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 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.

Prevalence Implications of the 2017 American Academy of Pediatrics Hypertension Guideline and Associations with Adult Hypertension.

OBJECTIVE: To evaluate the impact of the 2017 American Academy of Pediatrics hypertension Clinical Practice Guideline (CPG), compared with the previous guideline ("Fourth Report"), on the frequency of hypertensive blood pressure (BP) measurements in childhood and associations with hypertension in adulthood using data from the International Childhood Cardiovascular Cohort Consortium. STUDY DESIGN: Childhood BPs were categorized in normal, prehypertensive/elevated, and hypertensive (stage 1 and 2) ranges using the Fourth Report and the CPG. Participants were contacted in adulthood to assess self-reported hypertension. The associations between childhood hypertensive range BPs and self-reported adult hypertension were evaluated. RESULTS: Data were available for 34 014 youth (10.4 ± 3.1 years, 50.6% female) with 92 751 BP assessments. Compared with the Fourth Report, the CPG increased hypertensive readings from 7.6% to 13.5% and from 1.3% to 2.5% for stage 1 and 2 hypertensive range, respectively (P < .0001). Of 12 761 adults (48.8 ± 7.9 years, 43% male), 3839 (30.1%) had self-reported hypertension. The sensitivity for predicting adult hypertension among those with hypertensive range BPs at any point in childhood, as defined by the Fourth Report and the CPG, respectively, was 13.4% and 22.4% (specificity 92.3% and 85.9%, P < .001), with no significant impact on positive and negative predictive values. Associations with self-reported adult hypertension were similar and weak (c-statistic range 0.61-0.68) for hypertensive range BPs as defined by the Fourth Report and CPG. CONCLUSIONS: The CPG significantly increased the prevalence of childhood BPs in hypertensive ranges and improved the sensitivity, without an overall strengthened association, of predicting self-reported adult hypertension.

Early Atherosclerotic Inflammatory Pathways in Children with Obstructive Sleep Apnea.

OBJECTIVE: To evaluate structural and functional carotid changes and inflammatory profiles in children with obstructive sleep apnea (OSA) and healthy controls. STUDY DESIGN: Patients with OSA and matched controls (ages 5-13 years) were recruited. Proinflammatory cytokines and acute phase reactants were measured at 6:00 p.m. Common carotid artery measures were determined using ultrasound. Confirmatory factor analysis was used to determine subgroups of cytokines and their effects on carotid measures. RESULTS: Ninety-six patients participated (53 healthy controls, 43 patients with OSA). OSA was associated with increased proinflammatory cytokines (cluster of differentiation-40 ligand [CD40-L], interleukin [IL]-6, and IL-8) and high sensitivity C-reactive protein (P < .05 for all). One cytokine subgroup (IL-6 and IL-8) was negatively associated with markers of carotid function, indicating reduced arterial distensibility and increased stiffness (P < .05 for 3 ultrasound measures); and tumor necrosis factor-α had an opposing effect on carotid function compared with this cytokine subgroup (P < .05 for 2 ultrasound measures). Linear regression demonstrated significant associations between and tumor necrosis factor- α and 2 measures of carotid function (P < .05 for each). Children with OSA did not have functional or structural carotid changes compared with controls. CONCLUSION: OSA was not directly associated with structural and functional carotid changes but was associated with upregulation of key proinflammatory cytokines (sCD40-L, IL-6, and IL-8). Together, IL-6 and IL-8 were associated with changes in carotid function. Longitudinal studies are needed to demonstrate that the inflammatory milieu observed in our population is a precursor of atherosclerosis in children.

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.

Bone Mass and Density in Youth With Type 2 Diabetes, Obesity, and Healthy Weight.

OBJECTIVE: Youth-onset type 2 diabetes is an aggressive condition with increasing incidence. Adults with type 2 diabetes have increased fracture risk despite normal areal bone mineral density (aBMD), but the influence of diabetes on the growing skeleton is unknown. We compared bone health in youth with type 2 diabetes to control patients with obesity or healthy weight. RESEARCH DESIGN AND METHODS: Cross-sectional study of youth (56% African American, 67% female) ages 10-23 years with type 2 diabetes (n = 180), obesity (BMI >95th; n = 226), or healthy weight (BMI <85th; n = 238). Whole-body (less head) aBMD and lean mass as well as abdominal visceral fat were assessed via DXA. Lean BMI (LBMI) and aBMD SD scores (z scores) were computed using published reference data. RESULTS: We observed age-dependent differences in aBMD and LBMI z scores between the healthy weight, obese, and type 2 diabetes groups. In children, aBMD and LBMI z scores were greater in the type 2 diabetes group versus the obese group, but in adolescents and young adults, aBMD and LBMI z scores were lower in the type 2 diabetes group versus the obese group (age interactions P < 0.05). In the type 2 diabetes group and the obese group, aBMD was about 0.5 SDs lower for a given LBMI z score compared with healthy weight control patients (P < 0.05). Further, aBMD was lower in those with greater visceral fat (ß = -0.121, P = 0.047). CONCLUSIONS: These results suggest that type 2 diabetes may be detrimental to bone density around the age of peak bone mass. Given the increased fracture risk in adults with type 2 diabetes, there is a pressing need for longitudinal studies aimed at understanding the influence of diabetes on the growing skeleton.

Racial Differences in the Influence of Risk Factors in Childhood on Left Ventricular Mass in Young Adulthood.

OBJECTIVE(S): To examine racial differences in the relationship between cardiovascular (CV) risk factors measured since age 10 years and left ventricular mass index (LVMI) in adulthood in the National Heart, Lung, and Blood Institute Growth and Health Study. STUDY DESIGN: Longitudinal investigation with CV risk factors measured throughout childhood and LVMI measured in adulthood. In total, 556 black and white girls were recruited from schools in the greater Cincinnati area. Analyses examined traditional CV risk factors at baseline, follow-up, and over time (ie, area under the curve [AUC]). LVMI was collected with 2-dimensional guided echocardiographic imaging at a mean age of 25.7 ± 1.7 years. RESULTS: Black girls had higher adiposity and insulin and lower heart rate across time (all P < .05). Blacks had higher LVMI compared with whites in adulthood. Major determinants of young adult LVMI, were race, body mass index z score AUC, systolic blood pressure z score AUC, percent body fat by skin fold AUC, heart rate AUC, and an interaction between race and heart rate (model R2 = 0.40, P < .0001). CONCLUSIONS: The major determinants of LVMI in young female adults are race, adiposity, and systolic blood pressure.

A Pilot Study of School-Based Comprehensive Cardiovascular Screening in Middle School Children.

Although recommended, most children are not routinely screened for lipid abnormalities and diabetes. We report a pilot of universal screening for diabetes, lipid abnormalities, and hypertension in the middle-school setting. Of 45 children screened, 34.8% had lipid or hemoglobin A1c abnormalities and 2 had hemoglobin A1c values in the diabetes range.

Live Video Diet and Exercise Intervention in Overweight and Obese Youth: Adherence and Cardiovascular Health.

OBJECTIVE: To evaluate adherence of overweight and obese adolescents to a live video lifestyle intervention. The impact on vascular and functional health was also assessed. STUDY DESIGN: Twenty adolescents 14.5 ± 2.1 years of age with body mass index z-score 1.94 ± 0.43 were enrolled. The 12-week intervention included 3-times-weekly videoconference sessions with a trainer and weekly diet consultations. Adherence was evaluated by completion rate and percentage of sessions attended. Vascular health indices and traditional cardiovascular risk factors were obtained at baseline and study end. RESULTS: Seventeen participants (85%) completed the intervention. The participants attended 93 ± 11% of scheduled sessions. Reasons for absences included illness/injury (23%), school activities (21%), holidays (18%), forgetting the appointment (8%), Internet connectivity issues (7%), and family emergency (7%). Significant changes were observed in waist-hip ratio (0.87 ± 0.08 vs 0.84 ± 0.08, P = .03), total (159 ± 27 vs 147 ± 23 mg/dL, P = .004) and low-density lipoprotein cholesterol levels (91 ± 20 vs 81 ± 18 mg/dL, P = .004), volume of inspired oxygen per heartbeat at peak exercise (69 ± 16 vs 72 ± 15%, P = .01), and functional movement score (13 ± 2 vs 17 ± 1, P < .001). Participants with abnormal vascular function at baseline showed improvement in endothelial function and arterial stiffness indices (P = .01 and P = .04, respectively). CONCLUSIONS: A 12-week live video intervention promotes adherence among overweight and obese adolescents and shows promise for improving vascular and functional health. Integrating telehealth into preventive care has the potential to improve cardiovascular health in the youth at risk.

Smoking and arterial stiffness in youth with type 1 diabetes: the SEARCH Cardiovascular Disease Study.

OBJECTIVE: To evaluate the effects of smoking on early markers of cardiovascular disease (arterial stiffness) in adolescents with and without type 1 diabetes (T1D) in the SEARCH Cardiovascular Disease Study. STUDY DESIGN: Participants included 606 youth (18.9 ± 3.3 years, 83% non-Hispanic white; 50% male). Six groups were defined: (1) smokers with T1D (n = 80); (2) former smokers with T1D (n = 88); (3) nonsmokers with T1D (n = 232); (4) smokers without T1D (n = 40); (5) former smokers without T1D former (n = 51); and (6) nonsmokers without T1D (n = 115). Arterial stiffness measurements included pulse wave velocity (PWV), augmentation index, and brachial distensibility. Multivariate linear regression was used to assess the independent and joint effects of T1D and smoking on arterial stiffness. RESULTS: Nearly 20% of both youth with and without T1D and T1D were smokers. In youth without T1D, smokers had higher trunk and arm PWV. After adjustment for potential confounders, T1D, but not smoking, was an independent predictor of PWV (P < .05). Moreover, smoking status did not modify the association between T1D and increased arterial stiffness. CONCLUSIONS: We found a high prevalence of smoking among youth with and without T1D; however, smoking status was not independently associated with increased arterial stiffness in youth with T1D.

Urinary phthalates are associated with higher blood pressure in childhood.

OBJECTIVE: To examine associations of urinary phthalate levels with blood pressure (BP) and serum triglyceride and lipoprotein levels in children. STUDY DESIGN: We performed a cross-sectional analysis of a subsample of US children aged 6-19 years who participated in the National Health and Nutrition Examination Survey between 2003 and 2008. We quantified exposure to 3 families of phthalates--low molecular weight, high molecular weight and di-2-ethylhexylphthalate (DEHP)--based on molar concentration of urinary metabolites. We assessed descriptive, bivariate, and multivariate associations with BP and lipid levels. RESULTS: Controlling for an array of sociodemographic and behavioral factors, as well as diet and body mass index, levels of metabolites of DEHP, a phthalate commonly found in processed foods, were associated with higher age-, sex-, and height-standardized BP. For each log unit (roughly 3-fold) increase in DEHP metabolites, a 0.041 SD unit increase in systolic BP z-score was identified (P = .047). Metabolites of low molecular weight phthalates commonly found in cosmetics and personal care products were not associated with BP. Phthalate metabolites were not associated with triglyceride levels, high-density lipoprotein level, or prehypertension. CONCLUSIONS: Dietary phthalate exposure is associated with higher systolic BP in children and adolescents. Further work is needed to confirm these associations, as well as to evaluate opportunities for intervention.

Relationship between elevated arterial stiffness and increased left ventricular mass in adolescents and young adults.

OBJECTIVE: To determine whether arterial stiffness relates to left ventricular mass (LVM) in adolescents and young adults. STUDY DESIGN: Demographic, anthropometric, laboratory, echo, carotid ultrasound and arterial stiffness data were obtained in 670 subjects 10 to 24 years of age (35% male, 62% non-Caucasian). Global stiffness index (GSI) was calculated from five measures of carotid artery stiffness, augmentation index, brachial distensibility, and pulse wave velocity (1 point if ≥95th% for subjects with body mass index <85th%). Stiff arteries (S = 73) were defined as GSI ≥95th%. Differences between flexible (F = 597) and S groups were evaluated by t tests. Models were constructed to determine whether GSI was an independent determinant of LVM index or relative wall thickness (RWT). RESULTS: The S group had more adverse cardiovascular risk factors, higher LVM index and RWT (P ≤ .05) with a trend for abnormal cardiac geometry. Independent determinants of LVM index were higher GSI, age, body mass index, systolic blood pressure, heart rate, glycated hemoglobin A1c, male sex, and sex-by-heart rate interaction (r(2) = 0.52; P ≤ .05). GSI was also an independent determinant of RWT. CONCLUSIONS: Increased arterial stiffness in adolescents and young adults is associated with LVM index independently of traditional cardiovascular risk factors. Screening for arterial stiffness may be useful to identify high risk adolescents and young adults.

Cardiovascular impact of the pediatric obesity epidemic: higher left ventricular mass is related to higher body mass index.

OBJECTIVE: To compare secular changes in body mass index (BMI) and left ventricular mass (LVM) in today's children versus children of a generation earlier. STUDY DESIGN: All healthy patients aged 2 to 19 years who underwent echocardiography at a single US academic medical center in 1986 to 1989 (prior era) and 2008 (current era) were included in this retrospective cross-sectional study. BMI, BMI z score, LVM indexed to height (LVMI), LVM z score, and relative wall thickness were calculated. Cardiac geometries were assigned based on LVM z score and relative wall thickness and classified as normal, concentric hypertrophy, eccentric hypertrophy, or concentric remodeling. Stepwise regression analysis was performed to identify determinants of LVMI. RESULTS: There were 350 subjects in the prior era and 350 age- and sex-matched subjects in the current era. Mean BMI and LVMI were both significantly higher in the current era than in the prior era (BMI, 19.9 ± 5.6 kg/m(2) vs 18.1 ± 3.8 kg/m(2), P = .0004; LVMI, 32.7 ± 7.8 g/m(2.7) vs 31.5 ± 8.1 g/m(2.7); P = .02). Determinants of LVMI in both eras were BMI z score, younger age, male sex, and African-American race. CONCLUSIONS: Today's children have higher BMI, LVMI, and predicted cardiovascular risk than their counterparts a generation earlier. Reversal of these trends is needed, and intervention is required.

Prevalence of increased arterial stiffness in children with type 1 diabetes mellitus differs by measurement site and sex: the SEARCH for Diabetes in Youth Study.

OBJECTIVE: To discuss vascular stiffness commonly encountered in children with type 1 diabetes mellitus (T1DM). STUDY DESIGN: We examined 535 subjects with T1DM (14.6 years; 53% male, 88% non-Hispanic white) and 241 healthy control subjects (17.8 years; 42% male, 39% non-Hispanic white). Abnormalities in brachial distensibility (BrachD), pulse wave velocity, and augmentation index corrected to a HR of 75 (AIx-75) were examined. RESULTS: Subjects with T1DM had higher body mass index, LDL-cholesterol, fasting glucose, and blood pressure than control subjects. Diabetic subjects had lower BrachD and higher AIx-75 indicating increased stiffness. Age-adjusted pulse wave velocity-trunk (aorto-femoral) was higher in cases (all P

Colesevelam hydrochloride: efficacy and safety in pediatric subjects with heterozygous familial hypercholesterolemia.

OBJECTIVE: Evaluate the efficacy and safety of colesevelam hydrochloride in children with heterozygous familial hypercholesterolemia (heFH). STUDY DESIGN: This was a randomized, double-blind, 41-site study in 194 children aged 10 to 17 years (inclusive) with heFH (statin-naïve or on a stable statin regimen). After a 4-week stabilization period (period I), subjects were randomized 1:1:1 to placebo, colesevelam 1.875 g/d, or colesevelam 3.75 g/d for 8 weeks (period II). All then received open-label colesevelam 3.75 g/d for 18 weeks (period III), with follow-up 2 weeks later. The primary endpoint was percent change in low-density lipoprotein (LDL)-cholesterol from baseline to week 8. Secondary endpoints included percent change in other lipoprotein variables, including non-high-density lipoprotein (non-HDL)-cholesterol. Adverse events were also evaluated. RESULTS: At week 8, a significant difference from baseline in LDL-cholesterol was reported with colesevelam 1.875 g/d (-6.3%; P = .031) and colesevelam 3.75 g/d (-12.5%; P < .001) compared with placebo. Significant treatment effects were also reported for total cholesterol (-7.4%), non-HDL-cholesterol (-10.9%), HDL-cholesterol (+6.1%), apolipoprotein A-I (+6.9%), and apolipoprotein B (-8.3%) and a nonsignificant effect for triglycerides (+5.1%) with colesevelam 3.75 g/d compared with placebo at week 8. These treatment effects were maintained during period III. CONCLUSIONS: Colesevelam significantly lowered LDL-cholesterol levels in children with heFH.