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      Relationship of Circulating Endothelial Cells With Obesity and Cardiometabolic Risk Factors in Children and Adolescents

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          Abstract

          Background

          Circulating endothelial cells (CECs) reflect early changes in endothelial health; however, the degree to which CEC number and activation is related to adiposity and cardiovascular risk factors in youth is not well described.

          Methods and Results

          Youth in this study (N=271; aged 8–20 years) were classified into normal weight (body mass index [BMI] percentage <85th; n=114), obesity (BMI percentage ≥95th to <120% of the 95th; n=63), and severe obesity (BMI percentage ≥120% of the 95th; n=94) catagories. CEC enumeration was determined using immunohistochemical examination of buffy coat smears and activated CEC (percentage of vascular cell adhesion molecule‐1 expression) was assessed using immunofluorescent staining. Cardiovascular risk factors included measures of body composition, blood pressure, glucose, insulin, lipid profile, C‐reactive protein, leptin, adiponectin, oxidized low‐density lipoprotein cholesterol, carotid artery intima–media thickness, and pulse wave velocity. Linear regression models examined associations between CEC number and activation with BMI and cardiovascular risk factors. CEC number did not differ among BMI classes ( P>0.05). Youth with severe obesity had a higher degree of CEC activation compared with normal weight youth (8.3%; 95% CI, 1.1–15.6 [ P=0.024]). Higher CEC number was associated with greater body fat percentage (0.02 per percentage; 95% CI, 0.00–0.03 [ P=0.020]) and systolic blood pressure percentile (0.01 per percentage; 95% CI, 0.00–0.01 [ P=0.035]). Higher degree of CEC activation was associated with greater visceral adipose tissue (5.7% per kg; 95% CI, 0.4–10.9 [ P=0.034]) and non–high‐density lipoprotein cholesterol (0.11% per mg/dL; 95% CI, 0.01–0.21 [ P=0.039]).

          Conclusions

          Methods of CEC quantification are associated with adiposity and cardiometabolic risk factors and may potentially reflect accelerated atherosclerosis as early as childhood.

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          Most cited references43

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          Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.

          Endothelial dysfunction is an early event in experimental studies of atherogenesis, preceding formation of plaques. We have devised a non-invasive method for testing endothelial function, to find out whether abnormalities are present in symptom-free children and young adults at high risk of atherosclerosis. With high-resolution ultrasound, we measured the diameter of the superficial femoral and brachial arteries at rest, during reactive hyperaemia (with increased flow causing endothelium-dependent dilatation), and after sublingual glyceryl trinitrate (GTN; causing endothelium-independent dilatation) in 100 subjects--50 controls without vascular risk factors (aged 8-57 years), 20 cigarette smokers (aged 17-62 years), 10 children with familial hypercholesterolaemia (FH; aged 8-16 years), and 20 patients with established coronary artery disease (CAD). Adequate scans were obtained in all but 6 cases. Flow-mediated dilatation was observed in arteries from all control subjects. Dilatation was inversely related to baseline vessel diameter (r = -0.81, p < 0.0001); in arteries of 6.0 mm or less, mean dilatation was 10 (SE 2)%. In smokers, FH children, and adults with CAD, flow-mediated dilatation was much reduced or absent (p < 0.001 for comparison with each relevant control group). Dilatation in response to GTN was present in all groups. Endothelial dysfunction is present in children and adults with risk factors for atherosclerosis, such as smoking and hypercholesterolaemia, before anatomical evidence of plaque formation in the arteries studied. This may be an important early event in atherogenesis.
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            Prevalence of Obesity and Severe Obesity in US Children, 1999–2016

            To provide updated prevalence data on obesity trends among US children and adolescents aged 2 to 19 years from a nationally representative sample.
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              Body-Mass Index in 2.3 Million Adolescents and Cardiovascular Death in Adulthood.

              In light of the worldwide increase in childhood obesity, we examined the association between body-mass index (BMI) in late adolescence and death from cardiovascular causes in adulthood.
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                Author and article information

                Contributors
                soltero@bcm.edu
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                29 December 2020
                05 January 2021
                : 10
                : 1 ( doiID: 10.1002/jah3.v10.1 )
                : e018092
                Affiliations
                [ 1 ] Department of Pediatrics Children’s Nutrition Research Center Baylor College of Medicine Houston TX
                [ 2 ] Vascular Biology Center Division of Hematology Oncology & Transplantation University of Minnesota Medical School Minneapolis MN
                [ 3 ] Department of Medicine University of Minnesota Medical School Minneapolis MN
                [ 4 ] Division of Biostatistics School of Public Health University of Minnesota Minneapolis MN
                [ 5 ] Center for Pediatric Obesity Medicine University of Minnesota Medical School Minneapolis MN
                [ 6 ] Department of Pediatrics University of Minnesota Medical School Minneapolis MN
                [ 7 ] Center for Health Promotion and Disease Prevention Arizona State University Phoenix AZ
                [ 8 ] Department of Pediatric Endocrinology and Diabetes Phoenix Children’s Hospital Phoenix AZ
                [ 9 ] School of Kinesiology University of Minnesota Minneapolis MN
                Author notes
                [*] [* ] Correspondence to: Erica G. Soltero, PhD, Department of Pediatrics, Children’s Nutrition Research Center, Baylor College of Medicine, 1100 Bates Avenue, Houston, TX, 77030. E‐mail: soltero@ 123456bcm.edu

                Author information
                https://orcid.org/0000-0002-7202-9262
                https://orcid.org/0000-0002-0660-7933
                https://orcid.org/0000-0002-7506-9497
                https://orcid.org/0000-0001-5616-5857
                Article
                JAH35730
                10.1161/JAHA.120.018092
                7955458
                33372524
                24b22295-7bf0-492d-8b5b-913fa71c6d58
                © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 19 June 2020
                : 22 October 2020
                Page count
                Figures: 0, Tables: 5, Pages: 8, Words: 13536
                Categories
                Original Research
                Original Research
                Pediatric Cardiology
                Custom metadata
                2.0
                05 January 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.6 mode:remove_FC converted:05.01.2021

                Cardiovascular Medicine
                adolescents,cardiovascular risk,children,endothelial health,novel biomarkers,obesity,biomarkers,endothelium/vascular type/nitric oxide,pediatrics,primary prevention,atherosclerosis

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