Cardiorespiratory fitness and development of childhood cardiovascular risk: The EXAMIN YOUTH follow-up study.

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 (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. Registration: http://www.clinicaltrials.gov/ (NCT02853747).

Bivariate relation of vascular health and blood pressure progression during childhood.

BACKGROUND AND AIMS: Hypertension is a major risk factor for the development of cardiovascular disease (CVD) in adulthood. High blood pressure (BP) is associated with subclinical vascular impairments as early as childhood. We aimed to assess the association of retinal microvascular diameters and large artery pulse wave velocity (PWV) with progression of childhood BP. METHODS: In our prospective Basel cohort study, 1171 children aged 6-8 years were screened for BP, body mass index, retinal vessel diameters and PWV using standardized protocols. After 4 years, all parameters were assessed in 749 children using the same protocols. RESULTS: Children with narrower central retinal arteriolar diameters (CRAE) and higher PWV at baseline developed higher systolic BP after 4 years (ß [95% CI] 0.6 [0.072 to 1.164] mmHg per 10 µm decrease, p = 0.026 and ß [95% CI] 0.6 [0.331 to 0.838] mmHg per 0.1 m/s increase, p < 0.001, respectively). Children with increased systolic BP at baseline developed narrower CRAE and higher PWV at follow-up (ß [95% CI] -3.3 [-4.43 to -2.09] µm per 10 mmHg increase, p < 0.001 and ß [95% CI] 0.13 [0.10 to 0.16] m/s per 10 mmHg increase, p < 0.001, respectively). CONCLUSIONS: Retinal arteriolar diameter and PWV independently predict progression of childhood BP, while initial BP is linked to development of micro- and macrovascular impairments, describing a bivariate temporal relationship between vascular health and BP. Childhood may present a window of opportunity for initiation of primary prevention strategies for the treatment of high BP to help prevent manifestation of CVD later in life.

Obesity, blood pressure and retinal microvascular phenotype in a bi-ethnic cohort of young children.

BACKGROUND AND AIMS: Childhood obesity and high blood pressure (BP) are main determinants for cardiovascular disease development with regional and ethnic differences. Narrower arteriolar (CRAE) and wider venular (CRVE) retinal vessel diameters are sensitive markers of early vascular compromise in children. We aimed to compare retinal vessel diameters and investigate associations and odds ratios with body mass index (BMI) and BP in a multi-national/ethnic childhood study. METHODS: BMI, systolic (SBP) and diastolic BP (DBP) were screened in 929 black and white South African (SA) and 1171 Swiss children (aged 5-9 years). Retinal assessments were performed using a retinal vessel analyzer to determine CRAE and CRVE. RESULTS: Black SA children had wider CRVE compared to white SA and Swiss children (all p < 0.001). However, BMI or BP was not associated with CRVE in black SA children. Higher BMI and BP associated with narrower CRAE in all children, except for BMI in black SA children, in whom narrower CRAE was found for every unit increase in SBP (ß = -0.199 µm, p = 0.001) and DBP (ß = -0.312 µm, p < 0.001). Obesity (OR:1.38[1.01; 1.89]), hypertension (OR:1.90[1.53; 2.36]) and black ethnicity (OR:1.50[1.18; 1.92]) increased the likelihood for arteriolar narrowing. CONCLUSIONS: Black SA children presented with wider retinal venules compared to their white SA and Swiss peers, which was unexplained by conventional risk factors. The overall risk of arteriolar narrowing was driven by obesity, hypertension and ethnicity. Our findings indicate the importance to differentiate cardiovascular risk by microvascular phenotype in different populations and ethnicity early in life.

Association of blood pressure, obesity and physical activity with arterial stiffness in children: a systematic review and meta-analysis.

Central pulse wave velocity (cPWV) is a biomarker for cardiovascular (CV) risk and a predictor for CV events in adulthood. Alterations of arterial stiffness have also been associated with CV risk in childhood. The study aimed to systematically review and meta-analyze the association of blood pressure (BP), body mass index (BMI), and cardiorespiratory fitness (CRF) with cPWV in children. Literature search was through the databases PubMed, Web of Science, Embase and the Cochrane Register of Controlled Trials. Twenty-two articles were included in the systematic review and eight articles in the meta-analysis. Higher systolic and diastolic BP were associated with higher cPWV (pooled estimated effect size (ES) 0.02 (95% CI: 0.012-0.027; P < 0.001), and ES 0.02 (95% CI: 0.011-0.029; P < 0.001); respectively). Higher BMI correlated with higher cPWV (ES 0.025 (95% CI: 0.013-0.038; P < 0.001)). CRF was inversely associated with cPWV (ES -0.033 (95% CI: -0.055 to -0.011; P = 0.002)). In children, higher BP and BMI are already related to increased cPWV, and enhanced CRF may be a preventive strategy to counteract development of CV disease later in life. IMPACT: This meta-analysis suggests that elevated blood pressure and body mass index in childhood correlate with increased central pulse wave velocity. Children with higher cardiorespiratory fitness appear to have favorably lower arterial stiffening. Elevated blood pressure and altered arterial stiffness originate early in life and childhood risk stratification as well as timely initiation of exercise treatment may help counteract development of manifest cardiovascular disease later in life.

Body Composition and Physical Fitness Affect Central Hemodynamics in Young Children.

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.

Cardiorespiratory Fitness, Blood Pressure and Ethnicity Are Related to Salivary Cortisol Responses after an Exercise Test in Children: The ExAMIN Youth SA Study.

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.

Association of Parental Socioeconomic Status and Physical Activity with Development of Arterial Stiffness in Prepubertal Children.

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.

Socioeconomic Status and Parental Lifestyle Are Associated With Vascular Phenotype in Children.

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.

Changes in physical activity behavior and development of cardiovascular risk in children.

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 (ß [95% CI] -0.35 [-0.46 to -0.25] kg/m2 per stage, P ≤ .001) and thereby developed wider CRAE (ß [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 (ß [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.

Potassium excretion and blood pressure are associated with heart rate variability in healthy black adults: The African-PREDICT study.

BACKGROUND AND AIMS: Heart rate variability (HRV) is a main determinant of autonomic function and related to the development of hypertension and cardiovascular (CV) disease. Hypertension develops in black populations at an earlier age, which could be due to differences in the autonomic nervous system activity and sodium/potassium handling in black and white populations. We investigated whether HRV is associated with 24 h urinary sodium and potassium excretion and blood pressure (BP) in a young bi-ethnic cohort. METHODS AND RESULTS: We examined 423 black and 483 white healthy adults (aged 24.5 ± 3.1 years) for 24 h HRV, including standard deviation of normal RR intervals (SDNN) reflecting autonomic variations over time, and root mean square of successive differences (RMSSD) reflecting parasympathetic activity. We measured 24 h urinary sodium and potassium concentration and BP. The black group had lower SDNN and potassium excretion as well as higher RMSSD, sodium and Na/k ratio compared to the white group (all p < 0.05). Only in black individuals, urinary potassium excretion was independently and negatively associated with SDNN (ß[95% CI];-0.26[-0.50;-0.02]ms) and RMSSD (-0.14[-0.27;-0.01]ms, p < 0.05). One unit increase in sodium/potassium (Na/K) ratio was associated with higher SDNN (ß[95% CI]; 3.04[0.89; 5.19]ms) and RMSSD (1.60[0.41; 2.78]ms) in the black cohort only (both p < 0.001). In both groups elevated 24 h diastolic BP was associated with lower RMSSD (p < 0.05). CONCLUSION: Lower potassium excretion and higher Na/K ratio related independently to higher HRV in young and healthy black adults. A better ethnic-specific understanding of sodium and potassium handling is required as part of preventive cardiology, especially in black individuals. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03292094; URL: https://clinicaltrials.gov/ct2/show/NCT03292094.

Adiposity and physical activity are related to heart rate variability: the African-PREDICT study.

BACKGROUND: Physical inactivity contributes significantly to the development of obesity-related cardiovascular disease. Adiposity may lead to reduced heart rate variability (HRV), whereas increased physical activity (PA) has the potential to improve autonomic activity. These associations remain largely unexplored in healthy individuals. We therefore investigated whether adiposity and physical activity (PA) are associated with reduced heart rate variability (HRV) in young adults. MATERIALS AND METHODS: We examined 403 black and 461 white healthy adults (aged 20-30 years) for HRV, including standard deviation of normal RR intervals (SDNN) and root mean square of successive differences (RMSSD). We measured adiposity, PA levels and blood pressure (BP). Body mass index (BMI) of ≥ 30 kg/m2 indicated obesity. RESULTS: Participants with obesity had lower mean HRV than normal weight (SDNN [95% CI]; 138 [131-145]s vs 161 [158-165]ms), where those with the highest PA had higher SDNN (164 [160-169]ms) and RMSSD (51 [49-53]ms) than the least active individuals (150 [146-155]s) and 46 [44-48]ms)(all P < .01). BMI, waist circumference and body fat associated with lower SDNN (P < .001). With each unit increase of vigorous PA, a favourable higher RMSSD was found (P < .05). One unit increase in diastolic BP was associated with decreased SDNN and RMSSD (P < .001). These findings remained significant in multivariable-adjusted analyses. CONCLUSIONS: Adiposity and low PA associated independently with depressed autonomic activity in young healthy adults. Sympathovagal imbalance seems to already contribute to elevated diastolic BP at young ages. Our study supports population-based prevention programmes in young adults, improving PA and healthy diet, to curb the development of cardiovascular disease.

Retinal Vessel Diameters and Blood Pressure Progression in Children.

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 (ß [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 (ß [95% CI] -0.154 [-0.294 to -0.014] µm per 1mmHg, P=0.031 and ß [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.

Cardiovascular Risk Markers and Cognitive Performance in Children.

Markers of cardiovascular risk and cognitive performance were assessed in 347 children. In contrast with body mass index and blood pressure, only retinal microcirculation explained a unique proportion of variance in inhibitory control and information processing, when dependencies between markers of cardiovascular risk were accounted for.

Blood Pressure Increase and Microvascular Dysfunction Accelerate Arterial Stiffening in Children: Modulation by Physical Activity.

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 (ß [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 (ß [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 (ß [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.

Association of physical fitness with skin autofluorescence-derived advanced glycation end products 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.

Lung function, obesity and physical fitness in young children: The EXAMIN YOUTH study.

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 ±â€¯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.

Exercise and Arterial Stiffness in the Elderly: A Combined Cross-Sectional and Randomized Controlled Trial (EXAMIN AGE).

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).

Exercise and Arterial Modulation in Children: The EXAMIN YOUTH Study.

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.

Obesity, High Blood Pressure, and Physical Activity Determine Vascular Phenotype in Young Children.

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.