Intensity or volume: the role of physical activity in longevity.

AIMS: To investigate how physical activity (PA) volume, intensity, duration, and fragmentation are associated with the risk of all-cause and cardiovascular disease mortality. To produce centile curves for PA volume and intensity representative of US adults. METHODS: This study is based on the observational 2011-2014 National Health and Nutrition Examination Survey (NHANES). Adults (age ≥20) with valid accelerometer, covariate, and mortality data were included. Average acceleration (AvAcc), intensity gradient (IG), and total PA served as proxies for volume, intensity, and duration of PA, respectively. Weighted Cox proportional hazard models estimated associations between outcome and PA metrics. RESULTS: In 7518 participants (52.0% women, weighted median age 49), there were curvilinear inverse dose-response relationships of all-cause mortality risk (81-month follow-up) with both AvAcc (-14.4% [95% CI -8.3 to -20.1%] risk reduction from 25th to 50th percentile) and IG (-37.1% [95% CI -30.0 to -43.4%] risk reduction from 25th to 50th percentile), but for cardiovascular disease mortality risk (N=7016, 82-month follow-up) only with IG (-41.0% [95% CI -26.7 to -52.4%] risk reduction from the 25th to 50th percentile). These relationships plateau at AvAcc: ∼35-45 mg and IG: -2.7 to -2.5. Associations of PA with all-cause and cardiovascular disease mortality are primarily driven by intensity and secondary by volume. Centile curves for volume and intensity were generated. CONCLUSION: Intensity is a main driver of reduced mortality risk suggesting that the intensity of PA rather than the quantity matters for longevity. The centile curves offer guidance for achieving desirable PA levels for longevity.

This study shows that the distribution of the intensity of physical activity accumulated across the day may be more important for mortality reduction than the quantity (volume), underscoring the relevance of integrating physical activity of higher intensity into daily routines for health optimisation.Higher physical activity intensity is more closely associated with reduced mortality risk than physical activity volume, particularly for cardiovascular disease mortality.We provide initial evidence suggesting health benefits when accumulating intense physical activity in continuous bouts rather than sporadically across the day.

Reliability and validity of the German version of the University of Jyvaskyla Active Aging Scale (UJACAS-G).

BACKGROUND: The University of Jyvaskyla Active Aging Scale (UJACAS) assesses active aging through willingness, ability, opportunity, and frequency of involvement in activities. Recognizing the lack of a German version, the Finnish original was translated (UJACAS-G). This study aimed: (1) to evaluate the test-retest reliability of UJACAS-G; and (2) to explore correlations with health-related parameters (concurrent validity). METHODS: The study (test-retest design) targeted healthy older adults aged 65+. Reliability of UJACAS-G (total and subscores) was assessed using Bland-Altman analyses and Intraclass Correlation Coefficients (ICCs). Furthermore, correlations (Spearman's rho) between UJACAS-G scores and physical function (walking speed, handgrip strength, balance, 6-minute walk distance), physical activity (International Physical Activity Questionnaire), life-space mobility (Life-Space Assessment), and health-related quality of life (Short Form-36 Health Survey) were calculated. RESULTS: Bland-Altman analyses (N = 60; mean age 72.3, SD 5.9 years; 50% women) revealed mean differences close to zero and narrow limits of agreement for all scores (total score: mean difference -1.9; limits -31.7 to 27.9). The ability subscore showed clustering at its upper limit. ICC was 0.829 (95% CI 0.730 to 0.894) for the total score and ranged between 0.530 and 0.876 for subscores (all p-values < 0.001). The total score correlated with walking speed (rho = 0.345; p = 0.008), physical activity (rho = 0.279; p = 0.033) and mental health (rho = 0.329; p = 0.010). CONCLUSIONS: UJACAS-G is reliable for assessing active aging among German-speaking healthy older adults. A potential 'ceiling effect' regarding the ability subscore should be considered when applying UJACAS-G to well-functioning populations. Analyses of concurrent validity indicated only weak correlations with health-related parameters.

Unified Language for Knowledge Dissemination: The Vascular Ageing Glossary, an Initiative by VascAgeNet.

Objectives: In general, a terminology shared and agreed by different stakeholders is important to facilitate communication and cooperation. This holds true in the field of vascular ageing for the benefit of global cardiovascular health. The need to promote a common language and understanding across this area was recognised by VascAgeNet, a collaborative network with relevant and diverse expertise in the vascular ageing field, supported by the European Cooperation in Science and Technology. To contribute to the spread of unified terms in the vascular ageing field, a glossary was created by VascAgeNet and this paper describes the systematic process used for its development. Methods: An initial list of terms and preliminary definitions were collated from the network. A dedicated team was created to design the glossary development process, to facilitate its implementation and to maximise outreach and dissemination. The key steps of the process were to determine: (1) the target audience; (2) a list of priority terms; (3) a template structure for definitions; (4) methods for collecting feedback and (5) the dissemination plan. Results: An implementation strategy was provided for each key step and shared within the network; main decisions were agreed by all members of the glossary team. Small groups of definitions were released on a regular basis within a pilot phase including 19 terms (status: 05.09.2023) that were published openly at https://vascagenet.eu/official-glossary. Conclusions: The strategy for creating the first Vascular Ageing Glossary has been successfully designed and developed within VascAgeNet. A pilot phase covering the first publicly available terms was completed. The glossary is a living document, available to the scientific community, which aims to unify the vascular ageing language. Supplementary Information: The online version contains supplementary material available at 10.1007/s44200-023-00041-5.

Deceived by the Fick principle: blood flow distribution in heart failure.

AIMS: The Fick principle states that oxygen uptake (V̇O2) is cardiac output (Qc)*arterial-venous O2 content difference [ΔC(a-v)O2]. Blood flow distribution is hidden in Fick principle and its relevance during exercise in heart failure (HF) is undefined.To highlight the role of blood flow distribution, we evaluated peak-exercise V̇O2, Qc and ΔC(a-v)O2, before and after HF therapeutic interventions. METHODS: Symptoms-limited cardiopulmonary exercise tests with Qc measurement (inert-gas-rebreathing) was performed in 234 HF patients before and 6 months after successful exercise training, cardiac-resynchronization therapy or percutaneous-edge-to-edge mitral valve repair. RESULTS: Considering all tests (n=468) a direct correlation between peakV̇O2 and peakQc (R2=0.47) and workload (R2=0.70) were observed. Patients were grouped according to treatment efficacy in group 1 (peakV̇O2 increase >10%, n=93), group 2 (peakV̇O2 change between 0 and 10%, n=60) and group 3 (reduction in peakV̇O2, n=81). Post-treatment peakV̇O2 changes poorly correlated with peakQc and peakΔC(a-v)O2 changes. Differently, post-procedures peakQc vs. peakΔC(a-v)O2 changes showed a close negative correlation (R2=0.46), becoming stronger grouping patients according to peakV̇O2 improvement (R2=0.64, 0.79 and 0.58 in group 1, 2 and 3, respectively). In 76% of patients peakQc and ΔC(a-v)O2 changes diverged regardless of treatment. CONCLUSION: The bulk of these data suggests that blood flow distribution plays a pivotal role on peakV̇O2 determination regardless of HF treatment strategies. Accordingly, for assessing HF treatment efficacy on exercise performance the sole peakV̇O2 may be deceptive and the combination of V̇O2, Qc and ΔC(a-v)O2, must be considered.

This study aimed to understand how oxygen uptake during exercise is affected by heart failure therapeutic intervention. We evaluated 234 heart failure patients before and after treatments such as exercise training, cardiac resynchronization therapy, or mitral valve repair, finding that changes in oxygen uptake were poorly correlated with changes in cardiac output and oxygen content difference between arteries and veins. However, we observed a strong negative correlation between changes in cardiac output and oxygen content difference, especially in patients with significant improvement in oxygen uptake. This suggests that blood flow distribution is crucial for oxygen uptake during exercise, regardless of treatment. Therefore, relying solely on oxygen uptake may not accurately assess treatment effectiveness, and considering a combination of oxygen uptake, cardiac output, and oxygen content difference is important. Oxygen uptake during exercise was strongly related to cardiac output and workload.Changes in cardiac output and oxygen content difference were closely related after treatments, especially in patients with significant improvement in oxygen uptake.

Physiological Profiles of Male and Female CrossFit Athletes.

OBJECTIVE: To (1) establish extensive physiological profiles of highly trained CrossFit® athletes using gold-standard tests and (2) investigate which physiological markers best correlate with CrossFit Open performance. METHODS: This study encompassed 60 participants (30 men and 30 women), all within the top 5% of the CrossFit Open, including 7 CrossFit semifinalists and 3 CrossFit Games finalists. Isokinetic dynamometers were employed to measure maximum isometric and isokinetic leg and trunk strength. Countermovement-jump height and maximum isometric midthigh-pull strength were assessed on a force plate. Peak oxygen uptake (VO2peak) was measured by a cardiopulmonary exercise test, and critical power and W' were evaluated during a 3-minute all-out test, both on a cycle ergometer. RESULTS: Male and female athletes' median (interquartile range) VO2peak was 4.64 (4.43, 4.80) and 3.21 (3.10, 3.29) L·min-1, critical power 314.5 (285.9, 343.6) and 221.3 (200.9, 238.9) W, and midthigh pull 3158 (2690, 3462) and 2035 (1728, 2347) N. Linear-regression analysis showed strong evidence for associations between different anthropometric variables and CrossFit Open performance in men and women, whereas for markers of cardiorespiratory fitness such as VO2peak, this was only true for women but not men. Conventional laboratory evaluations of strength, however, manifested minimal evidence for associations with CrossFit Open performance across both sexes. CONCLUSIONS: This study provides the first detailed insights into the physiology of high-performing CrossFit athletes and informs training optimization. Furthermore, the results emphasize the advantage of athletes with shorter limbs and suggest potential modifications to CrossFit Open workout designs to level the playing field for athletes across different anthropometric characteristics.

Heart rate vARiability and physical activity in inpatient treatMent of burnOut and DepressIon (HARMODI): protocol of a cross-sectional study with up to 8-week follow up.

INTRODUCTION: Chronic stress can cause an imbalance within the autonomic nervous system, thereby affecting cardiovascular and mental health. Physical activity (PA) may have a positive effect on the autonomic nervous system and stress-related disorders, such as depression and burnout. Heart rate variability (HRV) is a non-invasive marker of the autonomic nervous system. However, limited and inconsistent data exist on the exact relationship between HRV, PA and depression and burnout symptoms. The HARMODI study aims to explore whether HRV is a feasible marker of depression and burnout symptoms and aims to evaluate the role of PA in the treatment of stress-related disorders. METHODS AND ANALYSES: This is an observational study with a cross-sectional up to 8 week follow-up study design. A total of 153 patients, undergoing psychiatric inpatient treatment with burnout syndrome (Z73) and depressive episode (F32 or F33) or adjustment disorder (F43.2), will be recruited. Data on depression and burnout symptoms, HRV recordings (24-hour, supine, standing and exercise stress test), cognitive function, cardiorespiratory fitness, cardiovascular health, balance and strength will be collected at baseline (T1) and after up to 8 weeks (T2). Continuous data on PA and Ecological Momentary Assessments of exhaustion, mood and tension will be monitored daily throughout inpatient treatment. Multiple regression models, adjusted for potential confounders, will assess the association between HRV as the primary outcome, PA and depression and burnout severity score. ETHICS AND DISSEMINATION: The protocol has been approved by Swiss Ethics Committee, Cantonal Ethics Committee Zürich. Results of HARMODI will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05874856.

Lower extremity physical function and quality of life in patients with stroke: a longitudinal cohort study.

PURPOSE: Lower extremity physical function (LEPF) is a key component for mobility and is impacted in stroke-related disability. A reduction in LEPF can have a significant impact on an individual's Quality of Life (QoL). The aim of this study is to characterise the relationship between LEPF and QoL. METHODS: The MOBITEC-Stroke Study is a longitudinal cohort-study including patients with their first occurrence of ischaemic stroke. Using a linear mixed-effects model, the relationship between LEPF (timed up-and-go performance (TUG); predictor) and QoL (Stroke Specific Quality of Life scale (SS-QoL); outcome) at 3 and 12 months post stroke was investigated and adjusted for sex, age, Instrumental Activities of Daily Living (IADL), fear of falling (Falls Efficacy Scale-International Version, FES-I), and stroke severity (National Institute of Stroke Severity scale, NIHSS), accounting for the repeated measurements. RESULTS: Data of 51 patients (65 % males, 35% females) were analysed. The mean age was 71.1 (SD 10.4) years, median NIHSS score was 2.0. SS-QoL was 201.5 (SD 20.5) at 3 months and 204.2 (SD 17.4) at 12 months; the mean change was 2.7 (95% CI -2.4 to 7.7), p= 0.293. A positive association was found between baseline TUG performance (estimate log score -13.923; 95% CI -27.495 to -0.351; p=0.048) and change in SS-QoL score in multivariate regression analysis. CONCLUSION: Higher LEPF (i.e better TUG performance) at baseline, was associated with an improvement in QoL from 3- to 12-months post stroke. These results highlight the critical role of physical function, particularly baseline LEPF, in influencing the QoL of stroke survivors.

Effects of exercise training on cardiac output in subjects with heart failure with preserved ejection fraction (HFpEF) - a protocol for a systematic review and meta-analysis.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) commonly experience exercise intolerance, resulting in reduced cardiorespiratory fitness. This is characterised by a decreased maximal oxygen uptake (V̇O2peak), which is determined by the product of cardiac output (CO) and arteriovenous oxygen difference (a-vDO2). While exercise training has been shown to improve V̇O2peak in HFpEF patients, the effects on CO remain unclear. The aim of this study is to systematically review and analyse the current evidence on the effects of supervised exercise training on CO in patients with HFpEF. METHODS: We will systematically search for literature describing the effects of supervised exercise training on CO in patients with HFpEF. All eligible studies published before 30 June 2023 in the following electronic databases will be included: MEDLINE (Ovid), Embase (Ovid), SPORTDiscus (EBSCOhost), and CENTRAL (Cochrane Library). Effect sizes will be extracted for CO before and after a supervised exercise training intervention at rest and maximal exercise. Mass of heterogeneity (I2) will be calculated, and either fixed-effect models or random-effect models will be used for meta-analysis. To detect a potential publication bias, funnel plot analyses will be performed. DISCUSSION: While several studies have reported a positive effect of supervised exercise training on cardiorespiratory fitness, attempts to assess the underlying determinants of V̇O2peak, CO, and a-vDO2 are much scarcer, especially in patients with HFpEF. From a physiological perspective, measuring CO before and after supervised exercise training seems to be a reasonable way to accurately operationalise a potential improvement in cardiac function. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022361485.

Lifestyle factors as determinants of atherosclerotic cardiovascular health.

A sedentary lifestyle, low levels of physical activity and fitness, poor dietary patterns, and psychosocial stress are strongly associated with increased morbidity and mortality from atherosclerotic cardiovascular disease (ASCVD). Conversely, engaging in regular physical activity, maintaining optimal fitness levels, adhering to a heart-healthy dietary pattern, effectively managing body weight, ensuring adequate sleep, implementing stress-reduction strategies, and addressing psychosocial risk factors are associated with a reduced risk of ASCVD. This comprehensive review synthesizes current evidence from large observational studies and randomized controlled trials on lifestyle factors as determinants of ASCVD health. It also briefly reviews mechanistic insights into how factors such as low shear stress, increased reactive oxygen species production, chronic inflammation, platelets and coagulation activation, endothelial dysfunction, and sympathetic hyperactivity contribute to the initiation and exacerbation of ASCVD risk factors. These include obesity, hyperglycemia, type 2 diabetes, hypertension, and dyslipidemia, subsequently leading to the development and progression of atherosclerosis, ultimately resulting in chronic ASCVD or acute cardiovascular events. To bridge the translational gap between epidemiologic and trial-based evidence and clinical practice, practical recommendations are summarized to facilitate the translation of scientific knowledge into actionable interventions to promote ASCVD health. Acknowledged is the gap between the evidence-based knowledge and adoption within healthcare systems, which remains a crucial objective in advancing cardiovascular health at the population level.

Effect of an eight-week high-intensity interval training programme on circulating sphingolipid levels in middle-aged adults at elevated cardiometabolic risk (SphingoFIT)-Protocol for a randomised controlled exercise trial.

INTRODUCTION: Evidence indicates that sphingolipid accumulation drives complex molecular alterations promoting cardiometabolic diseases. Clinically, it was shown that sphingolipids predict cardiometabolic risk independently of and beyond traditional biomarkers such as low-density lipoprotein cholesterol. To date, little is known about therapeutic modalities to lower sphingolipid levels. Exercise, a powerful means to prevent and treat cardiometabolic diseases, is a promising modality to mitigate sphingolipid levels in a cost-effective, safe, and patient-empowering manner. METHODS: This randomised controlled trial will explore whether and to what extent an 8-week fitness-enhancing training programme can lower serum sphingolipid levels of middle-aged adults at elevated cardiometabolic risk (n = 98, 50% females). The exercise intervention will consist of supervised high-intensity interval training (three sessions weekly), while the control group will receive physical activity counselling based on current guidelines. Blood will be sampled early in the morning in a fasted state before and after the 8-week programme. Participants will be provided with individualised, pre-packaged meals for the two days preceding blood sampling to minimise potential confounding. An 'omic-scale sphingolipid profiling, using high-coverage reversed-phase liquid chromatography coupled to tandem mass spectrometry, will be applied to capture the circulating sphingolipidome. Maximal cardiopulmonary exercise tests will be performed before and after the 8-week programme to assess patient fitness changes. Cholesterol, triglycerides, glycated haemoglobin, the homeostatic model assessment for insulin resistance, static retinal vessel analysis, flow-mediated dilatation, and strain analysis of the heart cavities will also be assessed pre- and post-intervention. This study shall inform whether and to what extent exercise can be used as an evidence-based treatment to lower circulating sphingolipid levels. TRIAL REGISTRATION: The trial was registered on www.clinicaltrials.gov (NCT06024291) on August 28, 2023.

Letter to the editor: fasting decreases expression of microRNAs linked to endothelial pathophysiology in mononuclear cells of healthy subjects.

This study explores how 14-15 h fasting or acute exercise affects immune cell epigenetics, specifically focusing on miRNAs in mononuclear cells. Findings suggest fasting significantly impacts microRNAs associated with endothelial metabolism compared to exercise, but does not directly connect these changes to cell apoptosis or autophagy. This enhances comprehension of cellular self-consumption under health-promoting interventions.

Exercise Therapy for Chronic Symptomatic Peripheral Artery Disease: A Clinical Consensus Document of the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Diseases in Collaboration With the European Society of Vascular Medicine and the European Society for Vascular Surgery.

All guidelines worldwide strongly recommend exercise as a pillar in the management of patients affected by lower extremity peripheral artery disease (PAD). Exercise therapy in this setting presents different modalities, and a structured programme provides optimal results. This clinical consensus paper is intended to promote and assist the set up of comprehensive exercise programmes and best advice for patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are described based on the current best evidence. The document ends by highlighting supervised exercise programme access disparities across Europe and the evidence gaps requiring further research.

Exercise therapy for chronic symptomatic peripheral artery disease.

All guidelines worldwide strongly recommend exercise as a pillar of the management of patients affected by lower extremity peripheral artery disease (PAD). Exercise therapy in this setting presents different modalities, and a structured programme provides optimal results. This clinical consensus paper is intended for clinicians to promote and assist for the set-up of comprehensive exercise programmes to best advice in patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are narratively described based on the current best evidence. The document ends by highlighting disparities in access to supervised exercise programmes across Europe and the series of gaps for evidence requiring further research.

Exercise therapy for chronic symptomatic peripheral artery disease.

All guidelines worldwide strongly recommend exercise as a pillar in the management of patients affected by lower extremity peripheral artery disease (PAD). Exercise therapy in this setting presents different modalities, and a structured programme provides optimal results. This clinical consensus paper is intended to promote and assist the set up of comprehensive exercise programmes and best advice for patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are described based on the current best evidence. The document ends by highlighting supervised exercise programme access disparities across Europe and the evidence gaps requiring further research.

A verification phase adds little value to the determination of maximum oxygen uptake in well-trained adults.

PURPOSE: The objective was to investigate if performing a sub-peak or supra-peak verification phase following a ramp test provides additional value for determining 'true' maximum oxygen uptake ( V ˙ O2). METHODS: 17 and 14 well-trained males and females, respectively, performed two ramp tests each followed by a verification phase. While the ramp tests were identical, the verification phase differed in power output, wherein the power output was either 95% or 105% of the peak power output from the ramp test. The recovery phase before the verification phase lasted until capillary blood lactate concentration was ≤ 4 mmol·L-1. If a V ˙ O2 plateau occurred during ramp test, the following verification phase was considered to provide no added value. If no V ˙ O2 plateau occurred and the highest V ˙ O2 ( V ˙ O2peak) during verification phase was < 97%, between 97 and 103%, or > 103% of V ˙ O2peak achieved during the ramp test, no value, potential value, and certain value were attributed to the verification phase, respectively. RESULTS: Mean (standard deviation) V ˙ O2peak during both ramp tests was 64.5 (6.0) mL·kg-1·min-1 for males and 54.8 (6.2) mL·kg-1·min-1 for females. For the 95% verification phase, 20 tests showed either a V ˙ O2 plateau during ramp test or a verification V ˙ O2peak < 97%, indicating no value, 11 showed potential value, and 0 certain value. For the 105% verification phase, the values were 26, 5, and 0 tests, respectively. CONCLUSION: In well-trained adults, a sub-peak verification phase might add little value in determining 'true' maximum V ˙ O2, while a supra-peak verification phase adds no value.

Spatiotemporal gait characteristics across the adult lifespan: Reference values from a healthy population - Analysis of the COmPLETE cohort study.

BACKGROUND: Gait changes with aging have been investigated, but few studies have examined a wide range of gait parameters across the adult lifespan. This study aimed to investigate gait differences across age groups stratified by sex. METHODS: This cross-sectional study included 629 healthy, normal-weight (i.e., BMI < 30 kg/m2) participants from Switzerland of the COmPLETE cohort study, aged 20 to over 90 years. Gait metrics were assessed using an inertial measurement unit (IMU)-based gait analysis system, including speed, cycle duration variability, asymmetry, stride length, cycle duration, cadence, double support, stance (time foot is on the ground during a gait cycle), swing (time foot is in the air during a gait cycle), loading (early part of the stance phase), foot-flat (mid-stance phase when foot is flat), and pushing (late stance phase leading to toe-off) phases. Percentile curves were calculated using generalized additive models for location, scale, and shape. RESULTS: Gait data from 545 participants (273 men and 272 women) were analyzed. Participants were equally distributed across the seven age decades, with an average of 40 men and 40 women representing every decade. Both men and women showed a reduction in gait speed and stride length, and an increase in cycle duration variability and asymmetry with aging. Gait speed and stride length declined across the age groups, with a significant difference found in participants aged 80 to 91 compared to younger age groups. SIGNIFICANCE: Age-related changes in gait parameters were seen in both men and women. These may be attributed to the typical decline in muscle strength, balance, coordination, and neuromuscular function. The results of this study contribute to the understanding of gait changes throughout the lifespan and can be used for comparison with other populations and as reference values for individual patients.

Using Machine Learning-Based Algorithms to Identify and Quantify Exercise Limitations in Clinical Practice: Are We There Yet?

INTRODUCTION: Well-trained staff is needed to interpret cardiopulmonary exercise tests (CPET). We aimed to examine the accuracy of machine learning-based algorithms to classify exercise limitations and their severity in clinical practice compared with expert consensus using patients presenting at a pulmonary clinic. METHODS: This study included 200 historical CPET data sets (48.5% female) of patients older than 40 yr referred for CPET because of unexplained dyspnea, preoperative examination, and evaluation of therapy progress. Data sets were independently rated by experts according to the severity of pulmonary-vascular, mechanical-ventilatory, cardiocirculatory, and muscular limitations using a visual analog scale. Decision trees and random forests analyses were calculated. RESULTS: Mean deviations between experts in the respective limitation categories ranged from 1.0 to 1.1 points (SD, 1.2) before consensus. Random forests identified parameters of particular importance for detecting specific constraints. Central parameters were nadir ventilatory efficiency for CO 2 , ventilatory efficiency slope for CO 2 (pulmonary-vascular limitations); breathing reserve, forced expiratory volume in 1 s, and forced vital capacity (mechanical-ventilatory limitations); and peak oxygen uptake, O 2 uptake/work rate slope, and % change of the latter (cardiocirculatory limitations). Thresholds differentiating between different limitation severities were reported. The accuracy of the most accurate decision tree of each category was comparable to expert ratings. Finally, a combined decision tree was created quantifying combined system limitations within one patient. CONCLUSIONS: Machine learning-based algorithms may be a viable option to facilitate the interpretation of CPET and identify exercise limitations. Our findings may further support clinical decision making and aid the development of standardized rating instruments.

Accelerometer Metrics: Healthy Adult Reference Values, Associations with Cardiorespiratory Fitness, and Clinical Implications.

PURPOSE: Accelerometer-assessed physical activity (PA) can be summarized using cut-point-free or population-specific cut-point-based outcomes. We aimed to 1) examine the interrelationship between cut-point-free (intensity gradient (IG) and average acceleration (AvAcc)) and cut-point-based accelerometer metrics, 2) compare the association between cardiorespiratory fitness (CRF) and cut-point-free metrics to that with cut-point-based metrics in healthy adults aged 20 to 89 yr and patients with heart failure, and 3) provide age-, sex-, and CRF-related reference values for healthy adults. METHODS: In the COmPLETE study, 463 healthy adults and 67 patients with heart failure wore GENEActiv accelerometers on their nondominant wrist and underwent cardiopulmonary exercise testing. Cut-point-free (IG: distribution of intensity of activity across the day; AvAcc: proxy of volume of activity) and traditional (moderate-to-vigorous and vigorous activity) metrics were generated. The "interpretablePA" R-package was developed to translate findings into clinical practice. RESULTS: IG and AvAcc yield complementary information on PA with both IG ( P = 0.009) and AvAcc ( P < 0.001) independently associated with CRF in healthy individuals (adjusted R2 = 73.9%). Only IG was independently associated with CRF in patients with heart failure ( P = 0.043, adjusted R2 = 38.4%). The best cut-point-free and cut-point-based model had similar predictive value for CRF in both cohorts. We produced age- and sex-specific reference values and percentile curves for IG, AvAcc, moderate-to-vigorous PA, and vigorous PA for healthy adults. CONCLUSIONS: IG and AvAcc are strongly associated with CRF and thus indirectly with the risk of noncommunicable diseases and mortality, in healthy adults and patients with heart failure. However, unlike cut-point-based metrics, IG and AvAcc are comparable across populations. Our reference values provide a healthy age- and sex-specific comparison that may enhance the translation and utility of cut-point-free metrics in clinical practice.

Cardiovascular Risk in Childhood is Associated With Carotid Intima-Media Thickness and Stiffness in Adolescents and Young Adults: The KiGGS Cohort.

PURPOSE: Cardiovascular risk factors are widespread among children and adolescents and may lead to accelerated vascular aging in middle adulthood. However, data are scarce on shorter-term consequences, for example, on associated distinctive vascular properties before age 30 years. This study analyzes the association of childhood exposure to cardiovascular risk factors with carotid properties in adolescents and young adults. METHODS: Four thousand thirty one participants from the population-based German Health Interview and Examination Survey for Children and Adolescents cohort (aged 3-17 years) had carotid intima-media thickness (CIMT) and distensibility coefficient (DC) measurements at the second follow-up (aged 14-28 years). The assessment of cardiovascular risk factors at baseline included information about arterial hypertension, obesity, dyslipidemia, and passive smoking. RESULTS: Single risk factors and the exposure to multiple cardiovascular risk factors were associated with elevated CIMT and decreased DC. Relative risks for CIMT ≥ 90th centile and/or DC ≤ 10th centile were increased in participants exposed to two (RRCIMT = 1.45 [95% confidence interval 1.11-1.91], p < .05; RRDC = 1.37 [1.02-1.84], p < .05) and ≥ three risk factors (RRCIMT = 1.66 [1.05-2.62], p < .05; RRDC = 1.25 [0.71-2.21], p > .05). DISCUSSION: Exposure to multiple cardiovascular risk factors starting in childhood is associated with measurably increased CIMT and carotid stiffness in late adolescence and early adulthood. These findings underline the importance of population-wide preventive measures to promote optimal cardiovascular health.

Association of blood pressure and heart rate with carotid markers of vascular remodeling in the young: a case for early prevention.

OBJECTIVE: The association of childhood blood pressure (BP) and heart rate (HR) with intermediate markers of cardiovascular disease several decades later has been shown, but studies on more short-term outcomes are scarce. Using population-based data, this study investigates the association of four BP parameters and HR in childhood with three carotid markers for vascular remodeling one decade later. METHODS: At the 11-year follow-up, 4607 participants of the nationwide KiGGS cohort aged 14 to 28 years had semi-automated sonographic carotid intima media thickness (CIMT) measurements. We investigated associations of baseline (age 3-17 years) and follow-up SBP, DBP, mean arterial pressure (MAP), pulse pressure (PP) and resting heart rate (RHR), with CIMT and lumen diameter at or above the 90th percentile and distensibility coefficient at or below the tenth percentile in logistic regressions. Analyses were further adjusted using a composite cardiovascular risk (CVR) score of BMI, triglycerides, total/HDL-cholesterol-ratio and HbA1c. RESULTS: SBP, DBP, MAP and RHR were significantly and similarly associated with all carotid measures 11 years later, for example an odds ratio (OR) of 1.17 [confidence interval (CI) 1.06-1.29] for one standard deviation SBP increase with elevated CIMT when adjusting for sex, age and CVR score. Cross-sectionally, the strongest association was found for MAP with reduced distensibility coefficient (OR 1.76; CI 1.59-1.94). CONCLUSION: This population-based cohort study shows robust and consistent associations between childhood BP and RHR and three carotid measures of vascular remodeling only one decade later, clearly underscoring the potential importance of preventing high BP already early in the life course.