Objective To determine a simplified method to identify presence of left ventricular hypertrophy (LVH) in pediatric populations because the relationship between heart growth and body growth in ...children has made indexing difficult for younger ages. Study design Healthy children (n = 400; 52% boys, 0-18 years of age) from 2 different European hospitals were studied to derive a simplified formula. Left ventricular mass (LVM) was calculated according to the Devereux formula. The derived approach to index LVM was tested on a validation cohort of 130 healthy children from a different hospital center. Results There was a strong nonlinear correlation between height and LVM. LVM was best related to height to a power of 2.16 with a correction factor of 0.09. Analysis of residuals for LVM/(height2.16 ) + 0.09 showed an homoscedastic distribution in both sexes throughout the entire height range. A partition value of 45 g/m2.16 was defined as the upper normal limit for LVM index. As opposed to formula suggested by current guidelines (ie, LVM/height2.7 ) when applying the proposed approach in the validation cohort of 130 healthy participants, no false positives for LVH were found (0% vs 8%; P < .01). Conclusions Our data support the possibility to have a single partition (ie, 45 g/m2.16 ) value across the whole pediatric age range to identify LVH, without the time-consuming need of computing specific percentiles for height and sex.
BACKGROUND
Aortic pulse wave velocity (PWV), an indicator of arterial stiffness, independently predicts cardiovascular mortality risk in adults. Arterial stiffening advances with age and seems ...accelerated in children with certain disease conditions such as chronic kidney disease or diabetes. The Vicorder, an oscillometric device to measure PWV, has been validated in children, but reference values in a large pediatric cohort, association to carotid stiffness and influence of individual and family risk factors have not been determined.
METHODS
Pulse waves were captured in 1,003 healthy children (aged 6–18 years) in 6 centers and gender-specific reference data normalized to age/height were constructed. In 589 children carotid distensibility and intima media thickness were measured. Gestational and family history was reported.
RESULTS
PWV correlated with age (r = 0.57, P < 0.0001) with significant gender-related differences starting at age 9. Further significant correlations were seen for height, weight, body mass index, blood pressure, pulse pressure, and heart rate. Independent predictors for PWV in a multivariate regression analysis were gender, age, height, weight, mean arterial pressure, and heart rate. Risk factors for higher PWV included small for gestational age at birth, secondhand smoking, parental hypertension, and obesity. PWV showed weak correlations with 2 of the carotid distensibility measures, but not with intima media thickness.
CONCLUSION
This study defines reference values for PWV captured by the Vicorder device in children and adolescents and reveals associations with potential cardiovascular risk factors in a healthy population. Gender-specific percentiles for age/height will allow for the assessment of pediatric cohorts using this oscillometric method.
Background
Pulse wave velocity (PWV) is an indicator of aortic stiffness and a predictor of cardiovascular risk. Applanation tonometry (e.g., SphygmoCor) is a well-established method to measure ...aortic PWV (aPWV). The Vicorder, a new oscillometric device, has not been validated in children and adolescents.
Methods
We performed intra- and interobserver repeatability studies in 14 individuals using the Vicorder. Vicorder and SphygmoCor measurements were compared in 156 healthy children (6-18 years) using two different path length measurements.
Results
Intra- and interobserver repeatabilities of the Vicorder were excellent with coefficients of variation of 5.6% and 5.8% and intraclass correlation coefficients (ICCs) of 0.8 and 1.0. aPWV calculated using the distances (suprasternal notch-to-femoral recording point) - (suprasternal notch-to-carotid artery), the path length most commonly used in adults, revealed a mean of 4.8 ± 0.7 m/s for SphygmoCor and 4.9 ± 0.6 m/s for Vicorder. The percentage deviation between both devices was 13.0% and the limit of agreement (LoA) ranged from −1.0 to 1.7 m/s reflecting a good concordance. Using a path length that measured the distance from suprasternal notch to femoral recording point via the umbilicus (Umb), an even better agreement was found (percentage deviation: 11.8%, LoA: −1.0 to 1.6 m/s).
Conclusions
Vicorder aPWV values are similar to those obtained by SphygmoCor applanation tonometry. The best agreement between devices was obtained with the path length that most accurately describes the aortic tree. Excellent intra- and interobserver repeatability and ease of measurements make Vicorder appropriate for large multicentre studies in children and adolescents.
American Journal of Hypertension, advance online publication 25 August 2011; doi:10.1038/ajh.2011.147
Children and adolescents with chronic kidney disease (CKD) are at high risk for cardiovascular morbidity and mortality. A systemic arteriopathy and cardiomyopathy has been characterized in pediatric ...dialysis patients by the presence of morphologic and functional abnormalities.
The Cardiovascular Comorbidity in Children with CKD (4C) Study is a multicenter, prospective, observational study aiming to recruit more than 600 children, aged 6 to 17 years, with initial GFR of 10 to 45 ml/min per 1.73 m(2). The prevalence, degree, and progression of cardiovascular comorbidity as well as its association with CKD progression will be explored through longitudinal follow-up. The morphology and function of the heart and large arteries will be monitored by sensitive noninvasive methods and compared with aged-matched healthy controls. Multiple clinical, anthropometric, biochemical, and pharmacologic risk factors will be monitored prospectively and related to the cardiovascular status. A whole-genome association study will be performed to identify common genetic variants associated with progression of cardiovascular alterations and/or renal failure. Monitoring will be continued as patients reach end-stage renal disease and undergo different renal replacement therapies.
While cardiovascular morbidity in adults is related to older age and additional risk factor load (e.g., diabetes), the role of CKD-specific factors in the initiation and progression of cardiac and vascular disease are likely to be characterized with greater sensitivity in the pediatric age group.
The 4C study is expected to provide innovative insight into cardiovascular and renal disease progression in CKD.
The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth ...hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort.
Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6-18 years with an estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1.73 m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group.
Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score.
Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: The biological properties of oxidized and non-oxidized PTH are substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating properties, whereas non-oxidized PTH ...(n-oxPTH) is a full agonist of the receptor. This was described in more than 20 well published studies in the 1970s and 80s. However, PTH oxidation has been ignored during the development of PTH assays for clinical use so far. Even the nowadays used third generation assay systems do not consider oxidation of PTH We recently developed an assay to differentiate between oxPTH and n-oxPTH. In the current study we established normal values for this assay system. Furthermore, we compare the ratio of oxPTH to n-oxPTH in different population with chronic renal failure: 620 children with renal failure stage 2-4 of the 4C study, 342 adult patients on dialysis, and 602 kidney transplant recipients. In addition, we performed modeling of the interaction of either oxPTH or n-oxPTH with the PTH receptor using biophysical structure approaches. Results: The children had the highest mean as well as maximum n-oxPTH concentrations as compared to adult patients (both patients on dialysis as well as kidney transplant recipients). The relationship between oxPTH and n-oxPTH of individual patients varied substantially in all three populations with renal impairment. The analysis of n-oxPTH in 89 healthy control subjects revealed that n-oxPTH concentrations in patient with renal failure were higher as compared to healthy adult controls (2.25-fold in children with renal failure, 1.53-fold in adult patients on dialysis, and 1.56-fold in kidney transplant recipients, respectively). Computer assisted biophysical structure modeling demonstrated, however, minor sterical- and/or electrostatic changes in oxPTH and n-oxPTH. This indicated that PTH oxidation may induce refolding of PTH and hence alters PTH-PTH receptor interaction via oxidation induced three-dimensional structure alteration of PTH. Conclusion: A huge proportion of circulating PTH measured by current state-of-the-art assay systems is oxidized and thus not biologically active. The relationship between oxPTH and n-oxPTH of individual patients varied substantially. Non-oxidized PTH concentrations are 1.5 - 2.25 fold higher in patients with renal failure as compared to health controls. Measurements of n-oxPTH may reflect the hormone status more precise. The iPTH measures describes most likely oxidative stress in patients with renal failure rather than the PTH hormone status. This, however, needs to be demonstrated in further clinical studies.
Carotid intima-media thickness (cIMT) and carotid artery distensibility are reliable screening methods for vascular alterations and the assessment of cardiovascular risk in adult and pediatric ...cohorts. We sought to establish an international reference data set for the childhood and adolescence period and explore the impact of developmental changes in body dimensions and blood pressure (BP) on carotid wall thickness and elasticity. cIMT, the distensibility coefficient, the incremental modulus of elasticity, and the stiffness index β were assessed in 1155 children aged 6 to 18 years and sex-specific reference charts normalized to age or height were constructed from 1051 nonobese and nonhypertensive children. The role of body dimensions, BP, and family history, as well as the association between cIMT and distensibility, was investigated. cIMT increased and distensibility decreased with age, height, body mass index, and BP. A significant sex difference was apparent from the age of 15 years. Age- and height-normalized cIMT and distensibility values differed in children who are short or tall for their age. By stepwise multivariate analysis, standardized systolic BP and body mass index were independently positively associated with cIMT SD scores (SDS). Systolic BP SDS independently predicted all distensibility measures. Distensibility coefficient SDS was negatively and β SDS positively associated with cIMT SDS, whereas incremental modulus of elasticity was independent of cIMT. Morphological and functional aspects of the common carotid artery are particularly influenced by age, body dimensions, and BP. The reference charts established in this study allow to accurately compare vascular phenotypes of children with chronic conditions with those of healthy children.
Cardiovascular disease is the most important comorbidity affecting long-term survival in children with CKD.
The Cardiovascular Comorbidity in Children with CKD Study is a multicenter, prospective, ...observational study in children ages 6-17 years old with initial GFR of 10-60 ml/min per 1.73 m
. The cardiovascular status is monitored annually, and subclinical cardiovascular disease is assessed by noninvasive measurements of surrogate markers, including the left ventricular mass index, carotid intima-media thickness, and central pulse wave velocity. We here report baseline data at study entry and an explorative analysis of variables associated with surrogate markers.
A total of 737 patients were screened from October of 2009 to August of 2011 in 55 centers in 12 European countries, and baseline data were analyzed in 688 patients. Sixty-four percent had congenital anomalies of the kidney and urinary tract; 26.1% of children had uncontrolled hypertension (24-hour ambulatory BP monitoring; n=545), and the prevalence increased from 24.4% in CKD stage 3 to 47.4% in CKD stage 5. The prevalence of left ventricular hypertrophy was higher with each CKD stage, from 10.6% in CKD stage 3a to 48% in CKD stage 5. Carotid intima-media thickness was elevated in 41.6%, with only 10.8% of patients displaying measurements below the 50th percentile. Pulse wave velocity was increased in 20.1%. The office systolic BP SD score was the single independent factor significantly associated with all surrogate markers of cardiovascular disease. The intermediate end point score (derived from the number of surrogate marker measurements >95th percentile) was independently associated with a diagnosis of congenital anomalies of the kidney and urinary tract, time since diagnosis of CKD, body mass index, office systolic BP, serum phosphorus, and the hemoglobin level.
The baseline data of this large pediatric cohort show that surrogate markers for cardiovascular disease are closely associated with systolic hypertension and stage of CKD.
Childhood overweight and obesity is a relevant health condition with multi-organ involvement. Obesity shows significant tracking into adult life and is associated with an increased risk of serious ...adverse health outcomes both during childhood and later adulthood. The classical sequelae of obesity such as hypertension, metabolic syndrome and inflammation do develop at a paediatric age. Cardiovascular consequences, such as increased carotid intima-media thickness, and left ventricular hypertrophy, as well as functional alterations of the heart and arteries, are commonly traceable at an early age. Renal involvement can occur at a young age and is associated with a high probability of progressive chronic kidney disease. There is solid evidence suggesting that consequent treatment including both lifestyle changes and pharmacological therapy can reduce cardiovascular, metabolic and renal risks in obese children and adolescents.
CKD has been linked to increased arterial stiffness in adults, but data in children with CKD remain conflicting. We aimed to investigate the longitudinal dynamics and determinants of pulse wave ...velocity in children with CKD and its association with CKD progression.
We performed an analysis of the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study, which prospectively followed children aged 6-17 years with CKD stages 3-5. Follow-up was censored at the time of KRT initiation. Two separate analyses were performed: with absolute pulse wave velocity (primary outcome) and with pulse wave velocity standardized to height (
score; restricted to participants ≤17 years) as a sensitivity analysis.
In total, 667 patients with a mean baseline eGFR of 27 ml/min per 1.73 m
were included. Pulse wave velocity above the 95th percentile was observed in 124 (20%) patients at baseline. Absolute pulse wave velocity increased gradually over the median follow-up of 2.7 (interquartile range, 0.7-4.4) years, whereas pulse wave velocity
score remained relatively stable. Absolute pulse wave velocity over time associated with time; older age; higher mean arterial pressure, LDL cholesterol, and albuminuria; and lower ferritin. Pulse wave velocity
score (
=628) was associated with the same variables and additionally, with higher diastolic BP
score, lower height
score, younger age, and girls. Of 628 patients, 369 reached the composite end point of CKD progression (50% eGFR loss, eGFR <10 ml/min per 1.73 m
, or the start of KRT) during a median follow-up of 2.4 (interquartile range, 0.9-4.6) years. Pulse wave velocity
score did not associate with CKD progression by univariable or multivariable proportional hazard analysis correcting for the established predictors eGFR, proteinuria, and BP.
Pulse wave velocity is increased in children with CKD but does not associate with eGFR or CKD progression.
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