Familial Hypercholesterolemia In Children Research Articles

Statins for children with familial hypercholesterolemia.

Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low-density lipoprotein cholesterol levels or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid-lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels. While statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review. To assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia. Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline. Date of most recent search: 04 November 2019. Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone. Two authors independently assessed studies for inclusion and extracted data. We found 26 potentially eligible studies, of which we included nine randomized placebo-controlled studies (1177 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (high-quality evidence). There may be little or no difference in liver function (serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations) between treated and placebo groups at any time point (low-quality evidence). There may be little or no difference in myopathy (as measured in change in creatinine levels) (low-quality evidence) or clinical adverse events (moderate-quality evidence) with statins compared to placebo. One study on simvastatin showed that this may slightly improve flow-mediated dilatation of the brachial artery (low-quality evidence), and on pravastatin for two years may have induced a regression in carotid intima media thickness (low-quality evidence). No studies reported rhabdomyolysis (degeneration of skeletal muscle tissue) or death due to rhabdomyolysis, quality of life or compliance to study medication. Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. Few or no safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.

P4442miR-200c is up-regulated in lesional skin and plasma of patients affected by psoriasis and correlates with disease severity and cardiovascular risk

Abstract Background Psoriasis is a common, chronic inflammatory disease involving skin. Psoriatic patients mostly show the plaque-type clinical form and several comorbidities, including cardiovascular (CV) diseases. We previously showed that miR-200 family members (miR-200s) is induced by reactive oxygen species (ROS). miR-200c is the most up-regulated member and is responsible for apoptosis, senescence, endothelial dysfunction, ROS increase and nitric oxide decrease. Circulating miR-200c is upregulated in Familial Hypercholesterolemia in children, a pathology associated with ROS increase and atherosclerosis. miR-200c increases also in carotid plaques and plasma of atherosclerotic pts vs healthy subjects and positively correlates with plaque instability biomarkers. Purpose Given the role of miR-200s in ROS modulation, endothelial dysfunction, cardiac remodelling and inflammation, all features associated with psoriasis, we wondered whether miR-200s were modulated in lesional skin (LS) and plasma of psoriatic patients (Pso) and whether miR-200 levels correlated with CV risk. Methods 29 Pso were compared to 29 control subjects (Ctrl) age- and sex-matched. All Pso had a severe psoriasis, defined as Psoriasis Area and Severity Index (PASI) >10 and one of the following: at least two systemic psoriasis treatments, psoriasis onset <40 years of age, disease duration >10 years. Exclusion criteria were: diabetes, cerebrovascular events, myocardial infarction, and/or myocardial revascularization, psoriatic arthritis. Total RNA was extracted from plasma and miR-200 levels assayed by quantitative real-time PCR. The clinical parameters were similar between the two groups except for Total Cholesterol (mg/dl) (Ctrl 193.3±6.2; Pso 213.2±6.9; P<0.05). Blood pressure measurement, wave reflection analysis and pulse wave velocity (PWV) were similar between groups, echocardiographic parameters were different for left ventricular (LV) mass index (g/m2) (Ctrl 84.2±5.2; Pso 102.5±4.7; P<0.05) and relative wall thickness (RWT) (Ctrl 0.4±0.0; Pso 0.48±0.0; P<0.01). Total RNA was extracted from biopsies of nonlesional (NLS) and LS of 6 Pso and 6 healthy subject skin (HS). Results miR-200s were increased in LS vs NLS samples. miR-200c was the most expressed and was upregulated also in LS vs HS (2.0+0.2 fold-increase; P<0.01). Circulating miR-200c (2.5+0.5 fold-increase; P<0.05) and miR-200a (4.8+0.7 fold; P<0.0001) were up-regulated in Pso vs Ctr. Circulating miR-200c positively correlated with LV mass (Rs=0.32; P<0.05), RWT (Rs=0.32; P<0.05) and diastolic dysfunction assessed with E/e' parameters (Rs=0.34; P<0.05). Circulating miR-200a correlated only with LV mass, although not significantly (Rs=0.30; P=0.06). miR-200c exhibited a significant positive correlation with PASI (Rs=0.43; P<0.05) and with disease duration of (Rs=0.40; P<0.05). Conclusion miR-200c is upregulated in skin plaques and plasma of Pso, and might be involved in inflammatory and CV risk increase in these patients. Acknowledgement/Funding Ministero della Salute RF-2016-02362708 to AM and MCC

Homozygous familial hypercholesterolaemia in childhood – The first case report in Southeast Europe

Homozygous familial hypercholesterolaemia (HoFH) is the rare, severe, but treatable disease characterised by exceedingly high levels of low-density lipoprotein cholesterol (LDL-C) and subsequent premature coronary heart disease. Of note, HoFH detection rate and patient access to healthcare and treatment modalities still differ considerably across EU countries. To our current knowledge, there are still no published reports describing HoFH in the paediatric population of Southeastern Europe.In this case report, a few important topics on obstacles in getting adequate health care service and management of HoFH children from Southeastern Europe are tackled.

Familial hypercholesterolaemia: what’s new?

Abstract Autosomal Dominant Familial Hypercholesterolaemia (FH) is the commonest inherited disorder of lipoprotein metabolism. Untreated monogenic FH caused by mutations in the LDLR, APOB or PCSK9 genes result in early onset cardiovascular death (below the age of 60 years). In the UK the prevalence of heterozygous FH is 1 in 270 and homozygous FH is 160,000 approximately. The introduction of statins nearly three decades ago has altered the natural history of FH, with a significant reduction of cardiovascular related morbidity and mortality. There is increasing evidence that early childhood interventions such as lifestyle choices, healthy eating and commencing statins by the age of 10 years would potentially prevent early onset cardiovascular disease and mortality in monogenic FH. The medium term safety of statins in children has been demonstrated. The UK paediatric FH register data has shown that children with FH are less obese than the normal population and the register aims to monitor the longer-term safety of statins in children with FH. Child-parent screening would potentially benefit the child and enables identifying a parent with FH, before the onset of a life threatening cardiovascular event. In addition, genetic cascade testing of relatives of an affected individual has been shown to be highly cost effective. We review the current literature with brief updates on genetics, the UK paediatric FH register data, published recommendations for the management of homozygous and heterozygous FH, lipid lowering therapies in children and screening for FH in childhood.

Familial Hypercholesterolemia in Children and Adolescents: Diagnosis and Treatment.

Familial hypercholesterolemia is a hereditary genetic disorder predisposing in premature atherosclerosis and cardiovascular complications. Early diagnosis as well as effective treatment strategies in affected children are challenges among experts. Universal screening and cascade screening among families with familial hypercholesterolemia are being controversially discussed. Diagnosis of familial hypercholesterolemia in children and adolescents is usually based on clinical phenotype upon LDL-C levels and family history of premature cardiovascular and/or elevated LDL-C. Treatment approaches for familial hypercholesterolemia in the pediatric population are multidisciplinary and aim to reduce total cardiovascular risk. The most widely recommended and effective pharmacotherapy in the pediatric age group is currently statins. Ezetimibe and bile acid sequestrants are usually used as second-line agents. New therapeutic approaches, such as mipomersen and PCSK9 inhibitors seem promising. The main gap of evidence remains the lack of longitudinal follow up studies investigating cardiovascular outcomes, side effects, and effectiveness of treatment starting from childhood. Evidence would be expected in the near future by cohort and registry studies.

Identifying Perceptions and Preferences of the General Public Concerning Universal Screening of Children for Familial Hypercholesterolaemia

Background/Aims: Familial hypercholesterolaemia (FH) is a common genetic disorder that, if untreated, predisposes individuals to premature coronary heart disease. As most individuals with FH remain undiagnosed, new approaches to detection are needed and should be considered a priority in public health genomics. Universal screening of children for FH has been proposed, and this study explores public perspectives on the acceptability of this approach. Methods: A one-day deliberative public forum was held in Perth, WA, Australia. Thirty randomly selected individuals were recruited, with self-reported sociodemographic characteristics used to obtain discursive representation. Participants were presented with information from a variety of perspectives and asked to discuss the information provided to identify points of consensus and disagreement. The data collected were analysed using thematic analysis. Results: Of the 17 participants at the forum, 16 deemed universal screening of children for FH to be acceptable. Fifteen of these 16 believed this was best performed at the time of an immunisation. Participants proposed a number of conditions that should be met to reduce the likelihood of unintended harm resulting from the screening process. Discussion/Conclusion: The outcomes of the forum suggest that establishing a universal screening programme for FH in childhood is acceptable to the general public in WA.

The clinical and molecular diversity of homozygous familial hypercholesterolemia in children: Results from the GeneTics of clinical homozygous hypercholesterolemia (GoTCHA) study

Homozygous familial hypercholesterolemia (hoFH) is either diagnosed on the identification of pathogenic genetic variants in LDLR, APOB, or PCSK9 or by phenotypic parameters of which an extremely elevated LDL-C level >13mmol/L (>500mg/dL) is the most prominent hallmark. Little is known about the clinical spectrum in children with hoFH. We set out to investigate the phenotypical spectrum of genetically defined hoFH in our pediatric cohort and evaluated how many pediatric patients, now classified as heterozygous, carry a second mutation, which would reclassify these patients as hoFH. We analyzed the data of a total of 1903 children with molecularly proven FH. Subsequently we performed candidate gene sequencing in the cohort of heterozygous familial hypercholesterolemia children in whom the LDL-C level was above the lowest level measured in the pediatric patients with hoFH. Of our 13 hoFH children, 8 (62%) had LDL-C levels below the clinical hoFH criteria of 13mmol/L (500mg/dL). In the remaining 1890 patients with heterozygous familial hypercholesterolemia, 64 (3.4%) had LDL-C levels equal to or above the lowest LDL-C level in a patient with hoFH carrying 2 deleterious variants (8.36mmol/L or 323.3mg/dL). No additional pathogenic variants in LDLR and APOB were identified. In 2 related patients, a PCSK9 gain of function mutation was found. We show that LDL-C levels vary among pediatric patients with molecularly proven hoFH, and that most of these patients do not meet the clinical LDL-C criteria for hoFH. The levels overlap with LDL-C levels in true heterozygous patients. This warrants a critical reappraisal of the current LDL-C cutoffs for the phenotypic diagnosis of hoFH in children.

ESTIMATION OF THE THICKNESS OF THE INTIMA-MEDIA COMPLEX IN CHILDREN WITH FAMILIAL HYPERCHOLESTEROLEMIA

Objective:to evaluate the diagnostic significance of measuring the thickness of the intima-media complex (IMC) in children with autosomal dominant familial hypercholesterolemia for early diagnostics and prompt treatment of atherosclerosis.Materials and methods.The study included 109 children – 64 children with familial hypercholesterolemia and 45 healthy children. Both groups were divided into 2 subgroups according to the age – from 3 to 8 years and from 9 to 18 years. We measured the intimamedia thickness (IMT) of the common carotid artery in all the children. To evaluate IMT we used an ultrasound scanner HD11XE (Philips, USA) with a linear (3–12MHz) sensor IMT.Results.We found a statistically significant difference (p=0.012) of the IMT of the common carotid artery in children with familial hypercholesterolemia (0.61 ± 0.02 mm) in comparison with the control group (0.49±0.02 mm), starting from the age of 9 years. There were no sex differences of IMT in patients older than 9 years.Conclusion.We found that children with familial hypercholesterolemia have higher values of IMT already from the age of 9 as compared with healthy children; the increase in TCIM is an additional criterion for the early diagnostics of atherosclerosis and evaluation of cardiovascular risk. These results emphasize the relevance of lipid-lowering therapy for patients with familial hypercholesterolemia in childhood, before the first signs of atherosclerosis appear.

Universal screening for familial hypercholesterolemia in children: The Slovenian model and literature review

Background and aimsFamilial hypercholesterolemia (FH) is arguably the most common monogenic disorder in humans, but severely under-diagnosed. Individuals with untreated FH have an over 10-fold elevated risk of cardiovascular complications as compared to unaffected individuals; early diagnosis and timely management substantially reduce this risk.Slovenia has gradually implemented the program of universal FH screening in pre-school children, consisting of a two step approach: (1) universal hypercholesterolemia screening in pre-school children at the primary care level; (2) genetic FH screening in children referred to the tertiary care level according to clinical guidelines (with additional cascade screening of family members). The program is presented in detail. MethodsWe analyzed retrospective data (2012–2016), to assess the efficiency of the universal FH screening program. In that period, 280 children (59.3% female) were referred to our center through the program for having TC > 6 mmol/L (231.7 mg/dL) or >5 mmol/L (193.1 mg/dL), with a positive family history of premature cardiovascular complications at the universal hypercholesterolemia screening. Results170 (57.1% female) of them were fully genotyped, 44.7% had an FH disease-causing variant (28.8% in LDLR gene, 15.9% in APOB, none in PCSK9), one patient was LIPA positive, and 40.9% of the remaining patients carried an ApoE4 isoform; genetic analysis is still ongoing for one-third of the referred patients. For almost every child with confirmed FH, one parent had highly probable FH. ConclusionsFH was confirmed in almost half of the referred children, detected through the universal screening for hypercholesterolemia.

Plasma IDOL, soluble LDLR and PCSK9 levels as potential biomarkers of familial hypercholesterolemia in children

Aim: Familial hypercholesterolemia (FH) in children is poorly detected. Plasma biomarkers associated with LDL receptor function could help identifying FH children. We aim to assess the clinical value of IDOL, soluble LDLR (sLDLR) and PCSK9 plasma concentrations in children with FH compared to control children (CCh).

Parents\u2019 views of genetic testing and treatment of familial hypercholesterolemia in children: a qualitative study

Familial hypercholesterolemia (FH) is a serious inherited disorder, which greatly increases individuals’ risk of cardiovascular disease (CVD) in adult life. However, medical treatment and lifestyle adjustments can fully restore life expectancy. Whilst European guidance advises that where there is a known family mutation genetic testing is undertaken in early childhood, the majority of the at-risk population remain untested and undiagnosed. To date, only a small number of studies have explored parents’ and children’s experiences of testing and treatment for FH, and little is known about interactions between health professionals, parents, and children in clinic settings. In this study, in-depth interviews were undertaken with parents who had attended a genetics and/or lipid clinic for FH with their children (n = 17). A thematic analysis revealed four main themes: undertaking early prevention, postponing treatment, parental concerns, and the importance of the wider family context. The majority of parents supported genetic testing for FH in childhood. However, although some were very supportive of following early treatment recommendations, others expressed reluctance. Importantly, some parents were concerned that inappropriate information had been shared with their children and wished that more time had been given to discuss how, when, and what to tell in advance. Future research is needed to explore the long-term outcomes for children who undertake genetic testing and early treatment for FH and to trial interventions to improve the engagement, follow-up, and support of children who are at risk, or diagnosed, with this disorder.

Improving Familial Hypercholesterolaemia Diagnosis – Functional in Vitro Analysis of LDLR Missense Variants Found in the Portuguese FH Cohort

Familial hypercholesterolemia (FH) is underdiagnosed in children. We assessed a combination of two screening methods. The first method was to detect hypercholesteraemic children and then study the parents (Ch-P pathway), and the second one was to study the offspring of FH-affected parents (P-Ch pathway).In the Ch-P path, primary care paediatricians were asked to include lipid profiling or, at least, total cholesterol (TC) and then lipid profiling if TC was higher than 5.2 mmol/L in any clinically indicated blood test. Children with LDL-C ≥ 3.5 mmol/L, plus either a family history of early cardiovascular disease or one parent with severe hypercholesterolemia, were referred to the lipid unit where the parents, rather than their children, were studied. In parents with definite, clinical FH, a genetic study was performed. Focused genetic testing was performed on all offspring of genetically positive parents. The P-Ch path consisted of the active study of children from definite FH adults.Fifty-nine paediatricians covering a total population of 63,616 children agreed to participate in the project. Of the 216 children (122 Ch-P and 94 P-Ch) who were ultimately referred to the lipid unit, 87 children with FH (84% genetically positive) were identified. Additionally, 41 parents (from 40 families) were newly diagnosed with FH (63% genetically positive). Forty-nine different mutations were detected: 46 in the LDLR, 2 in the PCSK9 and 1 in APOB gene.The implementation of active strategies to detect FH in children, in close collaboration with primary care paediatricians, provides a high-performance method for early FH detection.

Évaluation des connaissances et pratiques sur le dépistage de l’hypercholestérolémie familiale hétérozygote chez l’enfant

IntroductionDominant heterozygous familial hypercholesterolemia (FH) is frequent (prevalence, 1/500 to 1/250) and leads to severe and premature cardiovascular complications. It is easily detected, and its treatment is effective. However, recommendations for screening are not followed worldwide. ObjectivesThe aim of this study was to evaluate the knowledge and practices of doctors in the Isère department, France, regarding screening and treatment of FH in children. MethodsA questionnaire was distributed by email or during training sessions to general practitioners, doctors working in Infant and Mother Protection (IMP) services, and pediatricians in private practice in Isère. ResultsFifty-nine doctors completed the questionnaire (overall response rate, 61%). Respondents were general practitioners (36%), IMP doctors (36%), and pediatricians in private practice (28%). Generalized screening for all children was done by only 8% of the respondents, while cascade screening, in case of familial cardiovascular medical history, was done by only 36%, of which 5% were general practitioners while 53% were doctors with a clinical practice focused on children. The most recent French recommendations by the Société française de pédiatrie and the Nouvelle Société française d’athérosclérose, which were published in 2010, had been read by only nine doctors (15%). Having read them led to a better policy of generalized screening, either generalized to all children (OR=12.0 [2.3–64.0], P=0.004) or in cascade (OR=22.8 [4.2–123.2], P<0.001). DiscussionThe number of questionnaires collected was small, with possible selection and declaration bias, but the different types of pediatric practice were equally represented. ConclusionScreening of FH in children is not very well organized and recommendations are not followed by doctors in Isère, France. Children with FH are probably underdiagnosed and undertreated.

Plasma inducible degrader of the LDLR, soluble low-density lipoprotein receptor, and proprotein convertase subtilisin/kexin type 9 levels as potential biomarkers of familial hypercholesterolemia in children

Familial hypercholesterolemia (FH) in children is under-detected. Plasma biomarkers associated with low-density lipoprotein receptor (LDLR) function could help identifying FH children. We aim to assess the clinical value of inducible degrader of the LDLR (IDOL), soluble LDLR (sLDLR), and proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma concentrations in children with FH compared with control children (CCh). This was a cross-sectional study performed in a Lipid Unit from a University hospital. The participants were 177 children distributed into FH (n=77) and CCh (n=100). Main outcomes were changes in IDOL, sLDLR, and PCSK9 plasma concentrations between children groups; secondary outcomes were the association between IDOL, sLDLR, and PCSK9 and lipid profile determined by 2-dimensional nuclear magnetic resonance. The IDOL levels were higher in FH compared with CCh (P=.007). The PCSK9 levels were elevated in FH (P<.001). The sLDLR levels had no significant differences between groups. IDOL was significantly positively associated to total and LDL cholesterol and ApoB100 but not to LDL particle number. However, a robust correlation with Lp(a) (P=.001) was observed. PCSK9 had the strongest correlation with LDL-associated parameters including particle number. sLDLR was associated with triglyceride levels (P<.001) and triglyceride-rich particles and inversely to LDL size. The IDOL and PCSK9 plasma levels are significantly higher in FH children. Interestingly, sLDLR was associated with atherogenic dyslipidemia components. IDOL concentrations show a robust association with Lp(a) levels. To study the role of plasma biomarkers associated with LDLR expression in FH is warranted.

Sensitivity and specificity of biochemical screening for Familial Hypercholesterolaemia in childhood: Avon Longitudinal Study of Parents and Children (ALSPAC)

Sensitivity and specificity of biochemical screening for Familial Hypercholesterolaemia in childhood: Avon Longitudinal Study of Parents and Children (ALSPAC)

The prevalence of familial hypercholesterolemia in children from Timisoara

Aim: Introduction: FH is one of the most frequent monogenic cholesterol disorders. It’s prevalence is not very well known, in adults variations between 1/200-1/137 individuals have been reported. Due to the persistent hypercholesterolemia, these patients are exposed to a high risk of developing early cardiovascular disease. Although cardiovascular events usualy occur in early adulthood, the atherosclerotic process starts asymptomaticaly in childhood.

LDL cholesterol and familial hypercholesterolemia in children. Significance of familial history in detecting familial hypercholesterolemia

Aim: Determine the percentage of children with LDL cholesterol values (LDL-C) (>4mmol/l) where familiar hypercholesterolemia ( FH) is suspected, and (>5mmol/l) where diagnosis is recommended to be confirmed, in relation to family history, with previously excluded secondary causes of high LDL-C.

SEnsitivity and specificity of biochemical screening for familial hypercholesterolaemia in childhood: avon longitudinal study of parents and children (ALSPAC)

SEnsitivity and specificity of biochemical screening for familial hypercholesterolaemia in childhood: avon longitudinal study of parents and children (ALSPAC)

Beyond cascade screening: detection of familial hypercholesterolaemia at childhood immunization and other strategies.

Familial hypercholesterolaemia is a common genetic disorder that accelerates premature coronary heart disease. Although effective treatments are available, the majority of individuals remain undiagnosed. We review new evidence for improving the detection of familial hypercholesterolaemia. Recent studies have demonstrated that universal screening of children for familial hypercholesterolaemia may be highly effective at the time of immunization if combined with reverse cascade testing of adult family members, who have a more immediate risk of a coronary event. Alerts on laboratory reports and the application of bioinformatics to electronic health records may also be useful for identifying familial hypercholesterolaemia in community settings. Effective detection, diagnosis, and codification of familial hypercholesterolaemia are essential for the development of registries. Although the cost-effectiveness of screening programs for familial hypercholesterolaemia in childhood remains to be established, combining universal and reverse cascade screening, complemented by opportunistic identification of individuals in high-risk settings, use of laboratory alerts, and screening of electronic health records are likely to have a high yield in the detection of familial hypercholesterolaemia in the community.

Statins for children with familial hypercholesterolemia.

Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low-density lipoprotein cholesterol levels or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid-lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels. While statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review. To assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia. Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline.Date of most recent search: 20 February 2017. Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone. Two authors independently assessed studies for inclusion and extracted data. We found 26 potentially eligible studies, of which we included nine randomized placebo-controlled studies (1177 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (moderate quality evidence). Serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations, did not differ between treated and placebo groups at any time point (low quality evidence). The risks of myopathy (low quality evidence) and clinical adverse events (moderate quality evidence) were very low and also similar in both groups. In one study simvastatin was shown to improve flow-mediated dilatation of the brachial artery (low quality evidence), and in another study treatment with pravastatin for two years induced a significant regression in carotid intima media thickness (low quality evidence). Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. No significant safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.