The significance of central blood pressure for cardiovascular target organ damage in children and adolescents after kidney transplantation.

BACKGROUND: Cardiovascular (CV) complications are important causes of morbidity and mortality in children after kidney transplantation (KTx). In adults, central blood pressure (cBP) is an accepted predictor of CV sequelae. We aimed to assess the prognostic value of cBP over peripheral blood pressure (pBP) for existing CV damage. METHODS: We measured cBP and pBP in 48 pediatric KTx recipients (mean age: 13.5 ± 4.2 years). Assessment of left ventricular mass index (LVMI) and aortic pulse wave velocity (PWV) allowed detection of CV target organ damage. LVMI and PWV were used as endpoints in multivariable linear regression models, in which cBP and pBP were compared for their predictive value. RESULTS: Using cBP z-scores, we identified a larger number of patients with uncontrolled or untreated hypertension compared to pBP (36% vs. 7%). Central systolic blood pressure (cSBP) was a significant independent predictor of LVMI, while peripheral systolic blood pressure (pSBP) was not. Comparing central (cDBP) and peripheral (pDBP) diastolic blood pressure for their predictive value on PWV revealed a greater estimate for cDBP (0.035 vs. 0.026 for pDBP) along with a slightly better model fit for cDBP. CONCLUSIONS: Our data in a small group of patients provide first evidence that cBP measurements in pediatric KTx recipients might be helpful in identifying patients at risk for the development of CV sequelae. Investigating a larger patient number, ideally repeatedly, is needed to create further evidence supporting our findings. In light of available devices measuring cBP noninvasively, the implementation of such clinical studies post-KTx care should be feasible. A higher resolution version of the Graphical abstract is available as Supplementary information.

Arterial stiffness and blood pressure increase in pediatric kidney transplant recipients.

BACKGROUND: Pulse wave velocity (PWV) is a measure of arterial stiffness. We investigated PWV and blood pressure (BP) to determine to what extent BP changes contribute to arterial stiffness, and secondly, to identify influencing factors on BP in children after kidney transplantation. METHODS: Seventy children ≥ 2.5 years post-transplantation with at least two PWV measurements were included. Changes of systolic (Δ SBP) and diastolic BP (Δ DBP) were classified into "stable/decreasing," "1-10 mmHg increase," and " > 10 mmHg increase." Linear mixed modeling for PWV z-score (PWVz) adjusted either for Δ SBP or Δ DBP was performed. An extended dataset with monthly entries of BP, immunosuppression, and creatinine was obtained in 35 participants over a median of 74 months to perform linear mixed modeling for SBP and DBP. RESULTS: PWVz increased with a rate of 0.11/year (95% CI 0.054 to 0.16). Compared to participants with stable BP, those with 1-10-mmHg SBP and DBP increase showed a higher PWVz of 0.59 (95% CI 0.046 to 1.13) and 0.86 (95% CI 0.43 to 1.30), respectively. A > 10-mmHg BP increase was associated with an even higher PWVz (SBP ß = 0.78, 95% CI 0.22 to 1.34; DBP ß = 1.37, 95% CI 0.80 to 1.94). Female sex and participants with lower eGFR showed higher PWVz. In the extended analysis, DBP was positively associated with cyclosporin A and everolimus trough levels. CONCLUSIONS: A higher increase of PWV is seen in patients with greater BP increase, with higher cyclosporin A and everolimus trough levels associated with higher BP. This emphasizes the role of BP as a modifiable risk factor for the improvement of cardiovascular outcome after transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Impact of Sex and Obesity on Echocardiographic Parameters in Children and Adolescents.

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.

Children and Adolescents' Behavioral Patterns in Response to Escalating COVID-19 Restriction Reveal Sex and Age Differences.

PURPOSE: The COVID-19 pandemic affects students in a myriad of different ways. Our prospective, longitudinal study in a cohort of students in Hannover, Germany explores behavioral patterns during escalating COVID-19 restrictions. METHODS: In total, 777 students between the age of 9 and 20 were assessed for their activity engagement, travel patterns, and self-assessed compliance with protective recommendations at six time points between June 2020 and June 2021 (3,564 observations) and were monitored for severe acute respiratory syndrome coronavirus 2 infection by nasal swab polymerase chain reaction and serum antibody titers. RESULTS: Activity engagement decreased, but self-assessed compliance with measures such as mask wearing and social distancing was stable during escalating restrictions. Although we found no sex difference during the summer break, when incidence was lowest, females engaged in a higher variety of activities than males for all other time points. Older students engaged in more activities and self-assigned themselves lower compliance values than younger ones. Greater involvement in different activities was seen in households which traveled more frequently. Infection rate in our cohort was low (0.03% acute infections, 1.94% positive seroprevalence). DISCUSSION: Our study supports the view that, overall, students show high compliance with COVID-19 recommendations and restrictions. The identification of subsets, such as female and older students, with higher risk behavioral patterns should be considered when implementing public information campaigns. In light of the low infection rate in our cohort, we conclude that in-person learning can occur safely if extensive protective measures are in place and the incidence in the general population remains moderate.

Students' age and parental level of education influence COVID-19 vaccination hesitancy.

Widespread vaccination in pursuit of herd immunity has been recognized as the most promising approach to ending the global pandemic of coronavirus disease 19 (COVID-19). The vaccination of children and adolescents has been extensively debated and the first COVID-19 vaccine is now approved in European countries for children aged > 12 years of age. Our study investigates vaccination hesitancy in a cohort of German secondary school students. We assessed 903 students between age 9 and 20 in the period between 17 May 2021 and 30 June 2021. 68.3% (n = 617) reported intention to undergo COVID-19 vaccination, while 7% (n = 62) did not want to receive the vaccine and 15% (n = 135) were not yet certain. Age and parental level of education influenced COVID-19 vaccine hesitancy. Children under the age of 16 as well as students whose parents had lower education levels showed significantly higher vaccine hesitancy.  Conclusion: Identifying subsets with higher vaccination hesitancy is important for targeting public information campaigns in support of immunization. What is Known: • The willingness to receive COVID-19 vaccination among adults in Europe is about 70%, but data for children and adolescents is lacking. • The lack of immunization in younger cohorts represents a significant barrier to achieving herd immunity, and also leaves children and adolescents vulnerable to acute and long-term morbidity from natural COVID-19 infections. What is New: • Intention-to-vaccinate among children and adolescents is high (~ 70%); conversely, vaccination hesitancy is low. • Age and parental level of education influenced COVID-19 vaccine hesitancy among children and adolescents.

Prospective assessment of subclinical cardiovascular damage and associated factors in liver transplant recipients.

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 (ß = 0.069, P < 0.001 and ß = 0.022, P = 0.005) and higher IMT (ß = 0.005, P < 0.001 and ß = 0.001, P = 0.029), while higher body mass index was associated with higher IMT (ß = 0.004, P = 0.023). Higher systolic BP (ß = 0.200, P = 0.034), male sex (ß = 8.847, P = 0.031) and lower glomerular filtration rate (ß = -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.

Early Effects of Renal Replacement Therapy on Cardiovascular Comorbidity in Children With End-Stage Kidney Disease: Findings From the 4C-T Study.

BACKGROUND: The early impact of renal transplantation on subclinical cardiovascular measures in pediatric patients has not been widely investigated. This analysis is performed for pediatric patients participating in the prospective cardiovascular comorbidity in children with chronic kidney disease study and focuses on the early effects of renal replacement therapy (RRT) modality on cardiovascular comorbidity in patients receiving a preemptive transplant or started on dialysis. METHODS: We compared measures indicating subclinical cardiovascular organ damage (aortal pulse wave velocity, carotid intima media thickness, left ventricular mass index) and evaluated cardiovascular risk factors in 166 pediatric patients before and 6 to 18 months after start of RRT (n = 76 transplantation, n = 90 dialysis). RESULTS: RRT modality had a significant impact on the change in arterial structure and function: compared to dialysis treatment, transplantation was independently associated with decreases in pulse wave velocity (ß = -0.67; P < 0.001) and intima media thickness (ß = -0.40; P = 0.008). Independent of RRT modality, an increase in pulse wave velocity was associated with an increase in diastolic blood pressure (ß = 0.31; P < 0.001). Increasing intima media thickness was associated with a larger increase in body mass index (ß = 0.26; P = 0.003) and the use of antihypertensive agents after RRT (ß = 0.41; P = 0.007). Changes in left ventricular mass index were associated with changes in systolic blood pressure (ß = 1.47; P = 0.01). CONCLUSIONS: In comparison with initiating dialysis, preemptive transplantation prevented further deterioration of the subclinical vascular organ damage early after transplantation. Classic cardiovascular risk factors, such as hypertension and obesity are of major importance for the development of cardiovascular organ damage after renal transplantation.