Guidance for Pediatric Familial Hypercholesterolemia 2017

Abstract

This paper describes consensus statement by Joint Working Group by Japan Pediatric Society and Japan Atherosclerosis Society for Making Guidance of Pediatric Familial Hypercholesterolemia (FH) in order to improve prognosis of FH.FH is a common genetic disease caused by mutations in genes related to low density lipoprotein (LDL) receptor pathway. Because patients with FH have high LDL cholesterol (LDL-C) levels from the birth, atherosclerosis begins and develops during childhood which determines the prognosis. Therefore, in order to reduce their lifetime risk for cardiovascular disease, patients with FH need to be diagnosed as early as possible and appropriate treatment should be started.Diagnosis of pediatric heterozygous FH patients is made by LDL-C ≥ 140 mg/dL, and family history of FH or premature CAD. When the diagnosis is made, they need to improve their lifestyle including diet and exercise which sometimes are not enough to reduce LDL-C levels. For pediatric FH aged ≥ 10 years, pharmacotherapy needs to be considered if the LDL-C level is persistently above 180 mg/dL. Statins are the first line drugs starting from the lowest dose and are increased if necessary. The target LDL-C level should ideally be < 140 mg/dL. Assessment of atherosclerosis is mainly performed by noninvasive methods such as ultrasound.For homozygous FH patients, the diagnosis is made by existence of skin xanthomas or tendon xanthomas from infancy, and untreated LDL-C levels are approximately twice those of heterozygous FH parents. The responsiveness to pharmacotherapy should be ascertained promptly and if the effect of treatment is not enough, LDL apheresis needs to be immediately initiated.

Comparison of the characteristics at diagnosis and treatment of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries

“…This is not surprising given the very different care-pathways, policies and diagnostic strategies used in the different countries and to a large extent reflects the maturity of the FH child diagnostic work across Europe, with the paediatrician in Greece having started clinical practice more than 20 years ago, routinely testing cholesterol concentrations in all children before the age of 3. In the other countries where diagnosis is performed mainly through family cascade screening (after known diagnosis in parent) the median age at diagnosis is between 8 and 11 years, which is in line with paediatric FH guidelines that recommend the testing and identification of children at risk of FH by the age of 8-10 years [9][10][11][12][13][14]. The lipid profile at diagnosis is relatively uniform across countries, with mean LDL-C 5.70 ( ± 1.44) mmol/l, although with Greece having the highest and Austria the lowest values, due most probably to patient selection criteria.…”

“…However, there are a sizable proportion, which differs between countries, of children aged over 10 years old who have LDL-C above the EAS guideline recommendation of 3.5 mmol/l, who are not being treated with statin or other lipid lowering medication. Since ultrasound studies have demonstrated significant carotid intima-media thickening in non-treated FH children of this age compared to their non-FH siblings [34][35][36], and clinical trials have shown that statin treatment can reverse this [19,37,38], considering initiation of statin therapy by the age of 8-10 years is a recommendation in most recent guidelines [9][10][11][12][13][14]. While, for ethical and practical reasons, there are no long term randomised-placebo controlled trials to examine the benefit of statin initiation at this age and LDL-C level, observational studies over at least 20 years support the reduction of CVD risk associated with this approach [17].…”

“…While this data may be more relevant in making a clinical decision about statin initiation, the accuracy of such data is often hard to verify. However age of onset of premature CHD in relatives is a key factor in the clinical decision as to the age to initiate statin therapy [9][10][11][12][13][14][15], and therefore standardisation of this information would be very helpful. Similarly, we requested plasma levels of Lp(a), a well-known CHD risk marker, but this had not been routinely measured across the countries.…”

“…In the last 10 years, many National and European guidelines have been published for the identification and management of children with FH [1,2,[9][10][11][12][13][14][15]. The UK Simon Broome FH diagnostic thresholds for children under the age of 16 years include: total cholesterol > 6.…”

“Apple does not fall far from the tree” – subclinical atherosclerosis in children with familial hypercholesterolemia.

“…Moreover, atherosclerotic cardiovascular disease (ASCVD) that usually starts in middle age or letter was also reported to progresses rapidly at an age of around 10 years in patients with FH. Hence, guidelines for Europe and America highlights that early diagnosis of FH and statin treatment from childhood are necessary for preventing the early-onset ASCVD [4,5].…”