Management of familial hypercholesterolaemia in children and adolescents

Abstract

Familial hypercholesterolaemia is a disorder of low-density lipoprotein (LDL) cholesterol metabolism, which is associated with the onset of vascular changes associated with coronary heart disease in childhood. This disorder has co-dominant transmission with a prevalence of one in 500 in the general population. Cascade screening is the most effective method of identifying children. Children in the at-risk group should have their cholesterol levels checked between the age of 2 and 10 years. Children with LDL cholesterol levels ≥ 3.4 mmol/L are likely to suffer from this disorder, although at this level there is a significant false positive rate. Molecular genetic testing is available for the LDL receptor gene, APOB gene and the PCSK9 gene. This is the most specific test for familial hypercholesterolaemia but has a false negative rate of 20-50%. Once diagnosed, treatment should be considered in children with an LDL cholesterol level ≥ 4.9 mmol/L. If the child has two other risk factors or a positive family history, this threshold should be lowered to ≥4.1 mmol/L. Guidelines recommend that treatment should be commenced by the age of 10 years, although some advise waiting until menarche in females. Statin therapy is currently recommended as first line treatment. Randomised placebo trials have shown that statin therapy reduces LDL cholesterol levels by 25% and is not associated with increased risk of adverse events. These are short-term studies, and longer follow-up will be required to definitively prove efficacy and safety.

Treatment of familial hypercholesterolaemia in children and adolescents in the last three decades

“…17,18 Currently, it is well accepted that statin monotherapy should be used in children at high risk for coronary heart disease. [13][14][15][16] All available statins have been studied in children and adolescents and were found to be effective, well tolerated, and safe in the short term. However, the studies were small, lacked a control group, or had a short follow-up period of a few weeks to 2 years.…”

“…[1][2][3][4][5][6][7][8][9] The need for intensive drug therapy in children with familial hypercholesterolaemia has been strongly accepted by all authorities. [10][11][12][13][14][15][16] Bile acid sequestrants have long been considered the drug of choice in children. 17,18 However, statin therapy is currently recommended as first-line treatment, and should be commenced by the age of 10 years, although some advise waiting until menarche in girls.…”

“…17,18 However, statin therapy is currently recommended as first-line treatment, and should be commenced by the age of 10 years, although some advise waiting until menarche in girls. [13][14][15][16] Over the last two decades, statins have been studied extensively in small groups of children with heterozygous familial hypercholesterolaemia, demonstrating that they are efficacious, well tolerated, and safe in the short term. [19][20][21][22][23][24][25][26][27][28] Nevertheless, there are concerns regarding the initiation at young ages and long-term efficacy and safety.…”

“…[19][20][21][22][23][24][25][26][27][28] Nevertheless, there are concerns regarding the initiation at young ages and long-term efficacy and safety. 13,16,29 This study explores a three-decade-long experience of treatment and follow-up of children and adolescents with heterozygous familial hypercholesterolaemia, the long-term use of statins, the achieved low-density lipoprotein cholesterol levels, and the effect on cardiovascular risk.…”

POR*28 Snp is Associated with Lipid Response to Atorvastatin in Children and Adolescents with Familial Hypercholesterolemia

“…In children with FH there is broad consensus that statin therapy is the treatment of choice, and it should be commenced by the POR*28 SNP is associated with lipid response to atorvastatin in children and adolescents with familial hypercholesterolemia future science group Research Article Drogari, Ragia, Mollaki, Elens, Van Schaik & Manolopoulos age of 10 years, after initiation of diet and physical activity management [3][4][5][6]. The American Academy of Pediatrics (AAP) has recommended that statins should be started as early as 8 years of age.…”