasting glycaemia [OR 4.69; 95% CI (1.12-192.78); p = 0.04], but not AHI or oxyhemoglobin desaturation index were independently associated with higher rate of insulin resistance. The deleterious metabolic effect of asymptomatic OSA in the population may be indirectly mediated via perturbations in lipids, and is particularly likely to become manifest in severe apneic subjects with higher glycemic levels.

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.

Predictors of high-degree conduction disturbances and pacemaker implantation after transcatheter aortic valve replacement: Prognostic role of the electrophysiological study.

BACKGROUND: Predictors of high-degree atrioventricular block (HAVB) after transcatheter aortic valve replacement (TAVR) are recognized, but the electrophysiological study's (EPS) role is still a subject to debate. The objective of our study was to determine factors associated with PPM implantation including the potential role of EPS before and/or after TAVR. METHODS AND RESULTS: Seventy four consecutive patients (pts) were included and 21 pts (28.4%) received a PPM during the immediate postoperative follow-ups (until Day 5): HAVB in 15 pts (71.4%), prophylactic implantation due to a documented increased HV interval ≥ 95-100 ms plus LBBB in 2 pts (9.5%), a high-degree HV block evidenced at the EPS plus LBBB in 3 pts (14.3%) and one additional patient was implanted for AV-block in presence of AFib (4.8%). In the multivariate model 1 including parameters before TAVR, both prosthesis diameter and PR lengthening remained significantly associated with PPM as well RBBB. In the multivariate model 2 including parameters after TAVR, only HV remained significantly associated with the risk of PPM (OR = 1.15 (1.05-1.26), p = .004). When all the significant variables in models 1 and 2 were analyzed together in model 3, only HV after TAVR remained significantly associated with an increased risk of PPM. CONCLUSIONS: In this prospective observational study, it was revealed that a Day 4-5 EPS is likely to more precisely stratify the risk of PPM implantation regarding its ability to discover asymptomatic severe infra-hisian conduction disturbances particularly in presence of LBBB. Multivariate analysis confirmed the prognostic value of HV alteration.

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.

Leukoaraiosis and Gray Matter Volume Alteration in Older Adults: The PROOF Study.

Background and Purpose: Leukoaraiosis, also called white matter hyperintensities (WMH), is frequently encountered in the brain of older adults. During aging, gray matter structure is also highly affected. WMH or gray matter defects are commonly associated with a higher prevalence of mild cognitive impairment. However, little is known about the relationship between WMH and gray matter. Our aim was thus to explore the relationship between leukoaraiosis severity and gray matter volume in a cohort of healthy older adults. Methods: Leukoaraiosis was rated in participants from the PROOF cohort using the Fazekas scale. Voxel-based morphometry was performed on brain scans to examine the potential link between WMH and changes of local brain volume. A neuropsychological evaluation including attentional, executive, and memory tests was also performed to explore cognition. Results: Out of 315 75-year-old subjects, 228 had punctuate foci of leukoaraiosis and 62 had begun the confluence of foci. Leukoaraiosis was associated with a decrease of gray matter in the middle temporal gyrus, in the right medial frontal gyrus, and in the left parahippocampal gyrus. It was also associated with decreased performances in memory recall, executive functioning, and depression. Conclusion: In a population of healthy older adults, leukoaraiosis was associated with gray matter defects and reduced cognitive performance. Controlling vascular risk factors and detecting early cerebrovascular disease may prevent, at least in part, dementia onset and progression.

Electronic cigarettes and health with special focus on cardiovascular effects: position paper of the European Association of Preventive Cardiology (EAPC).

BACKGROUND: Tobacco use is the single largest preventable risk factor for premature death of non-communicable diseases and the second leading cause of cardiovascular disease. In response to the harmful effects of tobacco smoking, the use of electronic cigarettes (e-cigarettes) has emerged and gained significant popularity over the past 15 years. E-cigarettes are promoted as safe alternatives for traditional tobacco smoking and are often suggested as a way to reduce or quit smoking. However, evidence suggests they are not harmless. DISCUSSION: The rapid evolution of the e-cigarette market has outpaced the legislator's regulatory capacity, leading to mixed regulations. The increasing use of e-cigarettes in adolescents and young individuals is of concern. While the long-term direct cardiovascular effects of e-cigarettes remain largely unknown, the existing evidence suggests that the e-cigarette should not be regarded as a cardiovascular safe product. The contribution of e-cigarette use to reducing conventional cigarette use and smoking cessation is complex, and the impact of e-cigarette use on long-term cessation lacks sufficient evidence. CONCLUSION: This position paper describes the evidence regarding the prevalence of e-cigarette smoking, uptake of e-cigarettes in the young, related legislations, cardiovascular effects of e-cigarettes and the impact of e-cigarettes on smoking cessation. Knowledge gaps in the field are also highlighted. The recommendations from the population science and public health section of the European Association of Preventive Cardiology are presented.

Role of Gender and Physical Activity Level on Cardiovascular Risk Factors and Biomarkers of Oxidative Stress in the Elderly.

BACKGROUND: Cardiovascular diseases remain as the leading cause of morbidity and mortality in industrialized countries. Ageing and gender strongly modulate the risk to develop cardiovascular diseases but very few studies have investigated the impact of gender on cardiovascular diseases in the elderly, which represents a growing population. The purpose of this study was to test the impact of gender and physical activity level on several biochemical and clinical markers of cardiovascular risk in elderly individuals. METHODS: Elderly individuals (318 women (75.8 ± 1.2 years-old) and 227 men (75.8 ± 1.1 years-old)) were recruited. Physical activity was measured by a questionnaire. Metabolic syndrome was defined using the National Cholesterol Education Program Expert Panel's definition. Polysomnography and digital tonometry were used to detect obstructive sleep apnea and assess vascular reactivity, respectively. Blood was sampled to measure several oxidative stress markers and adhesion molecules. RESULTS: The frequency of cardiovascular diseases was significantly higher in men (16.4%) than in women (6.1%) (p < 0.001). Body mass index (25.0 ± 4.3 vs. 25.8 ± 3.13 kg.m-2) and glycaemia (94.9 ± 16.5 vs. 101.5 ± 22.6 mg.dL-1) were lower, and High Density Lipoprotein (HDL) (74.6 ± 17.8 vs. 65.0 ± 17.2 mg.dL-1) was higher in women compared to men (p < 0.05). Oxidative stress was lower in women than in men (uric acid: 52.05 ± 13.78 vs. 59.84 ± 13.58, advanced oxidation protein products: 223 ± 94 vs. 246 ± 101 µmol.L-1, malondialdehyde: 22.44 ± 6.81 vs. 23.88 ± 9.74 nmol.L-1). Physical activity was not associated with lower cardiovascular risk factors in both genders. Multivariate analyses showed an independent effect of gender on acid uric (ß = 0.182; p = 0.020), advanced oxidation protein products (ß = 0.257; p < 0.001), and HDL concentration (ß = -0.182; p = 0.026). CONCLUSION: These findings suggest that biochemical cardiovascular risk factors are lower in women than men which could explain the lower cardiovascular disease proportion observed in women in the elderly.

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.