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Background: Skin-derived advanced glycation end products (sAGEs) have been associated with cardiovascular (CV) risk and mortality in adults. We hypothesize that cardiorespiratory fitness (CRF), body mass index (BMI) and vascular health are associated with development of sAGEs during childhood. Methods: In our prospective cohort study, 1171 children aged 6-8 years were screened for sAGEs, BMI, retinal arteriolar diameters (CRAE) and pulse wave velocity (PWV), using standardized procedures. To determine CRF a 20 m shuttle run was performed. After four 4 years, all parameters were assessed in 675 children using the same protocols. Results: Higher initial CRF levels were significantly associated with lower sAGEs (β [95 CI] -0.02 [-0.03 to -0.002] au, p = 0.022) levels at follow-up, although they showed a greater change from baseline to follow-up (β [95 CI] 0.02 [0.002 to 0.03] au, p = 0.027). Moreover, individuals with higher sAGEs at baseline showed narrower CRAE (β [95% CI] -5.42 [-8.76 to -2.08] μm, p = 0.001) at follow-up and showed a greater change in CRAE (β [95% CI] -3.99 [-7.03 to -0.96] μm, p = 0.010) from baseline to follow-up. Conclusion: Exercise and higher CRF may help mitigate the formation of AGEs during childhood, thereby reducing the risk for development of CV disease associated with AGEs-induced damage. Preventive strategies may need to target CRF early in life to achieve improvement of CV risk factors and may counteract the development of CV disease later in life. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Obesity- and hypertension-related cardiovascular (CV) risk has been shown to originate in childhood. Higher body mass index (BMI) and blood pressure (BP) have been associated with increased large artery stiffness and a lower microvascular arteriolar-to-venular diameter ratio (AVR) in children. This study aimed to investigate the association of cardiorespiratory fitness (CRF) with development of BMI, BP and vascular health during childhood. Methods: In our prospective cohort study, 1,171 children aged 6-8 years were screened for CRF, BMI, BP, retinal vessel diameters and pulse wave velocity using standardized protocols. Endurance capacity was assessed by 20mshuttle run test. After 4 years, all parameters were assessed in 664 children using the same protocols. Results: Children with a higher CRF at baseline developed a significantly lower BMI (ß [95% CI] -0.09 [-0.11 to -0.06] kg/m², p < 0.001), a lower systolic BP (ß [95% CI] -0.09 [-0.15 to -0.03] mmHg, p = 0.004) and a higher AVR (ß [95% CI] 0.0004 [0.00004 to 0.0007] units, p = 0.027) after 4 years. The indirect association of CRF with development of retinal arteriolar diameters was mediated by changes in BMI. Conclusion: Our results identify CRF as a key modulator for the risk trajectories of BMI, BP and microvascular health in children. Obesity-related CV risk has been shown to track into adulthood, and achieving higher CRF levels in children may help counteract the development of CV risk and disease not only in pediatric populations, but may also help reduce the burden of CVD in adulthood. [ABSTRACT FROM AUTHOR]

Background: Grip strength is used to estimate whole-body strength for health surveillance purposes. Explosive strength is considered important, yet economic measures able to detect early deterioration of neuromuscular capabilities are lacking. Whether handgrip maximum rate of force development (GRFD) or whole-body strength tests are better predictors of lower body power than handgrip maximum strength (GFmax) and their trajectories throughout the life span are unknown. Hypothesis: GRFD should be more closely related to lower body power than GFmax, and its trajectories over the life span should more closely follow that of lower body power. Study Design: Cross-sectional. Level of Evidence: Level 2b. Methods: A total of 613 healthy participants aged 20 to 91 years were tested for countermovement jump peak power, GFmax, handgrip rate of force development, and midthigh pull peak force (MTP). Cubic splines and linear models were built for age trajectories, generalized additive models for quintile curves, and linear regression was used to assess predictive quality. Results: Peak power (Pmax) declined linearly to 60% of young adult level, with GRFD, GFmax, and MTP remaining stable up to age 50 years and then declining more sharply to 52% to 71% of young adult levels. Trajectories were similar for male and female participants. GRFD (β = 0.17) and MTP (β = 0.08) were worse predictors of Pmax than GFmax (β = 0.24) in models adjusted for age, sex, lean body mass, and vigorous physical activity levels. Conclusion: GRFD was not superior to maximum strength in predicting lower body power. For health surveillance purposes, it therefore appears that GFmax tests are more economical and equally good predictors of lower body explosive strength at older age. The data provided can be used as norm values for healthy subjects. Clinical Relevance: Incorporating countermovement jump testing for early detection of declines in explosive capabilities might be advised. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Lipoproteins are important cardiovascular (CV) risk biomarkers. This study aimed to investigate the associations of lipoprotein subclasses with micro- and macrovascular biomarkers to better understand how these subclasses relate to atherosclerotic CV diseases. One hundred and fifty-eight serum samples from the EXAMIN AGE study, consisting of healthy individuals and CV risk patients, were analysed with nuclear magnetic resonance (NMR) spectroscopy to quantify lipoprotein subclasses. Microvascular health was quantified by measuring retinal arteriolar and venular diameters. Macrovascular health was quantified by measuring carotid-to-femoral pulse wave velocity (PWV). Nineteen lipoprotein subclasses showed statistically significant associations with retinal vessel diameters and nine with PWV. These lipoprotein subclasses together explained up to 26% of variation (R2 = 0.26, F(29,121) = 2.80, p < 0.001) in micro- and 12% (R2 = 0.12, F(29,124) = 1.70, p = 0.025) of variation in macrovascular health. High-density (HDL-C) and low-density lipoprotein cholesterol (LDL-C) as well as triglycerides together explained up to 13% (R2 = 0.13, F(3143) = 8.42, p < 0.001) of micro- and 8% (R2 = 0.08, F(3145) = 5.46, p = 0.001) of macrovascular variation. Lipoprotein subclasses seem to reflect micro- and macrovascular end organ damage more precisely as compared to only measuring HDL-C, LDL-C and triglycerides. Further studies are needed to analyse how the additional quantification of lipoprotein subclasses can improve CV risk stratification and CV disease prediction. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to analyze whether V̇O2-kinetics during cardiopulmonary exercise testing (CPET) is a useful marker for the diagnosis of heart failure (HF) and to determine which V̇O2-kinetic parameter distinguishes healthy participants and patients with HF. Methods: A total of 526 healthy participants and 79 patients with HF between 20 and 90 years of age performed a CPET. The CPET was preceded by a 3-min low-intensity warm-up and followed by a 3-min recovery bout. V̇O2-kinetics was calculated from the rest to exercise transition of the warm-up bout (on-kinetics), from the exercise to recovery transition following ramp test termination (off-kinetics) and from the initial delay of V̇O2 during the warm-up to ramp test transition (ramp-kinetics). Results: V̇O2 off-kinetics showed the highest z -score differences between healthy participants and patients with HF. Furthermore, off-kinetics was strongly associated with V̇O2peak. In contrast, ramp-kinetics and on-kinetics showed only minimal z -score differences between healthy participants and patients with HF. The best on- and off-kinetic parameters significantly improved a model to predict the disease severity. However, there was no relevant additional value of V̇O2-kinetics when V̇O2peak was part of the model. Conclusion: V̇O2 off-kinetics appears to be superior for distinguishing patients with HF and healthy participants compared with V̇O2 on-kinetics and ramp-kinetics. If V̇O2peak cannot be determined, V̇O2 off-kinetics provides an acceptable substitute. However, the additional value beyond that of V̇O2peak cannot be provided by V̇O2-kinetics. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the association of changes in physical activity, screen time, and cardiorespiratory fitness (CRF) with development of body mass index (BMI), blood pressure (BP), and retinal microvascular health in children over four years. In 2014, 391 children aged 6‐8 years were screened, and thereof 262 children were reexamined after four years following standardized protocols. Retinal arteriolar (CRAE) and venular diameters were measured by a retinal vessel analyzer. CRF was objectively assessed by a 20 m shuttle run, physical activity, and screen time by use of a questionnaire. Children who achieved higher CRF levels reduced their BMI (β [95% CI] −0.35 [−0.46 to −0.25] kg/m2 per stage, P ≤.001) and thereby developed wider CRAE (β [95% CI] 0.25 [0.24 to 0.48] µm per stage, P =.03) at follow‐up. Moreover, children with elevated or high systolic BP at baseline, but lower levels of screen time during the observation period, had wider CRAE at follow‐up (β [95% CI] −0.37 [−0.66 to −0.08] µm per 10 min/d, P =.013). Change in CRF was not directly associated with better microvascular health at follow‐up. However, an increase of CRF over four years was associated with a reduced BMI and consequently wider retinal arterioles at follow‐up. In children with elevated or high systolic BP, a reduction of screen time significantly improved retinal microvascular health as a primary prevention strategy to promote childhood health and combat development of manifest CV disease later in life. [ABSTRACT FROM AUTHOR]

Background/Aims: Flicker-light induced retinal vessel dilatation (FID), a marker of microvascular endothelial function, has been shown to be blunted in sedentary cardiovascular risk patients (SR) as well as healthy physically active individuals (HA). This study aimed to quantify the retinal myogenic response to blood pressure (BP) peaks and its effects on consecutive FID for differentiation of microvascular health. Methods: Ten HA and eleven SR with a previously established restriction of arteriolar FID (aFID) (<2.2%) were invited in order to assess BP-induced myogenic constriction following a standardized handgrip task and a consecutive FID. BP was measured beat-to-beat. Results: The complete dataset of nine HA (3 female, mean age 65 years) and nine SR (5 female, mean age 61 years) individuals was analyzed. The central retinal arteriolar diameter equivalent (CRAE) was 183 ± 11 μm for HA and 176 ± 20 μm for SR. Initial baseline aFID was 1.6 ± 0.4% in HA and 1.6 ± 0.7% in SR. Systolic (p = 0.334) and diastolic (p = 0.245) BP increase following the handgrip task was in the range of 20–30% and comparable in both groups. BP increase was followed by a significantly higher arteriolar (−2.9 ± 1.3% vs. −1.3 ± 0.6%, p < 0.01) myogenic constriction in HA compared to SR. Moreover, in the consecutive assessment of FID directly after the BP-induced vessel constriction, aFID (4.1 ± 2.0% vs. 1.6 ± 0.9%, p < 0.01) was higher in HA compared to SR. Conclusion: Initial baseline aFID was blunted in HA and SR. Retinal myogenic constriction was impaired in SR compared to HA. The consecutive aFID after BP-induced myogenic constriction recovered in HA but remained blunted in SR. Additional assessment of retinal myogenic constriction needs to be considered to improve CV risk stratification and reduce false-positive findings of endothelial dysfunction in otherwise healthy active individuals. Clinical Trial Registration: ClinicalTrials.gov: NCT03986892 (https://clinicaltrials.gov/ct2/show/NCT03986892). [ABSTRACT FROM AUTHOR]

Objective: This study compared the robustness of a V˙O2 -plateau definition and a verification-phase protocol to day-to-day and diurnal variations in determining the true V˙O2max. Further, the additional value of a verification-phase was investigated. Methods: Eighteen 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. Results: Participants mean V˙O2peak 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 V˙O2 -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 V˙O2max. Conclusion: Compared to V˙O2 -plateau the verification-phase shows lower reliability, increases costs and only adds certain value in 2% of cases. [ABSTRACT FROM AUTHOR]

Background: Atherosclerotic remodeling starts early in life and can accelerate in the presence of cardiovascular risk (CV) factors. Regular physical activity (PA) can mitigate development of large and small artery disease during lifespan. We aimed to investigate the association of changes in body mass index (BMI), blood pressure (BP), PA behavior and retinal microvascular diameters with large artery pulse wave velocity (PWV) in prepubertal children over 4 years. Methods: The school-based prospective cohort study included 262 children initially aged 6–8 years, assessing the above CV risk factors and retinal vessels by standardized procedures at baseline (2014) and follow-up (2018). PWV was assessed by an oscillometric device at follow-up. Results: Children with increased systolic BP over 4 years showed higher PWV at follow-up (β [95% CI] 0.006 [0.002 to 0.011] mmHg per unit, P = 0.002). In contrast, increased vigorous PA corresponded to a lower PWV at follow-up (β [95% CI] −0.009 [−0.018 to <0−0.001] 10 min/day per unit, P = 0.047). Progression of retinal arteriolar narrowing and venular widening were linked to a higher PWV after 4 years (β [95% CI] −0.014 [−0.023 to −0.004] 0.01 changes per unit, P = 0.003). Conclusion: Increase in systolic BP and progression of microvascular dysfunction were associated with higher PWV after 4 years. Children with increasing levels of vigorous PA were found to have lower PWV at follow-up. Habitual vigorous PA has the potential to decelerate the process of early vascular aging in children and may thus help counteract CV disease development later in life. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT03085498. [ABSTRACT FROM AUTHOR]

Objectives: Physical activity and cardiorespiratory fitness (CRF) are relevant modifiers of cardiovascular risk. Their independent effects on arterial stiffness have not been assessed in people with obesity. This study aimed to assess the independent effects of light (LPA) and moderate-to-vigorous (MVPA) physical activity and CRF on Pulse wave velocity (PWV).Methods: Brachial-ankle PWV (baPWV) was measured cross-sectionally in 55 subjects (43.0 ± 13.8 years; 66% women) with moderate cardiovascular risk. Body composition was assessed with bioelectrical impedance-analysis. Daily minutes of LPA and MVPA were measured by accelerometry and CRF (peak oxygen uptake [VO2 peak]) with spiroergometry. Independent effects of LPA, MVPA, and VO2 peak on baPWV were analyzed in an age-, sex-, body fat mass-, and blood pressure-adjusted ANOVA.Results: Every 10 minutes increase of daily MVPA was associated with a 2.8% (0.32m/s [-0.64 to 0.001 m/s], P = .05) reduction of baPWV, whereas LPA and VO2 peak had only a little or no relevant effects on baPWV.Conclusions: Higher MVPA is associated with lower composite arterial stiffness independent of CRF and the number of metabolic risk factors in patients with obesity and further metabolic risk factors. Thus, lifestyle interventions should aim for an increase in MVPA. BaPWV may improve the monitoring of favorable effects of MVPA, even if an improvement of VO2 peak cannot be obtained. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate, for the first time, the effects of high‐intensity interval training (HIIT) on retinal microvascular endothelial function in cardiovascular (CV) risk patients. In the randomized controlled trial, middle‐aged and previously sedentary patients with increased CV risk (aged 58 ± 6 years) with ≥ two CV risk factors were randomized into a 12‐week HIIT (n = 33) or control group (CG, n = 36) with standard physical activity recommendations. A blinded examiner measured retinal endothelial function by flicker light‐induced maximal arteriolar (ADmax) and venular (VDmax) dilatation as well as the area under the arteriolar (AFarea) and venular (VFarea) flicker curve using a retinal vessel analyzer. Standardized assessments of CV risk factors, cardiorespiratory fitness, and retinal endothelial function were performed before and after HIIT. HIIT reduced body mass index, fat mass, and low‐density lipoprotein and increased muscle mass and peak oxygen uptake (VO2peak). Both ADmax (pre: 2.7 ± 2.1%, post: 3.0 ± 2.2%, P =.018) and AFarea (pre: 32.6 ± 28.4%*s, post: 37.7 ± 30.6%*s, P =.016) increased after HIIT compared with CG (ADmax, pre: 3.2 ± 1.8%, post: 2.9 ± 1.8%, P =.254; AFarea, pre: 41.6 ± 28.5%*s, post: 37.8 ± 27.0%*s, P =.186). Venular function remained unchanged after HIIT. There was a significant association between ∆‐change VO2peak and ∆‐changes ADmax and AFarea (P =.026, R2 = 0.073; P =.019, R2 = 0.081, respectively). 12‐weeks of HIIT improved retinal endothelial function in middle‐aged patients with increased CV risk independent of the reduction in classical CV risk factors. Exercise has the potential to reverse or at least postpone progression of small vessel disease in older adults with increased CV risk under standard medication. Dynamic retinal vessel analysis seems to be a sensitive tool to detect treatment effects of exercise interventions on retinal microvascular endothelial function in middle‐aged individuals with increased CV risk. [ABSTRACT FROM AUTHOR]

Time-of-day effects in strength performance have been extensively investigated due to their relevance in competitive sports. However, most studies use large measurement intervals making it difficult to monitor potential performance changes throughout the day. Furthermore, previous studies have exclusively focused on how the time of day affects strength on a group level and ignored the individual differences in the times of peak performance. Therefore, the main purpose of this study was to investigate the diurnal and day-to-day variations in isometric and isokinetic leg, arm and trunk strength over six different times of the day. Following a familiarization test, 19 trained males (age: 24.1 ± 2.5 years) performed isometric and isokinetic strength assessments at six different times of the day (7:00, 10:00, 13:00, 16:00, 19:00, and 21:00) with an isokinetic dynamometer. An eighth test session was performed at the same time of the day as the seventh test session to investigate the day-to-day variations and the difference between diurnal and day-to-day variations were compared. All tests were separated by at least 48 h. The start time for the first session was randomized. The mean maximum isometric leg strength was 5.85 ± 0.80 N.kg−1 and 4.99 ± 0.78 N.kg−1at the peak and at the nadir of the day, respectively. The mean difference (95% CI) was 0.86 ± 0.47 N.kg−1 (0.62; 1.10) for the diurnal variation and 0.30 ± 0.42 N.kg−1 (0.09; 0.52) for the day-to-day variation. The mean maximum isometric arm strength was 1.68 ± 0.33 N.kg−1 at the peak and 1.46 ± 0.19 N.kg−1 at the nadir of the day, respectively. The mean difference (95% CI) was 0.21 ± 0.16 N.kg−1 (0.14; 0.29) for the diurnal variation and 0.06 ± 0.05 N.kg−1 (0.03; 0.08) for the day-to-day variation. The linear mixed-effects model showed little evidence for differences in isometric leg strength between the different times of the day (all p-values >0.983). The present study demonstrated that diurnal variations in leg and arm strength are nearly three times higher than the day-to-day variations, but there was only little evidence for a time-of-day effect on a group level. The diurnal variations observed herein without time-of-day effects are suggestive that individuals achieve their peak performance at different times of the day. Therefore, performance tests should be carried out at the same time of the day to ensure comparability. Furthermore, depending on the difference between the time of competition and the time of peak performance, as well as the individual magnitude in diurnal variation, some athletes can have a clear disadvantage.Abbreviation: 95% CI, 95% confidence interval; SD, standard deviation; ICC, intraclass correlation coefficient. [ABSTRACT FROM AUTHOR]