Clinical practice recommendations on lipoprotein apheresis for children with homozygous familial hypercholesterolaemia: An expert consensus statement from ERKNet and ESPN.

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.

Evinacumab for Pediatric Patients With Homozygous Familial Hypercholesterolemia.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) levels due to profoundly defective LDL receptor (LDLR) function. Given that severely elevated LDL-C starts in utero, atherosclerosis often presents during childhood or adolescence, creating a largely unmet need for aggressive LDLR-independent lipid-lowering therapies in young patients with HoFH. Here we present the first evaluation of the efficacy and safety of evinacumab, a novel LDLR-independent lipid-lowering therapy, in pediatric patients with HoFH from parts A and B of a 3-part study. METHODS: The phase 3, part B, open-label study treated 14 patients 5 to 11 years of age with genetically proven HoFH (true homozygotes and compound heterozygotes) with LDL-C >130 mg/dL, despite optimized lipid-lowering therapy (including LDLR-independent apheresis and lomitapide), with intravenous evinacumab 15 mg/kg every 4 weeks. RESULTS: Evinacumab treatment rapidly and durably (through week 24) decreased LDL-C with profound reduction in the first week, with a mean (SE) LDL-C reduction of -48.3% (10.4%) from baseline to week 24. ApoB (mean [SE], -41.3% [9.0%]), non-high-density lipoprotein cholesterol (-48.9% [9.8%]), and total cholesterol (-49.1% [8.1%]) were similarly decreased. Treatment-emergent adverse events were reported in 10 (71.4%) patients; however, only 2 (14.3%) reported events that were considered to be treatment-related (nausea and abdominal pain). One serious treatment-emergent adverse event of tonsillitis occurred (n=1), but this was not considered treatment-related. CONCLUSIONS: Evinacumab constitutes a new treatment for pediatric patients with HoFH and inadequately controlled LDL-C despite optimized lipid-lowering therapy, lowering LDL-C levels by nearly half in these extremely high-risk and difficult-to-treat individuals. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04233918.

Clinical response to lifestyle counseling for dyslipidemia and elevated blood pressure in childhood cancer survivors.

BACKGROUND: Childhood cancer survivors (CCS) have increased risk of premature cardiovascular disease. Whether they respond similarly to lifestyle changes for elevated blood pressure (BP), body mass index (BMI), and dyslipidemia to those without history of childhood cancer is unknown. PROCEDURE: This retrospective cohort study included CCS and 3:1 age- and sex-matched controls treated at Boston Children's Hospital Preventive Cardiology (2010-2019) using lifestyle management based on National Heart, Lung, and Blood Institute (NHLBI) guidelines. Change in BMI, BP, and lipids were analyzed. RESULTS: We included 52 CCS and 162 controls with a median age of approximately 16 years. More CCS (84.3%) had elevated baseline fasting triglycerides (TG) than controls (49.4%) (p < .001). More CCS (62.5%) also had abnormal baseline high-density lipoprotein cholesterol (HDL-C) compared to controls (35.2%) (p = .001). Baseline BMI, BP, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were similar between groups. Over 15 weeks [IQR: 10.5-26], CCS had greater decrease in TG than controls (72.5 vs. 17 mg/dl decrease, p = .095). BP improved in 5% of CCS versus 38% of controls (p = .008). For both, BMI, TC, LDL-C, and HDL-C remained stable. CCS with stem cell transplantation (SCT) had a TC increase of 5% (6 mg/dl) compared to a decrease of 9% (19 mg/dl) among CCS without SCT (p = .02). CONCLUSIONS: CCS demonstrated similar improvement in lipids, but impaired BP lowering in response to lifestyle management compared to controls. Further prospective studies are needed to determine if earlier pharmaceutical treatment is warranted in this higher risk population and for the long-term risk reductions of these approaches.

Surgical Repair of Congenital Atresia of the Left Coronary Ostium.

Congenital left main coronary artery atresia is an exceedingly rare condition with potentially fatal consequences if not diagnosed in a timely fashion. We present a case series in children and adolescents, including surgical repair and outcomes. We describe the presenting symptoms and subsequent management of each patient, including surgical repair and outcomes. (Level of Difficulty: Advanced.).

Lipoprotein Particle Predictors of Arterial Stiffness after 17 Years of Follow Up: The Malmö Diet and Cancer Study.

BACKGROUND: Central arterial stiffness is a surrogate of cardiovascular risk and predicts cardiovascular mortality. Apolipoprotein B lipoproteins are also established cardiovascular risk factors. It is not known whether specific lipoprotein subclasses measured in the Malmö Diet and Cancer Study and previously shown to be associated with coronary heart disease also predict arterial stiffening after a mean period of 17 years. METHODS: Lipoprotein particle analysis was performed on 2,505 men and women from Malmö, Sweden, from 1991 to 1994, and arterial stiffness was assessed by carotid-femoral pulse wave velocity (c-fPWV) on this same cohort from 2007 to 2012. Associations between c-fPWV and lipoprotein particles were determined with multiple linear regression, controlling for sex, presence of diabetes, waist-to-hip circumference, and smoking status at baseline, as well as heart rate (measured at the carotid artery), mean arterial pressure, antihypertensive and lipid-lowering medications, C-reactive protein (CRP), and age at the time of c-fPWV measurement. RESULTS: The results confirm that triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c) but not low-density lipoprotein cholesterol (LDL-c) predict c-fPWV. We identify a positive predictive association for very small, small, and medium (high risk), but not large LDL particles. There was a negative association for large HDL particles. The relationships between c-fPWV and high-risk LDL particles were unaffected by adjusting for LDL-c or CRP and were only mildly attenuated by adjusting for the homeostatic model for insulin resistance (HOMA-IR). Due to the collinearity of very small, small, and medium LDL particles and dyslipidemia (elevated TG and decreased HDL-c), the observed relationship between c-fPWV and high-risk LDL particles became insignificant after controlling for the concentration of HDL-c, large cholesterol-rich HDL particles, and TG. CONCLUSIONS: The development of central arterial stiffness previously associated with combined dyslipidemia may be mediated in part by LDL particles, particularly the very small-, small-, and medium-sized LDL particles.

Clustering of Health Behaviors and Cardiorespiratory Fitness Among U.S. Adolescents.

PURPOSE: Decreased cardiorespiratory fitness (CRF) is associated with an increased risk of cardiovascular disease. However, little is known how the interaction of diet, physical activity (PA), and sedentary time (ST) affects CRF among adolescents. By using a nationally representative sample of U.S. adolescents, we used cluster analysis to investigate the interactions of these behaviors with CRF. We hypothesized that distinct clustering patterns exist and that less healthy clusters are associated with lower CRF. METHODS: We used 2003-2004 National Health and Nutrition Examination Survey data for persons aged 12-19 years (N = 1,225). PA and ST were measured objectively by an accelerometer, and the American Heart Association Healthy Diet Score quantified diet quality. Maximal oxygen consumption (V˙O2​max) was measured by submaximal treadmill exercise test. We performed cluster analysis to identify sex-specific clustering of diet, PA, and ST. Adjusting for accelerometer wear time, age, body mass index, race/ethnicity, and the poverty-to-income ratio, we performed sex-stratified linear regression analysis to evaluate the association of cluster with V˙O2​max. RESULTS: Three clusters were identified for girls and boys. For girls, there was no difference across clusters for age (p = .1), weight (p = .3), and BMI (p = .5), and no relationship between clusters and V˙O2​max. For boys, the youngest cluster (p < .01) had three healthy behaviors, weighed less, and was associated with a higher V˙O2​max compared with the two older clusters. CONCLUSIONS: We observed clustering of diet, PA, and ST in U.S. adolescents. Specific patterns were associated with lower V˙O2​max for boys, suggesting that our clusters may help identify adolescent boys most in need of interventions.

Clinicians' Adherence to Guidelines on Evaluation of Hypertension in Children and Adolescents.

BACKGROUND: Hypertension is increasingly prevalent among children. We sought to review provider adherence to the National High Blood Pressure Education Program (NHBPEP) recommendations at a single academic medical center. METHODS: We identified children 3-18 years of age with hypertension based on outpatient visit International Classification of Diseases, Ninth Edition, Clinical Modification codes from 2006 to 2012. We calculated the odds of individual tests administration for ten recommended tests, adjusting for demographic characteristics. RESULTS: We identified 3,588 (1.7%) of 216,855 children diagnosed with hypertension at a median age of 14 years (25th and 75th percentile 10 and 16, respectively). No child received all ten recommended tests. The median number of tests administered was 2 (1, 4) but varied significantly by race and age. Urine drug screen (<1%) and renin levels (1%) were the least common, whereas serum creatinine (49%) and echocardiogram (40%) were the most common tests. Male children were more likely to receive an echocardiogram (odds ratio 1.43; 95% confidence interval: 1.24-1.64), and black children and those ≥11 years old were less likely to have their serum creatinine checked. Adherence to the guidelines did not improve over time (P = .24). CONCLUSION: Children evaluated for hypertension in the outpatient setting infrequently receive the diagnostic tests recommended in the NHBPEP's report. Test administration frequency varies by patient demographics but has not improved significantly over time.