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Competing Interests: Competing interests: None declared.

Introduction: Arterial hypertension is a global healthcare burden that affects macrovascular and microvascular structure and function and can promote vascular end-organ damage. This study aimed 1) to evaluate differences in microvascular health between normotensive individuals and patients with arterial hypertension and 2) to assess the effects of short-term high-intensity interval training (HIIT) on microvascular health in the subgroup with arterial hypertension as add-on treatment to antihypertensive medication., Methods: In the cross-sectional part, central retinal arteriolar (CRAE) and venular diameter equivalent (CRVE), arteriolar-to-venular diameter ratio (AVR), and retinal oxygen saturation (O 2 -saturation) were investigated in 19 normotensive healthy controls (mean age 56 ± 7 years) and 41 patients with arterial hypertension (mean age 59 ± 7 years). In the subsequent randomized controlled trial (RCT), patients with arterial hypertension were randomized to an intervention group (HIIT 3×/week) or a control group that received standard physical activity recommendations after baseline assessment. Assessments of retinal vessel biomarkers and patients` characteristics were repeated after the intervention period of 8 weeks., Results: In the cross-sectional part, individuals with normal blood pressure (BP) showed lower body mass index (BMI), body fat, 24 h systolic and diastolic BP, higher peak oxygen uptake, wider CRAE (174 ± 17 μm vs. 161 ± 17 μm, p = 0.009), and higher AVR (0.84 ± 0.05 vs. 0.79 ± 0.05, p = 0.003) compared to patients with hypertension. In the RCT, patients with arterial hypertension showed reduced BMI and fasting glucose levels after HIIT and control condition. In addition, the intervention group reduced body fat percentage (27.0 ± 5.5 vs. 25.8 ± 6.1, p = 0.023) and increased peak oxygen uptake (33.3 ± 5.7 vs. 36.7 ± 5.1, p < 0.001). No changes in BP were found in either group. The intervention group showed narrower CRVE (β -4.8 [95 % CI, -8.85, -0.81] p = 0.020) and higher AVR (0.03 [0.01, 0.04] p < 0.001) after eight weeks of HIIT compared to the control group. No statistically significant changes in retinal O 2 -saturation were found in either group., Conclusion: Short-term HIIT proved to be an effective treatment to ameliorate hypertension-induced retinal microvascular abnormalities in patients with hypertension. Retinal vessel diameters may prove to be a sensitive biomarker to quantify treatment efficacy at the microvascular level, at the earliest possible stage in patients with hypertension., Competing Interests: Declaration of competing interest The authors have declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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 (β [95% CI] 0.6 [0.072 to 1.164] mmHg per 10 μm decrease, p = 0.026 and β [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 (β [95% CI] -3.3 [-4.43 to -2.09] μm per 10 mmHg increase, p < 0.001 and β [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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: High blood pressure is one of the main cardiovascular disease risk factors that contribute to vascular remodeling and dysfunction. We aimed to investigate I) group differences of the retinal microstructure between patients with hypertension and healthy individuals and II) the effects of a high-intensity interval training (HIIT) on hypertension-induced microvascular remodeling in patients with hypertension in a randomized controlled trial., Methods: Arteriolar and venular retinal vessel microstructure including retinal vessel wall (RVW), lumen diameter and wall-to-lumen ratio (WLR) of 41 hypertensive patients, treated with anti-hypertensive medication, and 19 normotensive healthy controls were screened based on high-resolution fundoscopies. Patients with hypertension were randomized to a control group receiving standard physical activity recommendations and an intervention group receiving a supervised and walking-based HIIT for eight weeks. Measurements were repeated after the intervention period., Results: Hypertensive patients showed thicker arteriolar RVW (28.0 ± 7.7mu vs. 21.4 ± 4.4mu, p = 0.003) and higher arteriolar WLR (58.5 ± 14.8 % vs. 42.5 ± 8.2 %, p < 0.001) compared to normotensive controls. The intervention group showed reductions in arteriolar RVW (β -3.1 (95 % CI, -4.38, -1.78) p < 0.001) and arteriolar WLR (-5.3 (-10.14, -0.39) p = 0.035) compared to the control group. The intervention effects were independent of age, sex, change in blood pressure and change in cardiorespiratory fitness., Conclusions: HIIT in patients with hypertension improves retinal vessel microvascular remodeling after eight weeks of training. In patients with hypertension, screening retinal vessel microstructure by fundoscopy and monitoring efficacy of short-term exercise treatment are sensitive diagnostic approaches to quantify microvascular health in these patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Arterial hypertension is a global health burden that affects vascular structure and function. Assessment of endothelial function can improve cardiovascular (CV) risk stratification. Exercise treatment reduces over all CV risk and improves vascular health. However, it is still not clear which part of the vascular bed is most sensitive to exercise treatment in patients with CV risk. This study aimed to investigate the effects of an 8-week walking based and supervised high-intensity interval training (HIIT) on macro- and microvascular endothelial function as add-on therapy in patients with arterial hypertension., Methods: Forty patients (mean age 58 ± 7 years) treated for arterial hypertension were randomized in the HIIT (3×/week) or control group (CG) receiving standard physical activity recommendations. Arteriolar (aFID) and venular (vFID) flicker light-induced dilatation for retinal microvascular and flow-mediated dilatation (FMD) for macrovascular endothelial function were assessed. In addition, standardized assessments of patients' characteristics were performed before and after 8 weeks., Results: Both groups reduced weight and body mass index but only the HIIT group reduced body fat, visceral fat, and increased peak oxygen uptake after 8 weeks. The control group reduced diastolic blood pressure. No blood pressure changes were found in the HIIT group. Arteriolar FID increased in the HIIT group independently of confounders (pre: 2.40 ± 0.98%, post: 3.19 ± 1.31%, p < 0.001) but not in the control group (pre: 3.06 ± 1.50%, post: 2.90 ± 1.46%, p = 0.280). No changes were found for FMD in either group., Conclusion: Arteriolar FID was found to be a sensitive vascular biomarker to assess exercise-induced microvascular improvements even in a short time setting of an 8-week exercise therapy with HIIT. Short-term exercise training affects microvascular endothelial function but not large artery endothelial function. Thus, retinal aFID appears to be a sensitive biomarker to detect short-term exercise efficacy on a vascular level. Dynamic retinal vessel analysis as a diagnostic approach may prove to be an ideal candidate vascular biomarker to monitor treatment effects of exercise in patients with hypertension on top of standard clinical care and may support clinical decision-making in the future., (© 2023 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Introduction: Higher blood pressure levels are associated with vascular dysfunction as early as childhood. Here, we aim to compare two blood pressure devices for use in childhood populations within a school setting to screen for elevated blood pressure in children., Methods: Systolic and diastolic blood pressure, mean arteriolar pressure (MAP) as well as heart rate (HR) were measured with the validated Oscillomate 9002 and Mindray VS-900 in 82 randomly selected children between 10 and 12 years taking part in the EXAMIN YOUTH study in 2020. Measurements were performed after 5 min at rest in a sitting position in the school environment., Results: Both devices showed strong correlations for systolic (r = 0.62, t[80] = 7, p < 0.001) and diastolic blood pressure (r = 0.73, t[80] = 9.52, p < 0.001), MAP (r = 0.75, t[80] = 10.22, p < 0.001) and HR (r = 0.89, t[79] = 17.77, p < 0.001). There was no evidence for a statistically significant difference of both devices for systolic (110 ± 9 mmHg vs. 111 ± 9 mmHg, p = 0.574), diastolic blood pressure (67 ± 9 mmHg vs. 66 ± 9 mmHg, p = 0.301) as well as MAP (81 ± 8 mmHg vs. 80 ± 8 mmHg, p = 0.400) and HR (83 ± 12 BPM vs. 83 ± 11 BPM, p = 0.994)., Discussion: Both devices, the older Oscillomate 9002 and the current Mindray VS-900 showed good agreement for the measurement of blood pressure in school children. It therefore appears to be feasible to measure childhood blood pressure with either device or replace one device with another in prospective long-term studies or screening programmes as long as both are validated for use in children., (© 2022 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Rationale: Premature birth is an independent predictor of long-term cardiovascular risk. Individuals affected are reported to have a lower rate of [Formula: see text]o 2 at peak exercise intensity ([Formula: see text]o 2PEAK ) and at the ventilatory anaerobic threshold ([Formula: see text]o 2VAT ), but little is known about their response to exercise training. Objectives: The primary objective was to determine whether the [Formula: see text]o 2PEAK response to exercise training differed between preterm-born and term-born individuals; the secondary objective was to quantify group differences in [Formula: see text]o 2VAT response. Methods: Fifty-two preterm-born and 151 term-born participants were randomly assigned (1:1) to 16 weeks of aerobic exercise training ( n  = 102) or a control group ( n  = 101). Cardiopulmonary exercise tests were conducted before and after the intervention to measure [Formula: see text]o 2PEAK and the [Formula: see text]o 2VAT . A prespecified subgroup analysis was conducted by fitting an interaction term for preterm and term birth histories and exercise group allocation. Measurements and Main Results: For term-born participants, [Formula: see text]o 2PEAK increased by 3.1 ml/kg/min (95% confidence interval [CI], 1.7 to 4.4), and the [Formula: see text]o 2VAT increased by 2.3 ml/kg/min (95% CI, 0.7 to 3.8) in the intervention group versus controls. For preterm-born participants, [Formula: see text]o 2PEAK increased by 1.8 ml/kg/min (95% CI, -0.4 to 3.9), and the [Formula: see text]o 2VAT increased by 4.6 ml/kg/min (95% CI, 2.1 to 7.0) in the intervention group versus controls. No significant interaction was observed with birth history for [Formula: see text]o 2PEAK ( P  = 0.32) or the [Formula: see text]o 2VAT ( P  = 0.12). Conclusions: The training intervention led to significant improvements in [Formula: see text]o 2PEAK and [Formula: see text]o 2VAT , with no evidence of a statistically different response based on birth history. Clinical trial registered with www.clinicaltrials.gov (NCT02723552).

Definition and management of arterial hypertension in children and adolescents are uncertain, due to different positions of current guidelines. The European Society of Cardiology task-force, constituted by Associations and Councils with interest in arterial hypertension, has reviewed current literature and evidence, to produce a Consensus Document focused on aspects of hypertension in the age range of 6-16 years, including definition, methods of measurement of blood pressure, clinical evaluation, assessment of hypertension-mediated target organ damage, evaluation of possible vascular, renal and hormonal causes, assessment and management of concomitant risk factors with specific attention for obesity, and anti-hypertensive strategies, especially focused on life-style modifications. The Consensus Panel also suggests aspects that should be studied with high priority, including generation of multi-ethnic sex, age and height specific European normative tables, implementation of randomized clinical trials on different diagnostic and therapeutic aspects, and long-term cohort studies to link with adult cardiovascular risk. Finally, suggestions for the successful implementation of the contents of the present Consensus document are also given., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Hypertension is a global healthcare burden that affects the structure and function of the macrocirculation and microcirculation and induces disease-specific end-organ damage. Vascular biomarkers are essential to timely diagnose this end-organ damage to improve cardiovascular (CV) risk stratification and medical decision making. Exercise therapy is an effective means to improve vascular health and reduce overall CV risk. However, it is still not clear whether high-intensity interval training (HIIT) is recommendable for patients with hypertension to reduce blood pressure, increase cardiorespiratory fitness and ameliorate vascular health., Methods and Analysis: The 'Hypertension and retinal microvascular dysfunction' trial will investigate macrovascular and microvascular impairments in hypertensive patients compared with healthy controls to investigate hypertension-induced end-organ damage by using gold-standard methods as well as newly developed unique retinal microvascular biomarkers. In addition, this trial will investigate the reversibility of retinal end-organ damage by assessing the effects of an 8-week supervised and walking based HIIT on blood pressure, cardiorespiratory fitness as well as macrovascular and microvascular health, compared with a control group following standard physical activity recommendations. Primary outcome will be the arteriolar-to-venular diameter ratio. Secondary outcomes will be arteriolar and venular diameters as well as the flicker-light-induced dilation. Further outcomes will be other retinal microvascular biomarkers, flow-mediated dilation of the brachial artery as well as blood pressure, cardiorespiratory fitness, microalbuminuria, hypertensive retinopathy and classical CV risk markers. Analysis of variance and analysis of covariance will be used to investigate group differences between healthy controls and hypertensive patients and training effects in hypertensive patients, respectively., Ethics and Dissemination: The Ethics Committee of Northwestern and Central Switzerland approved this study (EKNZ-2021-00086). All participants will give informed consent., Trial Registration Number: NCT04763005., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 (β = -0.199 μm, p = 0.001) and DBP (β = -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., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: New-onset hypertension affects approximately 10% of pregnancies and is associated with a significant increase in risk of cardiovascular disease in later life, with blood pressure measured 6 weeks postpartum predictive of blood pressure 5-10 years later. A pilot trial has demonstrated that improved blood pressure control, achevied via self-management during the puerperium, was associated with lower blood pressure 3-4 years postpartum. Physician Optimised Post-partum Hypertension Treatment (POP-HT) will formally evaluate whether improved blood pressure control in the puerperium results in lower blood pressure at 6 months post partum, and improvements in cardiovascular and cerebrovascular phenotypes., Methods and Analysis: POP-HT is an open-label, parallel arm, randomised controlled trial involving 200 women aged 18 years or over, with a diagnosis of pre-eclampsia or gestational hypertension, and requiring antihypertensive medication at discharge. Women are recruited by open recruitment and direct invitation around time of delivery and randomised 1:1 to, either an intervention comprising physician-optimised self-management of postpartum blood pressure or, usual care. Women in the intervention group upload blood pressure readings to a 'smartphone' app that provides algorithm-driven individualised medication-titration. Medication changes are approved by physicians, who review blood pressure readings remotely. Women in the control arm follow assessment and medication adjustment by their usual healthcare team. The primary outcome is 24-hour average ambulatory diastolic blood pressure at 6-9 months post partum. Secondary outcomes include: additional blood pressure parameters at baseline, week 1 and week 6; multimodal cardiovascular assessments (CMR and echocardiography); parameters derived from multiorgan MRI including brain and kidneys; peripheral macrovascular and microvascular measures; angiogenic profile measures taken from blood samples and levels of endothelial circulating and cellular biomarkers; and objective physical activity monitoring and exercise assessment. An additional 20 women will be recruited after a normotensive pregnancy as a comparator group for endothelial cellular biomarkers., Ethics and Dissemination: IRAS PROJECT ID 273353. This trial has received a favourable opinion from the London-Surrey Research Ethics Committee and HRA (REC Reference 19/LO/1901). The investigator will ensure that this trial is conducted in accordance with the principles of the Declaration of Helsinki and follow good clinical practice guidelines. The investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and any other publications arising from the study. Authors will acknowledge that the study was funded by the British Heart Foundation Clinical Research Training Fellowship (BHF Grant number FS/19/7/34148). Authorship will be determined in accordance with the ICMJE guidelines and other contributors will be acknowledged., Trial Registration Number: NCT04273854., Competing Interests: Competing interests: LM is supported by the NIHR Oxford Biomedical Research Centre and is a part-time employee of Sensyne Health PLC and holds shares in this company. RJM has received BP monitors for research from Omron and is working with them to develop a telemonitoring system. Any fees/consultancy from this work are paid to his institution., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Treatment of hypertension and its complications remains a major ongoing health care challenge. Around 25% of heart attacks in Europe are already attributed to hypertension and by 2025 up to 60% of the population will have hypertension. Physical inactivity has contributed to the rising prevalence of hypertension, but patients who exercise or engage in physical activity reduce their risk of stroke, myocardial infarction, and cardiovascular mortality. Hence, current international guidelines on cardiovascular disease prevention provide generic advice to increase aerobic activity, but physiological responses differ with blood pressure (BP) level, and greater reductions in BP across a population may be achievable with more personalized advice. We performed a systematic review of meta-analyses to determine whether there was sufficient evidence for a scientific Consensus Document reporting how exercise prescription could be personalized for BP control. The document discusses the findings of 34 meta-analyses on BP-lowering effects of aerobic endurance training, dynamic resistance training as well as isometric resistance training in patients with hypertension, high-normal, and individuals with normal BP. As a main finding, there was sufficient evidence from the meta-review, based on the estimated range of exercise-induced BP reduction, the number of randomized controlled trials, and the quality score, to propose that type of exercise can be prescribed according to initial BP level, although considerable research gaps remain. Therefore, this evidence-based Consensus Document proposes further work to encourage and develop more frequent use of personalized exercise prescription to optimize lifestyle interventions for the prevention and treatment of hypertension., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

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., (© 2020. International Pediatric Research Foundation, Inc.)

Objectives and Methods: Hypertension is a growing health concern in childhood populations and individuals of African descent. As the kidneys play a significant role in blood pressure regulation, we compared alpha-1 microglobulin (A1M) as a marker of proximal tubular function between young healthy black and white children (n = 957; aged: 5-9 years) and explored its association with blood pressure., Results: The black children had higher levels of A1M (P < 0.001) and higher DBP (P < 0.001) when compared with their white counterparts. In multiple regression analysis, SBP (adj. R2 = 0.173, β = 0.151; P < 0.001) and DBP (adj. R2 = 0.110, β = 0.179; P < 0.001) associated positively with A1M in the black children. In binary logistic regression, each standard deviation increase in A1M increased the odds of having elevated blood pressure by 28% (P = 0.002) in the black group, independent of age, sex, BMI z-score and body height. No significance was reached in the white children., Conclusion: Our findings highlight the importance of a marker of proximal tubular function, especially in children of black ethnicity, in the setting of elevated blood pressure. Early childhood screening for elevated blood pressure remains essential in order to promote primary prevention of hypertension and early onset kidney damage in children., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Obesity and hypertension prevalence among children are a concern, with limited evidence available on sex and ethnic differences in childhood blood pressure. We aimed to determine the number of children with hypertension and obesity to identify unique adiposity and blood pressure characteristics by sex and ethnicity, and to estimate the odds of having elevated blood pressure with increasing adiposity., Methods: We included 1062 healthy children (5-9 years of age) in an observational school-based study in South Africa. Pediatric validated automated devices were used to measure brachial blood pressure and performed pulse wave analysis to assess central hemodynamics. Standard anthropometry was carried out to determine body composition and demographic questionnaires were completed., Results: Almost 20% of children were overweight/obese and 14.1% had elevated blood pressure or hypertension (22.8%). Ethnic differences included greater adiposity in white compared with black children (all P < 0.0001), but higher DBP and total vascular resistance in black compared with white children (both P < 0.05). DBP and total vascular resistance were also higher in girls than boys (both P < 0.01). A 51-60% increased risk of developing elevated blood pressure was observed for 1SD (standard deviation) increase of sex-specific BMI [1.60 (1.4-1.8); P < 0.0001] and waist/height ratio [1.51 (1.3-1.7); P < 0.0001]., Conclusion: Unique sex and ethnic differences in body composition and blood pressure exist in prepubescent children, with overweight/obesity increasing the risk of elevated blood pressure. Our findings support primary prevention strategies to combat the growing burden of hypertension and obesity-related diseases in youth., Trial Registration: The study is registered on ClinicalTrials.gov (NCT04056377)., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To compare measurement of wall-to-lumen ratio (WLR) by means of high-resolution adaptive optics imaging (AO) with intuitive to use retinal vessel wall (VW) analysis (VWA). Moreover, to validate the techniques by comparing WLR of healthy young (HY) with healthy older patients., Methods: Ten retinal VW images of 13 HY (24 ± 2 years) and 16 healthy older (60 ± 8 years) were obtained with AO and VWA. The average of five measurements of VW, retinal vessel lumen and WLR of a single vessel from AO and VWA were calculated and compared., Results: WLR of AO and VWA images showed high correlations, r = 0.75, t(27) = 5.98, P < .001, but differed systematically (WLR: VWA, 40 ± 7% and AO, 35 ± 9%; P < .001). Comparable patterns were found for VW and vessel lumen. HY showed significantly lower WLR (AO, 31 ± 8% and VWA, 36 ± 8%) compared with healthy older (AO, 39 ± 9% [ P = .012]; VWA, 42 ± 5% [ P = .013])., Conclusions: Assessment of WLR by VWA showed a good correlation with laborious analysis of the microstructure by high-resolution AO. Measurement of WLR in different age groups indicated good validity. Deviations in VW, vessel lumen, and WLR between AO and VWA can be explained by systematic differences in image scale and resolution. Future studies are needed to investigate the clinical relevance of microvascular WLR assessment by retinal VWA and its prognostic value., Translational Relevance: Additional assessment of retinal WLR by use of digital VWA to evaluate microstructural remodeling may prove to be a valuable extension to the current use of retinal vessel diameters as biomarkers of cardiovascular risk., Competing Interests: Disclosure: L. Streese, None; L.Y. Brawand, None; K. Gugleta, None; P.M. Maloca, None; W. Vilser, Imedos Systems GmbH (I); H. Hanssen, None, (Copyright 2020 The Authors.)

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.

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.

Background: Hypertension prevalence in young adults has increased and is associated with increased incidence of cerebrovascular and cardiovascular events in middle age. However, there is significant debate regards how to effectively manage young adult hypertension with recommendation to target lifestyle intervention. Surprisingly, no trials have investigated whether lifestyle advice developed for blood pressure control in older adults is effective in these younger populations., Methods/design: TEPHRA is an open label, parallel arm, randomised controlled trial in young adults with high normal and elevated blood pressure. The study will compare a supervised physical activity intervention consisting of 16 weeks structured exercise, physical activity self-monitoring and motivational coaching with a control group receiving usual care/minimal intervention. Two hundred young adults aged 18-35 years, including a subgroup of preterm born participants will be recruited through open recruitment and direct invitation. Participants will be randomised in a ratio of 1:1 to either the exercise intervention group or control group. Primary outcome will be ambulatory blood pressure monitoring at 16 weeks with measure of sustained effect at 12 months. Study measures include multimodal cardiovascular assessments; peripheral vascular measures, blood sampling, microvascular assessment, echocardiography, objective physical activity monitoring and a subgroup will complete multi-organ magnetic resonance imaging., Discussion: The results of this trial will deliver a novel, randomised control trial that reports the effect of physical activity intervention on blood pressure integrated with detailed cardiovascular phenotyping in young adults. The results will support the development of future research and expand the evidence-based management of blood pressure in young adult populations., Trial Registration: Clinicaltrials.gov registration number NCT02723552 , registered on 30 March, 2016.

Context: Retinal vessel imaging is a noninvasive diagnostic tool used to evaluate cardiovascular risk. Childhood obesity and elevated blood pressure (BP) are associated with retinal microvascular alterations., Objective: To systematically review and meta-analyze associations between obesity, BP, and physical activity with retinal vessel diameters in children., Data Sources: We conducted a literature search through the databases of PubMed, Embase, Ovid, Web of Science, and the Cochrane Register of Controlled Trials., Study Selection: School- and population-based cross-sectional data., Data Extraction: General information, study design, participants, exposure, and outcomes., Results: A total of 1751 studies were found, and 30 full-text articles were analyzed for eligibility. Twenty-two articles (18 865 children and adolescents) were used for further assessment and reflection. Eleven articles were finally included in the meta-analysis. We found that a higher BMI is associated with narrower retinal arteriolar (pooled estimate effect size -0.37 [95% confidence interval (CI): -0.50 to -0.24]) and wider venular diameters (0.35 [95% CI: 0.07 to 0.63]). Systolic and diastolic BP are associated with retinal arteriolar narrowing (systolic BP: -0.63 [95% CI: -0.92 to -0.34]; diastolic BP: -0.60 [95% CI -0.95 to -0.25]). Increased physical activity and fitness are associated with favorable retinal vessel diameters., Limitations: Long-term studies are needed to substantiate the prognostic relevance of retinal vessel diameters for cardiovascular risk in children., Conclusions: Our results indicate that childhood obesity, BP, and physical inactivity are associated with retinal microvascular abnormalities. Retinal vessel diameters seem to be sensitive microvascular biomarkers for cardiovascular risk stratification in children., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Exercise training has different effects on arterial stiffness according to training modalities. The optimal exercise modality for improvement of arterial function in normotensive and hypertensive individuals has not been well established. In this review, we aim to evaluate the effects of aerobic, resistance and combined aerobic and resistance training on arterial stiffness in individuals with and without hypertension. We systematically searched the Pubmed and Web of Science database from 1985 until December 2013 for relevant randomised controlled trials (RCTs). The data were extracted by one investigator and checked by a second investigator. The training effects on arterial stiffness were estimated using weighted mean differences of the relative changes (%) with 95% confidence intervals (CIs). We finally reviewed the results from 17 RCTs. The available evidence indicates that aerobic exercise tends to have a beneficial effect on arterial stiffness in normotensive and hypertensive patients, but does not affect arterial stiffness in patients with isolated systolic hypertension. Resistance exercise has differing effects on arterial stiffness depending on type and intensity. Vigorous resistance training is associated with an increase in arterial stiffness. There seem to be no unfavourable effects on arterial stiffness if the training is of low intensity, in a slow eccentric manner or with lower limb in healthy individuals. Combined training has neutral or even a beneficial effect on arterial stiffness. In conclusion, our review shows that exercise training has varying effects on arterial stiffness depending on the exercise modalities.

Objective: Hypertension is characterized by microvascular remodeling resulting in increased wall/lumen ratio and elevated microvascular stiffness. Aiming to transform the measurement of macrovascular stiffness into a microvascular environment we introduce a noninvasive method to assess rPWV. rPWV alterations in early hypertension are investigated in detail. The developed methodology is compared with its possible computational alternatives., Methods: Time dependent alterations of retinal arterial diameter were assessed noninvasively by the DVA in 65 male normoalbuminuric normotensive to mildly hypertensive subjects (age: 28.7 ± 6.0 years). rPWV was computed using three different methods. "Method 1" used filtration at HR, "Method 2" filtered at higher HR multiples, and "Method 3" used in addition, linear fit for data averaging., Results: "Method 2" and "Method 3" applying filtration at high HR multiples showed strong associations with systolic BP throughout the cohort (r = 0.49, r = 0.63, p < 0.001). Based on the highest association, "Method 3" was proposed to characterize rPWV. Hypertensive patients showed higher rPWV (1243 ± 694 RU/sec) than subjects with high-normal BP (786 ± 486 RU/sec, p < 0.01) or normotensive subjects (442 ± 148 RU/sec, p < 0.001)., Conclusions: rPWV demonstrated a strong association with BP and can discriminate between optimal, high-normal, and mildly hypertensive BP values. rPWV may add detailed insights into early microvascular pathophysiology, potentially beyond microalbuminuria., (© 2013 John Wiley & Sons Ltd.)

Purpose: It was demonstrated previously that retinal pulse wave velocity (rPWV) as a measure of retinal arterial stiffness is increased in aged anamnestically healthy volunteers compared with young healthy subjects. Using novel methodology of rPWV assessment this finding was confirmed and investigated whether it might relate to the increased blood pressure usually accompanying the aging process, rather than to the aging itself., Methods: A total of 12 young 25.5-year-old (24.0-28.8) [median(1st quartile-3rd quartile)] and 12 senior 68.5-year-old (63.8-71.8) anamnestically healthy volunteers; and 12 senior 63.0-year-old (60.8-65.0) validated healthy volunteers and 12 young 33.0-year-old (29.5-35.0) hypertensive patients were examined. Time-dependent alterations of vessel diameter were assessed by the Dynamic Vessel Analyzer in a retinal artery of each subject. The data were filtered and processed using mathematical signal analysis and rPWVs were calculated., Results: rPWV amounted to 1200 (990-1470) RU (relative units)/s in the hypertensive group and to 1040 (700-2230) RU/s in anamnestically healthy seniors. These differed significantly from rPWVs in young healthy group (410 [280-500] RU/s) and in validated healthy seniors (400 [320-510] RU/s). rPWV associated with age and mean arterial pressure (MAP) in the pooled cohort excluded validated healthy seniors. In a regression model these associations remain when alternately adjusted for MAP and age. When including validated healthy seniors in the pooled cohort only association with MAP remains., Conclusions: Both aging (with not excluded cardiovascular risk factors) and mild hypertension are associated with elevated rPWV. rPWV increases to a similar extent both in young mildly hypertensive subjects and in aged anamnestically healthy persons. Healthy aging is not associated with increased rPWV.