Familial hypercholesterolaemia in children and adolescents
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1 Familial hypercholesterolaemia in children and adolescents Rationale and recommendations for early identification and treatment European Atherosclerosis Society Consensus Panel Slide deck adapted from: Wiegman A et al. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J 2015; [Epub ahead of print]
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3 Elevated LDL-C: one of the major risk factors for cardiovascular disease
4 LDL and atherosclerosis Retention of atherogenic apolipoprotein B-containing lipoproteins in the arterial wall is the key initiating event in atherosclerosis. LDL retained in the artery wall undergo modification and are taken up by macrophages, which ultimately become foam cells.
5 Genetic studies reaffirm the role of elevated LDL-C in atherosclerosis Mendelian randomisation studies, a type of natural randomisation have proven the case for LDL-C and CVD Genetic variation identifies risk status; polymorphisms in multiple different genes are associated with both lower LDL-C and a lower risk of CVD Provides the rationale for the benefit of lifelong low LDL-C levels Consistent with clinical trial data suggesting greater effect with longer LDL lowering interventions
6 Lower LDL-C: lower CVD risk Independent of how LDL-C is lowered There was a log-linear association between genetically mediated lower LDL-C and the risk of CVD The lower the LDL-C, the lower CVD risk The benefit from LDL-C lowering does not depend on how LDL-C is lowered, Ference BA et al. J Am Coll Cardiol 2015;65:
7 Higher LDL-C: higher CVD risk Familial hypercholesterolaemia (FH): exposure to elevated LDL-C from birth markedly increases CVD risk Severity of atherosclerosis is proportional to both extent and duration of elevated LDL-C the Cholesterol -Year- Score Age threshold for coronary heart disease : Schmidt HH et al. Am J Cardiol 1996;77:575-80
8 Why we need to identify and treat children with FH early
9 Untreated FH leads to accelerated atherosclerosis and early coronary events Newborn: Foetal exposure to cholesterol leads to disturbed flow Child at risk Risk factor exposure leads to early atherogenesis Young adult Plaque build-up Early plaque rupture and thrombosis leading to coronary events Impacts mortality, morbidity and quality of life
10 Treating FH early will prevent early coronary events Newborn: Foetal exposure to cholesterol leads to disturbed flow Identification of FH in childhood Targeted risk factor management Lifestyle counselling Early initiation of lipid-lowering treatment Monitoring of subclinical atherosclerosis Young adult Prevention of early coronary events?
11 Impact of early treatment on LDL-C burden Vuorio A et al. Atherosclerosis 2013;226:315-20
12 Statin treatment improves event-free survival in adults with FH Kaplan-Meier curve estimates of cumulative coronary heart disease-free survival among patients with FH according to statin treatment (p<0.001 for difference) Versmissen J et al. BMJ ;337:a2423.
13 Impact of statins: Treated FH children vs treated FH parents Braamskamp MJ et al. Circulation 2013;128:A17837,
14 How to identify children with FH Video: Dr Samuel Gidding, Nemours Cardiac Center, Wilmington, Delaware, USA discusses how to identify children with FH
15 FH diagnosis is driven by phenotypic criteria Family History + Hypercholesterolemia = FH in Children* *FH Foundation
16 EAS Consensus Panel Recommendations Diagnosis of FH in Children Cholesterol testing should be used to make a phenotypic diagnosis 5 mmol/l (190 mg/dl) on two successive occasions over 3 months 4 mmol/l (160 mg/dl) and positive family history of premature cardiovascular disease 3.5 mmol/l (130 mg/dl) and positive genetic diagnosis in the family Rule out secondary causes (thyroid, liver or renal dysfunction, concomitant medication, obesity) Genetic testing confirms the diagnosis (after parental testing) Wiegman A et al. Eur Heart J 2015 Epub ahead of print
17 Wiegman A et al. Eur Heart J 2015 Epub ahead of print Algorithm
18 Reverse CASCADE Screening Identify children with FH LDL cholesterol can be used to discriminate those with FH and those without in childhood Identify first degree family members with high LDL cholesterol Genotype the parents
19 Barriers to implementing cholesterol screening Awareness about FH Clinician Belief in preventing early atherogenesis Time/skill/reimbursement Family Competing health issues Education Financial resources Privacy concerns Society Cost, relative importance, publicity, guideline support
20 How to manage children with FH
21 EAS Consensus Panel Recommendations Management: Diet and Lifestyle Assess CVD risk factors including Lp(a) No Smoking Encourage Exercise Diet < 30% of calories from fat < 7% of calories from saturated fat < 200 mg cholesterol/day appropriate energy for normal growth sufficient in micronutrients Wiegman A et al. Eur Heart J 2015 Epub ahead of print
22 EAS Consensus Panel Recommendations Treatment Homozygous FH: start treatment at diagnosis For children aged 8-10 years, LDL-C is ideally reduced by 50% from pre-treatment levels. For children aged 10 years, especially if there are additional cardiovascular risk factors, including elevated Lp(a), target LDL-C should be<3.5 mmol/l (130 mg/dl). Adherence should be checked if heterozygous FH children fail to achieve LDL-C targets with combination lipid-lowering treatment. Wiegman A et al. Eur Heart J 2015 Epub ahead of print
23 Safety monitoring Check weight, growth, physical and sexual development, and well-being Hepatic aminotransferases: at least every 3 months if there is a history of liver disease; more frequently if levels increase >3-fold x ULN. Plasma CK levels: measure if musculoskeletal symptoms are reported. Fasting plasma glucose and/or random HbA1c: measure every 6 months in children on higher doses of statins, especially if obese or with impaired glucose tolerance Safety monitoring discussed by Dr Albert Wiegman, Academic Medical Center, Amsterdam, The Netherlands Wiegman A et al. Eur Heart J 2015 Epub ahead of print
24 Targeting children with FH can make premature CHD history Video: Dr Samuel Gidding, Nemours Cardiac Center, Wilmington, Delaware, USA discusses the importance of early identification and treatment of FH
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