Normative data and standard operating procedures for static and dynamic retinal vessel analysis as biomarker for cardiovascular risk

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

Prospective association of body mass index, blood pressure and physical activity with vascular health in children: The Sportcheck Follow-up Study

Background: Cardiovascular disease is the leading cause of mortality worldwide. Cardiovascular risk factors, such as obesity and hypertension often manifest in childhood. Both of these cardio-vascular risk factors track into adulthood and are independent predictors for cardiovascular disease events later in life. To date there are no prospective studies on the association of microvascular health with the development of blood pressure in children. Furthermore the association of changes in physical activity behavior on microvascular and macrovascular health in childhood are poorly understood. Aims: The aims of my PhD project were four-fold: 1) to analyze the association of retinal arteriolar diameters at baseline with blood pressure development over 4 years. 2) to analyze the as-sociation of changes in physical activity and fitness with development of body mass index (BMI), blood pressure and retinal vessel diameters over 4 years. 3) to systematically sum-marize and meta-analyze the association of BMI, blood pressure, physical activity and fit-ness with large artery pulse wave velocity (PWV). 4) to analyze the association of changes in BMI, blood pressure, physical activity and fitness as well as retinal vessel diameters with large artery PWV as outcome after 4 years of follow-up. Methods: My PhD is based on the Sportcheck Follow-up study. This prospective school-based cohort study included 262 prepubertal children, who were screened for the above mentioned CV risk factors and retinal vessel diameters at baseline (aged 6-8 years) and at follow-up (aged 10-12 years) using standardized protocols. PWV was measured by an oscillometric device and implemented at follow-up. Cardiorespiratory fitness was objectively assessed by a 20m shuttle run and physical activity was assessed by use of questionnaires. To achieve my third aim, a systematic literature search through the databases PubMed, Web of Science, Embase and the Cochrane Register of Controlled Trials was conducted. Only school and population-related cross-sectional data were included. Results: Our results demonstrated that children with narrower arteriolar vessel diameters at baseline developed a higher systolic blood pressure at follow-up. Elevated blood pressure at base-line was related to narrower arteriolar vessel diameters at follow-up. Children, who achieved a higher cardiorespiratory fitness level over the 4 years reduced their weight and subsequently developed wider arteriolar vessel diameters at follow-up. An increase in sed-entary behavior from baseline to follow-up was associated with narrower arteriolar vessel diameters in children with elevated or high systolic blood pressure at baseline. The results of the meta-analysis showed that a higher BMI and blood pressure is associated with high-er PWV in children. On the other hand a higher cardiorespiratory fitness level was inversely related to PWV. Furthermore increased blood pressure and narrower arteriolar vessel di-ameters over 4 years were related to higher PWV at follow-up. In contrast, children with increased vigorous physical activity from baseline to follow-up had a lower PWV at follow-up. Conclusions: Arteriolar narrowing was predictive for accelerated blood pressure progression. In turn, a higher initial blood pressure was associated with subsequent development of microvascular impairments. The findings postulate a bivariate temporal relationship between microvascu-lar health and blood pressure. Children, who achieved an increased cardiorespiratory fit-ness performance, reduced weight and improved microvascular phenotype. A reduction in sedentary behavior by even 10 min a day can ameliorate microvascular health in children with increased systolic blood pressure. The results from the meta-analysis suggest that a higher childhood BMI and blood pressure are related to impaired arterial stiffness, whereas higher cardiorespiratory fitness performance is associated with favorable arterial stiffness. Additionally increased vigorous physical activity over 4 years seems to decelerate the pro-cess of arterial stiffness in childhood. Based on our findings, we suggest that the assess-ment of vascular biomarkers from different vascular beds can optimize cardiovascular risk stratification. Our findings also highlight the potential of promoting physical activity and fit-ness, especially in children with increased cardiovascular risk to prevent the development of small and large vessel disease

Impact of Covid-19 pandemic on the secular trends in motor performance, overweight and obesity of first graders in Basel

Introduction The development of appropriate motor skills early in life enhances the likelihood of lifelong physical activity (Hulteen et al., 2018). Furthermore, good fitness has direct health implications for child and youth development (Ortega et al., 2008). Physical fitness and the development of motor performance may be influenced by various factors like the Covid-19 pandemic as current example over the last two years. The pandemic affected children’s life, particularly regarding the reduced ability to attend structured leisure time sports activities. This study aims to describe the impact of the Covid-19 pandemic on secular trends in motor performance and body composition in first graders in the city of Basel. Methods In the city of Basel, Switzerland, all first graders were tested yearly since 2014 with four motor performance parameters and anthropometrics: 20-meter shuttle run, 20-meter sprint, jumping sidewards, balancing backward, body weight and height. Children are categorized as overweight when they are above 90. Percentile for their age and sex in BMI and as obese when above 97. Percentile. Linear regression for motor performance parameters and logistic regression for weight status was used to predict 2021 and 2022 performance parameters based on data from 2014 to 2020. These predictions were compared to the performance achieved in 2021 and 2022. Results Four thousand six-hundred sixty-two children were tested from 2014 to 2020, 728 in 2021, and 708 in 2022. The cohorts in 2021 and 2022 outperformed the predicted values by 6.1% [95 % CI: 1.8; 10.4] and 5.5% [1.0; 10.1] for shuttle run, 0.2% [-0.6; 1.0] and 3.5% [2.7; 4.4] for 20-meter sprint, 6.4% [3.7; 9.2] and 2.7% [-0.2; 5.5] for jumping sidewards and 4.0% [-0.5; 8.4] and 17.3% [12.1; 22.5] for balancing backward. The proportion of overweight children in 2021 (16.4%) and 2022 (15.5%) was 47.4% [31.4; 63.3] and 62.2% [26.4; 98.1] higher than predicted. The percentage of obese children deviated strongly by 55.9% [33.9; 77.9] and 61.8% [14.1; 113.0] from predicted values. Boys were more affected by the impact of Covid-19 showing a 70.4% [38.5; 102.3] and 79.4% [14.0; 145.9] higher proportion of obesity than expected from secular trends for both cohorts compared to girls (34.8% [-1.0; 70.6] and 34.5% [-42.8; 111.7]). Conclusion Although more children were classified as overweight and obese than expected, the children performed better in all motor performance parameters. Preserving the possibility for unstructured activities and outdoor play at all times during the Covid-19 restrictions is a potential reason that the pandemic situation did not limit motor development. Nevertheless, the increased number of overweight and obese children is alarming. Potential reasons like changes in eating behaviour or mental health due to the pandemic situation remain speculative. However, public health interventions for these cohorts focusing on healthy body composition are strongly recommended. References Hulteen, R. M., Morgan, P. J., Barnett, L. M., Stotten, D. F., & Lubans, D. E. (2018). Development of foundational movement skills: A conceptual model for physical activity across the lifespan. Sports Medicine, 48(7), 1533–1540. https://doi.org/10.1007/s40279-018-0892-6 Ortega, F. B., Ruiz, J. R., Castillo, M. J., & Sjöström, M. (2008). Physical fitness in childhood and adolescence: A powerful marker of health. International Journal of Obesity, 32(1), 1–11. https://doi.org/10.1038/sj.ijo.080377

Physical activity and exercise improve retinal microvascular health as a biomarker of cardiovascular risk: A systematic review

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.; 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.; 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.; 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

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

Microvascular endothelial dysfunction in heart failure patients: An indication for exercise treatment?

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.; 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.; 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.; 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