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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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hauser, Lona, Köchli, Streese, Infanger, Faude and Hanssen.)

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 20 m shuttle 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 (β [95% CI] -0.09 [-0.11 to -0.06] kg/m 2 , p < 0.001), a lower systolic BP (β [95% CI] -0.09 [-0.15 to -0.03] mmHg, p = 0.004) and a higher AVR (β [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. Registration: http://www.clinicaltrials.gov/ (NCT02853747)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hauser, Lichtenstein, Nebiker, Streese, Köchli, Infanger, Faude and Hanssen.)

Objective: Central hemodynamics are related to cardiovascular (CV) outcomes in adults, but associations with childhood CV risk remain unclear. The study aimed to investigate the association of obesity, physical activity, and fitness with parameters of central pulse wave reflection in young prepubertal children. Methods: In this cross-sectional study, 1,324 primary school children (aged 7.2 ± 0.4 years) were screened for parameters of pulse wave reflection such as augmentation index (AIx), central pulse pressure (CPP), body mass index (BMI), and cardiorespiratory fitness (CRF) by standardized procedures for children. Results: The mean AIx and AIx@75 were 22.2 ± 7.7 and 29.2 ± 9.2%, respectively. With each unit increase in BMI, AIx [-0.226 (-0.328; -0.125)%] and AIx@75 [-0.444(-0.660; -0.229)%] decreased, whereas peak forward pulse wave increased ( p < 0.001). Increasing BMI was associated with higher CPP, but did not remain significant after adjustment for CRF and heart rate. One unit increase in CRF was associated with lower AIx@75 [-0.509(-0.844; -0.173)%, p = 0.003] and lower reflection magnitude [RM: -0.559 (-0.890; -0.227), p = 0.001], independent of body weight and height. Girls had significantly higher AIx, AIx@75, peak backward pulse wave, and RM compared with boys. Conclusion: Childhood obesity was associated with higher CPP but lower augmentation of the reflected pulse wave in children. Assessment of central blood pressures appears to be a valuable asset to childhood CV risk screening. The validity of augmentation indices during childhood development and the association with early vascular aging in children need to be verified in long-term follow-up studies. Physical activity and fitness have the potential to improve vascular hemodynamics in susceptible children and, thus, counteract vascular aging. Trial registry: ClinicalTrials.gov: Exercise and Arterial Modulation in Youth. Identifier: NCT02853747; URL: https://clinicaltrials.gov/ct2/show/NCT02853747., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling Editor declared a past collaboration with several of the authors SK, HH., (Copyright © 2021 Köchli, Deiseroth, Hauser, Streese, Schmidt-Trucksäss, Faude and Hanssen.)

The present study examined the prospective association of parental household income, education level, migration background, and physical activity (PA) behavior with the development of pulse wave velocity (PWV) in prepubertal children. A total of 223 children (initial age 6-8 years) were included in this prospective school-based cohort study from 2014 to 2018. Parental socioeconomic status, migration background, and PA behavior were assessed by the use of questionnaires at both times points. PWV was measured by an oscillometric device at follow-up (2018). No significant association of household income, education level, and parental migration background with PWV in children after four years was found. However, a high level of maternal PA was related to a lower childhood PWV at follow-up (mean (95% CI) 4.6 (4.54-4.66) m/s) compared to children of mothers with a low PA behavior (mean (95% CI) 4.7 (4.64-4.77) m/s) ( p = 0.049). Children of mothers with a high PA level revealed a beneficial arterial stiffness after four years. Little evidence for an association of socioeconomic status and migration background with childhood arterial stiffness was found. Increased parental PA seems to support the development of childhood vascular health and should be considered in the generation of future primary prevention strategies of childhood cardiovascular health.

Background: Childhood elevated circulatory stress mediators such as cortisol seem to play an important role in the development of hypertension and metabolic disorders later in life. Little is known about the association of body composition, cardiorespiratory fitness (CRF), blood pressure (BP) and ethnicity with cortisol reactivity in young children., Methods: In this cross-sectional study, 324 black and 227 white school children (aged 7.4 ± 1.0 years) were screened for salivary cortisol reactivity, body mass index, BP and CRF (shuttle run) by standardised assessments for children., Results: Children in the lower cortisol reactivity percentile (<25th) had a higher heart rate (87.0 ± 12.9 bpm) and a lower CRF (3.1 ± 1.3 stages) compared to children in the upper (>25th) percentile (86.2 ± 11.5 bpm and 3.5 ± 1.7 stages, respectively). At baseline, children of black ethnicity had a higher cortisol level ( p < 0.001). Immediately before the exercise test, no associations of obesity, BP, CRF and ethnicity with cortisol levels were found. In analysis of covariance (ANCOVA) we found that low CRF, high BP and black ethnicity were independently associated with lower cortisol reactivity by performing the shuttle run test ( p < 0.01)., Conclusion: Low CRF and high BP were associated with lower cortisol reactivity after a cardiorespiratory exercise test. Black children showed a lower cortisol reactivity which may contribute to the earlier onset of hypertension reported in black compared to white populations. Primary prevention programs need to focus on improving physical fitness to reduce the growing prevalence of cardiometabolic disorders during childhood.

Background/Aims: Socioeconomic barriers and lifestyle conditions affect development of cardiovascular disease in adults, but little is known about the association of parental lifestyle and education with childhood health. We aimed to investigate the association of socioeconomic status (SES), migration background, parental physical activity (PA) and smoking status with micro-and macrovascular health in children. Methods: In 2016/2017, 833 school children (aged 7.2 ± 0.4 years) in Basel (Switzerland) were screened for retinal arteriolar-to-venular ratio (AVR), pulse wave velocity (PWV), SES, migration background and parental PA as well as smoking status. Results: High parental PA levels were associated with a favorable higher AVR ( p = 0.020) and lower PWV ( p = 0.035), but not independent of parental smoking status. Children with parents who smoked had a higher PWV [4.39 (4.35-4.42) m/s] compared to children with non-smoking parents [4.32 (4.29-4.34) m/s, p = 0.001]. Children of parents with a low household income had a higher PWV [4.36 (4.32-4.41) m/s] compared to children of parents with a high household income [4.30 (4.26-4.34) m/s, p = 0.033]. Low parental educational level was associated with a lower AVR [0.86 (0.85-0.88)] compared to children with highly educated parents [AVR:0.88 (0.87-0.88), p = 0.007; PWV: 4.33 (4.30-4.35) m/s, p = 0.041]. Children with a European background showed a higher AVR [0.88 (0.87-0.88)] compared to non-European children [AVR: (0.86 (0.85-0.87), p = 0.034]. Conclusion: Parental PA is associated with better macro- and microvascular childhood health. However, the positive association is lost when parental smoking is considered in the analysis. Socioeconomic factors seem to associate with subclinical vascular alterations in children. Primary prevention programs should focus on including parental lifestyle interventions and educational programs to reduce the burden of lifestyle-associated barriers in order to improve cardiovascular health during lifespan. Clinical Trial Registration: ClinicalTrials.gov Exercise and Arterial Modulation in Youth, https://clinicaltrials.gov/ct2/show/NCT02853747, NCT02853747., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Köchli, Endes, Grenacher, Streese, Lona, Hauser, Deiseroth, Zahner and Hanssen.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Lona, Hauser, Köchli, Infanger, Endes, Faude and Hanssen.)

The prevalence of high childhood blood pressure (BP) is rising globally and has been associated with subclinical vascular impairments in children. Longitudinal data on the association of microvascular alterations with the development of high BP in children are lacking. We aimed to analyze the association of central retinal arteriolar (CRAE) and venular (CRVE) diameters with development of higher BP over 4 years in young school children. In 2014, 391 children aged 6 to 8 years were screened for BP and retinal vessel diameters using standardized protocols. Retinal vessel analysis was performed using a retinal vessel analyzer to determine CRAE and central retinal venular equivalent. In the follow-up of 2018, all parameters were assessed in 262 children using the same standardized protocols. During follow-up, systolic and diastolic BP increased significantly (Δ 3.965±8.25 and 1.733±7.63 mm Hg, respectively), while CRAE decreased by Δ -6.325±8.55 µm without significant changes in central retinal venular equivalent (Δ -0.163±7.94 µm). Children with narrower CRAE at baseline developed higher systolic BP after four years (β [95% CI] 0.78 [0.170-1.398] mm Hg per 10 µm decrease, P =0.012). Children with increased systolic or diastolic BP at baseline developed narrower CRAE (β [95% CI] -0.154 [-0.294 to -0.014] µm per 1mmHg, P =0.031 and β [95% CI] -0.02 [-0.344 to -0.057] µm per 1 mmHg, P =0.006, respectively) at follow-up. Narrowing of retinal arterioles predicted evolution of systolic BP. In turn, higher initial systolic and diastolic BP was associated with subsequent development of microvascular impairments. Our results give good evidence for a bivariate temporal relationship between BP and microvascular health in children.

Background: Advanced glycation end products (AGEs) accumulate with age and development of cardiovascular disease. Higher AGEs have been shown in children with diabetes but little is known about their association with lifestyle conditions in childhood. We hypothesized that BMI, blood pressure and cardiorespiratory fitness (CRF) are associated with subcutaneous AGEs formation in children., Methods: In this cross-sectional study, 1075 children (aged 7.2 ± 0.4 years) were screened for subcutaneous AGEs (skin autofluorescence; SAF), body mass index (BMI), blood pressure (BP), and CRF using standardized procedures. Group comparisons were performed in clinical BP and BMI categories and tertiles of CRF., Results: Children with higher physical fitness showed lower SAF (0.99(1.03;1.10)au) compared to children with low CRF (1.09(1.03;1.05)au, p < 0.001). An increase of one shuttle run stage was associated with a mean reduction in SAF of -0.033(CI: -0.042;-0.024)au, independent of BMI and BP (p < 0.001). BMI and BP were not independently associated with SAF-derived AGEs in this large cohort of primary school children., Conclusions: Low physical fitness but not BMI and BP were associated with higher levels of AGEs. Primary prevention programs in young children may need to focus on improving physical fitness in game settings in order to reduce the growing prevalence of metabolic disorders during childhood.

Objective: The prevalence of obesity and physical inactivity in children are increasing globally. The study aimed to investigate the association of obesity and cardiorespiratory fitness (CRF) with patterns of lung function in young children., Methods: In this cross-sectional study, lung function, body mass index (BMI), blood pressure (BP) and CRF (shuttle run stages) were measured in an unselected cohort of 1246 children aged 7.2 ± 0.4 years. All parameters and lung function, such as the ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC), were assessed by standardized procedures for children. Statistical models were applied for systematic adjustment of potential confounders., Results: Obese children had significantly higher FEV1 (Coef. (95% CI) (1.57 (1.50; 1.64) L) and FVC (1.75 (1.67; 1.83) L) compared to normal weight children (1.38 (1.37; 1.40) L; (1.53 (1.51; 1.54) L, respectively). However, with each unit increase of BMI, FEV1/FVC decreased (-0.003 (-0.005; -0.001)) due to a disproportional increase in FVC compared to FEV1. Per stage increase of CRF, FEV1 (0.017 (0.008; 0.025) L) and FVC increased (0.022 (0.012; 0.031) L)). In obese children, higher CRF was independently associated with higher FEV1/FVC (0.03 (0.5E-4; 0.06)) due to a higher increase of FEV1 over FVC with increasing fitness., Conclusions: The decrease of FEV1/FVC with increasing BMI suggests that childhood obesity is associated with an imbalance of ventilation and airway flow. In children with obesity, higher CRF is associated with an improved FEV1/FVC ratio. Physical exercise programs may have the potential to improve patterns of lung function in children with obesity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Arterial stiffness (AST) is a main determinant of cardiovascular (CV) mortality. Long-term physical activity (PA) is considered to decrease age-related progression of AST but effects of short-term exercise interventions on AST remain unclear., Methods: In a combined cross-sectional and interventional study approach, we investigated the effects of long-term PA and short-term high-intensity interval training (HIIT) on AST in an older population. 147 older individuals (mean age 59 ± 7 years) were assigned to three groups according to their PA and CV risk profile and compared: healthy active (HA, n = 35), healthy sedentary (HS, n = 33) and sedentary at risk (SR, n = 79). In addition, SR were randomized to either 12 weeks of HIIT or standard recommendations. Pulse wave velocity (PWV) was measured by applanation tonometry. Cardiorespiratory fitness (CRF) was performed by symptom-limited spiroergometry to determine maximal oxygen uptake (VO2max)., Results: Higher CRF was associated with lower PWV ( p < 0.001) and VO2max explained 18% of PWV variance. PWV was higher in SR (8.2 ± 1.4 m/s) compared to HS (7.5 ± 1.6 m/s) and HA (7.0 ± 1.1 m/s; p < 0.001). 12 weeks of HIIT did not change PWV in SR. HIIT-induced reduction in systolic BP was associated with a reduction in PWV ( p < 0.05)., Discussion: SR show higher PWV compared to HS and long-term PA is associated with lower PWV. Reduction of AST following short-term HIIT seems to depend on a concomitant decrease in blood pressure. Our study puts into perspective the effects of long- and short-term exercise on arterial wall integrity as treatment options for CV prevention in an older population., Clinical Trial Registration: ClinicalTrials.gov: NCT02796976 (https://clinicaltrials.gov/ct2/show/NCT02796976).

Background: Cardiovascular disease (CVD) remains to be one of the most frequent causes of death worldwide. Cardiovascular (CV) risk factors such as hypertension and obesity often manifest in childhood. The study examines the associations of blood pressure, body mass index and physical activity with cardiopulmonary, metabolic, and psychosocial health of children in a systems physiology approach. Methods/Design: This cross-sectional study will be performed in a cohort of 6 to 8 year old school children ( n = 1000). As a measure of vascular health, retinal microvascular diameters and large artery pulse wave velocity will be examined. Anthropometric parameters, such as weight, height, body mass index, and blood pressure will be assessed according to standardized protocols for children. Physical fitness and activity will be measured by a 20 m shuttle run, a 20 m sprint and a proxy-reported questionnaire on lifestyle behavior. Spirometry, assessment of heart rate variability and skin advanced glycation end products as well as a flanker test will be performed to determine systemic end organ alterations. Discussion: The study offers a unique integrative primary prevention concept that aims to set the grounds for a healthy and active lifestyle approach during childhood. It will help optimize CV risk stratification to identify children at risk of disease progression later in life. The study will demonstrate the importance of specific CV screening programs in children to reduce the growing burden of CV disease in adulthood. Prospective follow-up studies will have to prove the efficacy of primary prevention programs in children to achieve healthier aging as a long-term goal.

Cardiovascular disease often develops during childhood, but the determinants of vascular health and disease in young children remain unclear. The study aimed to investigate the association of obesity and hypertension, as well as physical fitness with retinal microvascular health and large artery stiffness, in children. In this cross-sectional study, 1171 primary school children (aged 7.2±0.4 years) were screened for central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) diameters, pulse wave velocity (PWV), body mass index, blood pressure (BP), and cardiorespiratory fitness by standardized procedures for children. BP was categorized according to the reference values of the population-based German KiGGS study (Kinder- und Jugendgesundheitssurvey [Children- and Adolescents Health Survey]) and the American Academy of Pediatrics guidelines. Overweight (mean [95% CI]: CRAE, 200.5 [197.9-203.2] µm; CRVE, 231.4 [228.6-234.2] µm; PWV, 4.46 [4.41-4.52] m/s) and obese children (CRAE, 200.5 [196.4-204.7] µm; CRVE, 233.3 [229.0-237.7] µm; PWV, 4.51 [4.43-4.60] m/s) had narrower CRAE, wider CRVE, and higher PWV compared with normal-weight children (CRAE: 203.3 [202.5-204.1] µm, P<0.001; CRVE: 230.1 [229.1-230.9] µm, P=0.07; PWV: 4.33 [4.31-4.35] m/s, P<0.001). Children with high-normal BP (CRAE, 202.5 [200.0-205.0] µm; PWV, 4.44 [4.39-4.49] m/s) and BP in the hypertensive range (CRAE, 198.8 [196.7-201.0] µm; PWV, 4.56 [4.51-4.60] m/s) showed narrower CRAE, as well as higher PWV, compared with normotensive peers (CRAE: 203.7 [202.9-204.6] µm, P<0.001; PWV: 4.30 [4.28-4.32] m/s, P<0.001). With each unit increase of body mass index and systolic BP, CRAE decreased and PWV increased significantly. Children with the highest cardiorespiratory fitness had wider CRAE, narrower CRVE, and lower PWV compared with least fit children. Childhood obesity and hypertension, even at preclinical stages, are associated with microvascular and macrovascular impairments in young children. Primary prevention programs targeting physical activity behavior may have the potential to counteract development of small and large vessel disease early in life. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02853747.