Short-term heart rate variability in resting conditions: methodological considerations

Low values on heart rate variability (HRV) derived parameters at resting have been used to predict cardiovascular diseases (CVD) and mortality. In this regard, short-term HRV recordings (usually from 5 to 15 minutes) are increasing their popularity because data acquisition can be performed under more controlled conditions than long-term recordings (e.g., 24 hours). However, different method ological aspects before, during, and after the HRV assessment could affect the quantification and the clinical interpretations of the HRV-derived parameters, as well as hamper comparisons across different studies. In the present study, we summarize these methodological aspects that should be considered in both the research and the clinical settings. These are: (1) the validity and reproducibility of the device used to assess the HRV; (2) the influence of the software used to perform the artefact correction; (3) previous conditions before the testing day; (4) establishing the proper conditions during the HRV assessment (e.g., controlled respiratory frequency); (5) after assessing the HRV, con sidering the “best” data selection and statistical analysis approach; and (6) the role of the heart rate on the associations between the different CVD risk factors outcomes (e.g., cardiorespiratory fitness) and the HRV-derived parameters

Effects of exercise on whole-blood transcriptome profile in children with overweight/obesity

Spanish Ministry of Economy and Competitiveness; MCIN/AEI/10.13039/ 501100011033ERFD A way of making Europe, Grant/Award Number: PID2021-127280OB-I00University of Jaén, Grant/Award Number: PAIUJAEI_ CTS02; Spanish Ministry of EducationCulture and Sport, Grant/Award Numbers: FPU 16/02760DEP2016-79512-R, DEP2013-47540; National Institutes of HealthGrant/Award Number: U01TR002004; Unit of Excellence on Exercise and Health; EXERNET Research Network on Exercise and Health in Special Populations, Grant/Award Number: DEP2005-00046/ ACTIUniversity of Granada, Plan Propio de Investigación 2016, Excellence actions; Junta de AndalucíaConsejería de Conocimiento, Investigaci on y UniversidadesEuropean Regional Development FundSigrid Jusélius Foundation; Jane and Aatos Erkko Foundation; Funding for open access charge: Universidad de Granada/CBU

Cardiorespiratory fitness in children with overweight/obesity: Insights into the molecular mechanisms

Spanish Ministry of Economy and Competitiveness, Grant/Award Number: DEP2013--47540, DEP2016-79512--R and DEP2017--91544--EXP; Spanish Ministry of Economy, Industry and Competitiveness (MINECO); European Regional Development Fund (FEDER), Grant/Award Number: RYC--2016--21199 and ENDORE SAF2017--87526--R; Junta de Andalucia, Grant/Award Number: BIO--302 and US--1254251; University of Jaen, Grant/Award Number: PAIUJA--EI_CTS02; Spanish Ministry of Education, Culture and Sport, Grant/Award Number: FPU 16/02760; NIH, Grant/Award Number:UO1 TR002004; PERC Systems Biology Fund; Unit of Excellence on EXERNET Research Network on Exercise and Health in Special Populations; Alicia Koplowitz Foundation; Henning Och Johan Throne--Holsts Stiftelse Grant; University of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES); Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades and European Regional Development Fund (ERDF), Grant/Award Number: SOMM17/6107/UGR; European Regional Development Funds, Grant/Award Number: B--CTS-355--UGR18 and B--CTS--500--UGR18; Funding for open access charge: Universidad de Granada/CBUAObjectives: High cardiorespiratory fitness (CRF) levels reduce the risk of developing cardiovascular disease (CVD) during adulthood. However, little is known about the molecular mechanisms underlying the health benefits of high CRF levels at the early stage of life. This study aimed to analyze the whole-blood transcriptome profile of fit children with overweight/obesity (OW/OB) compared to unfit children with OW/OB. Design: 27 children with OW/OB (10.14 ± 1.3 years, 59% boys) from the ActiveBrains project were evaluated. VO2peak was assessed using a gas analyzer, and participants were categorized into fit or unfit according to the CVD risk-related cut-points. Whole-blood transcriptome profile (RNA sequencing) was analyzed. Differential gene expression analysis was performed using the limma R/Bioconductor software package (analyses adjusted by sex and maturational status), and pathways’ enrichment analysis was performed with DAVID. In addition, in silico validation data mining was performed using the PHENOPEDIA database. Results: 256 genes were differentially expressed in fit children with OW/OB compared to unfit children with OW/OB after adjusting by sex and maturational status (FDR < 0.05). Enriched pathway analysis identified gene pathways related to inflammation (eg, dopaminergic and GABAergic synapse pathways). Interestingly, in silico validation data mining detected a set of the differentially expressed genes to be related to CVD, metabolic syndrome, hypertension, inflammation, and asthma. Conclusion: The distinct pattern of whole-blood gene expression in fit children with OW/OB reveals genes and gene pathways that might play a role in reducing CVD risk factors later in life.Spanish Ministry of Economy and Competitiveness DEP2013-47540 DEP2016-79512-R DEP2017-91544-EXPSpanish Ministry of Economy, Industry and Competitiveness (MINECO)European Commission RYC-2016-21199ENDORE SAF2017-87526-RJunta de Andalucia BIO-302 US-1254251University of Jaen PAIUJA-EI_CTS02Spanish Ministry of Education, Culture and Sport FPU 16/02760United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA UO1 TR002004PERC Systems Biology FundUnit of Excellence on EXERNET Research Network on Exercise and Health in Special PopulationsAlicia Koplowitz FoundationHenning Och Johan Throne-Holsts Stiftelse GrantUniversity of GranadaUnit of Excellence on Exercise and Health (UCEES)Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades and European RegionalDevelopment Fund (ERDF) SOMM17/6107/UGR European Commission B-CTS-355-UGR18 B-CTS-500-UGR18Universidad de Granada/CBU

Associations between Intra-Assessment Resting Metabolic Rate Variability and Health-Related Factors

In humans, the variation in resting metabolic rate (RMR) might be associated with health-related factors, as suggested by previous studies. This study explored whether the intra-assessment RMR variability (expressed as a coefficient of variation (CV; %)) is similar in men and women and if it is similarly associated with diverse health-related factors. The RMR of 107 young, and relatively healthy adults, was assessed using indirect calorimetry. Then, the CV for volumes of oxygen consumption (VO2) and carbon dioxide production (VCO2), respiratory exchange ratio (RER), and resting energy expenditure (REE) were computed as indicators of intra-assessment RMR variability. Body composition, cardiorespiratory fitness (peak VO2 uptake), circulating cardiometabolic risk factors, and heart rate and its variability (HR and HRV) were assessed. Men presented higher CVs for VO2, VCO2, and REE (all p <= 0.001) compared to women. Furthermore, in men, the intra-assessment RER variability was associated with vagal-related HRV parameters and with mean HR (standardized beta = -0.36, -0.38, and 0.41, respectively; all p < 0.04). In contrast, no associations were observed in women. In conclusion, men exhibited higher variability (CVs for VO2, VCO2, and REE) compared to women. The CV for RER could be a potential marker of cardiometabolic risk in young men.Spanish Ministry of Economy and Competitiveness (DEP2016-79512-R and PTA 12264-I)Spanish Ministry of Education, Culture and Sport (FPU15/04059, FPU16/02828, and FPU 16/02760)University of Granada, Plan Propio de Investigación 2020 Programa de Contratos PuenteGrant FJC2020-044453-I MCIN/AEI/10.13039/501100011033European Union NextGenerationEU/PRTRNIH grant #: U01 TR002004 (REACH project)Unit of Excellence on Exercise and Health (UCEES)EXERNET Research Network on Exercise and Health in Special Populations (DEP2005-00046/ACTI)Unit of Excellence in Sport and Health (UCEES)Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades and European Regional Development Funds (ref. SOMM17/6107/UGR

Associations between heart rate variability and maximal fat oxidation in two different cohorts of healthy sedentary adults

Background and aims: Resting heart rate variability (HRV) and maximal fat oxidation (MFO) during exercise are both considered as a noninvasive biomarkers for early detection of car-diovascular risk factors. Thus, this study aimed to analyze the relationship between resting HRV parameters and MFO during exercise, and the intensity of exercise that elicit MFO (Fatmax) in healthy sedentary adults. Methods and results: A total of 103 healthy young adults (22.2 +/- 2.3 years old, 67% female; from the ACTIBATE cohort) and 67 healthy middle-aged adults (53.1 +/- 5.0 years old, 52% female; from the FIT-AGEING cohort) were included in this cross-sectional study. HRV was assessed using a Polar RS800CX heart rate monitor, while MFO and Fatmax were determined during a graded ex-ercise treadmill test using indirect calorimetry. No significant associations were observed for healthy young adults (standardized b coefficients ranged from-0.063 to 0.094, and all P >= 0.347) and for middle-aged adults (standardized b coefficients ranged from-0.234 to 0.090, and all P >= 0.056). Nevertheless, only a weak association was observed between one HRV parameter in time-domain (the percentage of R-R intervals that shows a difference higher than 50 ms [pNN50]) and MFO in the cohort of middle-aged adults (b coefficient =-0.279, and P = 0.033). Conclusion: The results of this study suggest that resting HRV parameters are not associated with MFO and Fatmax during exercise in two independent cohorts of healthy sedentary young and middle-aged adults, respectively.Spanish Government DEP2016-79512-R PTA 12264-I FPU 16/02760 FPU15/04059 FPU14/04172University of Granada,PlanPropio de Investigacion 2020 Programa de Contratos PuenteUnit of Excel-lence on Exercise and Health (UCEES)EXERNET Research Network on Exercise and Health in Special Populations DEP2005-00046/ACTIUnit of Excellence in Sport and Health (UCEES) - University of GranadaJunta de AndaluciaEuropean Commission SOMM17/6107/UGRUniversidad de Granada / CBU

Transcriptional and Epigenetic Response to Sedentary Behavior and Physical Activity in Children and Adolescents: A Systematic Review

Background: The links of sedentary behavior and physical activity with health outcomes in children and adolescents is well known. However, the molecular mechanisms involved are poorly understood.We aimed to synthesize the current knowledge of the association of sedentary behavior and physical activity (acute and chronic effects) with gene expression and epigenetic modifications in children and adolescents. Methods: PubMed, Web of Science, and Scopus databases were systematically searched until April 2022. A total of 15 articles were eligible for this review. The risk of bias assessment was performed using the Joanna Briggs Institute Critical Appraisal Tool for Systematic Reviews and/or a modified version of the Downs and Black checklist. Results: Thirteen studies used candidate gene approach, while only 2 studies performed high-throughput analyses. The candidate genes significantly linked to sedentary behavior or physical activity were: FOXP3, HSD11B2, IL-10, TNF-a, ADRB2, VEGF, HSP70, SOX, and GPX. Non-coding Ribonucleic acids (RNAs) regulated by sedentary behavior or physical activity were: miRNA-222, miRNA-146a, miRNA-16, miRNA-126, miR-320a, and long non-coding RNA MALAT1. These molecules are involved in inflammation, immune function, angiogenic process, and cardiovascular disease. Transcriptomics analyses detected thousands of genes that were altered following an acute bout of physical activity and are linked to gene pathways related to immune function, apoptosis, and metabolic diseases. Conclusion: The evidence found to date is rather limited. Multidisciplinary studies are essential to characterize the molecular mechanisms in response to sedentary behavior and physical activity in the pediatric population. Larger cohorts and randomized controlled trials, in combination with multi-omics analyses, may provide the necessary data to bring the field forward.Spanish Government DEP2013-47540 DEP2016-79512-R DEP2017-91544-EXPEuropean Commission RYC-2016-21199 ENDORE SAF2017-87526-R 09/UPB/19 45/UPB/20 27/UPB/21 SOMM17/6107/UGRSpanish Government B-CTS-355 UGR18United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA B-CTS-500-UGR18PERC Systems Biology FundHuawei TechnologiesEXERNET Research Network on Exercise and Health A-CTS-614-UGR20 FPU 16/02760 FPU19/05561UO1 TR002004Alicia Koplowitz FoundationUniversity of GranadaJunta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades and European RegionalDevelopment Fund (ERDF) DEP2005- 00046/ACTI Junta de Andalucia PAIDI P20_0015

Determinants of Longitudinal Changes in Cardiometabolic Risk in Adolescents with Overweight/Obesity: The EVASYON Study

We investigated which determinants (socioeconomic, early life factors, body composition changes, fitness changes and/or physical activity changes) best predicted longitudinal outcomes in cardiometabolic risk profile (Z-score change) in adolescents with OW/OB who underwent a 13-month multidisciplinary lifestyle intervention. A total of 165 adolescents (13–16 y; 46% boys) from the EVASYON study were included. Socioeconomic variables and early life factors were obtained from the medical records. Body composition was assessed using anthropometry. Fitness and physical activity were measured with field-based tests and questionnaires. Cardiometabolic risk factors (fasting glucose, HDL cholesterol, triglycerides, blood pressure and waist circumference) were derived from standard methods in the hospital. Body weight changes, sex and mother’s education were selected in the stepwise process as the most important determinants of changes in cardiometabolic risk profile (R2 = 0.26, p = 0.002; R2 = 0.14, p = 0.013; and R2 = 0.14, p = 0.017, respectively). Both boys and girls showed a lower cardiometabolic risk score with the reduction in body weight (r = 0.535, p = 0.009 and r = 0.506, p = 0.005, respectively). There was no interaction between sex and body weight change (p = 0.614). In conclusion, the simple measure of changes in body weight should be considered to track changes in cardiometabolic risk profile in adolescents with OW/OB.Ministry of Health and Consumption via the Carlos III Institute of Health (FIS) PI051579AESAN (Spanish Agency for Food Safety and Nutrition) from the Spanish Ministry of Health and Consumer Affairs PI05236

Fit-Fat Index is better associated with heart rate variability compared to fitness and fatness alone as indicators of cardiometabolic human health

ObjectivesCardiorespiratory fitness and fatness indicators have been related to heart rate variability (HRV) parameters. The Fit-Fat Index (FFI) is a single index combining cardiorespiratory fitness and fatness indicators. To the best of our knowledge, no studies have previously analyzed whether FFI are related to cardiac autonomic nervous system activity assessed through HRV parameters. This study aimed (i) to examine the association of cardiorespiratory fitness, fatness indicators, and FFI with HRV parameters; and (ii) to report what of the different fatness indicators included in FFI is better associated with HRV parameters in sedentary adults. MethodsOne hundred and fifty healthy adults (74 women; 76 men), aged between 18 and 65 years old, participated in this cross-sectional study. We measured cardiorespiratory fitness (maximal oxygen consumption) and fatness indicators (waist-to-height ratio [WHR], fat mass percentage [FM%] and visceral adipose tissue [VAT]). Three FFIs were calculated as the quotient between cardiorespiratory fitness and one out of three possible fatness indicators: Fit-Fat Index calculated waist-to-height ratio (FFIWHR), Fit-Fat Index calculated with FM% (FFIFM%), and Fit-Fat Index calculated with VAT (FFIVAT). HRV parameters were measured in resting conditions using a Polar RS800CX. ResultsFFI(WTHR), FFIFM% and FFIVAT were related to different HRV parameters (beta ranges between -0.507 and 0.529; R-2 ranges between 0.096 and 0.275; all p < .001) and the association was stronger with HRV parameters than the isolated fitness or fatness indicators (beta ranges between -0.483 and 0.518; R-2 ranges between 0.071 and 0.263; all p < .001). FFIVAT was the index more consistently associated with HRV parameters (beta ranges between -0.507 and 0.529; R-2 ranges between 0.235 and 0.275; all p < .001). ConclusionOur study suggests that compound FFIs are better predictors of HRV parameters than either cardiorespiratory fitness or fatness indicators alone. The FFIVAT was the best index in terms of its association to HRV.Spanish Ministry of Education FPU16/02760, FPU14/04172United States Department of Health & Human Services National Institutes of Health (NIH) - USA U01 TR00200

Different exercise training modalities similarly improve heart rate variability in sedentary middle‑aged adults: the FIT‑AGEING randomized controlled trial

Funding for open access charge: Universidad de Granada/CBUA.Purpose This study aimed to investigate the influence of different exercise training modalities on heart rate variability (HRV) in sedentary middle-aged adults; and to study whether changes in health-related outcomes (i.e., body composition and cardiometabolic risk) are associated with those hypothetical HRV changes in sedentary middle-aged adults. Methods A total of 66 middle-aged adults (53.6 ± 4.4 years old; 50% women) were enrolled in the FIT-AGEING study. We conducted a 12-week randomized controlled trial. The participants were randomly assigned to 4 groups: (a) a control group (no exercise); (b) a physical activity recommendation from the World Health Organization group (PAR); (c) a high-intensity interval training group (HIIT); and (d) a high-intensity interval training group adding whole-body electromyostimulation (HIIT + EMS). Results All exercise training modalities induced changes in HRV parameters (all P ≤ 0.001) without statistical differences between them (all P > 0.05). We found associations between changes in body composition and cardiometabolic risk and exercise-related changes in HRV. Conclusion Our results suggest that different exercise interventions (i.e., PAR, HIIT and HIIT + EMS) induced an enhancement of HRV in sedentary middle-aged adults. Our findings support the notion that exercise-related changes in HRV are associated with changes in body composition and cardiometabolic risk after the intervention programUniversidad de Granada/CBU

Shared gene expression signatures between visceral adipose and skeletal muscle tissues are associated with cardiometabolic traits in children with obesity

Obesity in children is related to the development of cardiometabolic complications later in life, where molecular changes of visceral adipose tissue (VAT) and skeletal muscle tissue (SMT) have been proven to be fundamental. The aim of this study is to unveil the gene expression architecture of both tissues in a cohort of Spanish boys with obesity, using a clustering method known as weighted gene co-expression network analysis. For this purpose, we have followed a multi-objective analytic pipeline consisting of three main approaches; identification of gene co-expression clusters associated with childhood obesity, individually in VAT and SMT (intra-tissue, approach I); identification of gene co-expression clusters associated with obesitymetabolic alterations, individually in VAT and SMT (intra-tissue, approach II); and identification of gene co-expression clusters associated with obesity-metabolic alterations simultaneously in VAT and SMT (intertissue, approach III). In both tissues, we identified independent and inter-tissue gene co-expression signatures associated with obesity and cardiovascular risk, some of which exceeded multiple-test correction filters. In these signatures, we could identify some central hub genes (e.g., NDUFB8, GUCY1B1, KCNMA1, NPR2, PPP3CC) participating in relevant metabolic pathways exceeding multiple-testing correction filters. We identified the central hub genes PIK3R2, PPP3C and PTPN5 associated with MAPK signaling and insulin resistance terms. This is the first time that these genes have been associated with childhood obesity in both tissues. Therefore, they could be potential novel molecular targets for drugs and health interventions, opening new lines of research on the personalized care in this pathology. This work generates interesting hypotheses about the transcriptomics alterations underlying metabolic health alterations in obesity in the pediatric populationERDF/Health Institute Carlos III (grant numbers PI20/00711 and PI20/00563)ERDF/Regional Government of Andalusia/Ministry of Economic Transformation, Industry, Knowledge and Universities (grant numbers P18- RT-2248 and B-CTS-536-UGR20