| 1. |
- Charakida, M., et al.
(author)
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Endothelial dysfunction in childhood infection
- 2005
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In: Circulation. - 1524-4539. ; 111:13, s. 1660-5
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Journal article (peer-reviewed)abstract
- BACKGROUND: Atherosclerosis begins in early life, and endothelial dysfunction is recognized as a key initiating event in the development of atherosclerosis. Although infection has been implicated in endothelial dysfunction and atherogenesis, the impact of acute common childhood infections on the vascular endothelium is unknown. METHODS AND RESULTS: We studied 600 children aged 10 years drawn from the Avon Longitudinal Study of Parents and Children. The children were divided into 3 groups: those with current acute infection (AI; n=135; 73 boys and 62 girls); a convalescent group with infection in the past 2 weeks (n=166; 78 boys and 88 girls), and a healthy control group (n=299; 131 boys and 168 girls). Endothelial function was determined in all subjects by high-resolution ultrasound to measure brachial artery flow-mediated dilation (FMD) and was expressed as the percentage change in diameter from baseline after reactive hyperemia. FMD was repeated in 40 children in the AI group and 50 in the control group after a mean interval of 1 year. FMD was lower in both the AI group (6.3+/-2.7%, mean+/-SD) and the convalescent group (8.1+/-3.1%) than in the control group (9.7+/-2.5%; P<0.001 for both). The observed differences in FMD remained after adjustment for potential confounding variables. At the repeat visit, FMD was unchanged in controls (P=0.85) but improved in the AI group (P<0.001). CONCLUSIONS: Acute infection in childhood is associated with impaired endothelium-dependent vasodilation. These findings support a potential role for previously unsuspected extrinsic inflammatory stimuli in the pathogenesis of early atherosclerosis.
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| 2. |
- Dangardt, Frida, 1977, et al.
(author)
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Association between fat mass through adolescence and arterial stiffness: a population-based study from The Avon Longitudinal Study of Parents and Children
- 2019
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In: Lancet Child & Adolescent Health. - : Elsevier BV. - 2352-4642. ; 3:7, s. 474-481
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Journal article (peer-reviewed)abstract
- Background The link between adiposity, metabolic abnormalities, and arterial disease progression in children and adolescents remains poorly defined. We aimed to assess whether persistent high adiposity levels are associated with increased arterial stiffness in adolescence and any mediation effects by common metabolic risk factors. Methods We included participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) who had detailed adiposity measurements between the ages 9-17 years and arterial stiffness (carotid to femoral pulse wave velocity [PWV]) measured at age 17 years. Body-mass index (BMI) and waist-to-height ratio were calculated from weight, height, and waist circumference measurements whereas fat mass was assessed using repeated dual-energy x-ray absorptiometry (DEXA) scans. We used total and trunk fat mass indices (FMIs) to classify participants as normal (< 75th percentile) or high (> 75th percentile) FMI. We classified participants as being metabolically unhealthy if they had three or more of the following risk factors: high levels of systolic blood pressure, triglycerides, or glucose (all > 75th percentile) or low levels of high-density lipoprotein (< 25th percentile). We used multivariable linear regression analysis to assess the relationship between PWV and exposure to adiposity, and tested for linear trend of PVW levels across ordinal groups. We used latent class growth mixture modelling analysis to assess the effect of longitudinal changes in adiposity indices through adolescence on arterial stiffness. Findings We studied 3423 participants (1866 [54.5%] female and 1557 [45.5%] male). Total fat mass was positively associated with PWV at age 17 years (0.004 m/s per kg, 95% CI 0.001-0.006; p= 0.0081). Persistently high total FMI and trunk FMI between ages 9 and 17 years were related to greater PWV (0.15 m/s per kg/m(2), 0.05-0.24; p= 0.0044 and 0.15 m/s per kg/m(2), 0.06-0.25; p= 0.0021) compared with lower FMI. Metabolic abnormalities amplified the adverse effect of high total FMI on arterial stiffness (PWV 6.0 m/s [95% CI 5.9-6.0] for metabolically healthy participants and 6.2 m/s [5.9-6.4] for metabolically unhealthy participants). Participants who restored normal total FMI in adolescence (PWV 5.8 m/s [5.7-5.9] for metabolically healthy and 5.9 m/s [5.6-6.1] for metabolically unhealthy) had comparable PWV to those who had normal FMI throughout (5.7 m/s [5.7-5.8] for metabolically healthy and 5.9 m/s [5.8-5.9] for metabolically unhealthy). Interpretation Persistently high fat mass during adolescence was associated with greater arterial stiffness and was further aggravated by an unfavourable metabolic profile. Reverting to normal FMI in adolescence was associated with normal PWV, suggesting adolescence as an important period for interventions to tackle obesity in the young to maximise long-term vascular health. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
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| 3. |
- Dangardt, Frida, 1977, et al.
(author)
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Intimal and medial arterial changes defined by ultra-high-frequency ultrasound: Response to changing risk factors in children with chronic kidney disease
- 2018
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:6
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Journal article (peer-reviewed)abstract
- Background Patients with chronic kidney disease (CKD) are exposed to both traditional 'Framingham' and uremia related cardiovascular risk factors that drive atherosclerotic and arteriosclerotic disease, but these cannot be differentiated using conventional ultrasound. We used ultrahigh-frequency ultrasound (UHFUS) to differentiate medial thickness (MT) from intimal thickness (IT) in CKD patients, identify their determinants and monitor their progression. Fifty-four children and adolescents with CKD and 12 healthy controls underwent UHFUS measurements using 55-70MHz transducers in common carotid and dorsal pedal arteries. Annual follow-up imaging was performed in 31 patients. CKD patients had higher carotid MT and dorsal pedal IT and MT compared to controls. The carotid MT in CKD correlated with serum phosphate (p<0.001, r = 0.42), PTH (p = 0.03, r = 0.36) and mean arterial pressure (p = 0.03, r = 0.34). Following multivariable analysis, being on dialysis, serum phosphate levels and mean arterial pressure remained the only independent predictors of carotid MT (R-2 64%). Transplanted children had lower carotid and dorsal pedal MT compared to CKD and dialysis patients (p = 0.02 and p = 0.01 respectively). At 1-year follow-up, transplanted children had a decrease in carotid MT (p = 0.01), but an increase in dorsal pedal IT (p = 0.04) that independently correlated with annualized change in BMI. Using UHFUS, we have shown that CKD is associated with exclusively medial arterial changes that attenuate when the uremic milieu is ameliorated after transplantation. In contrast, after transplantation intimal disease develops as hypertension and obesity become prevalent, representing rapid vascular remodeling in response to a changing cardiovascular risk factor profile.
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| 4. |
- Donald, A. E., et al.
(author)
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Non-invasive assessment of endothelial function: which technique?
- 2006
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In: J Am Coll Cardiol. - 1558-3597. ; 48:9, s. 1846-50
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The purpose of this study was to compare 3 non-invasive techniques for assessment of endothelial function in adults and children and evaluate their utility in acute inflammation. BACKGROUND: Endothelial dysfunction is a key early event in pre-clinical atherosclerosis. Flow-mediated dilation (FMD), although the established technique, is expensive and technically demanding. Measurements of vascular responses to inhaled salbutamol by pulse wave analysis (PWA) or pulse contour analysis (PCA) are potential alternatives. METHODS: Sixteen adults (mean age 28 years, range 18 to 39) and 16 children (mean age 13 years, range 7 to 17) underwent concurrent vascular function testing on 2 occasions with ultrasound, PWA, and PCA. Eighteen men were also studied before and after typhoid vaccination. RESULTS: Reproducibility of FMD was high in adults and children (coefficient of variation [CV] = 7.1 and 6.3, respectively). Salbutamol responses were more variable with PWA (adults CV = 11.5, children CV = 17.1) and PCA particularly in children (adults CV = 18.2, children CV = 36.3). Flow-mediated dilation (p < 0.001) and PWA with salbutamol (p = 0.03) responses fell after typhoid vaccination, and PCA (p = 0.7) was unchanged. CONCLUSIONS: Vascular dysfunction during acute inflammation can be measured by FMD and by PWA with salbutamol. Flow-mediated dilation is less variable than PWA. Variability of PCA makes this technique currently unsuited to serial measures of endothelial function in children. Flow-mediated dilation remains the most reproducible method.
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