The evaluation of cascade testing for familial hypercholesterolemia

Abstract

Familial hypercholesterolemia (FH) is an autosomal dominant disorder with a high risk of coronary heart disease at a young age that can be reduced by cholesterol-lowering drugs. Computer simulation was used to estimate the screening performance of three strategies of cascade testing for FH (a process of searching for relatives with FH once an individual is diagnosed with FH): (i) testing parents, siblings, and children (1st degree relatives) of an FH index case, (ii) testing (i) and testing 1st degree relatives of subsequently identified relatives with FH, and (iii) testing (ii) and also testing aunts, uncles, nephews, nieces, grandparents, and first cousins (2nd or 3rd degree relatives) when 1st degree relatives of an individual with FH are not available. For cascade testing to achieve detection rates of 80%, (i) 25%, (ii) 11%, and (iii) 8% of FH index cases who are unrelated need to be identified. To identify these unrelated FH index cases, (i) 45% (ii) 23%, and (iii) 17% of all individuals with FH need to be identified independently of cascade testing. Cascade testing is not a suitable method of population screening for FH, because a separate method of systematically identifying new FH index cases is required to achieve a reasonable level of FH detection in the population. Such an alternative systematic method of identifying new cases could itself be the method of population screening.

The Agenda for Familial Hypercholesterolemia

“…Universal screening before 20 years of age and ideally at ≈6 to 12 years of age when LDL-C levels improve discrimination for FH is feasible. 126 However, no data exist on the implementation of universal pediatric screening or a reverse cascade screening strategy in which adult family members are identified from pediatric index cases, although a trial of its effectiveness is in progress. Ideally, universal and cascade screening methods for FH should be closely integrated.…”

“…Universal screening has the potential to detect more people in the community, and cascade screening with an adequate supply of probands has a greater yield and is more costeffective. 114,126 The success of screening methods is dependent on recognizing several barriers, including population awareness of FH and family, physician, and societal concerns about the value of screening for FH. 127 Novel approaches to pediatric screening such as school-based screening may be more effective.…”

Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation

“…Universal screening of children, followed by child-parent testing may be a more effective approach to detecting FH in the population than cascade screening alone [24]. Importantly, none of the aforementioned paediatric screening strategies for FH have hitherto been validated for efficacy, riskbenefit and cost-effectiveness [69].…”

“…However, experience concerning its use and implementation is very limited. From a population perspective, universal and cascade screening methods for FH should be closely integrated [24]. The success of all detection strategies will depend on adequately addressing several barriers, including population awareness of FH and family, physician and societal concerns of the value of screening for FH.…”

Clinical Management of Familial Hypercholesterolemia: New Insights from International Guidelines and Recent Studies

“…28 A combination of family screening allied with systematic population-based screening may be most effective way to optimize detection rates for FH. 29 The optimal age for lipid-based screening of the population for FH is about 10-12 years based on the greatest divergence between inherited and environmental lipid levels. 30 but most CVD screening programmes target the general population at age 40-75.…”