AIMS:The role of adult HDL-C in atherosclerotic cardiovascular disease (ASCVD) faces challenges from Mendelian randomizations and drug trials. However, the association between childhood HDL-C and its changes and adult ASCVD remains undefined. This study aimed to determine this association. METHODS AND RESULTS:Participants: Children in the International Childhood Cardiovascular Cohort (i3C) Consortium with childhood HDL-C and adult ASCVD follow-up. Age- and sex-standardized HDL-C z-scores were calculated for childhood (3-19 years), early childhood (3-11 years), and adolescence (12-19 years); low HDL-C defined as <1.03 mmol/L; participants classified as consistently normal, low to normal, normal to low, and consistently low based on HDL-C status at early childhood and adolescence. ASCVD events: Identified using self-reports adjudicated by medical records or death registries. Analysis: Cox proportional hazards models quantified the associations between childhood HDL-C and adult ASCVD. The study included 38 589 participants (49.7% males, mean age in 2016: 46.4 years) with 779 ASCVD and 784 imputed ASCVD events. After adjusting for sex, cohort, age, and HDL-C measurement year, higher HDL-C z-scores in childhood, early childhood, and adolescence were associated with lower adult ASCVD risk [hazard ratio (HR): 0.81-0.82], with the lowest risk at HDL-C > 1.50 mmol/L. Normal to low [HR 1.38, 95% confidence intervaI (CI) 1.04-1.82] and consistently low (HR 1.94, 95% CI 1.45-2.63) childhood HDL-C increased adult ASCVD risk compared to consistently normal HDL-C. Adjusting for body mass index and triglycerides weakened these associations. CONCLUSION:Childhood and adolescent HDL-C were prospectively and inversely associated with adult ASCVD, suggesting that low HDL-C could be a risk marker of adult ASCVD. Future replications, mechanistic studies, and Mendelian randomizations on childhood HDL-C may clarify its causal effects on adult ASCVD. LAY SUMMARY:We examined the association between childhood HDL-C measurement and adult atherosclerotic cardiovascular disease (ASCVD) at follow-up in data from the International Childhood Cardiovascular Cohort (i3C) Consortium.Higher HDL-C levels in childhood were associated with lower risk of a ASCVD event, irrespective of age (early childhood vs. adolescence). The lowest risk was observed at HDL-C concentrations of around and above 1.50 mmol/L (58 mg/dL). A decrease in HDL-C from early childhood to adolescence was associated with an increased risk of adult ASCVD.When additionally adjusted for body mass index z-score, attenuated associations were noted. Adding triglycerides to models attenuated associations towards null.

Advances in pediatric research have improved the lives of infants, children, adolescents, and society at large. A decade ago the American Academy of Pediatrics identified seven research achievements in the past 40 years that reduced morbidity and mortality worldwide: preventing disease with life-saving immunizations, reducing sudden infant death with "Back to Sleep," curing Acute Lymphoblastic Leukemia, helping premature babies breathe with surfactant, preventing Human Immunodeficiency Virus transmission from mother to baby, increasing life expectancy for children with Sickle Cell Anemia and Cystic Fibrosis, and saving lives with car seats and seat belts. This follow-up article forecasts the next great achievements in pediatric research and highlights what is needed to continue progress. The pediatric scientific community identified 10 areas of high research promise: genomics; mental and behavioral health; vaccines; artificial intelligence and digital health; perinatal health, including fetal medicine; precision and targeted therapeutics; social determinants of health; nutrition; environmental health; and advances in cancer treatment. Advances in each of these areas are already improving health outcomes. Amid increasing public distrust in science, celebrating scientific progress and committing to continued investment are critical to improving the health of children and the adults they will become. IMPACT: Advances in pediatric research have improved the lives of infants, children, adolescents, and society at large. The pediatric scientific community identified 10 exciting pediatric research breakthroughs on the horizon, which are reviewed in this article. Amid increasing public distrust in science, celebrating scientific progress and committing to continued investment are critical to improving the health of children and the adults they will become.

Background: Previous research has shown adverse childhood experiences (ACEs) – traumatic events such as witnessing domestic violence and experiencing physical abuse before age 18 – are associated with poorer cardiovascular health (CVH) in childhood. However, this association may be confounded by childhood home environment and other social determinants of health (SDOH). We explored this relationship using propensity score matching to control for selection bias. Methods: We conducted a propensity score (PS)-matched analysis in the Young Hearts study, a Chicago-based pediatric cohort study. We included participants aged 1-17y (N = 6,487) with available ACEs and behavioral CVH (bCVH) data (diet, exercise, nicotine exposure, sleep, and BMI). Participants self-reported whether the child was exposed to any of 17 possible ACEs. We calculated bCVH scores (0-100) using an age-appropriate adaptation of the Life’s Essential 8 framework. PS matching balanced the sample on key SDOH, including parental education, child sex, child race and ethnicity, birth year, and number of adults and children at home. Then, linear regression assessed the association of ACEs with bCVH scores. Results: The PS-matched sample included 3263 children without ACEs and 3078 children with at least 1 ACE. Individuals with >=1 ACE had significantly lower bCVH scores than those without ACEs (-4.72; 95% CI -5.36, -4.09) ( Figure ). Among individual CVH metrics, ACEs were most strongly associated with diet (-8.40, 95% CI = -9.65, -7.15) and physical activity (-5.48, 95% CI = -6.91, -4.05). Conclusion: This study highlights the significant impact of ACEs on children’s CVH. The use of propensity score matching to reduce SDOH-related confounding suggests that efforts to prevent the ACEs themselves would likely be complementary to important efforts to improve adverse SDOH. These findings underscore the need for early identification of and intervention for children experiencing ACEs to improve and preserve CVH.

BACKGROUND: Hypertension in adolescence is associated with subclinical target organ injury. We aimed to determine whether different blood pressure thresholds were associated with an increasing number of target organ injury markers in healthy adolescents. METHODS: A total of 244 participants (mean age 15.5±1.8 years, 60.1% male) were studied. Participants were divided based on systolic clinic and systolic awake ambulatory blood pressure into low- (<75th percentile), mid- (75th–90th percentile), and high-risk (>90th percentile) groups. The ambulatory blood pressure phenotype was classified as normotensive, white-coat, masked, or sustained hypertension. Target organ injury assessments included left ventricular mass, systolic and diastolic function, and vascular stiffness. A multivariable general linear model was constructed to evaluate the association of different participant characteristics with higher numbers of target organ injury markers. RESULTS: A total of 31.2% of participants had 1, 11.9% 2, 3.7% 3, and 0.8% 4 target organ injury markers. The number of target organ injury markers increased according to the risk groups: the percentage of participants with >1 marker in the low-, mid-, and high-risk groups was 6.7%, 19.1%, and 21.8% ( P =0.02) and 9.6%, 15.8%, and 32.2% ( P <0.001), based on clinic and ambulatory blood pressure, respectively. Participants with white-coat (23%), masked (35%), and sustained hypertension (32%) had significantly higher >1 target organ injury marker than normotensives (8%, P <0.001). The results were unchanged in multivariate analysis. CONCLUSIONS: High clinic and ambulatory blood pressure values, as well as ambulatory blood pressure phenotypes (white-coat, masked, and sustained hypertension), were independently associated with an increasing number of subclinical cardiovascular injury markers in adolescents.

Introduction: School environments play a crucial role in shaping the social and physical health of children, by promoting lifelong healthy habits. Therefore, we examined the association between harmful (peer-bullying) and positive (school connectedness) school-based experiences and behavioral CVH (bCVH) among children and adolescents. Methods: Data from 910 youth (14.9±1.9 years; 49.6% non-Hispanic White; 48% female) from the Young Hearts Study were analyzed. Self-reported experiences of peer bullying and school connectedness were measured via the School Experiences survey. Scores for bullying and school connectedness were derived by summing each of the four items pertaining to peer bullying and school connectedness, from their respective subdomain. A composite bCVH score was calculated by averaging scores for the four behavioral components of the American Heart Association Life’s Essential 8 [LE8; diet, physical activity (PA), sleep, and nicotine exposure] as well as body mass index (BMI), each scored on a 0 (poor) to 100 (ideal) scale. Linear regression was used to measure associations between school experiences and bCVH adjusting for age, sex, race, household income, and health insurance status. Results: Mean scores (±SD; range 0-16) for peer bullying and school connectedness were 1.65±2.53 and 12.3±3.8, respectively. Mean scores for the four components of the LE8 and BMI were: diet (39.4±22.0), PA (70.8±39.9), sleep (74.5±28.7), nicotine exposure (92.6±19.7), and BMI (77.9±32.3). In fully adjusted models, 1-unit higher score of connectedness or bullying were associated with 0.45-unit higher and 0.82-unit lower bCVH scores, respectively. Among individual bCVH components, connectedness was most strongly associated with BMI [0.77 (95% CI, 0.13, 1.41)] and nicotine exposure scores [0.76 (0.39, 1.12)], while higher bullying was associated with lower diet [-1.27 (-1.86, -0.67)] and nicotine exposure [-0.8 (-1.33, -0.27)] scores (Figure 1). Conclusions: Optimizing the school environment to promote social connectedness and anti-bullying practices may be an important strategy in promoting CVH among adolescents.

BACKGROUND:Primary hypertension in childhood tracks into adulthood and is associated with increased cardiovascular risk. Studies conducted in individuals aged <18 years, an age group without many of the confounding comorbid cardiovascular disease risk factors in adults, provide an opportunity to explore early cardiovascular target-organ injury. METHODS:Youths (n=132, mean age, 15.8 years) were stratified by blood pressure (BP) as low-BP, mid-BP, and high-BP and by left ventricular mass index as low-and high left ventricular mass index. Systemic circulating RNA, microRNA, and methylation profiles in peripheral blood mononuclear cells and deep proteome profiles in serum were determined using high-throughput sequencing techniques. In vitro cell culture experiments assessed angiotensin II- and microRNA-mediated Vash1 (vasohibin-1 protein) regulation and Vash1-mediated hypertrophic response. RESULTS:In high-BP youths, transcriptomics analysis identified 7 differentially expressed genes, including elevated VASH1 transcripts but correspondingly diminished levels of its microRNA (microRNA-24-3p and microRNA-335-5p). In vitro experiments revealed that either angiotensin II treatment, microRNA-24-3p or microRNA-335-5p overexpression, reduced endogenous VASH1 transcript levels. In contrast, exogenous Vash1 protein treatment induced cellular hypertrophy. Hypermethylation of GSE1, POTE1, and MN1; hypomethylation of MAD1L1 and SH3BP4; elevated Protein Z and diminished Superoxide dismutase 3 protein levels were observed in mid-BP and high-BP+high-left ventricular mass index groups. In youths with high-BP and high-left ventricular mass index, HYAL1 transcripts and Hyaluronidase 1 protein were elevated, suggesting the significant involvement of extracellular matrix in cardiovascular target-organ injury. CONCLUSIONS:The integration of multiomics data in this unique pediatric population during the early phase of high BP provides evidence of molecular changes that reveal both potential drug targets and strategies for ameliorating BP-mediated cardiovascular target-organ injury.

Despite specific national guidelines, the prevalence of pediatric universal lipid screening (ULS) remains low, and many people living with familial hypercholesterolemia (FH) remain undiagnosed. Recent studies demonstrate only 11% of youth between 9 and 21 years of age in the United States (US) had documented lipid screening,1 and 30%-60% of youth with dyslipidemia may be missed by targeted screening alone (ie, risk factors) compared with ULS.2 Identification of youth living with FH has the added benefit of triggering reverse cascade screening of family members, which can further identify at risk youth and adults.3 In 2011, the National Heart, Lung and Blood Institute (NHLBI) and the American Academy of Pediatrics (AAP) established guidelines for ULS, which recommended routine integration of cardiovascular risk assessment during well-child care, with measurement of a lipid profile once during the ages of 9-11 and again at 17-21 years.2 ULS promotes the early identification of children living with FH. This autosomal dominant genetic condition causes abnormally elevated low-density lipoprotein cholesterol (LDL-C) levels, detectable at birth in as many as 1:250 people.4 In FH, untreated elevated levels of LDL-C in childhood significantly increase the risk for premature atherosclerotic cardiovascular disease (ASCVD),5 which is the leading cause of death both in the US and worldwide.6 However, early initiation of statin therapy for children living with FH reduces the ASCVD risk in adulthood.5 ULS can also identify children with abnormal lipid profiles from other causes, some of which may benefit from modifiable lifestyle practices to reduce ASCVD risk. In 2024, the Family Heart Foundation (FHF) established the Leveraging Evidence and Data (LEAD) for Pediatric Cholesterol Screening Initiative. The overarching aim was to engage national experts and utilize FHF expertise, research networks, and community partnerships to improve implementation of guideline recommended ULS. The FHF is nonprofit organization that works to improve health outcomes for individuals and families at the highest risk for ASCVD due to inherited lipid disorders. The focus was not on creating new screening guidelines, but on developing strategies that will lead to better implementation of the current NHLBI/AAP screening recommendations, and with the overall goal of reducing global ASCVD burden.

Background: The association of parental stress and depression with child behavioral cardiovascular health (bCVH) has received limited attention in the literature. Methods: We used data from the Young Hearts study, a cohort examining CVH in children and adolescents. Parental stress was assessed using the Perceived Stress Scale (PSS-4), which consisted of 4 questions rated on a Likert scale (0-16), with a higher score indicating greater levels of stress. Parental depression was evaluated using the 2-item Patient Health Questionnaire (PHQ-2), with responses rated on a Likert scale (0-6). bCVH scores were calculated from the mean of the four behavioral metrics of the American Heart Association’s Life’s Essential 8 (physical activity, diet, nicotine exposure, and sleep; 0-100 points each, with a higher score = better CVH) and self-reported body mass index (BMI). We examined the association of parental stress and depression with child bCVH score, using linear regression, adjusting for age, sex, race, ethnicity, household income, and parental education level. Results: Our sample consisted of 6,427 children with complete data, with an average age of 8.2 years [SD 5.1]. Of the participants, 53.5% were male, and 46.3% were Non-Hispanic White. In adjusted models, a 1-unit higher parental depression score was associated with 1.30 (95% CL = -1.54, -1.07) point lower children’s bCVH. Parental stress also showed an association with bCVH though the effect size was smaller (-0.44 points; -0.54, -0.34). Among the individual behavioral components for parental depression, there were significant associations with physical activity (-1.75 points; -2.29, -1.21) and sleep (-1.98 points; -2.52, -1.44). Conclusion: Parental stress and depression are inversely associated with child bCVH, highlighting the need for further investigation of potential mechanisms to inform targeted family interventions.

Ambulatory hypertension is associated with elevated left ventricular mass index (LVMI), cardiac dysfunction, and increased arterial stiffness in adolescents. Whether the addition of measures of BP variability improves the prediction of subclinical cardiovascular target organ damage (TOD) over mean BP measures is not known. We assessed clinic and ambulatory BP (ABP), anthropometrics, and TOD in 397 adolescents. ABP means standard deviation (SD), BP, and heart rate (HR) dipping were calculated; coefficients of variability (CV) were calculated (SD/mean) to assess ABP variabilities. Measures of TOD included LVMI, left ventricular hypertrophy (LVH), LV systolic shortening, LV diastolic function (e′/a′), and pulse wave velocity. General linear models were used to determine if increased ABP variability measures were significant determinants of TOD in models containing mean ABP percentiles, age, sex, race/ethnicity, BMI z-score, and HR. Mean participant age was 15.6 ± 1.7 years (63

BACKGROUND:Emerging omics approaches, including metabolomics and proteomics, can be integrated into obesity treatment for better blood pressure management. We tested whether preoperative metabolomic and proteomic profiles predict long-term elevated blood pressure (EBP) changes better than known risk factors in adolescents undergoing bariatric surgery. METHODS:We included 108 participants from the Teen-LABS (Teen-Longitudinal Assessment of Bariatric Surgery). Plasma untargeted metabolomics (via liquid chromatography with high-resolution mass spectrometry) and Olink proteomics were assessed pre surgery. An elastic net model with stability selection was used to identify features predictive of EBP reductions 5 years post surgery. Models including identified metabolites, proteins, and known risk factors (age, sex, race, clinical sites, parents' education level, body mass index, systolic blood pressure, and diastolic blood pressure at baseline) were compared with known-risk-factors-only models. For biological relevance, the consistency of association directions was examined in a multiethnic non-interventional adolescent cohort (n=79). RESULTS:Metabolite-based models and protein-based models with known risk factors each outperformed known-risk- factors-only models in predicting EBP reductions (P<0.01). Higher levels of 4 metabolites (uric acid, taurocholic acid, nonadecanoic acid, and cystine) were consistently associated with reduced likelihood of EBP improvement or blood pressure improvement across cohorts. SERPINA11 (serine protease inhibitor, clade A, member 11), ICAM5 (intercellular adhesion molecule 5), and TINAGL1 (tubulointerstitial nephritis antigen-like 1) demonstrated consistent associations in both cohorts. CONCLUSIONS:This is the first study identifying potential preoperative biomarkers for EBP reductions in adolescents following bariatric surgery. Integrating metabolomics and proteomics with known risk factors substantially improved predictive models compared with known-risk-factors-only models. Larger and more diverse cohorts are needed to confirm these findings and whether identified features are associated with other blood pressure treatments.

Background: Household economic stability may alleviate life stressors, allowing children to develop healthy behaviors which in turn will delay the decline of cardiovascular health (CVH) in the life course. Here, we aimed to quantify the associations between household economic stability and behavioral CVH in childhood. Methods: Analyses used data from participants ages 0-18y in the Young Hearts study, an ongoing Chicago-based cohort. Guardians completed surveys on household economic stability and CVH behaviors. Household economic stability encompassed self-reported food security, perceived financial stability (based on difficulty paying for food, heating, or medical care), and having ≥6 months of savings. We calculated behavioral CVH scores by averaging scores on the behavioral components of the AHA Life’s Essential 8 (diet, physical activity, nicotine exposure, and sleep) and body mass index (BMI) score; component scores were 0-100 points each, with higher implying better CVH. Linear regression estimated associations between household economic stability and CVH adjusting for child age, sex, race, ethnicity, insurance, and household income. Results: Of 6,892 included children and adolescents, 47.6% were female, average age was 8.7 [SD 5.5] years, 46.0% were non-Hispanic White, 65.8% were food secure, 50.6% were financially stable, and 19.1% had ≥6 months of savings. Holding household income constant, food security, perceived financial stability, and ≥6 months of savings were associated with a 3.2 (95% CI 2.4, 4.0), 2.3 (1.5, 3.0), and 2.4 (1.7, 3.2) point higher behavioral CVH score, respectively. Additionally, BMI score was higher (more favorable) across all 3 metrics (food security 9.4 [7.1, 11.6]; financial security 10.7 [8.6, 12.8]; ≥6 months of savings 6.9 [4.9, 9.0] points). Conclusion: Household economic stability is associated with more ideal behavioral CVH and BMI in children and adolescents. Policies directed towards improving household financial stability could catalyze improvements in behavioral CVH habits that have long-term cascading impacts on lifetime CVH risk.

Background: Psychosocial factors in childhood, such as emotional and behavioral difficulties, contribute to long-term cardiovascular health (CVH). However, limited research has explored the relationship between these difficulties and childhood CVH. Methods: This cross-sectional analysis includes participants aged 2-18 (N = 6,892) from the Young Hearts cohort with complete behavioral CVH (bCVH) and Strengths and Difficulties Questionnaire (SDQ) data. SDQ scores included the Total Difficulties Score (TDS), measuring emotional and behavioral difficulties, and the Prosocial Behavior Score (PBS), reflecting empathy and cooperation. We calculated bCVH scores using the Life’s Essential 8 metrics (diet, exercise, nicotine exposure, sleep, and BMI). Linear regression was used to assess associations between TDS, PBS, and bCVH, adjusting for age, sex, race/ethnicity, parental education, financial stability, food security, and health insurance status. Results: The sample had a mean age of 8.7, 48% female, 46% non-Hispanic White, 28% Hispanic, and 15% non-Hispanic Black. Higher TDS was associated with lower bCVH (-1.91; 95% CI -2.27, -1.56), while higher PBS was linked to better bCVH (1.75; 95% CI 1.41, 2.1), and physical activity largely contributed to these differences (Figure 1). Conclusion: Psychosocial difficulties and prosocial behaviors have a strong association with physical activity, making it a potential intervention target for improving childhood CV outcomes. Enhancing prosocial behaviors through interventions like social-skills training may further support both psychosocial well-being and cardiovascular health in children.

Background: Feeding practices, such as using food as a reward or for emotional regulation, may impact the ability of children to develop healthy emotional coping strategies increasing the risk of weight gain. However, the association between feeding practices and behavioral cardiovascular health (bCVH) in children and adolescents is poorly understood. Methods: We utilized data from the Young Hearts study, an ongoing cohort of children and adolescents that aims to study CVH. Parents completed surveys on CVH behaviors and a modified version of the Comprehensive Feeding Practices Questionnaire. We included all children ages 0-17 with complete baseline surveys. Feeding practice scores were calculated by summing parent-reported behaviors (0-5). We calculated a composite bCVH score by averaging scores on the four behavioral components of the American Heart Association Life’s Essential 8 (diet, physical activity, nicotine exposure, and sleep) and self-reported body mass index (all ranging from 0=poorest to 100=most ideal). We used linear regression to assess the association between feeding practices and bCVH adjusting for age, sex, race, ethnicity, and household income. Results: Of 6,892 included children, 47.6% were female and 46% were non-Hispanic White, with an average age of 8.7 [SD 5.5] years. In adjusted models, each 1-unit higher score for food as reward and food for emotional regulation feeding practices, respectively, were associated with -2.23 (95% CI = -2.61,-1.86) and -2.81 (-3.20, -2.41) point lower bCVH scores. Among individual CVH metrics, food as reward was most strongly associated with diet (-4.90; -5.65, -4.15), whereas food for emotional regulation was most strongly associated with physical activity (-4.98; -5.90, -4.06). Conclusion: Select feeding practices are inversely associated with multiple CVH behaviors, not just diet quality, among children and adolescents. Promoting positive emotional coping strategies in place of food may improve CVH in children and adolescents.

Importance Many pediatric patients with heterozygous familial hypercholesterolemia (HeFH) cannot reach recommended low-density lipoprotein cholesterol (LDL-C) concentrations on statins alone and require adjunct lipid-lowering therapy (LLT); the use of alirocumab in pediatric patients requires evaluation. Objective To assess the efficacy of alirocumab in pediatric patients with inadequately controlled HeFH. Design, Setting, and Participants This was a phase 3, randomized clinical trial conducted between May 2018 and August 2022 at 43 centers in 24 countries. Pediatric patients aged 8 to 17 years with HeFH, LDL-C 130 mg/dL or greater, and receiving statins or other LLTs were included. Following consecutive enrollment into dosing cohorts, 25 of 99 patients screened for dosing every 2 weeks (Q2W) failed screening; 25 of 104 patients screened for dosing every 4 weeks (Q4W) failed screening. A total of 70 of 74 Q2W patients (95%) and 75 of 79 Q4W patients (95%) completed the double-blind period. Interventions Patients were randomized 2:1 to subcutaneous alirocumab or placebo and Q2W or Q4W. Dosage was based on weight (40 mg for Q2W or 150 mg for Q4W if <50 kg; 75 mg for Q2W or 300 mg for Q4W if >= 50 kg) and adjusted at week 12 if LDL-C was 110 mg/dL or greater at week 8. After the 24-week double-blind period, patients could receive alirocumab in an 80-week open-label period. Main Outcomes and Measures The primary end point was percent change in LDL-C from baseline to week 24 in each cohort. Results Among 153 patients randomized to receive alirocumab or placebo (mean [range] age, 12.9 [8-17] years; 87 [56.9%] female), alirocumab showed statistically significant reductions in LDL-C vs placebo in both cohorts at week 24. Least squares mean difference in percentage change from baseline was -43.3% (97.5% CI, -56.0 to -30.7; P < .001) Q2W and -33.8% (97.5% CI, -46.4 to -21.2; P < .001) Q4W. Hierarchical analysis of secondary efficacy end points demonstrated significant improvements in other lipid parameters at weeks 12 and 24 with alirocumab. Two patients receiving alirocumab Q4W experienced adverse events leading to discontinuation. No significant difference in adverse event incidence was observed between treatment groups. Open-label period findings were consistent with the double-blind period. Conclusions and Relevance The findings in this study indicate that alirocumab Q2W or Q4W significantly may be useful for reducing LDL-C and other lipid parameters and be well tolerated in pediatric patients with HeFH inadequately controlled with statins.

BACKGROUND:We studied whether increased systolic blood pressure (SBP), as determined by auscultatory SBP, ambulatory SBP, and the number of cardiovascular health risk indicators, are associated with neurocognition in adolescents. METHODS:This cross-sectional study included 365 adolescents (mean age, 15.5 years) from 6 academic medical centers in the United States. The sample was 59.5% male, 52.6% White, with 23.9% of the caregivers having less than or equal to a high school degree. Primary exposures included the following: auscultatory SBP, ambulatory SBP, and the number of cardiovascular risk factors. Neurocognitive outcomes comprised nonverbal IQ, attention, and parent ratings of executive functions. RESULTS:After examining the models for the effects of targeted covariates (eg, maternal education), higher auscultatory SBP was associated with lower nonverbal IQ (β=-1.39; P<0.001) and verbal attention (β=-2.39; P<0.05); higher ambulatory 24 hours. SBP (β=-21.39; P<0.05) and wake SBP (β=-21.62; P<0.05) were related to verbal attention; and all 3 ambulatory blood pressure measures were related to sustained attention accounting for small to medium amounts of variance (adjusted R2=0.08-0.09). Higher ambulatory blood pressure sleep SBP also was significantly associated with parent ratings of behavior regulation (β=12.61; P<0.05). These associations remained stable after a sensitivity analysis removed cases with hypertension. Number of cardiovascular risk factors performed similarly, with more risk factors being associated with lower nonverbal IQ (β=-1.35; P<0.01), verbal attention (β=-1.23; P<0.01), and all parent ratings of executive functions. CONCLUSIONS:Elevated SBP, even below the hypertension range, and general cardiovascular health are associated with neurocognitive outcomes in adolescents. How these findings might guide clinical care is worthy of additional study.

The association between hypertension in adulthood and cardiovascular morbidity and death is well known. Based on that association, a diagnosis of elevated blood pressure in children has been clinically interpreted as early cardiovascular disease. The objective of this review is to discuss historical data and new research on the relationship between elevated blood pressure and early preclinical and later adult cardiovascular disease. After summarizing the evidence, we will address the gaps in knowledge around Pediatric hypertension in an effort to stimulate research into the important role that control of blood pressure in youth may play in preventing adult cardiovascular disease.

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