Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment
Top Cited Papers
Open Access
- 25 May 2015
- journal article
- review article
- Published by Oxford University Press (OUP) in European Heart Journal
- Vol. 36 (36), 2425-2437
- https://doi.org/10.1093/eurheartj/ehv157
Abstract
Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD). Globally, one baby is born with FH every minute. If diagnosed and treated early in childhood, individuals with FH can have normal life expectancy. This consensus paper aims to improve awareness of the need for early detection and management of FH children. Familial hypercholesterolaemia is diagnosed either on phenotypic criteria, i.e. an elevated low-density lipoprotein cholesterol (LDL-C) level plus a family history of elevated LDL-C, premature coronary artery disease and/or genetic diagnosis, or positive genetic testing. Childhood is the optimal period for discrimination between FH and non-FH using LDL-C screening. An LDL-C ≥5 mmol/L (190 mg/dL), or an LDL-C ≥4 mmol/L (160 mg/dL) with family history of premature CHD and/or high baseline cholesterol in one parent, make the phenotypic diagnosis. If a parent has a genetic defect, the LDL-C cut-off for the child is ≥3.5 mmol/L (130 mg/dL). We recommend cascade screening of families using a combined phenotypic and genotypic strategy. In children, testing is recommended from age 5 years, or earlier if homozygous FH is suspected. A healthy lifestyle and statin treatment (from age 8 to 10 years) are the cornerstones of management of heterozygous FH. Target LDL-C is 10 years, or ideally 50% reduction from baseline if 8–10 years, especially with very high LDL-C, elevated lipoprotein(a), a family history of premature CHD or other cardiovascular risk factors, balanced against the long-term risk of treatment side effects. Identifying FH early and optimally lowering LDL-C over the lifespan reduces cumulative LDL-C burden and offers health and socioeconomic benefits. To drive policy change for timely detection and management, we call for further studies in the young. Increased awareness, early identification, and optimal treatment from childhood are critical to adding decades of healthy life for children and adolescents with FH.Keywords
Funding Information
- Amgen, Aegerion, AstraZeneca, Genzyme, Hoffman-La Roche, Kowa Europe, Novartis, and Sanofi-Aventis/Regeneron
This publication has 127 references indexed in Scilit:
- Use of targeted exome sequencing as a diagnostic tool for Familial HypercholesterolaemiaJournal of Medical Genetics, 2012
- Fatal Myocardial Infarction at 4.5 Years in a Case of Homozygous Familial HypercholesterolaemiaJIMD Reports, 2011
- Sudden Death in a 4-Year-Old Boy: A Near-Complete Occlusion of the Coronary Artery Caused by an Aggressive Low-Density Lipoprotein Receptor Mutation (W556R) in Homozygous Familial HypercholesterolemiaThe Journal of Pediatrics, 2011
- Lipoprotein(a) as a cardiovascular risk factor: current statusEuropean Heart Journal, 2010
- Positive screening and carrier results for the England-wide universal newborn sickle cell screening programme by ethnicity and area for 2005-07Journal of Clinical Pathology, 2010
- Genetic testing in asymptomatic minors: recommendations of the European Society of Human GeneticsEuropean Journal of Human Genetics, 2009
- Diagnosis of Familial Hypercholesterolemia in General Practice Using Clinical Diagnostic Criteria or Genetic Testing as Part of Cascade Genetic ScreeningPublic Health Genomics, 2008
- Child-parent screening for familial hypercholesterolaemia: screening strategy based on a meta-analysisBMJ, 2007
- Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levelsThe Journal of Pediatrics, 2006
- Effect of soy protein diet versus standard low fat, low cholesterol diet on lipid and lipoprotein levels in children with familial or polygenic hypercholesterolemiaThe Journal of Pediatrics, 1993