Combined Dyslipidemia in Children and Adolescents: a Proposed New Management Approach.

PURPOSE OF REVIEW: Combined dyslipidemia (CD), the predominant abnormal lipid pattern in children and adolescents, is characterized by moderate/severe triglyceride elevation with reduced high-density lipoprotein cholesterol. CD is prevalent, present in 30-50% of obese adolescents. Epidemiologic and lipid sub-population findings demonstrate CD to be highly atherogenic. In the short term, CD responds well to lifestyle change; long-term results are lacking. RECENT FINDINGS: Major longitudinal studies now confirm that CD in childhood predicts early cardiovascular disease events in adults. Targeted nutritional interventions can be safely and effectively introduced in young children. These findings support introduction of a new approach to CD management. New evidence supporting the atherosclerotic risk associated with CD and the effectiveness of lifelong diet interventions is reviewed and a new family-based primordial approach to CD beginning in infancy is proposed. Aligned with existing pediatric care recommendations, this has the potential to significantly decrease the development of CD.

Effectiveness and Safety of Statin Therapy in Children: A Real-World Clinical Practice Experience.

BACKGROUND: Statin use for hypercholesterolemia in children is predominantly reported from short-term clinical trials. In this study, we assess the efficacy and safety of statin treatment in clinical pediatric practice. METHODS: Records of all patients who began statin treatment at age <18 years and remained on statins for >6 months from 5 pediatric lipid clinics were reviewed. Information at baseline and from all clinic evaluations after statin initiation was recorded, including lipid measurements, statin drug/dose, safety measures (anthropometry, hepatic enzymes, creatine kinase levels), and symptoms. Lipid changes on statin therapy were assessed from baseline to 6 ± 3 months and from 6 ± 3 months to last follow-up with a mixed-effects model, using piecewise linear splines to describe temporal changes, controlling for repeated measures, sex, and age. RESULTS: There were 289 patients with median low-density lipoprotein cholesterol (LDL-C) of 5.3 mmol/L (interquartile range [IQR]:4.5-6.5) and mean age of 12.4 ± 2.9 years at statin initiation. Median duration of therapy was 2.7 years (IQR: 1.6-4.5) with 95% on statins at last evaluation. There were significant decreases in total cholesterol, LDL-C, and non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to 6 ± 3 months (P < 0.001) and from 6 ±3 months to last follow-up (P < 0.001). Triglycerides and HDL-C were unchanged but the triglyceride to HDL-C ratio decreased significantly by late follow-up. At final evaluation, median LDL-C had decreased to 3.4 mmol/L (IQR:2.8-4.2). No patient had statins discontinued for safety measures or symptoms. CONCLUSIONS: In real-world clinical practice, intermediate-term statin treatment is effective and safe in children and adolescents with severe LDL-C elevation.

CONTEXTE: Les statines sont fréquemment employées pour traiter l'hypercholestérolémie chez les enfants dans le cadre d'essais cliniques de courte durée. Dans l'étude présentée ici, nous évaluons l'efficacité et l'innocuité de l'emploi de statines dans la pratique clinique en pédiatrie. MÉTHODOLOGIE: Nous avons passé en revue les dossiers de tous les patients de cinq cliniques pédiatriques des lipides qui ont commencé à prendre une statine avant l'âge de 18 ans et qui ont poursuivi le traitement pendant plus de six mois. Les valeurs mesurées au départ et à chacune des évaluations cliniques après l'instauration d'un traitement par une statine ont été consignées, notamment la lipidémie, le type et la dose de la statine prescrite, les paramètres d'évaluation de l'innocuité (anthropométrie, enzymes hépatiques, taux de créatine kinase) et les symptômes. La variation de la lipidémie chez les patients recevant une statine a été évaluée sur deux périodes, soit entre le début du traitement et l'évaluation effectuée à 6 ± 3 mois ainsi qu'entre l'évaluation effectuée à 6 ± 3 mois et la dernière évaluation de suivi, à l'aide d'un modèle à effets mixtes et de splines linéaires par morceaux pour décrire les changements temporels, en contrôlant pour les mesures répétées, le sexe et l'âge. RÉSULTATS: L'étude portait sur 289 patients ayant un taux de cholestérol des lipoprotéines de basse densité (C-LDL) médian de 5,3 mmol/l (intervalle interquartile [IIQ] : 4,5 à 6,5) et âgés de 12,4 ± 2,9 ans en moyenne au moment de l'instauration du traitement par une statine. La durée médiane du traitement était de 2,7 ans (IIQ : 1,6 à 4,5), 95 % des sujets étant toujours sous statine à la dernière évaluation. Les taux de cholestérol total, de C-LDL et de cholestérol des lipoprotéines non de haute densité (C-non-HDL) avaient diminué de manière significative entre le début du traitement et l'évaluation à 6 ± 3 mois (p < 0,001) et entre l'évaluation à 6 ± 3 mois et la dernière évaluation de suivi (p < 0,001). Les taux des triglycérides et du C-HDL n'avaient pas bougé, mais le rapport triglycérides/C-HDL avait diminué considérablement vers la fin du suivi. À l'évaluation finale, le taux de C-LDL avait diminué à 3,4 mmol/l (IIQ : 2,8 à 4,2). Aucun patient n'avait abandonné le traitement par une statine en raison de problèmes d'innocuité ou des symptômes. CONCLUSIONS: En situation réelle dans la pratique clinique, le traitement à moyen terme par une statine est efficace et sûr chez les enfants et les adolescents présentant une élévation grave du taux de C-LDL.

Incorporating Risk Stratification Into the Practice of Pediatric Preventive Cardiology.

Atherosclerosis in its earliest stages is associated with the same traditional cardiovascular disease (CVD) risk factors as are associated with manifest CVD events in adulthood. Clustering of risk factors is associated with exponential increases in atherosclerotic burden from a young age. Some medical conditions and risk behaviours occurring in children can either increase the likelihood of higher levels of risk factors (such as chronic kidney disease) or the presence of risk factor clustering (such as obesity and cardiometabolic syndrome) or are associated with acquired coronary artery pathology (such as Kawasaki disease). This creates a milieu for-or increases the impact of-accelerated atherosclerosis that, in turn, increases the likelihood of premature CVD. This review highlights the importance of considering the total risk factor and risk-condition profile of pediatric patients. An algorithm is provided for stratifying patients into high-, moderate-, and at-risk categories, and practical examples are provided as to how the evaluation and management of 1 risk factor or risk condition might need to be intensified in the context of additional risk factors or risk conditions. For example, for treatment of an adolescent with familial hypercholesterolemia, the target low-density lipoprotein cholesterol level might be lowered by the concomitant presence of low high-density lipoprotein cholesterol or elevated lipoprotein(a) levels. As awareness of cardiovascular risk and atherosclerosis in pediatric patients increases, new at-risk conditions that warrant consideration are emerging. The identification and management of high-risk individuals is an important part of the overall practice of pediatric preventive cardiology.

Public Policy to Promote Healthy Cardiovascular Lifestyles in Children.

Health policy is an important component of prevention of cardiovascular disease (CVD) and promotion of health in childhood and adolescence, when major health behaviours are formed. Development of CVD-related health policy begins with continuous systematic collection, analysis, and interpretation of health-related data to establish the baseline prevalence of CV risk factors and behaviours. These findings allow identification of problems, initiation of focused research, and development of evidence-based interventions. Ultimately, these results inform development and implementation of population-level policies. This review focuses on CVD health-promotion policies in North American youth, for whom health surveillance is an ongoing part of public health policy, providing direct, objective, measurements of growth, lipids, blood pressure, physical activity and tobacco exposure for development of CV health research and policy. When national surveillance data identified significant risk of CVD in youth in the 1970s, major pediatric epidemiologic studies established the strong association between these risk factors and behaviours in childhood and the initiation and progression of atherosclerosis. This knowledge promoted development of the targeted public policies, which are reviewed in this paper. Public policy can directly and positively address cardiovascular health promotion in youth; the effective approach to smoking cessation exemplifies this. For more complex risk factors and behaviours, health policy can be a significant element in a comprehensive CV health promotion program.

Combined dyslipidemia in childhood.

Combined dyslipidemia (CD) is now the predominant dyslipidemic pattern in childhood, characterized by moderate-to-severe elevation in triglycerides and non-high-density lipoprotein cholesterol (non-HDL-C), minimal elevation in low-density lipoprotein cholesterol (LDL-C), and reduced HDL-C. Nuclear magnetic resonance spectroscopy shows that the CD pattern is represented at the lipid subpopulation level as an increase in small, dense LDL and in overall LDL particle number plus a reduction in total HDL-C and large HDL particles, a highly atherogenic pattern. In youth, CD occurs almost exclusively with obesity and is highly prevalent, seen in more than 40% of obese adolescents. CD in childhood predicts pathologic evidence of atherosclerosis and vascular dysfunction in adolescence and young adulthood, and early clinical cardiovascular events in adult life. There is a tight connection between CD, visceral adiposity, insulin resistance, nonalcoholic fatty liver disease, and the metabolic syndrome, suggesting an integrated pathophysiological response to excessive weight gain. Weight loss, changes in dietary composition, and increases in physical activity have all been shown to improve CD significantly in children and adolescents in short-term studies. Most importantly, even small amounts of weight loss are associated with significant decreases in triglyceride levels and increases in HDL-C levels with improvement in lipid subpopulations. Diet change focused on limitation of simple carbohydrate intake with specific elimination of all sugar-sweetened beverages is very effective. Evidence-based recommendations for initiating diet and activity change are provided. Rarely, drug therapy is needed, and the evidence for drug treatment of CD in childhood is reviewed.

Combined dyslipidemia in obese children: response to a focused lifestyle approach.

BACKGROUND: Combined dyslipidemia (elevated triglyceride [TG] ± non-high-density lipoprotein cholesterol [non-HDL-C] ± total cholesterol [TC] ± low-density lipoprotein cholesterol [LDL-C] ± reduced high-density lipoprotein cholesterol [HDL-C]) is seen in >40% of obese children. Primary recommended treatment is weight loss with limited reports of any other approach. OBJECTIVE: In children with combined dyslipidemia, evaluate the response to a clinical protocol focused on diet composition change and increased activity with no direct weight loss approach. METHODS: Retrospective review of lipid profile and growth parameter changes in patients 6 to 18 years of age with diagnosis of combined dyslipidemia seen between December 31, 2009, and December 31, 2011, managed with this protocol through 2 follow-up visits. Combined dyslipidemia diagnosed when ≥2 lipid values exceed the upper limit of normal for TC, TG, non-HDL-C, or LDL-C ± HDL-C below the lower limit of normal. RESULTS: Fifty-three patients were identified, 55% male, 92% obese, mean age 12.1 ± 3.4 years with mean follow-up 9.2 months. Lipid parameters (mean ± SD, mg/dL) improved significantly (P < .001): TC 209 ± 39 to 181 ± 32; TG 255 ± 119 to168 ± 99; non-HDL-C 167 ± 35 to 138 ± 30 and LDL-C 121 ± 43 to 106 ± 30. HDL-C was unchanged. Body mass index decreased in 58% and mean body mass index decreased 0.67 kg/m(2) (P < .05). CONCLUSIONS: Focused lifestyle changes significantly improved combined dyslipidemia in obese children. With no direct weight loss approach, body mass index decreased in 58%.

Distinguishing cardiac syncope from vasovagal syncope in a referral population.

OBJECTIVE: To identify characteristics that distinguish cardiac from vasovagal syncope. STUDY DESIGN: We compared characteristics of patients ≤18 years of age with vasovagal and cardiac syncope. Vasovagal syncope subjects represented all patients presenting to outpatient cardiology during a 1-year period for initial evaluation of syncope diagnosed with vasovagal syncope. Cardiac patients were all patients identified by review of diagnoses known to include syncope as a symptom who presented with syncope to the emergency department or inpatient or outpatient cardiology during a 10-year period identified with cardiac etiology. RESULTS: There were 89 patients 4-18 years of age with vasovagal syncope and 17 patients 4 months to 17 years of age with cardiac syncope. When we compared patients with cardiac syncope to those with vasovagal syncope, we found that syncope surrounding activity was present in 65% vs 18% (P < .001), family history of cardiac disease or sudden cardiac death was identified in 41% vs 25% (P = .2), abnormal findings on the physical examination supporting cardiac diagnosis were present in 29% vs 0% (P < .001), and abnormal findings on electrocardiograms were found in 76% vs 0%, respectively (P < .001). Screening for cardiac disease using any 1 of these 4 characteristics had a sensitivity of 100% and specificity of 60%. Using this screening rule, we found that 60% of patients with vasovagal syncope would not have been referred to cardiology. CONCLUSIONS: Cardiac and vasovagal syncope have dramatic differences in presentation. A screening rule that uses historic features, physical examination findings, and electrocardiogram will accurately separate patients requiring further evaluation for cardiac etiology from those with vasovagal syncope in whom cardiology referral is unnecessary.

Left ventricular hypertrophy in hypertensive children and adolescents: predictors and prevalence.

Left ventricular hypertrophy is an independent predictor of cardiovascular morbidity and mortality in adults. In children, the primary correlate of left ventricular mass (LVM) is lean body mass, but fat mass, gender and systolic blood pressure are also contributors. LVM can be estimated from echocardiographic measurements, and by indexing this allometrically to height to the 2.7 power, the left ventricular mass index (LVMI) can be calculated. LVMI optimizes detection of left ventricular hypertrophy with established normal curves for children from birth to 18 years. In children with sustained hypertension, 8-41 % have LVMI above the 95th percentile and in 10-15.5 % of these, LVMI is elevated above levels associated with increased mortality in adults. The presence of obesity is associated with higher LVMI than is found in children with hypertension alone. In children with chronic kidney disease, left ventricular hypertrophy develops relatively early and becomes more prevalent as kidney function decreases. In summary, left ventricular hypertrophy is a sensitive marker of target organ damage in children with BP elevation, obesity and chronic kidney disease providing important management information.

Hypertensive changes within the aortic arch of infants and children with isolated coarctation.

BACKGROUND: Despite repair, a significant proportion of patients with coarctation of the aorta (CoA) present with late hypertension. Increased gene expression of aortic wall collagen and vascular smooth muscle cell markers occurs in the presence of hypertension. Before repair, a patent ductus arteriosus (PDA) limits hypertension proximal to the coarctation. We hypothesize that preoperative collagen and vascular smooth muscle expression from the aortic arch in children is variable, depending on the presence or absence of a PDA. METHODS: We analyzed the expression patterns of collagen and vascular smooth muscle cell markers in 25 children with CoA using a quantitative polymerase chain reaction. Aortic arch tissue proximal to the CoA was normalized to descending aortic tissue distal to the coarctation. Collagen-I, transforming growth factor-ß, elastin, and calponin were analyzed. RESULTS: At repair, 19 patients were aged younger than 3 months (14 with a PDA, 5 with a ligamentum arteriosum), and the remaining 6 were older than 1 year. There was no difference in age or weight between infants with or without a PDA. Infants without a PDA had the greatest difference in collagen-I expression compared with infants with a PDA (7.0 ± 1.6-fold vs 0.8 ± 1.1-fold, p = 0.01). Expression of transforming growth factor-ß (4.3 ± 1.4 vs 2.6 ± 2.3, p = 0.01) and calponin (3.7 ± 0.7 vs 0.6 ± 1.1, p = 0.05) was lower from infants with vs without a PDA. CONCLUSIONS: Our findings provide evidence of preoperative changes in the aortic arch before repair, particularly in the absence of a PDA.

Percutaneous balloon dilation of Carpentier-Edwards porcine-valved right ventricle-to-pulmonary artery conduits.

Right ventricular outflow tract (RVOT) conduit stenosis remains a significant problem for patients with right ventricle-to-pulmonary artery (RV-to-PA) conduits placed as palliation for congenital heart disease. Previous reports on balloon dilation of RVOT conduits all describe small series with varying levels of success during limited follow-up evaluation. This study reviewed all patients with RV-to-PA conduits who underwent percutaneous balloon dilation for conduit stenosis at the authors' institution from 2000 to 2011. Patients with Carpentier-Edwards (CE) model 4300 porcine-valved conduits (Edwards Lifesciences Corp., Irvine, CA) (n = 19) were compared with patients who had all other types of conduits (n = 19). Successful balloon angioplasty was defined as a 20 % decrease in the RV-to-PA gradient, a 20 % decrease in the ratio of the RV systolic-to-aortic systolic pressure, or both. Balloon dilation was successful for 57.9 % of the patients with CE conduits and for 31.6 % of patients with other types of conduits (p = 0.10, Chi square test). Logistic regression analysis showed that balloon dilation was significantly more likely to be successful with CE valves than with other types (odds ratio [OR], 6.59; 95 % confidence interval [CI], 1.22-35.49). In a continuous series of patients with stenotic RV-to-PA conduits, the CE porcine-valved conduit was more amenable to percutaneous balloon dilation than other types of RV-to-PA conduits at the midterm follow-up evaluation. This has important ramifications in terms of valve selection for patients with congenital heart disease who will require surgical reintervention for RVOT stenosis.

Developing the 2011 Integrated Pediatric Guidelines for Cardiovascular Risk Reduction.

This article reviews aspects of development of the recently released "Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents" for pediatric care providers that remain in the area of human judgment. Discussed will be the context in which the guidelines were developed, the formal evidence review process, a consideration of how quality grades were established, key social/ethical issues that the panel confronted, and a critique of the final work with recommendations for future guideline development. Lessons learned are that both a formal evidence review process is essential to developing a credible document, and human judgment is critical to producing a meaningful result. Guideline development is a dynamic process that must be continuously self-critical as new evidence is acquired and sociopolitical and environmental contexts evolve.