Myocardial Injury Thresholds for 4 High-Sensitivity Troponin Assays in a Population-Based Sample of US Children and Adolescents.

BACKGROUND: Myocardial injury is an important pediatric diagnosis. Establishing normative data from a representative pediatric sample is vital to provide accurate upper reference limits (URLs) for defining myocardial injury using high-sensitivity cardiac troponin. METHODS: Among participants 1 to 18 years of age in the 1999-2004 National Health and Nutrition Examination Survey, we measured high-sensitivity troponin T using one assay (Roche) and high-sensitivity troponin I using 3 assays (Abbott, Siemens, and Ortho). In a strictly defined healthy subgroup, we estimated 97.5th and 99th percentile URLs for each assay using the recommended nonparametric method. RESULTS: Of 5695 pediatric participants, 4029 met criteria for the healthy subgroup (50% males; mean age 12.6 years). Our 99th percentile URL estimates for all 4 high-sensitivity troponin assays among children and adolescents were lower than the manufacturer-reported URLs (derived from adults). The 99th percentile URLs (95% CI) were 15 ng/L (95% CI, 12-17) for high-sensitivity troponin T, 16 ng/L (95% CI, 12-19) for high-sensitivity troponin I with the Abbott assay, 38 ng/L (95% CI, 25-46) for high-sensitivity troponin I with the Siemens assay, and 7 ng/L (95% CI, 5, 12) for high-sensitivity troponin I with the Ortho assay. The 95% CIs for age-, sex-, and race and ethnicity-specific 99th percentile URLs overlapped. However, the 97.5th percentile URL for each assay was measured with superior statistical precision (ie, tighter 95% CIs) and demonstrated differences by sex. For male compared with female children and adolescents, 97.5th percentile URLs were 11 ng/L (95% CI, 10-12) versus 6 ng/L (95% CI, 6-7) for high-sensitivity troponin T, 9 ng/L (95% CI, 7-10) versus 5 ng/L (95% CI, 4-6) for high-sensitivity troponin I with the Abbott assay, 21 ng/L (95% CI, 18-25) versus 11 ng/L (95% CI, 9-13) for high-sensitivity troponin I with the Siemens assay, and 4 ng/L (95% CI, 3-5) versus 2 ng/L (95% CI, 1-3) for high-sensitivity troponin I with the Ortho assay. In contrast to the 99th percentiles, the point estimates of 97.5th percentile pediatric URLs for high-sensitivity troponin were also much more stable to differences in the analytic approaches taken to estimate URLs. CONCLUSIONS: Because myocardial infarction is rare in children and adolescents, the use of statistically more precise and reliable sex-specific 97.5th percentile high-sensitivity troponin URLs might be considered to define pediatric myocardial injury.

Accuracy and Performance of Triage Blood Pressure Measurements in A Real-World Clinic Setting.

OBJECTIVES: To investigate the agreement and accuracy of triage blood pressure (BP) in a real-world clinic setting, compared with the reference standard. STUDY DESIGN: Paired triage and standardized BP measurements from patients 4 through 21 years old evaluated in an obesity-related hypertension clinic were obtained via chart-review. Triage BPs were measured by a medical assistant or nurse, often by automated device. Triplicate manual BPs were obtained by the clinic physician. Bland-Altman analyses determined mean differences between paired triage and mean standardized BPs. GEE-based multivariable relative risk (RR) regression determined the RR of triage BP overestimation by ≥ 5 mmHg. Overall agreement, sensitivity, specificity, positive predictive value, and negative predictive value of triage BP measurements identifying hypertensive BP were determined. RESULTS: One hundred thirty participants with 347 clinic encounters were included. Mean age was 13.3 years (SD 3.94), 76% were Black, and 58% were male. Overall mean systolic and diastolic BP difference was 8.7 mmHg (95% limits on agreement: -16.66, 34.07) and 4.1 mmHg (95% limits on agreement: -18.56, 26.68), respectively. Triage systolic BP was more likely overestimated by ≥ 5 mmHg when a large adult (RR = 1.49; 95% CI: 1.00, 2.21) or thigh cuff (RR = 1.94; 95% CI: 1.08, 3.51) was required compared with when a child/adult cuff was required. Overall agreement in identifying hypertensive BP was 57.6%. Sensitivity (52.6%), specificity (63.4%), positive predictive value (60.8%), and negative predictive value (55.3%) were low across all cuffs. CONCLUSIONS: There was poor agreement between usual triage and standardized BP measurements, with potential for significant clinical implications. CLINICAL TRIAL REGISTRATION: ReNEW Clinic Cohort Study (ReNEW), NCT03816462, https://clinicaltrials.gov/ct2/show/NCT03816462.

Association of Fibroblast Growth Factor 23 with Blood Pressure in Primary Proteinuric Glomerulopathies.

INTRODUCTION: Fibroblast growth factor 23 (FGF23) has direct effects on the vasculature and myocardium, and high levels of FGF23 are a risk factor for cardiovascular disease (CVD); however, the impact of FGF23 on CVD in primary proteinuric glomerulopathies has not been addressed. METHODS: The associations of baseline plasma intact FGF23 levels with resting blood pressure (BP) and lipids over time among adults and children with proteinuric glomerulopathies enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were analyzed using generalized estimating equation regression analyses. Models were adjusted for age, sex, glomerular diagnosis, follow-up time, estimated glomerular filtration rate, urine protein/creatinine ratio, obesity, and serum phosphorous levels. RESULTS: Two hundred and four adults with median FGF23 77.5 (IQR 51.3-119.3) pg/mL and 93 children with median FGF23 62.3 (IQR 44.6-83.6) pg/mL were followed for a median of 42 (IQR 20.5-54) months. In adjusted models, each 1 µg/mL increase in FGF23 was associated with a 0.3 increase in systolic BP index at follow-up (p < 0.001). Greater baseline FGF23 was associated with greater odds of hypertensive BP (OR = 1.0003; 95% CI 1.001-1.006, p = 0.03) over time. Compared to tertile 1, tertile 2 (OR = 2.1; 95% CI 1.12-3.99, p = 0.02), and tertile 3 (OR = 3; 95% CI 1.08-8.08, p = 0.04), FGF23 levels were associated with greater odds of hypertensive BP over time. Tertile 2 was associated with greater triglycerides compared to tertile 1 (OR = 48.1; 95% CI 4.4-91.9, p = 0.03). CONCLUSION: Overall, higher baseline FGF23 was significantly associated with hypertensive BP over time in individuals with proteinuric glomerulopathies. Further study of FGF23 as a therapeutic target for reducing CVD in proteinuric glomerular disease is warranted.

Screening and Management of Pediatric High Blood Pressure-Challenges to Implementing the Clinical Practice Guideline.

PURPOSE OF REVIEW: Elevated blood pressure (BP) and hypertension in childhood convey risk for hypertension and cardiovascular events in adulthood. Early recognition of abnormal BPs is key to preventing or lessening this risk. However, the process for making the diagnosis of hypertension is complex, and overall adherence to the 2017 American Academy of Pediatrics Clinical Practice Guidelines (CPG) is poor. We will review obstacles to adherence to the CPG and approaches designed to improve the diagnosis and management of hypertension in children. RECENT FINDINGS: Baseline data from the multi-center quality improvement intervention, "Boosting Primary Care Awareness and Treatment of Hypertension" (BP-CATCH), demonstrate that childhood hypertension remains underdiagnosed. Other studies confirm a lack of compliance with the process outlined in the CPG. The provision of electronic prompts, coaching, and education results in modest improvements. The combination of embedded medical record tools and education seems to offer the most hope for improvement.

Clinician response after receipt of abnormal pediatric ambulatory blood pressure monitoring - characteristics associated with inertia and action.

BACKGROUND: Ambulatory Blood Pressure Monitoring (ABPM) is recommended for diagnosis and management of hypertension. We aimed to identify characteristics associated with physician action after receipt of abnormal findings. METHODS: This was a retrospective cross-sectional analysis of patients 5-22 years old who underwent 24-h ABPM between 2003-2022, met criteria for masked or ambulatory hypertension, and had a pediatric nephrology clinic visit within 2 weeks of ABPM. "Action" was defined as medication change/initiation, lifestyle or adherence counseling, evaluation ordered, or interpretation with no change. Characteristics of children with/without 1 or more actions were compared using Student t-tests and Chi-square. Regression analyses explored the independent association of patient characteristics with physician action. RESULTS: 115 patients with masked (n = 53) and ambulatory (n = 62) hypertension were included: mean age 13.0 years, 48% female, 38% Black race, 21% with chronic kidney disease, and 25% overweight/obesity. 97 (84%) encounters had a documented physician action. Medication change (52%), evaluation ordered (40%), and prescribed lifestyle change (35%) were the most common actions. Adherence counseling for medication and lifestyle recommendations were documented in 3% of encounters. 24-h, wake SBP load, and sleep DBP load were significantly higher among those with physician action. Patients with > 1 action had greater adiposity, SBP, and dipping. Neither age, obesity, nor kidney disease were independently associated with physician action. CONCLUSIONS: While most abnormal ABPMs were acted upon, 16% did not have a documented action. Greater BP load was one of the few characteristics associated with physician action. Of potential actions, adherence counseling was underutilized.

Longitudinal analysis of blood pressure and lipids in childhood nephrotic syndrome.

BACKGROUND: In the current study, longitudinal BP and lipid measurements were examined in a NEPTUNE cohort of children with newly diagnosed nephrotic syndrome (cNEPTUNE). We hypothesized that hypertensive BP and dyslipidemia would persist in children with nephrotic syndrome, regardless of steroid treatment response. METHODS: A multi-center longitudinal observational analysis of data obtained from children < 19 years of age with new onset nephrotic syndrome enrolled in the Nephrotic Syndrome Study Network (cNEPTUNE) was conducted. BP and lipid data were examined over time stratified by disease activity and steroid exposure. Generalized estimating equation regressions were used to find determinants of hypertensive BP and dyslipidemia. RESULTS: Among 122 children, the prevalence of hypertensive BP at any visit ranged from 17.4% to 57.4%, while dyslipidemia prevalence ranged from 40.0% to 96.2% over a median of 30 months of follow-up. Hypertensive BP was found in 46.2% (116/251) of study visits during active disease compared with 31.0% (84/271) of visits while in remission. Dyslipidemia was present in 88.2% (120/136) of study visits during active disease and in 66.0% (101/153) while in remission. Neither dyslipidemia nor hypertensive BP were significantly different with/without medication exposure (steroids and/or CNI). In regression analysis, male sex and urine protein:creatinine ratio (UPC) were significant determinants of hypertensive BP over time, while eGFR was found to be a determinant of dyslipidemia over time. CONCLUSIONS: Results demonstrate persistent hypertensive BPs and unfavorable lipid profiles in the cNEPTUNE cohort regardless of remission status or concurrent steroid or calcineurin inhibitor treatment.

Growth in children with nephrotic syndrome: a post hoc analysis of the NEPTUNE study.

BACKGROUND: Steroids, the mainstay of treatment for nephrotic syndrome in children, have multiple adverse effects including growth suppression. METHODS: Anthropometric measurements in children < 18 years enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were collected. The longitudinal association of medication exposure and nephrotic syndrome characteristics with height z-score and growth velocity was determined using adjusted Generalized Estimating Equation regression and linear regression. RESULTS: A total of 318 children (57.2% males) with a baseline age of 7.64 ± 5.04 years were analyzed. The cumulative steroid dose was 216.4 (IQR 61.5, 652.7) mg/kg (N = 233). Overall, height z-scores were not significantly different at the last follow-up compared to baseline (- 0.13 ± 1.21 vs. - 0.23 ± 1.71, p = 0.21). In models adjusted for age, sex, and eGFR, greater cumulative steroid exposure (ß - 7.5 × 10-6, CI - 1.2 × 10-5, - 3 × 10-6, p = 0.001) and incident cases of NS (vs. prevalent) (ß - 1.1, CI - 2.22, - 0.11, p = 0.03) were significantly associated with lower height z-scores over time. Rituximab exposure was associated with higher height z-scores (ß 0.16, CI 0.04, 0.29, p = 0.01) over time. CONCLUSION: Steroid dose was associated with lower height z-score, while rituximab use was associated with higher height z-score.

Association of Childhood Blood Pressure with Left Atrial Size and Function: Study of High Blood Pressure in Pediatrics-Adult Hypertension in Youth (SHIP AHOY).

OBJECTIVE(S): To evaluate the cross-sectional association of cardiovascular disease risk factors with left atrial (LA) size and function among healthy youth, aged 11-18 years, with a wide range of blood pressures (BPs). STUDY DESIGN: Echocardiographic images of youth enrolled in the Study of High Blood Pressure in Pediatrics: Adult Hypertension Onset in Youth study were analyzed for LA measurements. The association of casual BP, ambulatory BP, and other cardiovascular disease risk factors with LA size and function were determined using descriptive statistics and multivariable regression. Regression models adjusting for age, sex, race, and body mass index z score determined the independent association between ambulatory systolic BP indices (mean systolic BP/50th %ile systolic BP) and BP phenotypes with LA outcomes while exploratory analyses investigated for additional predictors of LA outcomes. RESULTS: The study population consisted of 347 youth: median age 15.7 years, 60% male and 40% non-White. Greater-risk casual systolic BP groups had worse cardiometabolic profiles but no differences in LA size and function. Each 0.1 increase in ambulatory systolic BP day or night index was associated with a 9.9 mL/m2 increase in LA volume/body surface area (LAV/BSA; 95th% CI 2.8-17.0, P = .006) and a 6.8 mL/m2 increase in LAV/BSA (95th% CI 0.8-12.8, P = .03), respectively. Ambulatory hypertension was associated with greater odds of abnormal LAV/BSA, defined as >75th %ile (2014 ambulatory BP monitoring criteria: OR 3.2 [95th% CI 1.4-7.2; P = .002]; 2022 ambulatory BP monitoring criteria: OR 2.1 [95th% CI 1.0-4.1; P = .008]). CONCLUSIONS: Increasing ambulatory systolic BP and ambulatory hypertension are independently associated with LAV/BSA.

Experiences with recruitment and retention of adolescents and emerging adults in a weight loss intervention trial.

BACKGROUND/AIMS: Efficient and effective participant recruitment is key for successful clinical research. Adolescent and emerging adult recruitment into clinical trials can be particularly challenging, especially when targeting underrepresented groups. This study aimed to determine the most successful recruitment strategies from those employed during a pediatric trial testing the efficacy of a behavioral intervention on adiposity and cardiovascular disease risk. METHODS: We determined the effectiveness, cost, and diversity of the final research population by each recruitment method utilized in the EMPower trial, a randomized clinical trial designed to test the effect of a technology-delivered behavioral Healthy Lifestyle intervention on adiposity, blood pressure, and left ventricular mass among adolescents and emerging adults with overweight or obesity. Effectiveness was determined by respondent yield (RY; number of respondents/number contacted), scheduled yield (SY; number scheduled for a baseline visit/number of respondents), enrollment yield (EY; number enrolled/number of respondents), and retention (number completed/number enrolled). Cost-effectiveness of each recruitment method was calculated and demographics of participants recruited via each method was determined. RESULTS: A minimum of 109,314 adolescents and emerging adults were contacted by at least one recruitment method (clinic, web-based, postal mailing, electronic medical record (EMR) messaging) leading to 429 respondents. The most successful strategies in terms of RY were clinic-based recruitment (n = 47, 61% RY), community web-postings (n = 109, 5.33% RY), and EMR messaging (n = 163, 0.99% RY); however, website, postal mailings, and EMR recruitment led to more successful SY and EY. Postal mailings were the most costly strategy to employ (US$3261/completed participant) with EMR messaging the second most costly (US$69/completed participant). Community web-postings were free of charge. Clinic-based recruitment did not add additional costs, per se, but did require a substantial amount of personnel time (63.6 h/completed participant). Final cohort diversity primarily came from postal mailings (57% Black) and EMR messages (50% female). CONCLUSION: Electronic medical record messaging and web-based recruitment were highly successful and cost-effective strategies in a pediatric clinical trial targeting adolescents and emerging adults, but was less successful in recruiting a diverse cohort. Clinic recruitment and postal mailings, despite being costly and time-consuming, were the strategies that enrolled a greater proportion of underrepresented groups. While online forms of trial recruitment are growing in popularity, clinic-based recruitment and non-web-based strategies may be required to ensure participant diversity and representation.

Tobacco exposure in adults and children with proteinuric glomerulopathies: a NEPTUNE cohort study.

BACKGROUND: Tobacco exposure has been recognized as a risk factor for cardiovascular disease (CVD) and progression of kidney disease. Patients with proteinuric glomerulopathies are at increased risk for cardiovascular morbidity and mortality. Multiple studies have linked tobacco exposure to CVD and chronic kidney disease, but the relationships between smoking and proteinuric glomerulopathies in adults and children have not been previously explored. METHODS: Data from the Nephrotic Syndrome Study Network (NEPTUNE), a multi-center prospective observational study of participants with proteinuric glomerulopathies, was analyzed. 371 adults and 192 children enrolled in NEPTUNE were included in the analysis. Self-reported tobacco exposure was classified as non-smoker, active smoker, former smoker, or exclusive passive smoker. Baseline serum cotinine levels were measured in a sub-cohort of 178 participants. RESULTS: The prevalence of active smokers, former smokers and exclusive passive smoking among adults at baseline was 14.6%, 29.1% and 4.9%, respectively. Passive smoke exposure was 16.7% among children. Active smoking (reference non-smoking) was significantly associated with greater total cholesterol among adults (ß 17.91 95% CI 0.06, 35.76, p = 0.049) while passive smoking (reference non-smoking) was significantly associated with greater proteinuria over time among children (ß 1.23 95% CI 0.13, 2.33, p = 0.03). Higher cotinine levels were associated with higher baseline eGFR (r = 0.17, p = 0.03). CONCLUSION: Tobacco exposure is associated with greater risk for CVD and worse kidney disease outcomes in adults and children with proteinuric glomerulopathies. Preventive strategies to reduce tobacco exposure may help protect against future cardiovascular and kidney morbidity and mortality in patients with proteinuric glomerulopathies.

Pediatrician Adherence to Guidelines for Diagnosis and Management of High Blood Pressure.

OBJECTIVES: To assess pediatrician adherence to the 2017 American Academy of Pediatrics' clinical practice guideline for high blood pressure (BP). STUDY DESIGN: Pediatric primary care practices (n = 59) participating in a quality improvement collaborative submitted data for patients with high BP measured between November 2018 and January 2019. Baseline data included patient demographics, BP, body mass index (BMI), and actions taken. Logistic regression was used to test associations between patient BP level and BMI with provider adherence to guidelines (BP measurement, counseling, follow-up, evaluation). RESULTS: A total of 2677 patient charts were entered for analysis. Only 2% of patients had all BP measurement steps completed correctly, with fewer undergoing 3-limb and ambulatory BP measurement. Overall, 46% of patients received appropriate weight, nutrition, and lifestyle counseling. Follow-up for high BP was recommended or scheduled in 10% of encounters, and scheduled at the appropriate interval in 5%. For patients presenting with their third high BP measurement, 10% had an appropriate diagnosis documented, 2% had appropriate screening laboratory tests conducted, and none had a renal ultrasound performed. BMI was independently associated with increased odds of counseling, but higher BP was associated with lower odds of counseling. Higher BP was independently associated with an increased likelihood of documentation of hypertension. CONCLUSIONS: In this multisite study, adherence to the 2017 American Academy of Pediatrics' guideline for high BP was low. Given the long-term health implications of high BP in childhood, it is important to improve primary care provider recognition and management. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03783650.

Diet quality scores associated with improved cardiometabolic measures among African American adolescents.

BACKGROUND: The Reversing the Negative cardiovascular Effects on Weight (ReNEW) Clinic is a prospective cohort study in children and adolescents (≤21 years) at the Johns Hopkins Children's Center. METHODS: Cross-sectional analysis between diet quality using the Alternative Healthy Eating Index (AHEI-2010), pro-inflammatory potential using the Children's Dietary Inflammatory Index (C-DII), and cardiometabolic outcomes. AHEI-2010 and C-DII scores were assessed by median intake determined from the sample distribution and associated with cardiometabolic measures using linear regression models. Changes in measures were evaluated in a sub-sample of participants invited to attend follow-up visits due to the presence of hypertensive blood pressure (n = 33). RESULTS: Participants (n = 90) reported an average energy intake of 1790 kcal/day (SD ± 734), AHEI-2010 score of 55.04 (SD ± 9.86) (range: 0 to 110) and C-DII score of -0.12 (±0.86) (range -5 to 5). Participants with higher quality/anti-inflammatory diets trended towards more favorable cardiometabolic measures at baseline. Among the sub-sample (n = 33), there was a significant reduction in total energy (m = -302 kcal/day; p-value= 0.03) but no change in AHEI-2010 (p-value = 0.73) or C-DII score (p-value = 0.85) over follow-up. CONCLUSIONS: Despite stable diet quality scores, outpatient dietary and behavioral counseling may be an effective tool to reduce energy intake in youth with overweight/obesity and elevated blood pressure. IMPACT: Diet quality scores among obese, hypertensive, African American adolescents were low and reflect a pro-inflammatory diet. Reported intake was negligible for fruits, whole grains, nuts, and legumes, and well above the daily limit for sodium and saturated fat. Participants with high quality/anti-inflammatory diet quality scores trended toward improved cardiometabolic measures. Outpatient dietary counseling resulted in reduced total energy intake.

The performance of glycated albumin as a biomarker of hyperglycemia and cardiometabolic risk in children and adolescents in the United States.

OBJECTIVE: Diabetes and prediabetes are growing concerns among US youth. Fasting glucose (FG) and HbA1c are standard diabetes screening tests, but HbA1c may be unreliable in some settings and fasting is burdensome in children. Glycated albumin (GA) is a non-fasting test that was recently cleared for clinical use in the United States, but studies in youth without diabetes are limited. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional analysis in 6826 youth without diabetes aged 8-19 years in the 1999-2004 National Health and Nutrition Examination Survey. We evaluated the associations of GA with HbA1c, FG, and cardiometabolic risk factors. RESULTS: GA was poorly correlated with HbA1c (ρ = 0.074) and FG (ρ = -0.047) and was negatively associated with body mass index (BMI) and cardiometabolic risk factors. Compared to youth in the highest tertile of GA (≥13.5%), those in the lowest GA tertile (<12.4%) had a higher prevalence of obesity (29.9% vs. 7.6%), low high-density lipoprotein cholesterol (29.7% vs. 16.5%), and hypertensive blood pressure (4.0% vs. 2.7%). These inverse associations persisted after adjustment for age, sex, race/ethnicity, serum albumin, and C-reactive protein. CONCLUSIONS: GA was poorly correlated with traditional markers of hyperglycemia in youth without diabetes. Counterintuitively, there was a negative association between GA and BMI. Among youth without diabetes, GA does not identify youth at high cardiometabolic risk, and it does not appear to be an appropriate biomarker for screening of hyperglycemia.

Agreement between attended home and ambulatory blood pressure measurements in adolescents with chronic kidney disease.

BACKGROUND: This study aimed to compare attended home blood pressure (BP) measurements (HBPM) with ambulatory BP monitor (ABPM) readings and examine if level of agreement between measurement modalities differs overall and by subgroup. METHODS: This was a secondary analysis of data from a 2-year, multicenter observational study of children 11-19 years (mean 15, SD = 2.7) with chronic kidney disease. Participants had 3 standardized resting oscillometric home BPs taken by staff followed by 24-h ABPM within 2 weeks of home BP. BP indices (measured BP/95%ile BP) were calculated for mean triplicate attended HBPM and mean ABPM measurements. Paired HBPM and ABPM measurements taken during any of 5 study visits were compared using linear regression with robust standard errors. Generalized estimating equation-based logistic regression determined sensitivity, specificity, negative, and positive predictive values with ABPM as the gold standard. Analyses were conducted for the group overall and by subgroup. RESULTS: A total of 103 participants contributed 251 paired measurements. Indexed systolic BP did not differ between HBPM and daytime APBM (mean difference - 0.002; 95% CI: - 0.006, 0.003); the difference in indexed diastolic BP was minimal (mean difference - 0.033; 95% CI: - 0.040, - 0.025). Overall agreement between HBPM and 24-h ABPM in identifying abnormal BP was high (81.8%). HBPM had higher sensitivity (87.5%) than specificity (77.4%) and greater negative (89.8%) than positive (73.3%) predictive value, and findings were consistent in subgroups. CONCLUSIONS: Attended HBPM may be reasonable for monitoring BP when ABPM is unavailable. The greater accessibility and feasibility of attended HBPM may potentially help improve BP control among at-risk youth. A higher resolution version of the Graphical abstract is available as Supplementary information.

Left Ventricular Diastolic Dysfunction Among Youth with Obesity and History of Elevated Blood Pressure.

OBJECTIVE: To assess prevalence of and factors associated with left ventricular diastolic dysfunction (LVDD) in youth with obesity and elevated blood pressure (BP). STUDY DESIGN: This was a cross-sectional analysis of baseline and follow-up visits of 83 youth, 5-21 years, evaluated for overweight/obesity and elevated BP in a multidisciplinary clinic. LVDD was defined according to established adult criteria (LVDDadult; E/A < 1, E/e' > 14, or e'/a' < 0.8) and pediatric criteria (LVDDpeds; E/A <10th percentile, E/e' >99th percentile, or e'/a' <1st percentile) based on data from 103 age-sex matched healthy controls. Baseline factors associated with LVDDpeds were examined using Wilcoxon rank sum and χ2 tests. Multiple logistic regression analyses using generalized estimating equations to account for repeated measures evaluated the associations of adiposity and BP with LVDDpeds. RESULTS: The prevalence of LVDD ranged from 1.2% to 2.7% when we used adult criteria and 19% to 28% when we used pediatric criteria. Those with LVDDpeds were older, predominantly male, and non-African American and had greater weight, BP, BP medication use, and non-high-density lipoprotein cholesterol than those without LVDDpeds. Diastolic BP z score was associated with LVDDpeds by E/A (OR 1.95, 95% CI 1.15-3.32, P = .014) after we adjusted for age, sex, race, BP medications, and body mass index z score. CONCLUSIONS: LVDD was present in a substantial proportion of youth with overweight/obesity and elevated BP using pediatric criteria. Those with LVDDpeds had significantly greater measures of adiposity and BP compared with those without LVDDpeds, and diastolic BP z score was an independent predictor of LVDDpeds by E/A. These data emphasize the importance of prevention and treatment of cardiovascular disease risk factors in childhood.

Social Determinants of Cardiovascular Health in African American Children With CKD: An Analysis of the Chronic Kidney Disease in Children (CKiD) Study.

RATIONALE & OBJECTIVE: To identify differences in socioeconomic factors (SES) and subclinical cardiovascular disease (CVD) markers by race among Chronic Kidney Disease in Children (CKiD) participants and determine whether differences in CVD markers persist after adjusting for SES. STUDY DESIGN: Analysis of 3,103 visits with repeated measures from 628 children (497 White participants; 131 African American participants) enrolled in the CKiD study. SETTING & PARTICIPANTS: Children with mild-moderate CKD with at least 1 cardiovascular (CV) parameter (ambulatory blood pressure, left ventricular mass index [LVMI], or lipid profile) measured. EXPOSURE: African American race. OUTCOMES: Ambulatory hypertension, LVMI, triglycerides, high-density lipoprotein cholesterol. ANALYTICAL APPROACH: Due to increased CV risks of glomerular disease, the analysis was stratified by CKD cause. Inverse probability weighting was used to adjust for SES (health insurance, household income, maternal education, food insecurity, abnormal birth history). Linear and logistic regression were used to evaluate association of race with CV markers. RESULTS: African American children were disproportionately affected by adverse SES. African Americans with nonglomerular CKD had more instances of ambulatory hypertension and higher LVMI but more favorable lipid profiles. After adjustment for SES, age, and sex, the magnitude of differences in these CV markers was attenuated but remained statistically significant. Only LVMI differed by race in the glomerular CKD group, despite adjustment for SES. LIMITATIONS: Study design limits causal inference. CONCLUSION: African American children with CKD are disproportionately affected by socioeconomic disadvantages compared with White children. The degree to which CV markers differ by race is influenced by disease etiology. African Americans with nonglomerular CKD have increased LVMI, more ambulatory hypertension, and favorable lipid profile, but attenuation in magnitude after adjustment for SES was observed. African Americans with glomerular CKD had increased LVMI, which persisted after SES adjustment. As many social determinants of health were not captured, future research should examine effects of systemic racism on CV health in this population.

Higher Diet Quality in African-American Adolescents Is Associated with Lower Odds of Metabolic Syndrome: Evidence from the NHANES.

BACKGROUND: Development of clinical risk factors linked to metabolic syndrome (MetS) in adolescence is associated with higher incidence of atherosclerotic cardiovascular events in adulthood. Given the increasing burden of obesity and MetS in African-American (AA) youth, there is a need to establish the relation of MetS with modifiable risk factors such as diet quality, because these data may enhance preventative and treatment approaches. OBJECTIVES: The purpose of this study was to assess diet quality, measured by the Alternative Healthy Eating Index 2010 (AHEI-2010) and the Dietary Approaches to Stop Hypertension (DASH) pattern score, in AA adolescents and youth (aged 12-21 y) from the NHANES, and to investigate the association of diet quality with MetS and its components. METHODS: This study is a cross-sectional analysis of NHANES data from the 2005-2016 cycles (n = 2459). Survey-weighted logistic regression models were used to assess the association of diet quality with the prevalence of MetS and individual cardiometabolic components [overweight/obesity, hypertensive blood pressure (BP), impaired fasting glucose, low HDL cholesterol, hypertriglyceridemia]. RESULTS: The mean ± SD AHEI-2010 score was 38.9 ± 9.7 and DASH pattern score was 21.8 ± 4.4, which is equivalent to 35% adherence to recommendations to achieve an optimal diet quality and 45% adherence to the DASH-style dietary pattern, respectively. Compared with those within the lowest quartile of DASH pattern score, individuals in the fourth quartile group had 0.63 (95% CI: 0.41, 0.97) times the odds of having hypertensive BP. Among individuals with complete clinical measures (n = 1007), individuals within the highest-quartile AHEI-2010 group had 0.25 (95% CI: 0.06, 0.99) times the odds of having MetS compared with those within the lowest quartile. CONCLUSIONS: Diet quality in US AA youth is low. Higher DASH pattern scores were associated with lower odds of hypertensive BP and higher AHEI-2010 scores were associated with lower odds of MetS.

Adiposity, Sex, and Cardiovascular Disease Risk in Children With CKD: A Longitudinal Study of Youth Enrolled in the Chronic Kidney Disease in Children (CKiD) Study.

RATIONALE & OBJECTIVE: Traditional and nontraditional cardiovascular disease risk factors are highly prevalent in children with chronic kidney disease (CKD). We examined the longitudinal association of adiposity with cardiac damage among children with CKD and explored whether this association was modified by sex. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Children with mild-to-moderate CKD enrolled in the Chronic Kidney Disease in Children (CKiD) Study at 49 pediatric nephrology centers across North America. EXPOSURE: Age- and sex-specific body mass index (BMI) z score. OUTCOME: Age- and sex-specific left ventricular mass index (LVMI) z score and left ventricular hypertrophy (LVH). ANALYTICAL APPROACH: Longitudinal analyses using mixed-effects models to estimate sex-specific associations of BMI z scores with LVMI z score and with LVH, accounting for repeated measurements over time. RESULTS: Among 725 children with 2,829 person-years of follow-up, median age was 11.0 years and median estimated glomerular filtration rate was 52.6mL/min/1.73m2. Nearly one-third of both boys and girls were overweight or obese, median LVMI z score was 0.18 (IQR: -0.67, 1.08), and 11% had LVH. Greater BMI z scores were independently associated with greater LVMI z scores and greater odds of LVH. For each 1-unit higher BMI z score, LVMI z score was 0.24 (95% CI, 0.17-0.31) higher in boys and 0.38 (95% CI, 0.29-0.47) higher in girls (Pinteraction = 0.01). For each 1-unit higher BMI z score, the odds of LVH was 1.5-fold (95% CI, 1.1-2.1) higher in boys and 3.1-fold (95% CI, 1.8-4.4) higher in girls (Pinteraction = 0.005). LIMITATIONS: Not all children had repeated measurements. LVH is a surrogate and not a hard cardiac outcome. The observational design limits causal inference. CONCLUSIONS: In children, adiposity is independently associated with the markers of cardiac damage, LVMI z score and LVH. This association is stronger among girls than boys. Pediatric overweight and obesity may therefore have a substantial impact on cardiovascular risk among children with CKD.

Real-World Strategies to Treat Hypertension Associated with Pediatric Obesity.

PURPOSE OF REVIEW: To review the most recent literature on current strategies for the treatment of hypertension associated with pediatric obesity. RECENT FINDINGS: Over the last three decades, childhood and adolescent overweight and obesity prevalence in the USA has continued to rise. Unsurprisingly but rather disturbingly, this rising prevalence has been paralleled by an increase in cardiovascular disease (CVD) risk factors in childhood such as hypertension, dyslipidemia, and diabetes that become manifest earlier than previously reported. These childhood CVD risk factors are not only associated with target organ damage in childhood but also track into adulthood, increasing the risk of long-term CVD morbidity and mortality. There have been several mechanisms proposed to explain the role of obesity on the development of hypertension in childhood. However, central to the management of obesity-related hypertension is a multifaceted approach targeting lifestyle modifications and weight loss. Effective treatment often also requires a pharmacologic approach and rarely bariatric surgery.

Management of high blood pressure in children: similarities and differences between US and European guidelines.

Over the last several decades, many seminal longitudinal cohort studies have clearly shown that the antecedents to adult disease have their origins in childhood. Hypertension (HTN), which has become increasingly prevalent in childhood, represents one of the most important risk factors for cardiovascular diseases (CVD) such as heart disease and stroke. With the risk of adult HTN much greater when HTN is manifest in childhood, the future burden of CVD worldwide is therefore concerning. In an effort to slow the current trajectory, professional societies have called for more rigorous, evidence-based guideline development to aid primary care providers and subspecialists in improving recognition, diagnosis, evaluation, and treatment of pediatric HTN. In 2016 the European Society of Hypertension and in 2017 the American Academy of Pediatrics published updated guidelines for prevention and management of high blood pressure (BP) in children. While there are many similarities between the two guidelines, important differences exist. These differences, along with the identified knowledge gaps in each, will hopefully spur clinical researchers to action. This review highlights some of these similarities and differences, focusing on several of the more important facets regarding prevalence, prevention, diagnosis, management, and treatment of childhood HTN.