Cardiorespiratory Fitness Research Articles

Trends in physical fitness among children and adolescents in Europe: A systematic review and meta-analyses during and after the COVID-19 pandemic.

Cardiorespiratory fitness in relation to cardiometabolic health in adult Mexican Rarámuri.

Background The objective of the present study was to elucidate the impact of a 12-week caffeine consumption before sprint interval training on the physical and physiological adaptations in obese women. Methods Thirty overweight and obese women volunteered and were randomly divided into three groups: Caffeine (3 mg·kg −1 body mass, n = 10), Placebo (3 mg·kg −1 body mass in cellulose, n = 10), and Control ( n = 10). Over 12 weeks, subjects in the Caffeine and Placebo groups consumed their supplements three times per week, ~60 min before each sprint interval training session. Fat mass, lower body strength, and cardiorespiratory fitness were evaluated at baseline and after the intervention. Fasting glucose, lipid profiles, and adipokines (leptin, adiponectin, and irisin) were measured 48 h before and after the intervention. Results Both the Caffeine and Placebo groups exhibited significant improvements ( p < 0.05) in these variables after 12 weeks of training. The Caffeine group showed significantly greater adaptive responses ( p < 0.05) than the Placebo group in reducing fat mass (SMD = −0.27), enhancing strength (SMD = 0.30) and cardiorespiratory fitness (SMD = 0.43), and altering fasting glucose (SMD = −0.74), leptin (SMD = −0.23), adiponectin (SMD = 0.18), and irisin (SMD = 0.42) after the intervention. Conclusion Supplementation of 3 mg·kg −1 body mass caffeine before sprint interval training resulted in greater reductions in fat mass and improvements in strength and cardiorespiratory fitness, as well as more pronounced changes in fasting glucose and adipokines among overweight and obese women.

Background: Sedentary aging is linked to low cardiorespiratory fitness and poor cardiovascular health. People with smaller left ventricles, particularly females, are more likely to have low fitness levels, which is an important risk factor for developing heart failure. Endurance exercise training can reverse the effects of sedentary aging in middle age, but it remains to be determined whether the cardiovascular adaptations to training are influenced by initial heart size and sex. Methods: Twenty-eight sedentary adults [15 females; age: 54±5 yr, peak oxygen uptake (VO 2 ): 28.8±4.8 mL/min/kg] completed 2 years of endurance exercise training, with changes in left ventricular end-diastolic volume indexed to body surface area (LV EDVi) and cardiorespiratory fitness assessed following 10 months of progressive training and an additional 14 months of maintenance training. Results: Despite baseline sex differences in LV EDVi at rest (male: 53.3±8.4 vs. female: 46.3±8.4 mL/m 2 ; main effect: p =0.004), both male (Δ = 7.7±6.6 mL/m 2 ) and female (Δ = 6.6±7.5 mL/m 2 ) participants experienced similar increases in EDVi with 2 years of training (main effect of time: p <0.001). Male ( r =-0.650, p =0.016) and female ( r =-0.776, p <0.001) participants with the smallest initial resting LV EDVi experienced the greatest increase in EDVi with training (Figure), suggesting the greatest cardiac remodeling occurred in individuals with the smallest LV on baseline testing. The increase in peak VO 2 (sex × time: p <0.001) of female participants after 2 years (Δ = 0.26±0.14 L/min) was ~50% of the increase observed in male participants (Δ = 0.53±0.20 L/min), which was a consequence of smaller increases in peak stroke volume (sex × time interaction: p =0.013) and cardiac output (sex × time: p =0.005). The changes in arteriovenous O 2 difference at peak exercise with training did not interact with the effect of sex (sex × time: p =0.129). Pre-training LV EDVi was not associated with the increase in peak VO 2 with training ( r =0.263, p =0.176). Conclusion: Two years of structured endurance exercise training in middle age resulted in similar degrees of cardiac remodeling for both sexes; however, female participants still had blunted increases in cardiorespiratory fitness compared to male participants. Critically, the magnitude of improvement in cardiorespiratory fitness with endurance exercise training was not impaired in previously sedentary adults who had the smallest starting LV EDVi.

Background: Early identification of women at high risk for pregnancy-related cardiovascular (CV) complications has the potential to significantly reduce maternal mortality. Peak VO 2 is the gold-standard metric of cardiorespiratory fitness and has been shown to predict adverse outcomes in pregnant women, but ascertainment is costly and requires specialized equipment and expertise. We previously developed a deep learning model to accurately estimate peak VO 2 from the resting 12-lead electrocardiogram (ECG). We sought to examine the association of deep learning ECG-predicted peak VO 2 and incident pregnancy-related CV complications. Methods: We ascertained ECG-estimated peak VO 2 among individuals who underwent clinical 12-lead ECG testing between 1 year prior to pregnancy and 13 weeks of gestation in a multi-institutional electronic health record cohort of pregnant women. Age-adjusted logistic regression models were used to examine the association of ECG-estimated peak VO 2 with subsequent pregnancy-related CV complications up to 1 year postpartum (maternal death, severe hypertensive disorders of pregnancy [HDP], and major adverse cardiac events [MACE]). Results: Among 3650 pregnancies from 3437 women (mean age at delivery 33 ± 6 years), the median ECG-estimated VO 2 was 26.5 mL/kg/min, and 26% experienced a pregnancy-related CV complication. Lower ECG-estimated peak VO 2 was associated with greater risk of a pregnancy-related CV complication (odds ratio [OR] 1.18 per 1-unit lower metabolic equivalent (MET = 3.5 kg/m 2 ), 95% CI 1.15-1.23, p<0.001). Women in the lowest quartile of ECG-estimated peak VO 2 had nearly twice the odds of developing a pregnancy-related CV complication compared with the highest quartile (OR 2.36, 95% CI 1.91-2.93, p<0.001, Figure 1 ). Conclusions: Lower estimated cardiorespiratory fitness from a validated deep learning model based on resting 12-lead ECG is strongly and independently associated with higher risk of pregnancy-related CV complications. Artificial intelligence-enabled analysis of ECGs performed routinely in antepartum care may enable scalable risk assessment for identifying high-risk pregnancies in routine clinical settings.

Regular vigorous exercise brings about cardiovascular adaptations, but the relationship between cardiac magnetic resonance-derived T1 and T2 mapping and physical fitness is not fully understood, with conflicting literature results. This study aims to define the associations between cardiorespiratory fitness evaluated using cardiopulmonary exercise testing (CPET) and cardiac remodelling using cardiac magnetic resonance (CMR), including T1 and T2 mapping. We enrolled elite, healthy athletes undergoing pre-participation screening (including personal and family history, physical examination, and 12-lead ECG) who volunteered for maximal CPET and non-contrast CMR with a 1.5T scanner, performed no more than 31 days apart. Our study population comprised 125 athletes: median age 19 [16-24.5] years; 65% males; median hours of training 20 [15-24.5]; 9% power, 36% endurance, 55% mixed. Overall, female athletes showed less pronounced cardiorespiratory and cardiac morphological remodelling compared to their male counterparts, and endurance athletes exhibited the highest levels of cardiorespiratory fitness and the most pronounced cardiac remodelling of the sport types considered. Greater overall fitness was associated with larger cardiac volumes and mass, and lower T1 and T2 values. In multivariate analysis, sex, sport type, LVMi, EDWT, VO2 max, and peak lactate collectively explained ∼27% of the variation in T1 values. Cardiac remodelling in athletes appears to be influenced by training load, sex, and sport type. In this study, we demonstrate for the first time an association between myocardial tissue characteristics, assessed by mapping, and cardiopulmonary fitness, evaluated through CPET. This finding suggests a potential link between aerobic adaptation and tissue-level myocardial properties. Further studies are warranted to validate these associations and to clarify their role in distinguishing physiological athletic remodelling from early pathological changes.

Introduction Resting-state plasma proteins are predictive of exercise performance, but limited data exist regarding acute changes in the plasma proteome with exercise. Hypothesis: Prominent changes in the plasma proteome occur with acute exercise, a subset of which also relate to peak VO 2 as an objective measure of cardiorespiratory fitness. Methods: Among community-based participants in the multi-ethnic Dallas Heart Study who participated in the third study phase (2020-2024) and underwent protocol cardiopulmonary exercise testing, we measured aptamer-based plasma proteomics (SomaLogic; 7172 aptamers corresponding to 6490 unique proteins) at rest and immediately post-exercise in 73 participants (146 paired samples). We tested for associations between log2 protein levels and rest/exercise status using linear mixed effects models adjusted for age, sex, BMI, rest and exercise heart rate and systolic blood pressure. For proteins that changed with exercise, we assessed associations of rest protein values with percent peak VO2 using linear regression models adjusted for age, sex, and BMI. Finally, associations with HF were assessed in a case-control study of 58 prevalent cases and matched controls using logistic regression. The Bonferroni method was used for multiple testing correction. Results: Mean age was 54±11 years, 64% were male, BMI was 28.3±8.7 kg/m 2 , and percent peak VO2 was 85±33%. After multiple testing correction, 415 protein aptamers changed from rest to exercise: 242 increased and enriched for pathways related to RNA processing and translation; 173 decreased and enriched for pathways related to extracellular matrix organization, and immune response. Of these, 4 proteins were also associated with peak VO2 after multiple test correction: higher peak VO 2 associated with decrease in LEP consistent with prior reports, and with increases in CIB1, ITGB1|ITGA11, and CYB5R3. In addition to proteins involved in metabolism (LEP, CYB5R3), these proteins reflect processes related to signal transduction (ITGB1, LEP), extracellular matrix organization (ITGB1|ITGA11) and biological pathway regulation (CIB1). Higher resting ITGB1|ITGA11 value was also associated with decreased odds of HF (OR per 1-sd 0.20 [95% CI 0.067-0.55], p= 0.003). Conclusions: Acute exercise impacts the plasma proteome, with exercise-induced changes in LEP, CIB1, ITGB1|ITGA11, and CYB5R3 associated with cardiorespiratory fitness. Higher resting values of ITGB1|ITGA11 associate with lower HF risk.

Background: Exercise interventions are foundational in cardiovascular disease prevention and management. High-Intensity Interval Training (HIIT) and Moderate-Intensity Continuous Training (MICT) are widely studied modalities, yet their comparative efficacy on cardiovascular outcomes remains debated. Objective: To evaluate and compare the effects of HIIT and MICT on cardiovascular outcomes in adults based on randomized controlled trials (RCTs) published from 2015 to 2025. Methods: A systematic search of studies exported from EndNote identified 27 RCTs meeting the following inclusion criteria: adult participants (≥18 years), English language, publication date between 2015–2025, and comparison of HIIT versus MICT with reported cardiovascular outcomes. Primary outcomes included peak oxygen uptake (VO2 peak), left ventricular function, endothelial function, blood pressure, lipid profiles, and adverse cardiovascular events. Data were extracted and pooled using a random-effects model. Standardized mean differences (SMDs) and risk ratios (RRs) were calculated with 95% confidence intervals (CIs). Heterogeneity was assessed using I^2 statistics. Results: Across 27 RCTs (n = 2,743 participants), HIIT significantly improved VO2 peak compared to MICT (SMD: 0.51; 95% CI: 0.34–0.68; p < 0.001; I^2 = 43%). Left ventricular ejection fraction (LVEF) improved modestly with HIIT (SMD: 0.24; 95% CI: 0.10–0.38; p = 0.001). HIIT also demonstrated greater reductions in systolic blood pressure (mean difference: –5.6; 95% CI: –7.2 to –4.0; p < 0.001) and improved endothelial function (flow-mediated dilation: SMD: 0.39; 95% CI: 0.19–0.58; p < 0.001). No significant difference was observed in major adverse cardiovascular events between groups (RR: 0.96; 95% CI: 0.84–1.09; p = 0.51). Adherence and safety profiles were comparable between HIIT and MICT. Conclusion: HIIT demonstrates superior improvements in cardiorespiratory fitness, ventricular function, and vascular health compared to MICT in adults, with similar safety and adherence. These findings support the incorporation of HIIT as an effective alternative or adjunct to MICT in cardiovascular prevention and rehabilitation programs. Further long-term studies are warranted to assess the impacts on clinical cardiovascular events.

RECOMMENDATIONS 1. Aerobic PA (30 - 60 minutes of moderate to vigorous intensity most days of the week) can be considered for adults who want to:a. achieve small amounts of body weight and fat loss (Level 2a, Grade B)b. achieve reductions in abdominal visceral fat (Level 1a, Grade A) and ectopic fat such as liver and heart fat (Level 1a, Grade A),even in the absence of weight lossc. favour weight maintenance after weight loss (Level 2a, Grade B)d. favour the maintenance of fat-free mass during weight loss (Level 2a, Grade B)e. increase cardiorespiratory fitness (Level 2a, Grade B)[9] and mobility (Level 2a, Grade B). 2. For adults living with overweight or obesity, resistance training may promote weight maintenance or modest increases in muscle mass or fat-free mass and mobility (Level 2a, Grade B) 3. Increasing exercise intensity, including high-intensity interval training (HIIT), can achieve greater increases in cardiorespiratory fitness compared with moderate-intensity aerobic activity, and reduce the amount of time required to achieve similar benefits (Level 2a, Grade B). 4. Regular PA, with and without weight loss, can improve many cardiometabolic risk factors in adults who have overweight or obesity, including: a. hyperglycaemia and insulin sensitivity (Level 2b, Grade B) b. high blood pressure (Level 1a, Grade B) c. dyslipidaemia (Level 2a, Grade B). 5. Regular PA can improve health-related quality of life, mood disorders (i.e. depression, anxiety) and body image in adults with overweight or obesity (Level 2b, Grade B).

Introduction: Preliminary data suggest that patients with takotsubo syndrome (TTS) have altered activation of stress-related brain regions. The medial prefrontal cortex (mPFC) plays a central role in processing stress-related information and initiating the associated cardiovascular response. The aim of this study is to determine whether changes in mPFC hemodynamics are present in patients with TTS during the acute hospitalization compared to in recovery, and whether mPFC hemodynamics correlate with cardiac function and peak oxygen consumption (peak VO 2 ), a measure of cardiorespiratory fitness and a strong predictor of cardiovascular outcomes. Methods: Medial prefrontal cortex (mPFC) hemodynamics were evaluated non-invasively with near-infrared spectroscopy in patients hospitalized with TTS and controls. TTS patients were then reassessed 90±30 days after discharge (follow-up). We assessed mPFC hemodynamics for ten minutes with the patient resting in the semi-fowler position. In follow-up, a symptom-limited cardiopulmonary exercise test was also completed to assess peak VO 2 . Comparisons were assessed with Wilcoxon or Mann-Whitney testing as appropriate, and correlations were made with Spearman rank testing. Data are median [IQR]. Results: Patients with TTS (n=14) were assessed during hospitalization (LVEF: 34 [28-40] %, troponin I: 1,392 [405-2,626] ng/L, BNP: 873 [459-996] pg/mL). Controls were matched for age, sex, and LVEF to TTS patients at follow-up. We observed significantly lower mPFC hemodynamics in TTS (48 [43-53] μM) compared to controls (63 [58-69] μM; p =0.008; Fig 1A). At follow-up (n=9), cardiac function in TTS improved (LVEF: 57 [53-60] %, troponin I: 3 [3-5] ng/L, BNP: 32 [24-72] pg/mL), however, mPFC hemodynamics were not different from hospitalization (46 [39-55] μM; p =0.65) and remained significantly reduced compared to controls ( p =0.004). Peak VO 2 in TTS (18 [17-23] ml.kg -1 .min -1 ) was also significantly reduced compared to controls (30 [28-32] ml.kg -1 .min -1 ; p= 0.006), and peak VO 2 correlated with mPFC hemodynamics in follow-up (R=0.37; p =0.04; n=11; Fig 1B). Conclusion: These data suggest that in TTS, mPFC hemodynamics are reduced during hospitalization and remain reduced in follow-up. Further, peak VO 2 is poor in those with TTS and positively correlates with mPFC hemodynamics. Additional research is needed to address how mPFC hemodynamics may influence cardiorespiratory fitness in TTS.

Introduction: Excess or dysfunctional adipose tissue contributes to cardio-kidney-metabolic (CKM) syndrome through the secretion of proinflammatory mediators. However, fat depot-specific inflammatory profiles remain poorly characterized. Aims: Identify inflammatory plasma proteins associated with fat depots and with components of Stage 2 CKM syndrome. Methods: Among participants in the community-based Dallas Heart Study (DHS) 3 rd visit (2020-24), we measured 248 inflammatory plasma proteins using an ultra-high sensitivity immunoassay (NULISA™). Participants underwent measurements of subcutaneous and visceral fat volumes, and liver and thigh intramuscular fat percentages through whole-body MRI. Associations of individual proteins with fat depots at FDR significance were assessed using multivariable linear regression models adjusted for age, sex, and BMI. We further assessed the associations of identified proteins with individual components of Stage 2 CKM (metabolic syndrome, diabetes, CKD, hypertension, hypertriglyceridemia) using multivariable logistic models and with peak VO2 assessed through cardiopulmonary exercise test using multivariable linear models. Results: Among 104 participants (age 59±13 years; 50% female; 52% self-reported Black race), mean BMI was 30±9 kg/m 2 , subcutaneous fat volume 9±5 L, visceral fat volume 4±2 L; liver fat 4±5%; thigh intramuscular fat 9±3%. Nine proteins associated with higher visceral fat, 18 with higher subcutaneous fat, 11 with higher liver fat, and 12 with higher intramuscular fat (Figure). Of those, 6 uniquely associated with subcutaneous fat (FLT4, ICAM1, KDR, LILRB2, TEK, TLR3), 2 with liver fat (BST2, TREM2), 4 with intramuscular fat (CHI3L1, IL16, THBS2, TNFRSF1A), and none with visceral fat, while 14 proteins (CCL25, CRP, CSF1R, FGF21, FURIN, HGF, ICOSLG, IL18R1, IL1RN, IL6, LGALS9, LIF, SELE, TSLP) had shared associations with two or more fat depots. Among fat depot-associated proteins, 4 (15%) were associated with higher prevalence of diabetes; 9 (35%) with higher prevalence of CKD; 5 (19%) with higher prevalence of metabolic syndrome; and 12 (46%) with lower peak VO2. None were associated with hypertension or hypertriglyceridemia. Conclusion: We identified inflammatory plasma proteins associated with specific fat depots and with higher prevalence of stage 2 CKM syndrome components and lower cardiorespiratory fitness. They have potential as CKM biomarkers and might inform adiposity-related pathophysiology.

Background/Objectives: Exercise-induced hypertension (EIH) in runners predisposes them to cardiovascular diseases, including myocardial hypertrophy, arrhythmias, and coronary artery disease. Blood flow restriction (BFR) training has been reported to exert non-pharmacological benefits in runners with EIH by improving blood pressure, myocardial workload, and cardiorespiratory fitness. The purpose of this study was to investigate whether changes in myocardial structure and function accompany these effects of BFR training in middle-aged runners with EIH. Methods: Participants who exhibited a maximal systolic blood pressure of ≥210 mmHg during an exercise stress test were assigned either to a BFR training group (BFRTg, n = 15) or to a control group without BFR training (non-BFRTg, n = 14). The BFRTg underwent a two-month BFR training program, performed twice per week for 20 min per session. Cardiac structure and function were evaluated before and after the intervention, and exercise stress test data were obtained from secondary sources of a previous study. Results: Compared with controls, the BFR group showed lower maximal exercise SBP, longer exercise duration, and higher VO2max. Echocardiography revealed reduced interventricular septal thickness and improved diastolic indices (higher E′/A′, lower E/E′), while systolic function remained unchanged. Conclusions: In conclusion, reductions in septal thickness and improvements in diastolic function induced by blood flow restriction training in runners with exercise-induced hypertension suggest a favorable cardiac adaptation, accompanied by concurrent improvements in exercise blood pressure and cardiorespiratory fitness.

Higher cardiorespiratory fitness is associated with reduced type 2 diabetes mellitus (T2D) risk, but the underlying mechanisms remain incompletely understood. We investigated whether biological aging mediates the association between maximal oxygen uptake (VO2max) and incident T2D risk. This prospective cohort study included 54 418 UK Biobank participants aged 39-70 years without baseline diabetes. VO2max was estimated using a validated algorithm incorporating resting heart rate, physical activity, age, sex and body mass index. Biological age (BA) and phenotypic age (PhenoAge) were calculated from clinical biomarkers. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for sociodemographic, lifestyle and clinical factors. Linear regression analyses assessed cross-sectional associations between VO2max and standardised glycaemic and lipid biomarkers. Mediation analysis quantified the proportion of association explained by biological aging measures. During 694 986 person-years of follow-up, 2628 participants developed T2D (incidence rate: 3.78 per 1000 person-years). Compared to the lowest VO2max quartile, participants in the highest quartile had a 56% lower T2D risk (HR 0.44, 95% CI = 0.39-0.50). Each standard deviation increase in VO2max was associated with a 28% lower risk (HR 0.72, 95% CI = 0.68-0.76). BA acceleration mediated 8.2% (95% CI = 6.1%-10.8%) and PhenoAge acceleration mediated 9.1% (95% CI = 6.8%-12.1%) of the VO2max-T2D association. Protective associations were consistent across sex, age, ethnicity and genetic risk subgroups. VO2max showed strong inverse correlations with glucose (β = -0.32), glycated haemoglobin (β = -0.28), triglycerides (β = -0.31) and a positive correlation with high-density lipoprotein (HDL) cholesterol (β = 0.29). Higher cardiorespiratory fitness demonstrates robust protective associations against T2D incidence, with biological aging mechanisms partially mediating this relationship.

Managing clinically significant primary mitral regurgitation is challenging. Right ventricular-pulmonary arterial coupling, assessed with tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (sPAP) ratio, reflects right ventricular adaptability to afterload. This international multicenter cohort study aimed to evaluate the prognostic value of rest TAPSE/sPAP and exercise TAPSE (exTAPSE)/sPAP in primary mitral regurgitation. Between January of 2019 and December of 2023, 211 patients assigned to a derivation cohort (64±12 years of age, 40% women) and 146 patients assigned to a validation cohort (66±13 years of age, 39% women), all of whom had moderate or severe primary mitral regurgitation, no or discordant symptoms, and no left ventricular systolic dysfunction or atrial fibrillation, underwent semisupine cycle-ergometry cardiopulmonary exercise testing combined with exercise echocardiography. TAPSE/sPAP was measured at rest and at intermediate (defined as the first ventilatory threshold) and peak exercise. The primary end point was a composite of cardiovascular death, unplanned cardiovascular hospitalizations, and new atrial fibrillation. In the derivation cohort, 48 patients reached the composite outcome (median follow-up, 24 months [interquartile range, 12-51]). Intermediate and peak exTAPSE/sPAP were strongly correlated (r=0.84; P<0.001), with intermediate exTAPSE/sPAP offering superior feasibility (98% versus 92%) with comparable prognostic accuracy to peak exTAPSE/sPAP (area under the receiver operating characteristic curve, 0.794 [0.730-0.849] versus 0.765 [0.698-0.823]) and therefore was used as the exercise TAPSE/sPAP measure. Patients with a reduced rest TAPSE/sPAP (cutoff 0.8 mm/mm Hg) and intermediate exTAPSE/sPAP (cutoff 0.6 mm/mm Hg) had a lower event-free survival (log-rank P<0.0001). Intermediate exTAPSE/sPAP and percent-predicted peak VO2 were independently associated with the primary end point (hazard ratio, 0.64 [0.51-0.80] per 0.1 mm/mm Hg increase [P<0.001] and hazard ratio, 2.03 [1.05-3.93] if <80% [P=0.04], respectively) and had incremental prognostic value beyond age, left atrial volume index, mitral regurgitation severity, rest TAPSE/sPAP, and mitral valve intervention (time-dependent covariable). Similar results were found when rest and intermediate exTAPSE/sPAP were included in the multivariable model as categorical measures. Validation in an independent cohort confirmed the consistent and robust performance of both multivariable models, irrespective of whether TAPSE/sPAP was modeled as a continuous or categorical variable. Exercise right ventricular-pulmonary arterial coupling, particularly intermediate exTAPSE/sPAP, is a robust and feasible measure independently associated with adverse outcomes, and provides prognostic information beyond resting variables and cardiorespiratory fitness, potentially refining risk stratification and guiding management in patients with primary mitral regurgitation.

Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as an obesity-driven condition, with excess adiposity serving both as a risk factor and a defining comorbidity. Paradoxically, once HFpEF is established, higher body mass index (BMI) is often associated with improved survival, a phenomenon termed the "obesity paradox." Epidemiological studies, including analyses of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial and large registries, show that overweight and obese HFpEF patients experience lower all-cause mortality compared with normal-weight counterparts, while underweight patients face the worst prognosis due to frailty and cachexia. The survival benefit, however, appears to be shaped by factors beyond BMI. Evidence suggests that favorable body composition, particularly greater lean mass and metabolic reserve, underlies much of the observed advantage. Cardiorespiratory fitness further modifies outcomes, with "fat but fit" individuals driving much of the paradox, while sarcopenic obesity portends poor survival. Inflammatory signaling and adipokine patterns also contribute, with differences in leptin, adiponectin, and cytokine profiles potentially buffering obese patients from catabolic stress. Importantly, fat distribution is critical: visceral and epicardial fat confer risk, whereas subcutaneous fat may be relatively benign, challenging the validity of BMI as a prognostic marker. Critics highlight confounding from cachexia-related weight loss, lead-time bias, and BMI's inability to distinguish fat from muscle. Emerging therapies, including glucagon-like peptide-1 receptor agonists and structured exercise regimens, demonstrate that intentional, controlled weight loss, especially targeting visceral fat while preserving lean mass, can improve symptoms, function, and quality of life. Ultimately, the obesity paradox underscores the need for nuanced, phenotype-specific management rather than complacency toward obesity in HFpEF.

Assessment of cardiorespiratory fitness and body composition in marathon runners with type 1 diabetes: an observational study

Interpretable framework for predicting preoperative cardiorespiratory fitness using wearable data.

A cross-sectional study on the relationship between cardiorespiratory fitness, inhibitory control, and event-related potentials moderated by severity of symptoms in patients with major depressive disorder.

Adapted physical activity (PA) programs benefit patients with non‑communicable diseases, but access barriers limit reach. Hybrid programs mixing in‑person and telehealth sessions may overcome these constraints. The purpose of this study was to evaluate the acceptability and effectiveness of a 3‑month hybrid APA program compared with usual face‑to‑face care and to examine whether benefits persist up to 36 months. Twenty patients with chronic diseases completed an APA program that began onsite and transitioned to videoconference plus home exercises. A historical cohort of 100 patients who received the standard onsite program and matched baseline characteristics served as controls. Changes in self-reported PA, physical capacities, and body composition of patients from both programs were measured at baseline and 3, 6, 12, 4, 36 months and analyzed using random-effect models. Adherence and satisfaction were also evaluated. Participants in the hybrid program showed high adherence and acceptability to the program, significant improvements in cardiorespiratory capacity, and reported increased PA levels. Overall effect sizes between the two groups were small. Importantly, the effects of both programs on these variables persisted 3 months after the end of the program with meaningful effect sizes and up to 33 months after the end of the program for 6 MWT. However, dropout rates during follow-up were high. Despite high acceptability and adherence for most patients of the hybrid group, some patients demonstrated lower participation. In conclusion, a hybrid program including telehealth was feasible, well‑accepted, and produced durable, clinically meaningful gains in cardiorespiratory fitness, and physical activity that matched conventional rehabilitation. Larger randomized trials are warranted to confirm these findings.

Kynurenine pathway (KP) metabolites modulate inflammatory activity and neuronal viability. The consequences of KP imbalance partly resemble the molecular mechanisms of multiple sclerosis (MS). An improved understanding of KP imbalance and its relevance in MS requires holistic approaches beyond single-metabolite investigations. Thus, we aimed to explore the presence of KP metabolite patterns in MS and to evaluate their relevance in relation to participant characteristics and clinical measures. In this multinational cross-sectional analysis, we determined serum concentrations of KP metabolites in persons with MS and healthy individuals using targeted metabolomics (LC-MS/MS). Analyses were conducted between March 24, 2022, and August 9, 2024. The source studies were conducted in Denmark, Germany, and Switzerland. All participants were aged 18 years or older and free of acute or chronic diseases besides MS. Persons with MS had mild to moderate disease severity (Expanded Disability Status Scale [EDSS] score ≤6.5). Following the investigation of individual metabolites, we explored KP metabolite patterns using exploratory factor analysis. Associations between KP metabolite patterns and participant characteristics, MS symptoms, and MRI metrics were investigated using correlation analyses, proportional odds regression, and multiple linear regression. The MS cohort included 353 participants (67.1% female) with a mean (SD) age of 46.1 (12.4) years. The mean (SD) EDSS score was 3.1 (1.8). The healthy control (HC) cohort included 111 participants (53.2% female) with a mean (SD) age of 45.7 (16.6) years. Persons with MS showed 2 distinct KP metabolite patterns: an inflammation-driven neurotoxic pattern (NeuroTox) and a neuroprotective pattern (NeuroPro). Greater NeuroTox was associated with a higher EDSS score, older age, and higher body fat percentage. Greater NeuroPro was associated with a lower EDSS score and higher cardiorespiratory fitness. Using a data-driven approach, we demonstrate the presence of 2 KP metabolite patterns, NeuroTox and NeuroPro, in MS. Greater NeuroTox and lower NeuroPro were both associated with greater disease severity. Future studies need to investigate the KP metabolite patterns across the MS disability spectrum and may use comparable approaches to investigate whether KP imbalance follows similar or disease-specific patterns in diseases other than MS. NCT03322761, NCT02661555, NCT04762342, NCT04356248, DRKS00017091, DRKS00031445, DRKS00028792, DRKS00029105.