Homozygous familial hypercholesterolaemia is a life-threatening genetic condition, which causes extremely elevated LDL-C levels and atherosclerotic cardiovascular disease very early in life. It is ...vital to start effective lipid-lowering treatment from diagnosis onwards. Even with dietary and current multimodal pharmaceutical lipid-lowering therapies, LDL-C treatment goals cannot be achieved in many children. Lipoprotein apheresis is an extracorporeal lipid-lowering treatment, which is used for decades, lowering serum LDL-C levels by more than 70% directly after the treatment. Data on the use of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia mainly consists of case-reports and case-series, precluding strong evidence-based guidelines. We present a consensus statement on lipoprotein apheresis in children based on the current available evidence and opinions from experts in lipoprotein apheresis from over the world. It comprises practical statements regarding the indication, methods, treatment goals and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation.
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•Early intervention is vital to prevent cardiovascular disease in homozygous familial hypercholesterolaemia (HoFH).•This consensus statement provides guidance on performing lipoprotein apheresis in children with HoFH.•Using the Delphi method involving 40 international experts, 22 statements were developed.•Statements cover indication, methods, treatment goals and follow-up of lipoprotein apheresis in children with HoFH.•Furthermore, the role of lipoprotein(a) and liver transplantation in children with HoFH is discussed.
Background Optimally treated patients with coarctation of the aorta remain at risk for late vascular dysfunction. The effect of treatment modality on vascular function is unknown. The LOVE-COARCT ...(Long-term Outcomes and Vascular Evaluation After Successful Coarctation of the Aorta Treatment) study was done to compare vascular function in patients with coarctation of the aorta treated with surgery, balloon dilation (BD), or stent implantation. Methods and Results In treated coarctation of the aorta patients without residual coarctation, we prospectively compared aortic stiffness by applanation tonometry and cardiac magnetic resonance; endothelial function by endothelial pulse amplitude testing; blood pressure ( BP ) phenotype by office BP , ambulatory BP monitoring, and BP response to exercise; left ventricular mass by cardiac magnetic resonance; and blood biomarkers of endothelial function, inflammation, vascular wall function, and extracellular matrix. Participants included 75 patients treated with surgery (n=28), BD (n=23), or stent (n=24). Groups had similar age at enrollment, coarctation of the aorta severity, residual gradient, and metabolic profile, but differed by age at treatment. Prevalence of systemic hypertension, aortic stiffness, endothelial function, and left ventricular mass were similar among treatment groups. However, BD patients had more-distensible ascending aortas, lower peak systolic BP during exercise, less impairment in diurnal BP variation, and lower inflammatory biomarkers. Results were unchanged after adjustment for potential confounders, including age at treatment. Conclusions In our cohort of patients without residual coarctation, treatment modality was not associated with major vascular outcomes, even though there were some favorable vascular characteristics in the BD patients. Although this suggests that choice of treatment modality should continue to be driven by likelihood of achieving a good anatomical result, more long-term studies are required to assess the clinical significance of the more-optimal results of secondary markers of vascular function in BD patients. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 03262753.
Kawasaki disease (KD) is a systemic vasculitis of young children that can lead to development of coronary artery aneurysms. We aimed to identify diagnostic markers to distinguish KD from other ...pediatric inflammatory diseases.
We used the proximity extension assay to profile proinflammatory mediators in plasma samples from healthy pediatric controls (n = 30), febrile controls (n = 26), and patients with KD (n = 23), multisystem inflammatory syndrome in children (MIS-C; n = 25), macrophage activation syndrome (n = 13), systemic and nonsystemic juvenile idiopathic arthritis (n = 14 and n = 10, respectively), and juvenile dermatomyositis (n = 9). We validated the key findings using serum samples from additional patients with KD (n = 37) and febrile controls (n = 28).
High-fidelity proteomic profiling revealed distinct patterns of cytokine and chemokine expression across pediatric inflammatory diseases. Although KD and MIS-C exhibited many similarities, KD differed from MIS-C and other febrile diseases in that most patients exhibited elevation in one or more members of the interleukin-17 (IL-17) cytokine family, IL-17A, IL-17C, and IL-17F. IL-17A was particularly sensitive and specific, discriminating KD from febrile controls with an area under the receiver operator characteristic curve of 0.95 (95% confidence interval 0.89-1.00) in the derivation set and 0.91 (0.85-0.98) in the validation set. Elevation of all three IL-17-family cytokines was observed in over 50% of KD patients, including 19 of 20 with coronary artery aneurysms, but was rare in all other comparator groups.
Elevation of IL-17 family cytokines is a hallmark of KD and may help distinguish KD from its clinical mimics.
Objective To describe the safety and efficacy of warfarin for patients with Kawasaki disease and giant coronary artery aneurysms (CAAs, ≥8 mm). Giant aneurysms are managed with combined ...anticoagulation and antiplatelet therapies, heightening risk of bleeding complications. Study design We reviewed the time in therapeutic range; percentage of international normalization ratios (INRs) in range (%); bleeding events, clotting events; INRs ≥6; INRs ≥5 and <6; and INRs <1.5. Results In 9 patients (5 male), median age 14.4 years (range 7.1-22.8 years), INR testing was prescribed weekly to monthly and was done by home monitor (n = 5) or laboratory (n = 3) or combined (1). Median length of warfarin therapy was 7.2 years (2.3-13.3 years). Goal INR was 2.0-3.0 (n = 6) or 2.5-3.5 (n = 3), based on CAA size and history of CAA thrombosis. All patients were treated with aspirin; 1 was on dual antiplatelet therapy and warfarin. The median time in therapeutic range was 59% (37%-85%), and median percentage of INRs in range was 68% (52%-87%). INR >6 occurred in 3 patients (4 events); INRs ≥5 <6 in 7 patients (12 events); and INR <1.5 in 5 patients (28 events). The incidence of major bleeding events and clinically relevant nonmajor bleeding events were each 4.3 per 100 patient-years (95% CI 0.9-12.6). New asymptomatic coronary thrombosis was detected by imaging in 2 patients. Conclusions Bleeding and clotting complications are common in patients with Kawasaki disease on warfarin and aspirin, with INRs in range only two-thirds of the time. Future studies should evaluate the use of direct oral anticoagulants in children as an alternative to warfarin.
The familial hypercholesterolemias (FH) are a group of genetic defects resulting in severe elevations of blood cholesterol levels and increased risk of premature coronary heart disease. FH is among ...the most commonly occurring congenital metabolic disorders. FH is a treatable disease. Aggressive lipid lowering is necessary to achieve the target LDL cholesterol reduction of at least 50% or more. Even greater target LDL cholesterol reductions may be necessary for FH patients who have other CHD risk factors. Despite the prevalence of this disease and the availability of effective treatment options, FH is both underdiagnosed and undertreated, particularly among children. Deficiencies in the diagnosis and treatment of FH indicate the need for greatly increased awareness and understanding of this disease, both on the part of the public and of healthcare practitioners. This document provides recommendations for the screening, diagnosis and treatment of FH in pediatric and adult patients developed by the National Lipid Association Expert Panel on Familial Hypercholesterolemia. This report goes beyond previously published guidelines by providing specific clinical guidance for the primary care clinician and lipid specialist with the goal of improving care of patients with FH and reducing their elevated risk for CHD.
Poor childhood cardiovascular health translates into poor adult cardiovascular health. We hypothesized care in a preventive cardiology clinic would improve cardiovascular health after lifestyle ...counseling. Over a median of 3.9 months, mean cardiovascular health score (range 0-11) improved from 5.8 ± 2.2 to 6.3 ± 2.1 (P < .001) in 767 children.
The prevention and management of cardiovascular risk factors during the transition from childhood to adulthood is critically important in defining cardiovascular health trajectories. Unfortunately, ...many young people fall out of clinical care during this important time, leading to worsening cardiovascular risk and missed opportunities to modify future outcomes. The field of health care transition has evolved to support young people with complex health needs in developing self-management and self-advocacy skills to promote positive health outcomes despite changes in health care providers and resources. While transitional care efforts are largely focused on childhood-onset chronic illnesses such as sickle cell disease and cystic fibrosis, young people with cardiovascular risk factors such as hypertension, obesity, and dyslipidemia also stand to benefit from structured supports to ensure continuity in care and positive health behaviours. On the backdrop of the broader health care transition literature, we offer practical insights and suggestions for ensuring that young people with cardiovascular risk factors experience uninterrupted high-quality care and support as they enter the adult health care system. Starting transition preparation in early adolescence, actively engaging all key stakeholders throughout the process, and remaining mindful of the developmental underpinnings and social context of transition are keys to success.
La prévention et la prise en charge des facteurs de risque cardiovasculaire durant la transition de l’enfance à l’âge adulte jouent un rôle crucial dans la définition des trajectoires en santé cardiovasculaire. Beaucoup de jeunes cessent malheureusement d’être suivis durant cette période importante, ce qui entraîne une aggravation du risque cardiovasculaire et des occasions manquées d’améliorer les résultats futurs. Le domaine de la transition des soins de santé a évolué afin d’aider les jeunes ayant des besoins complexes en matière de santé à acquérir les compétences nécessaires pour être autonomes et s’autoreprésenter, et ce, dans le but de favoriser l’obtention de résultats de santé positifs malgré les changements de fournisseurs et de ressources de soins de santé. Les initiatives de transition des soins visent principalement les patients atteints de maladies chroniques apparaissant durant l’enfance, comme la drépanocytose et la fibrose kystique, mais les jeunes présentant des facteurs de risque cardiovasculaire comme l’hypertension, l’obésité et la dyslipidémie pourraient aussi tirer des bienfaits de programmes structurés pour les aider à continuer de recevoir les soins dont ils ont besoin et à adopter des comportements favorisant la santé. Fondées sur l’ensemble des publications traitant de la transition des soins de santé, les observations et les suggestions pratiques présentées visent à s’assurer que les jeunes présentant des facteurs de risque cardiovasculaire continuent de recevoir des soins de qualité supérieure et de l’aide lorsqu’ils passent au système de soins de santé pour adultes. La réussite de la transition repose sur trois éléments : la préparation à la transition dès le début de l’adolescence, la mobilisation active des intervenants clés tout au long du processus et le souci des fondements du développement et du contexte social de la transition.
To describe enrollment characteristics of youth in the Cascade Screening for Awareness and Detection of FH Registry.
This is a cross-sectional analysis of 493 participants aged <18 years with ...heterozygous familial hypercholesterolemia recruited from US lipid clinics (n = 20) between April 1, 2014, and January 12, 2018. At enrollment, some were new patients and some were already in care. Clinical characteristics are described, including lipid levels and lipid-lowering treatments.
Mean age at diagnosis was 9.4 (4.0) years; 47% female, 68% white and 12% Hispanic. Average (SD) highest Low-density lipoprotein cholesterol (LDL-C) was 238 (61) mg/dL before treatment. Lipid-lowering therapy was used by 64% of participants; 56% were treated with statin. LDL-C declined 84 mg/dL (33%) among those treated with lipid-lowering therapy; statins produced the greatest decline, 100 mg/dL (39% reduction). At enrollment, 39% had reached an LDL-C goal, either <130 mg/dL or ≥50% decrease from pre-treatment; 20% of those on lipid-lowering therapy reached both goals.
Among youth enrolled in the Cascade Screening for Awareness and Detection of FH Registry, diagnosis occurred relatively late, only 77% of children eligible for lipid-lowering therapy were receiving treatment, and only 39% of those treated met their LDL-C goal. Opportunities exist for earlier diagnosis, broader use of lipid-lowering therapy, and greater reduction of LDL-C levels.
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