Subclinical alterations in left ventricular structure and function are detectable in adolescents with hypertension or obesity. However, data on early echocardiographic abnormalities in seemingly ...healthy children are lacking. Sex differences in cardiac structure and function have been previously reported, but sex-specific reference values are not available. Specifically, the potential interaction of sex and overweight has not been addressed at all. Anthropometric data, blood pressure and exercise tests were obtained in 356 healthy children. Echocardiographic parameters comprised peak early (
E
) and late (
A
) mitral inflow Doppler velocities,
E
/
A
ratio, tissue Doppler peak velocities of early (
e
′) and late diastolic (
a
′) excursion of mitral/septal annulus and isovolumetric relaxation time (IVRT). Left ventricular mass index (LVMI) and LVMI
z
-score were calculated. Interaction terms between BMI and sex and stratification by sex were used for analysis. We provide values for echocardiographic parameters for children of two age groups separated by BMI. Overweight/obese children had a significant higher LVMI, lower
E
/
A
ratio, higher
E
/
e
′ ratios and a longer IVRT. For a given BMI in the upper ranges we demonstrated a higher LVMI in girls than in boys, the IVRT extended significantly more in girls than in boys with increasing BMI. There are sex differences in structural and functional echocardiographic parameters in children and adolescents. Our data not only confirms the importance of overweight and obesity, but demonstrates important interactions between sex and overweight. The greater susceptibility of overweight girls toward echocardiographic changes associated with potential long-term functional impairment needs further exploration and follow-up.
Trial registration number DRKS00012371; Date 18.08.2017.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Mortality in children with kidney failure is higher in girls than boys with cardiovascular complications representing the most common causes of death. Pulse wave velocity (PWV), a measure of vascular ...stiffness, predicts cardiovascular mortality in adults. Here, PWV in children with kidney failure undergoing kidney replacement therapy was investigated to determine sex differences and potential contributing factors. Two-hundred-thirty-five children (80 girls; 34%) undergoing transplantation (150 pre-emptive, 85 with prior dialysis) having at least one PWV measurement pre- and/or post-transplantation from a prospective cohort were analyzed. Longitudinal analyses (median/maximum follow-up time of 6/9 years) were performed for PWV z-scores (PWVz) using linear mixed regression models and further stratified by the categories of time: pre-kidney replacement therapy and post-transplantation. PWVz significantly increased by 0.094 per year and was significantly higher in girls (PWVz +0.295) compared to boys, independent of the underlying kidney disease. During pre-kidney replacement therapy, an average estimated GFR decline of 4ml/min/1.73m(2) per year was associated with a PWVz increase of 0.16 in girls only. Higher diastolic blood pressure and low density lipoprotein were independently associated with higher PWVz during pre-kidney replacement therapy in both sexes. In girls post-transplantation, an estimated GFR decline of 4ml/min/1.73m(2) per year pre-kidney replacement therapy and a longer time (over 12 months) to transplantation were significantly associated with higher PWVz of 0.22 and of 0.57, respectively. PWVz increased further after transplantation and was positively associated with time on dialysis and diastolic blood pressure in both sexes. Thus, our findings demonstrate that girls with advanced chronic kidney disease are more susceptible to develop vascular stiffening compared to boys, this difference persist after transplantation and might contribute to higher mortality rates seen in girls with kidney failure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Advances in allogeneic hematopoietic stem cell transplantation (HSCT) in malignant and non-malignant diseases result in more long-term survivors, in whom cardiovascular (CV) disease is one leading ...non-cancer cause of death. This study aimed to evaluate risk factors and subclinical CV organ damage in survivors after HSCT in pediatric age. We enrolled 64 children in a cross-sectional approach 3.3 ± 3.1 years after HSCT. Anthropometric data, laboratory values, office and 24-h ambulatory blood pressure monitoring (ABPM) were evaluated, showing a high prevalence of obesity, hypertension and dyslipidemia. CV organ damage was determined by non-invasive measurements of aortic pulse wave velocity (PWV), left ventricular mass index (LVMI), and carotid intima media thickness (IMT). Increased IMT and elevated PWV reflecting subclinical vascular damage were detected in 48% (IMT) and 6% (PWV) of our population. For IMT, physical activity had a positive impact and was worsened by time after HSCT. Our results show a surprisingly high rate of subclinical CV organ damage and classical risk factors. Therefore, diagnosis and management of well-known CV risk factors belong to clinical care after HSCT.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Cardiovascular (CV) events account for 8%‐13% of deaths after liver transplantation (LT) in adulthood. Although CV risk factors (RFs) are present, little is known about the prevalence of subclinical ...CV target organ damage (TOD) in children after LT. The aim of this prospective observational study was to assess the prevalence of subclinical CV TOD in children after LT and to identify RFs contributing to CV damage as potential targets for clinical intervention. In this study, 104 children after LT (54% female, 46% male; aged 11.5 ± 3.8 years) underwent cross‐sectional assessment of subclinical TOD by carotid‐femoral pulse wave velocity (PWV), carotid intima‐media thickness (IMT), and left ventricular mass index (LVMI). Results were correlated with the presence of CV RFs (obesity, hypertension, dyslipidemia, renal impairment, anemia, and microinflammation). Of the patients, 22% were exposed to 2 CV RFs, and 36% displayed 3 or more CV RFs. Pathological results for PWV, IMT, and LVMI were found in 21.9%, 57.0%, and 11.1% of patients, respectively. In the multivariate analysis, diastolic blood pressure (P = 0.01) and estimated glomerular filtration rate (eGFR; P = 0.03) were independently associated with PWV, eGFR (P = 0.005), and age at LT (P = 0.048) with IMT and body mass index with LVMI (P = 0.004). In conclusion, patients after pediatric LT carry a substantial burden of subclinical CV TOD. Identification of modifiable CV RFs opens opportunities for targeted intervention in order to reduce CV morbidity and mortality in the future.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Cardiovascular (CV) disease plays a major role after liver transplantation (LT). This prospective study assessed subclinical CV damage after LT by measuring pulse wave velocity (PWV), ...intima‐media thickness (IMT) and left‐ventricular mass index (LVMI) and characterized associated risk factors. We included 112 patients with a median of 1.8 years after LT (q1–q3 0.9–9.2). Fifty‐three percent (n = 59) of patients had ≥2 annual assessments (median follow‐up 1.6 years, q1–q3 1.1–2.0), with a total of 195 assessments. We found increased PWV (indicating arteriosclerosis) in 16% (n = 17), elevated IMT in 5% (n = 5; indicating atherosclerosis) and increased LVMI in 25% (n = 24; indicating left‐ventricular hypertrophy). A linear mixed model analysis using all 195 assessments revealed that higher age and systolic blood pressure (BP) were associated with higher PWV (β = 0.069, P < 0.001 and β = 0.022, P = 0.005) and higher IMT (β = 0.005, P < 0.001 and β = 0.001, P = 0.029), while higher body mass index was associated with higher IMT (β = 0.004, P = 0.023). Higher systolic BP (β = 0.200, P = 0.034), male sex (β = 8.847, P = 0.031) and lower glomerular filtration rate (β = −0.288, P < 0.001) were associated with higher LVMI. Our data highlight not only the rate of subclinical CV damage in LT patients, but also the impact of classical CV risk factors (such as BP and body mass index) which outweighed LT‐related factors. These modifiable risk factors are suitable targets for interventions to reduce CV morbidity in LT patients.
In Celiac disease (CD), cytoskeletal integrity of intestinal cells is disrupted by gliadin exposure. This study investigates the role of heat shock protein (Hsp)70 during cytoskeletal recovery in CD ...by assessing its induction and effects on junctional proteins.
Using an in-vitro model of CD, cytoskeletal injury and recovery was assessed in gliadin-exposed Caco-2 cells by measuring cellular distribution of ezrin, E-cadherin, and Hsp70 by differential centrifugation. Effects of Hsp70 were tested by an in-vitro repair assay, based on the incubation of injured or recovered cytoskeletal cellular fractions in noncytoskeletal supernatants containing low or high levels of Hsp70, or by transient transfection of Caco-2 cells with Hsp70.
Cytoskeletal disruption of ezrin and E-cadherin was demonstrated in gliadin-exposed Caco-2 cells by their significant shift from the cytoskeletal pellet into the noncytoskeletal supernatant fraction. Recovery from gliadin exposure was associated with induction and cytoskeletal redistribution of Hsp70. The in-vitro repair assay delineated direct evidence for HSP-mediated repair by stabilization of junctional proteins by Hsp70. Overexpression of Hsp70 resulted in significantly increased cytoskeletal integrity.
Our results establish an essential role of HSP-mediated cytoskeletal repair in Caco-2 cells during recovery from in-vitro gliadin exposure.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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