Lipometabolic disorders in children: Don't screen everyone, but rather the right ones

The German Institute for Quality and Efficiency in Health Care (IQWiG) was commissioned by the Federal Joint Committee (G-BA) to assess the benefit of universal blood lipid screening for the early detection of familial hypercholesterolaemia in children and adolescents. Based on the available studies, no benefit can be derived from universal screening of all children and adolescents.

However, the available data show that, in principle, it is reasonable to identify children and adolescents with familial hypercholesterolaemia who are at high risk of premature heart attacks and strokes. This is because early treatment with lipid-lowering statins reduces the risk of cardiovascular disease in this particularly vulnerable group. IQWiG therefore recommends that the introduction of cascade screening should be discussed. Such cascade screening is based on family members (especially parents) who were diagnosed with familial hypercholesterolaemia after a cardiovascular event or during a health check-up.

Hereditary metabolic disorder can lead to early heart attacks and strokes

Familial hypercholesterolaemia is a hereditary, congenital lipid metabolism disorder. People with the condition have high levels of LDL cholesterol in their blood from childhood with an increased risk of heart attacks and strokes, sometimes even in young adulthood.

In order to reduce or delay the risk of cardiovascular events, children and adolescents with known familial hypercholesterolaemia can be treated early with statins, i.e. lipid-lowering drugs.

There is currently no standardized procedure in Germany for identifying children and adolescents with the condition. Members of a statutory health insurance fund are entitled to a lipid profile, including the measurement of LDL cholesterol, from the age of 18 if they are at higher risk, for example if they have a positive family history. However, the introduction of screening with a blood cholesterol test at a younger age is currently being discussed as a universal measure, i.e. for all children and adolescents.

Dutch study provides a hint of a benefit of early statin therapy

The aim of universal screening for familial hypercholesterolaemia is to identify and then treat affected children at an earlier stage. In its worldwide literature search, IQWiG did not find any studies that investigated such screening in all children and adolescents, followed by treatment. IQWiG therefore searched for studies on bringing forward lipid-lowering therapy. There is one study by a Dutch working group led by Ilse Luirink that looked at the effect of starting statin therapy earlier.

In the Luirink study published in 2019, 214 people with familial hypercholesterolaemia received statins from an average age of 14 years. 20 years later, only one person in this group had experienced a cardiovascular event. The situation was different for the parents of these early-treated children, who had also previously been diagnosed with familial hypercholesterolaemia: In this time-shifted control group, around a quarter had already had a heart attack or stroke by their late thirties. The 156 mothers and fathers could not have received statins before the age of 35, as these drugs have only been available since 1988.

"It is remarkable that, despite statin therapy, the children did not reach the LDL cholesterol target levels recommended in some guidelines - and yet did not experience a cardiovascular event," says Stefan Sauerland, Head of IQWiG's Department of Non-Drug Interventions. "Thus, for the treatment of children and adolescents, the results of the Luirink study do not support the “the lower the better” approach that is sometimes propagated, but suggest that a fixed average dose of a statin is sufficient as standard treatment for cardiovascular protection."

However, Sauerland emphasizes that it should be borne in mind that the results of the Luirink study cannot be applied to all children and adolescents with familial hypercholesterolaemia without additional evidence, as the study participants are a selected group: "These are children who were identified by cascade screening and a considerable proportion of their parents had already experienced a cardiovascular event."

Cascade screening as an alternative to universal screening

Michaela Eikermann, Deputy Director of IQWiG, explains: "However, the alternative to universal lipid screening in childhood or adolescence is not simply to dispense with screening for this age group. In Germany, health check-ups are already a generally available option to also identify young adults with familial hypercholesterolaemia. These check-ups, and knowing who is already affected, could be used to find and treat other affected family members - especially children and adolescents".

This approach, known as cascade screening, has the particular advantage over universal screening of identifying more severe subtypes of familial hypercholesterolaemia. This is because people whose family members are affected by very early or severe symptoms are more likely to seek medical care and can therefore be targeted for cascade screening without an additional invitation. Similarly, treatment would be focused on those who need it most - also thanks to the expected higher adherence.

IQWiG Director Thomas Kaiser concludes: "Identifying children and adolescents with familial hypercholesterolaemia and a high risk of heart attacks makes sense, as early statin therapy can reduce the risk of cardiovascular events. We therefore suggest discussing the introduction of cascade screening, starting with affected family members, especially parents. This approach was successful in the children investigated in the Luirink study. The introduction of cascade screening should definitely be accompanied by a targeted, pragmatic and cost-effective evaluation. Part of this evaluation should also be a comparative study conducted in an everyday health care setting that addresses the still open research question of the optimal time to start statin therapy.“

The present rapid report outlines initial considerations for an accompanying evaluation.

Procedure of report production

In February 2024, the G-BA commissioned IQWiG to prepare the report on screening for familial hypercholesterolaemia in children and adolescents in an accelerated procedure as a rapid report. Therefore, no intermediate products were published and no comments were invited. The G-BA received this rapid report in August 2024, and it was published in August 2024. An English translation was published in November 2024.