ABSTRACT
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 (ß [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 (ß [95 CI] 0.02 [0.002 to 0.03] au, p = 0.027). Moreover, individuals with higher sAGEs at baseline showed narrower CRAE (ß [95% CI] -5.42 [-8.76 to -2.08] µm, p = 0.001) at follow-up and showed a greater change in CRAE (ß [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
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.
Subject(s)
Cardiovascular Diseases , Hypertension , Child , Humans , Blood Pressure , Cohort Studies , Prospective Studies , Pulse Wave Analysis , Hypertension/diagnosis , Hypertension/epidemiologyABSTRACT
Objectives: Early predictors for back pain need to be identified for the development of prevention strategies starting as early as childhood. For this purpose, the relationship between physical fitness and spinal flexibility at the age of six years and its prediction for the development of non-specific back pain (BP) during childhood were analyzed. Methods: In this prospective cohort study with 4-year follow-up, school children from the Swiss Canton Basel-Stadt, aged 6-8 (2014) at baseline and 10-12 years (2018) at follow-up, were recruited from 26 primary schools (n = 238) within a mandatory evaluation of motor skills. Data for spinal flexibility were collected by use of a hand-held computer-assisted device and physical fitness was assessed by shuttle run performance at both time points. Occurrence of non-specific BP was determined by use of a questionnaire at follow-up. Results: Children with higher physical fitness at baseline achieved a better spinal flexibility four years later (ß [95% CI] 3.75 [2.19-5.3] degree per 1 stage increase, p < 0.001). Higher spinal flexibility by 1 degree at baseline was associated with 2% less odds for non-specific BP at follow-up (OR [95% CI] 0.98 [0.97-0.99] per 1 degree increase, p = 0.032). There was little evidence for a direct association between physical fitness at baseline and development of non-specific BP at follow-up (OR [95% CI] 1.13 [0.96-1.34] per 1 stage increase, p = 0.128). Conclusion: Fitness performance is associated with the development of better childhood spinal flexibility over four years. Moreover, a better spinal flexibility at baseline was associated with less non-specific BP at follow-up. This study suggests that physical fitness may be a key modulator of spinal flexibility which itself is a main determinant of non-specific BP during childhood development. Further long-term studies are warranted to confirm our assumptions and to prove trajectories into adolescents and adulthood.
ABSTRACT
It is important to monitor secular trends in children's motor performance, as healthy and physically active children are more likely to become healthy and physically active adults. However, studies with regular and standardized monitoring of motor performance in childhood are scarce. Additionally, the impact of COVID-19 mitigation measures on secular trends is unknown. This study describes secular changes in balancing backwards, jumping sidewards, 20-m sprint, 20-m Shuttle Run Test (SRT) and anthropometric data in 10'953 Swiss first graders from 2014 to 2021. Multilevel mixed-effects models were used to estimate secular trends for boys vs. girls, lean vs. overweight and fit vs. unfit children. The potential influence of COVID-19 was also analysed. Balance performance decreased (2.8% per year), whereas we found improvements for jumping (1.3% per year) and BMI (-0.7% per year). 20-m SRT performance increased by 0.6% per year in unfit children. Children affected by COVID-19 measures had an increased BMI and were more overweight and obese, but motor performance was mostly higher. In our sample, secular changes in motor performance show promising tendencies from 2014 to 2021. The effects of COVID-19 mitigation measures on BMI, overweight and obesity should be monitored in additional birth cohorts and follow-up studies.
Subject(s)
COVID-19 , Overweight , Male , Adult , Female , Humans , Child , Overweight/epidemiology , Body Mass Index , Switzerland/epidemiology , COVID-19/epidemiology , Obesity , SchoolsABSTRACT
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.
Subject(s)
Hypertension , Pediatric Obesity , Blood Pressure/physiology , Child , Child, Preschool , Ethnicity , Humans , Hypertension/diagnosis , Hypertension/epidemiology , Pediatric Obesity/diagnosis , Pediatric Obesity/epidemiology , Phenotype , Retinal VesselsABSTRACT
BACKGROUND: Endothelial dysfunction represents a diagnostic marker to differentiate disease severity in chronic heart failure (CHF) patients. Retinal vessel phenotyping was applied in CHF patients as it has been acknowledged as a sensitive diagnostic tool to quantify microvascular health and overall cardiovascular risk. METHODS: The central retinal arteriolar (CRAE) and venular diameter equivalents (CRVE) as well as the retinal microvascular function, quantified by arteriolar (aFID) and venular flicker-light induced dilatation (vFID), were analyzed in 26 CHF patients. These data were compared with 26 age- and sex-matched healthy peers. The effects of an exercise intervention on retinal microvascular health in one CHF patient were investigated to demonstrate potentially beneficial effects of exercise treatment in a case report format as proof of concept. RESULTS: CHF patients showed narrower CRAE (170 ± 16 µm vs. 176 ± 16 µm, p = 0.237) and wider CRVE (217 ± 20 µm vs. 210 ± 17 µm, p = 0.152), resulting in a significantly lower arteriolar-to-venular diameter ratio (AVR, 0.79 ± 0.07 vs. 0.84 ± 0.06, p = 0.004) compared to controls. More strikingly, CHF patients showed significantly lower mean aFID (1.24 ± 1.14% vs. 3.78 ± 1.85%, p < 0.001) and vFID (2.89 ± 1.33% vs. 3.88 ± 1.83%, p = 0.033). Twelve weeks of exercise therapy induced wider CRAE (143 ± 1.0 µm vs. 153 ± 0.9 µm), narrower CRVE (183 ± 3.1 µm vs. 180 ± 2.4 µm) and improved aFID (0.67% vs. 1.25%) in a male 78 years old CHF patient. CONCLUSIONS: aFID is a sensitive diagnostic tool to quantify microvascular impairments in CHF patients. Exercise treatment in CHF patients has high potential to improve retinal microvascular health as a marker for vascular regeneration and overall risk reduction, which warrants further examination by randomized controlled trials.
Subject(s)
Heart Failure , Vascular Diseases , Aged , Arterioles , Exercise , Heart Failure/diagnosis , Heart Failure/therapy , Humans , Male , Retinal Vessels , VenulesABSTRACT
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.
Subject(s)
Cardiovascular Diseases , Hypertension , Vascular Stiffness , Adult , Blood Pressure/physiology , Child , Exercise , Humans , Obesity , Pulse Wave AnalysisABSTRACT
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.
Subject(s)
Vascular Stiffness , Child , Cohort Studies , Exercise , Female , Humans , Prospective Studies , Pulse Wave Analysis , Social ClassABSTRACT
Retinal vessel phenotype is predictive for cardiovascular outcome. This cross-sectional population-based study aimed to quantify normative data and standard operating procedures for static and dynamic retinal vessel analysis. We analysed central retinal arteriolar (CRAE) and venular (CRVE) diameter equivalents, as well as retinal endothelial function, measured by flicker light-induced maximal arteriolar (aFID) and venular (vFID) dilatation. Measurements were performed in 277 healthy individuals aged 20 to 82 years of the COmPLETE study. The mean range from the youngest compared to the oldest decade was 196 ± 13 to 166 ± 17 µm for CRAE, 220 ± 15 to 199 ± 16 µm for CRVE, 3.74 ± 2.17 to 3.79 ± 2.43% for aFID and 4.64 ± 1.85 to 3.86 ± 1.56% for vFID. Lower CRAE [estimate (95% CI): - 0.52 (- 0.61 to - 0.43)], CRVE [- 0.33 (- 0.43 to - 0.24)] and vFID [- 0.01 (- 0.26 to - 0.00)], but not aFID, were significantly associated with older age. Interestingly, higher blood pressure was associated with narrower CRAE [- 0.82 (- 1.00 to - 0.63)] but higher aFID [0.05 (0.03 to 0.07)]. Likewise, narrower CRAE were associated with a higher predicted aFID [- 0.02 (- 0.37 to - 0.01)]. We recommend use of defined standardized operating procedures and cardiovascular risk stratification based on normative data to allow for clinical implementation of retinal vessel analysis in a personalized medicine approach.
Subject(s)
Arterioles/diagnostic imaging , Cardiovascular Diseases/diagnosis , Heart Disease Risk Factors , Retinal Vessels/diagnostic imaging , Venules/diagnostic imaging , Adult , Aged , Aged, 80 and over , Aging/pathology , Aging/physiology , Arterioles/pathology , Cardiovascular Diseases/diagnostic imaging , Cardiovascular Diseases/pathology , Female , Humans , Male , Middle Aged , Precision Medicine , Retina/metabolism , Retina/pathology , Retinal Vessels/pathology , Risk Factors , Venules/physiologyABSTRACT
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.
Subject(s)
Life Style , Pulse Wave Analysis , Adolescent , Adult , Child , Humans , Parents , Phenotype , Social Class , Switzerland/epidemiologyABSTRACT
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.
Subject(s)
Body Mass Index , Cardiorespiratory Fitness/physiology , Cardiovascular Diseases/etiology , Exercise/physiology , Retinal Vessels/anatomy & histology , Arterioles/anatomy & histology , Blood Pressure/physiology , Blood Pressure Determination , Cardiovascular Diseases/prevention & control , Child , Female , Follow-Up Studies , Fundus Oculi , Humans , Male , Retinal Vessels/physiology , Risk Factors , Screen Time , Sedentary Behavior , Venules/anatomy & histologyABSTRACT
BACKGROUND AND AIMS: Physical activity (PA) and fitness are important modulators of vascular ageing and may therefore help expand individual health span. We aimed to systematically review the association of PA and fitness, as well as the effects of exercise interventions on the new microvascular biomarkers retinal arteriolar (CRAE) and venular (CRVE) diameters and the retinal flicker light-induced dilatation (FID) in children and adults. METHODS: PubMed, Ovid, The Cochrane, EMBASE and Web of Science were searched. 805 studies were found, and 25 full-text articles analysed. Twenty-one articles were included in this systematic review. RESULTS: Higher PA levels were associated with narrower CRVE in children and adults. Physical inactivity was associated with wider CRVE in both age groups. Combined aerobic and motor skill training in school settings lead to wider CRAE in children. Aerobic exercise interventions in adults with or without CV risk factors induced wider CRAE and narrower CRVE. Studies on the effect of exercise on FID are scarce. In a twelve-week randomized controlled trial, high-intensity interval training significantly improved FID in older patients with CV risk factors. CONCLUSIONS: Higher PA and fitness levels were associated with improved retinal microvascular health in children and adults. Short-term exercise interventions in healthy children and adults, as well as CV risk patients, improved retinal microvascular structure and function. Exercise has the potential to counteract microvascular remodelling and development of small vessel disease during lifespan. Retinal vessel analysis can differentiate the beneficial effects of exercise on target microvascular organ damage.
Subject(s)
Cardiovascular Diseases , Adult , Aged , Biomarkers , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/prevention & control , Child , Exercise , Heart Disease Risk Factors , Humans , Microcirculation , Randomized Controlled Trials as Topic , Retinal Vessels , Risk FactorsABSTRACT
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.
Subject(s)
Blood Pressure/physiology , Cardiorespiratory Fitness/physiology , Retinal Vessels/diagnostic imaging , Child , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , MaleABSTRACT
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.