Cardiovascular diseases are still the leading cause of morbidity and mortality worldwide. Current research indicates that arterial stiffness is an independent risk factor for cardiovascular diseases and represents a potential target for personalized prevention and therapeutic approaches. Physical activity is a low-cost intervention for vascular prevention via pleiotropic mechanisms (e.g., reduced systemic inflammation, improved endothelial function, reduced arterial stiffness). In this clinical review we (i) highlight the clinical significance of arterial stiffness, (ii) recap current measurement methods, (iii) summarize the current evidence of the effects of physical activity on arterial stiffness and (iv) outline future directions for arterial stiffness research in sports medicine. Key Words: Prevention, Exercise, Vascular Aging, Cardiovascular Disease, Intervention, Inflammation, Cardiology

Abstract Objectives High cardiorespiratory fitness is a vital part of cardiovascular prevention in health and disease. However, the optimal age of aerobic exercise interventions is unclear and animal studies suggest a blunted effect of training on cardiorespiratory fitness with a priori endothelial dysfunction. This study aims to assess the effect of pre-existing endothelial dysfunction on the association between age and cardiorespiratory fitness as well as the change of the latter in response to 8 weeks of aerobic exercise training. Methods Cardiorespiratory fitness (peak oxygen consumption [ $$\dot{V}$$ O2peak]), brachial-arterial flow-mediated dilation (baFMD) and cardiovascular risk were assessed in 164 apparently healthy disease-free middle-aged adults with and without pre-existing endothelial dysfunction and cardiovascular risk factors (n = 36 arterial hypertension, n = 59 obesity, n = 118 dyslipidemia, n = 15 diabetes mellitus type II, n = 30 chronic inflammation). 30 of them underwent a randomized-controlled and supervised 8-week aerobic training intervention followed by a second assessment of $$\dot{V}$$ O2peak, baFMD and cardiovascular risk. Multiple linear regression models were used to address the study aims. Results No clear evidence was found for a moderating effect of baFMD on the relationship of $$\dot{V}$$ O2peak with age (F(3, 151) = 1.37, p = 0.254). The improvement of $$\dot{V}$$ O2peak by aerobic exercise was significantly attenuated with lower baseline baFMD (F(3, 5.33) = 43.13, df = 3, p < 0.001). Conclusions The results provide evidence in middle-aged adults for an attenuated response of cardiorespiratory fitness to aerobic exercise in the presence of endothelial dysfunction, advocating for the early involvement of aerobic exercise within primary prevention of cardiovascular diseases and low cardiorespiratory fitness. Trial Registration TRN: (COmPLETE Health cohort [NCT03986892] and VascuFit cohort [NCT05235958]).

Since the conceptualization of early vascular aging (EVA) in 2008, significant efforts have been made to develop and improve its assessment. Initially lead by the investigation of arterial stiffness through pulse wave velocity (PWV), several additional vascular aging biomarkers have gained prominence in recent years. Despite expanding literature addressing methodological concerns associated with these biomarkers in youth, a standardized approach for clinical evaluation of EVA remains elusive, leaving pertinent gaps in understanding the optimal methodology. This article, resulting from international consensus efforts from the Youth Vascular Consortium, aims to provide an updated overview of methods available to measure EVA in youth and to discuss challenges in translating these methods into clinical practice.

Background and aims: Endothelial dysfunction predicts elevated cardiovascular (CV) risk in healthy individuals. Aerobic exercise reduces endothelial dysfunction in part by improving CV risk factors. Yet, this explains less than 50 % of the effect and a direct influence of exercise training on the endothelium is discussed as possible contributor. The VascuFit study applied non-linear periodized aerobic exercise (NLPE) training to assess its multilevel effects on endothelial function including potential epigenetic endothelial modifications by circulating micro-ribonucleic acids (endomiRs). Methods: Sedentary adults with elevated CV risk between 40 and 60 years were randomized 2:1 and engaged in an eight-week ergometer-based NLPE training (n = 30) or received standard exercise recommendations (n = 14). Macro-, microvascular, cellular and molecular adaptations were assessed via brachial-arterial flow-mediated dilation (baFMD), static retinal vessel analysis (SVA), flow cytometry, and endomiRs regulating key pathways of endothelial function. Statistics included ANCOVA, Principal Component Analysis (PCA), and regression analyses. Results: baFMD improved by 2.38 % (CI:0.70-4.06, p = 0.007) independent of CV risk, whereas SVA parameters and circulating endothelial (progenitor) cells did not significantly change in the NLPE group. The mean distance between baseline and follow-up PCA loadings of the endomiR dataset explaining 44.2 % of dataset variability was higher in the NLPE-group compared to the control group (2.71 +/- 2.02 vs. 1.65 +/- 0.93). However, regression analyses showed no evidence of endomiRs explaining the improvement of baFMD. Conclusions: The improvement of macrovascular endothelial function by aerobic exercise training was independent from CV risk factors. Increased heterogeneity among endomiRs did not explain this effect, but suggests an adaptive response to the exercise stimulus on the epigenetic level.

Coronary artery disease (CAD) remains a leading cause of death worldwide and imposes a substantial socioeconomic burden on healthcare. Improving risk stratification in clinical practice could help to combat this burden. As amino acids are biologically active metabolites whose involvement in CAD remains largely unknown, this study investigated associations between circulating amino acid levels and CAD phenotypes. A high-coverage quantitative liquid chromatography-mass spectrometry approach was applied to acquire the serum amino acids profile of age- and sex-coarsened-matched patients with CAD (n = 46, 66.9 years, 74.7% male) and healthy individuals (n = 120, 67.4 years, 74.7% male) from the COmPLETE study. Multiple linear regressions were performed to investigate associations between amino acid levels and (a) the health status (CAD vs. healthy), (b) the number of affected coronary arteries, or (c) the left ventricular ejection fraction. Regressions were adjusted for age, sex, daily physical activity, sampling, and fasting time. Urea cycle amino acids (ornithine, citrulline, homocitrulline, aspartate, and arginine) were significantly and negatively associated with CAD, the number of affected coronary arteries, and the left ventricular ejection fraction. Lysine, histidine, and the glutamine/glutamate ratio were also significantly and negatively associated with the CAD phenotypes. Overall, patients with CAD displayed lower levels of urea cycle amino acids, highlighting a potential role for urea cycle amino acid profiling in cardiovascular risk stratification.Trial registrationThe study was registered on https://www.clinicaltrials.gov (NCT03986892) on June 5, 2019.

video games, a surrogate of sedentary behaviour, was not associated with higher blood glucose 37 levels. However, higher socioeconomic status and higher healthy eating index were associated 38 with lower blood glucose levels. These observations demonstrate an association between 39 lifestyle behaviour and cardiovascular risk exposure already in young children. Further 40 evidence suggests that the improvement of cardiovascular risk factors in paediatric populations 41 via lifestyle modifications may lead to a more favourable vascular phenotype in adulthood 42 reducing the likelihood of cardiovascular events (Juonala et al., 2010).43 44It is beyond doubt that high cardiorespiratory fitness and regular physical activity exert 45 beneficial effects on cardiovascular risk factors (Blair, 2009) and also directly on the vascular

Accelerated biological vascular ageing is still a major driver of the increasing burden of cardiovascular disease and mortality. Exercise training delays this process, known as early vascular ageing, but often lacks effectiveness due to a lack of understanding of molecular and clinical adaptations to specific stimuli. This narrative review summarizes the current knowledge about the molecular and clinical vascular adaptations to acute and chronic exercise. It further addresses how training characteristics (frequency, intensity, volume, and type) may influence these processes. Finally, practical recommendations are given for exercise training to maintain and improve vascular health. Exercise increases shear stress on the vascular wall and stimulates the endothelial release of circulating growth factors and of exerkines from the skeletal muscle and other organs. As a result, remodeling within the vascular walls leads to a better vasodilator and -constrictor responsiveness, reduced arterial stiffness, arterio- and angiogenesis, higher antioxidative capacities, and reduced oxidative stress. Although current evidence about specific aspects of exercise training, such as F-I-T-T, is limited, and exact training recommendations cannot be given, some practical implications can be extracted. As such, repeated stimuli 5–7 days per week might be necessary to use the full potential of these favorable physiological alterations, and the cumulative volume of mechanical shear stress seems more important than peak shear stress. Because of distinct short- and long-term effects of resistance and aerobic exercise, including higher and moderate intensities, both types of exercise should be implemented in a comprehensive training regimen. As vascular adaptability towards exercise remains high at any age in both healthy individuals and patients with cardiovascular diseases, individualized exercise-based vascular health prevention should be implemented in any age group from children to centenarians.

The authors regret that an affiliation was omitted for Julia Charlotte Büschges. The complete list of affiliations for all authors appears above. The authors would like to apologise for any inconvenience caused. Carotid IMT and Stiffness in the KiGGS 2 National Survey: Third-Generation Measurement, Quality Algorithms and Determinants of CompletenessUltrasound in Medicine and BiologyVol. 47Issue 2PreviewCarotid intima–media thickness (cIMT) and carotid stiffness (CS) are important markers of atherosclerotic risk in the young. We assessed a novel third-generation method for its applicability in large population-based epidemiologic studies to determine strengths, limitations, completeness and predictors of unsuccessful measurement. Four thousand seven hundred ninety-eight 14- to 31-y-old participants of the German KiGGS cohort, which is based on a nationally representative sample with 11-y follow-up, underwent B-mode ultrasound examinations of the left and right common carotid artery with semi-automatic edge detection and automatic electrocardiogram-gated real-time quality control based on a sophisticated snake algorithm and subpixel interpolation. Full-Text PDF

Prevention of cardiovascular disease (CVD) remains one of the largest public health challenges of our time. Identifying individuals at increased cardiovascular risk at an asymptomatic, sub-clinical stage is of paramount importance for minimizing disease progression as well as the substantial health and economic burden associated with overt CVD. Vascular ageing (VA) involves the deterioration in vascular structure and function over time and ultimately leads to damage in the heart, brain, kidney, and other organs. Vascular ageing encompasses the cumulative effect of all cardiovascular risk factors on the arterial wall over the life course and thus may help identify those at elevated cardiovascular risk, early in disease development. Although the concept of VA is gaining interest clinically, it is seldom measured in routine clinical practice due to lack of consensus on how to characterize VA as physiological vs. pathological and various practical issues. In this state-of-the-art review and as a network of scientists, clinicians, engineers, and industry partners with expertise in VA, we address six questions related to VA in an attempt to increase knowledge among the broader medical community and move the routine measurement of VA a little closer from bench towards bedside.

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.

Isoprene has received widespread attention in breath research because of its potential to serve as a sensitive and non-invasive biomarker for the detection and monitoring of several metabolic effects. To date, research activity on breath isoprene focused on mass spectrometry-based measurement techniques, which are not portable and require skilled operators. Here, we show, for the first time to our knowledge, selective isoprene monitoring in exhaled breath (148 breath samples, 60–1250 parts-per-billion, ppb) with an inexpensive, user-friendly and compact filter–sensor device. This detector is based on a previously developed concept comprising a sorption filter of activated alumina that removes hydrophilic volatiles ahead of a micro gas sensor consisting of chemoresistive Si-doped WO3 nanoparticles to quantify the isoprene down to few ppb concentrations. When tested on humans during exercise and at rest, the detector accurately followed breath isoprene dynamics in linear (Pearson’s coefficient 0.89) correlation to proton transfer reaction mass spectrometry measurements. Most importantly, the output from the device is not interfered by high and variable concentrations of other breath volatile compounds, specifically acetone, ethanol and methanol. This isoprene detector can be readily applied for online monitoring of physical activity.

Background: Cardiovascular health scores, such as Life’s Simple 7 from the American Heart Association, and the assessment of arterial properties are independently used to determine cardiovascular risk. However, evidence of their association remains scarce, especially in healthy, middle-aged to older populations. Methods: A healthy sample of the Swiss population aged 50–91 years as part of the COmPLETE cohort study was included. Carotid intima–media thickness (cIMT), carotid lumen diameter (cLD), carotid distensibility coefficient (DC), flow-mediated dilation (FMD), and brachial–ankle pulse wave velocity (baPWV) were used to determine arterial properties. The Life’s Simple 7 cardiovascular health score was calculated using seven categories (body-mass index, cholesterol, systolic blood pressure, hemoglobin A1c, smoking status, physical activity, and diet). In accordance with the American Heart Association, for each category, two points were given for an ideal health metric level, intermediate scores one point, and poor scores zero points. Intermediate and ideal health scores corresponded to a total of 5–9 and 10–14 points, respectively. Results: A total of 280 participants (50.7% male) were included. After adjusting for age and sex, an ideal health score was associated with lower cIMT (−0.038 mm, 95% CI: −0.069 mm–−0.007 mm, p = 0.017), lower cLD (−0.28 mm, 95% CI: −0.46 mm–−0.11 mm, p = 0.002), and lower baPWV (−0.05 m/s, 95% CI: −0.08 m/s–−0.02 m/s, p = 0.003). No differences were found for FMD and DC. Conclusions: Even in a healthy sample of middle-aged and older adults, individuals with an ideal cardiovascular health score showed more favorable biomarkers of vascular aging than those with an intermediate score. This stresses the relevance of promoting an optimal lifestyle, even among the healthy population.

BackgroundIndividuals with a higher lifelong cardiorespiratory fitness show better vascular health with aging. Studies on fitness-related effects on endothelial function either analyzed samples with a narrow age-range or incompletely assessed endothelial responsiveness. This study aims to assess the impact of cardiorespiratory fitness on the association of brachial-arterial flow-mediated vasodilation (FMD) and low flow-mediated vasoconstriction (L-FMC) with age in healthy adults and patients with cardiovascular diseases.MethodsFMD, L-FMC and V.O2peak were prospectively measured in a population-based sample including 360 healthy adults and 99 patients with cardiovascular disease of European descend. Non-linear models were applied to assess V.O2peak-associated variations in age-related differences of endothelial function independent of classical cardiovascular risk factors.ResultsFMD was negatively associated with age in healthy adults (adjusted R2 = 0.27, partial R2 = 0.07, p < 0.001) and in cardiovascular patients (adjusted R2 = 0.29, partial R2 = 0.05, p = 002). L-FMC showed no association with age. In models predicting the change of FMD with higher age, V.O2peak accounted for 2.8% of variation in FMD (χ2(5) = 5.37, p = 0.372, s = 1.43). Thereby, V.O2peak-stratified changes of FMD started to fan out at around 30 years of age in women and 50 years of age in men, with 7–12% lower values at old age with V.O2peak ≤3rd percentile compared to V.O2peak ≥97th percentile) in both, the healthy sample and in cardiovascular patients.ConclusionThe statistical effect of cardiorespiratory fitness on the association of FMD with age independent of classical cardiovascular risk factors was small in both, healthy aging adults as well as patients with cardiovascular diseases. Its clinical significance should be assessed further.

Abstract Background Early vascular aging (EVA) is increasingly prevalent in the general population. Exercise is important for primary cardiovascular prevention, but often insufficient due to ineffective training methods and a lack of biomarkers suitable to monitor its vascular effects. VascuFit will assess the effectiveness of non-linear periodized aerobic exercise (NLPE) in a non-athletic sedentary population to improve both established and promising biomarkers of EVA. Methods Forty-three sedentary adults, aged 40–60 years, with elevated cardiovascular risk will either engage in 8 weeks of ergometer-based NLPE (n = 28) or receive standard exercise recommendations (n = 15). The primary outcome will be the change of brachial-arterial flow-mediated dilation (baFMD) after versus before the intervention. Secondary outcomes will be the change in static vessel analysis (SVA; clinical biomarker of microvascular endothelial function), endomiRs (microRNAs regulating key molecular pathways of endothelial cell homeostasis) and circulating cellular markers of endothelial function (mature endothelial cells, endothelial progenitor cells). Tertiary outcomes will be the change in sphingolipidome, maximum oxygen capacity, and traditional cardiovascular risk factors (blood pressure, triglycerides, cholesterol, fasting glucose, high-sensitivity C-reactive protein). Discussion We expect an improvement of baFMD of at least 2.6% and significant pre-post intervention differences of SVA and endomiRs as well as of the tertiary outcomes in the intervention group. VascuFit may demonstrate the effectiveness of NLPE to improve endothelial function, thus vascular health, in the general sedentary population. Furthermore, this project might demonstrate the potential of selected molecular and cellular biomarkers to monitor endothelial adaptations to aerobic exercise. Trial registration The trial was registered on www.clinicaltrials.gov (NCT05235958) in February 11th 2022.

Background: This study aimed to derive carotid intima media thickness (CIMT) percentiles from a population-based sample of adolescents and young adults using improved technology, standardization and quality control, and to investigate the association of CIMT with hypertensive blood pressure (BP) and obesity. Methods: Four thousand seven hundred nine 14- to 28-year-old participants of the German KiGGS cohort 11-year follow-up, which was based on a nationwide population sample, had B-mode ultrasound CIMT measurement with semi-automated edge-detection and automatic ECG-gated real-time quality control. CIMT percentiles were estimated from far wall CIMT during 2 to 6 heart cycles using the GAMLSS statistical model. Hypertensive BP, overweight, obesity, and a risk score from added Z scores of triglycerides, total/HDL (high-density lipoprotein)-cholesterol ratio, and glycated hemoglobin were based on standardized measurements at baseline and follow-up. Results: CIMT differed by sex at all ages, furthermore by age and height in a nonlinear fashion. Percentiles were estimated simultaneously by age and height. Hypertensive BP and obesity were associated cross-sectionally and longitudinally with a higher risk of CIMT ≥75th percentile in log-binomial regression models adjusted for age, sex, height, current smoking, and cardiovascular risk score. For CIMT ≥90th percentile, the relative risk effect estimates were consistently >1 but often had large confidence intervals including 1, largest adjusted relative risk 3.37 (95% CI, 1.41–8.04) for the combination of hypertensive BP and obesity at follow-up. Conclusions: Based on state-of-the-art measurements and statistical techniques, these population-based CIMT percentiles by sex, age and height add unbiased evidence for the association of subclinical atherosclerosis with hypertensive BP and obesity in the young.

CONTEXT:Overtraining syndrome (OTS) is a condition characterized by a long-term performance decrement, which occurs after a persisting imbalance between training-related and nontraining-related load and recovery. Because of the lack of a gold standard diagnostic test, OTS remains a diagnosis of exclusion. OBJECTIVE:To systematically review and map biomarkers and tools reported in the literature as potentially diagnostic for OTS. DATA SOURCES:PubMed, Web of Science, and SPORTDiscus were searched from database inception to February 4, 2021, and results screened for eligibility. Backward and forward citation tracking on eligible records were used to complement results of database searching. STUDY SELECTION:Studies including athletes with a likely OTS diagnosis, as defined by the European College of Sport Science and the American College of Sports Medicine, and reporting at least 1 biomarker or tool potentially diagnostic for OTS were deemed eligible. STUDY DESIGN:Scoping review following the guidelines of the Joanna Briggs Institute and PRISMA Extension for Scoping Reviews (PRISMA-ScR). LEVEL OF EVIDENCE:Level 4. DATA EXTRACTION:Athletes' population, criteria used to diagnose OTS, potentially diagnostic biomarkers and tools, as well as miscellaneous study characteristics were extracted. RESULTS:The search yielded 5561 results, of which 39 met the eligibility criteria. Three diagnostic scores, namely the EROS-CLINICAL, EROS-SIMPLIFIED, and EROS-COMPLETE scores (EROS = Endocrine and Metabolic Responses on Overtraining Syndrome study), were identified. Additionally, basal hormone, neurotransmitter and other metabolite levels, hormonal responses to stimuli, psychological questionnaires, exercise tests, heart rate variability, electroencephalography, immunological and redox parameters, muscle structure, and body composition were reported as potentially diagnostic for OTS. CONCLUSION:Specific hormones, neurotransmitters, and metabolites, as well as psychological, electrocardiographic, electroencephalographic, and immunological patterns were identified as potentially diagnostic for OTS, reflecting its multisystemic nature. As exemplified by the EROS scores, combinations of these variables may be required to diagnose OTS. These scores must now be validated in larger samples and within female athletes.

Using state-of-the-art sonography and centiles computed with novel statistical methods, this study confirms that, at the population level, hypertensive blood pressure in childhood is linked to increased carotid stiffness in young adulthood. The results emphasize that healthy lifestyles and healthy living environments in childhood and adolescence represent an early investment in cardiovascular health.

Background: Carotid intima-media thickness (cIMT) and stiffness (cS) are predictive markers of early vascular aging and atherosclerotic risk. This study assessed, whether exercise has protective effects on carotid structure and function or on vascular risk in the young.Methods: Volume and change of exercise (recreational and organized sports participation) of German adolescents and young adults was assessed within the prospective population-study KiGGS at KiGGS-Wave-1 (2009-2012) and KiGGS-Wave-2 (2014-2017) using standardized self-reporting questionnaires. CIMT and cS were measured by real-time B-mode ultrasound sequences with semi-automated edge-detection and automatic electrocardiogram-gated quality control in 2,893 participants (14-28 years, 49.6% female). A cumulative index for atherosclerotic risk (CV-R) included z-scores of mean arterial pressure, triglycerides, total/HDL-cholesterol-ratio, body mass index, and HbA1c.Results: At KiGGS-Wave-2 cross-sectional CV-R but not cS and cIMT was lower in all exercise-groups compared to "no exercise" (B = -0.73, 95%-CI = -1.26 to 0.19, p = 0.008). Longitudinal volume of exercise was negatively associated with CV-R (B = -0.37, 95%-CI = -0.74 to 0.00, p = 0.048) but not with cS and cIMT. Cross-sectional relative risk of elevated CV-R but not cS and cIMT was lower in all exercise-groups compared to "no exercise" (RR = 0.80, 95%-CI = 0.66 to 0.98, p = 0.033). High exercise volumes were associated with lower relative risk of elevated CV-R (RR = 0.80, 95%-CI = 0.65-0.97, p = 0.021) and cS in tendency but not with cIMT.Conclusions: Increased levels of exercise are associated with a better cardiovascular risk profile in young individuals, but not with cS and cIMT. Our study confirms previous recommendations on exercise in this age group without demonstrating a clear benefit on surrogate markers of vascular health.

ObjectiveThis study compared the robustness of a [Formula: see text]-plateau definition and a verification-phase protocol to day-to-day and diurnal variations in determining the true [Formula: see text]. Further, the additional value of a verification-phase was investigated.MethodsEighteen adults performed six cardiorespiratory fitness tests at six different times of the day (diurnal variation) as well as a seventh test at the same time the sixth test took place (day-to-day variation). A verification-phase was performed immediately after each test, with a stepwise increase in intensity to 50%, 70%, and 105% of the peak power output.ResultsParticipants mean [Formula: see text] was 56 ± 8 mL/kg/min. Gwet's AC1 values (95% confidence intervals) for the day-to-day and diurnal variations were 0.64 (0.22, 1.00) and 0.71 (0.42, 0.99) for [Formula: see text]-plateau and for the verification-phase 0.69 (0.31, 1.00) and 0.07 (-0.38, 0.52), respectively. In 66% of the tests, performing the verification-phase added no value, while, in 32% and 2%, it added uncertain value and certain value, respectively, in the determination of [Formula: see text].ConclusionCompared to [Formula: see text]-plateau the verification-phase shows lower reliability, increases costs and only adds certain value in 2% of cases.

PURPOSE:Cardiopulmonary exercise testing (CPET) is an important measurement in clinical practice, and its primary outcome, maximal oxygen uptake (V˙O2peak), is inversely associated with morbidity and mortality. The purposes of this study are to provide CPET reference values for maximal and submaximal parameters across the adult age spectrum of a healthy European cohort, to compare V˙O2peak values with other reference data sets, and to analyze the associations between physical activity (PA) levels and CPET parameters. METHODS:In this cross-sectional study, we prospectively recruited 502 participants (47% female) from 20 to 90 yr old. The subjects performed a CPET on a cycle ergometer using a ramp protocol. PA was objectively and continuously measured over 14 d using a triaxial accelerometer. Quantile curves were calculated for CPET parameters. To investigate the associations between CPET parameters and PA levels, linear regression analysis was performed. RESULTS:V˙O2peak values observed in the group of 20-29 yr were 46.6 ± 7.9 and 39.3 ± 6.5 mL·kg⋅min for males and females, respectively. On average, each age category (10-yr increments) showed a 10% lower V˙O2peak relative to the next younger age category. V˙O2peak values of previous studies were on average 7.5 mL·kg⋅min (20%) lower for males and 6.5 mL·kg⋅min (21%) lower for females. There was strong evidence supporting a positive association between the V˙O2peak (mL·kg⋅min) and the level of habitual PA performed at vigorous PA (estimate, 0.26; P < 0.001]. CONCLUSION:Maximal and submaximal CPET reference values over a large age range are novel, and differences to other studies are clinically highly relevant. Objectively measured vigorous-intensity PA showed a strong positive association with higher V˙O2peak and other performance-related CPET parameters, supporting the implementation of higher-intensity aerobic exercise in health promotion.