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The article discusses a follow-up study of children with familial hypercholesterolemia (FH) who received statin therapy until adulthood. Topics discussed include the predisposition of FH to pre-mature atherosclerosis and cardiovascular disease, higher mean carotid intima-media thickness (IMT) in patients with FH and adverse events resulting to some patients discontinuing statin therapy.

"...it has been suggested that high cholesterol levels during pregnancy could induce increased cholesterol levels and confer increased cardiovascular risk for the offspring." [ABSTRACT FROM AUTHOR]

Background: Familial hypercholesterolemia is characterized by severely elevated low-density lipoprotein (LDL) cholesterol levels and premature cardiovascular disease. The short-term efficacy of statin therapy in children is well established, but longer follow-up studies evaluating changes in the risk of cardiovascular disease are scarce.Methods: We report a 20-year follow-up study of statin therapy in children. A total of 214 patients with familial hypercholesterolemia (genetically confirmed in 98% of the patients), who were previously participants in a placebo-controlled trial evaluating the 2-year efficacy and safety of pravastatin, were invited for follow-up, together with their 95 unaffected siblings. Participants completed a questionnaire, provided blood samples, and underwent measurements of carotid intima-media thickness. The incidence of cardiovascular disease among the patients with familial hypercholesterolemia was compared with that among their 156 affected parents.Results: Of the original cohort, 184 of 214 patients with familial hypercholesterolemia (86%) and 77 of 95 siblings (81%) were seen in follow-up; among the 214 patients, data on cardiovascular events and on death from cardiovascular causes were available for 203 (95%) and 214 (100%), respectively. The mean LDL cholesterol level in the patients had decreased from 237.3 to 160.7 mg per deciliter (from 6.13 to 4.16 mmol per liter) - a decrease of 32% from the baseline level; treatment goals (LDL cholesterol <100 mg per deciliter [2.59 mmol per liter]) were achieved in 37 patients (20%). Mean progression of carotid intima-media thickness over the entire follow-up period was 0.0056 mm per year in patients with familial hypercholesterolemia and 0.0057 mm per year in siblings (mean difference adjusted for sex, -0.0001 mm per year; 95% confidence interval, -0.0010 to 0.0008). The cumulative incidence of cardiovascular events and of death from cardiovascular causes at 39 years of age was lower among the patients with familial hypercholesterolemia than among their affected parents (1% vs. 26% and 0% vs. 7%, respectively).Conclusions: In this study, initiation of statin therapy during childhood in patients with familial hypercholesterolemia slowed the progression of carotid intima-media thickness and reduced the risk of cardiovascular disease in adulthood. (Funded by the AMC Foundation.). [ABSTRACT FROM AUTHOR]

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 well established since three decades, lowering serum LDL-C levels by more than 70% per session. 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 targets and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation.

Familial hypercholesterolaemia is a common, dominantly inherited disease that results in high concentrations of low-density lipoprotein cholesterol and in premature cardiovascular disease. To prevent cardiovascular disease and premature mortality, patients with the condition need to be identified and to start treatment early in life. In this Review, we discuss the treatment of heterozygous and homozygous familial hypercholesterolaemia in children, including lifestyle modifications, current pharmacological treatment options, and promising novel lipid-lowering treatments. In particular, these new therapies are expected to improve outcomes for patients with severe heterozygous familial hypercholesterolaemia or statin intolerance. For patients with homozygous familial hypercholesterolaemia, lipoprotein apheresis is currently the most valuable therapy available, but new approaches might reduce the need for this effective yet invasive, time-consuming, and expensive treatment., Competing Interests: Declaration of interests AW reports research support for pharmaceutical trials of lipid-modifying agents from Amgen, Regeneron, and Novartis. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Statins are currently the preferred pharmacological therapy in children with familial hypercholesterolemia (FH) with the aim to prevent premature cardiovascular disease (CVD). However, concerns have been raised that lowering cholesterol levels with statins could interfere with hormone production. In this study hormone concentrations were assessed in young adult FH subjects before and 10 years after the initiation of statins, and compared with their unaffected siblings., Methods: All 214 FH children (8-18 years) who were previously randomized into a placebo-controlled trial evaluating the 2-year efficacy and safety of pravastatin, and their 95 unaffected siblings, were eligible. Women using oral contraceptives were excluded. Fasted blood samples were taken to measure lipids and testosterone (males), estradiol (females), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and dehydroepiandosterone (DHEAS)., Results: After ten years, gonadal steroid and gonadotropin concentrations were within the reference interval and did not differ between FH subjects (n = 88) and unaffected siblings (n = 62). Mean DHEAS concentrations (±standard deviation) in the FH subjects and female siblings were normally distributed within the reference interval, whereas male siblings had a higher mean DHEAS concentration than their FH brothers (12.9 [± 4.9] vs. 8.4 [± 3.0] μmol/L, respectively, p < 0.0001)., Conclusion: After ten years of statin treatment, testosterone, estradiol, LH and FSH concentrations in young adult FH patients are within the reference interval and comparable to their unaffected siblings. These results strengthen current guidelines that statins in FH subjects could be safely used from childhood onwards to prevent premature CVD., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Autosomal dominant hypercholesterolemia (ADH) is characterized by elevated low-density lipoprotein cholesterol levels and premature cardiovascular disease. Mutations in the genes encoding for low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9) underlie ADH. Nevertheless, a proportion of individuals who exhibit the ADH phenotype do not carry mutations in any of these 3 genes. Estimates of the percentage of such cases among the ADH phenotype vary widely. We therefore investigated a large pediatric population with an unequivocal ADH phenotype to assess the molecular basis of hereditary hypercholesterolemia and to define the percentage of individuals with unexplained dyslipidemia., Methods and Results: We enrolled individuals with low-density lipoprotein cholesterol levels above the 95th percentile for age and gender and an autosomal dominant inheritance pattern of hypercholesterolemia from a large referred pediatric cohort of 1430 children. We excluded children with thyroid dysfunction, nephrotic syndrome, autoimmune disease, liver disease, primary biliary cirrhosis, and obesity (body mass index >75th percentile for age and gender), as well as children referred via a cascade screening program and those from families with a known molecular diagnosis. Of the 269 children who remained after the exclusion criteria were applied, 255 (95%) carried a functional mutation (LDLR, 95%; APOB, 5%)., Conclusion: In the vast majority of children with an ADH phenotype, a causative mutation can be identified, strongly suggesting that most of the large-effect genes underlying ADH are known to date.

Importance of the Field: Atherosclerosis, the condition underlying cardiovascular disease (CVD), often begins in childhood. A disturbance in lipoprotein metabolism is one of the major modifiable risk factors for the development of atherosclerosis and ensuing CVD. Therefore, strategies to prevent CVD should be implemented at an early age, especially in populations at high risk., Areas Covered in This Review: We discuss the current treatment options for a number of primary and secondary dyslipidaemias. A literature search was done using PubMed, and references from 1973 to 2009 are cited., What the Reader Will Gain: The reader will gain a comprehensive review on pharmacological and non-pharmacological treatment options for primary and secondary dyslipidaemia in childhood., Take Home Message: Dyslipidaemia may require early diagnosis and management, especially when it is familial with elevated cholesterol levels from birth onwards. If target goals for low-density lipoprotein reduction cannot be reached with lifestyle modification, drug therapy can be considered.