Development of sensitive and specific age- and gender-specific low-density lipoprotein cholesterol cutoffs for diagnosis of first-degree relatives with familial hypercholesterolaemia in cascade testing

Abstract

The cutoffs developed here are designed to give the greatest overall accuracy when testing relatives of FH patients in the absence of a genetic diagnosis. They have a more balanced specificity and sensitivity than the MEDPED cutoffs that are designed to achieve higher specificity, which is more appropriate for cascade testing purposes. The data suggest that country-specific LDL-C cutoffs may lead to greater accuracy for identifying FH patients, but should be used with caution and only when a genetic diagnosis (DNA) is not available.

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

“…Plasma LDL-cholesterol level alone has excellent discrimination between those with and without FH below the age of 10 years [67,70,71]. However, because of biological variation [29,72], the average of at least two fasting LDL-cholesterol levels should be used to make the diagnosis of FH [19,20,65].…”

Clinical utility gene card for: Hyperlipoproteinemia, TYPE II

“…21 While in most cases the genetic test results will not influence the therapeutic strategy, there are several scenarios where the therapeutic route is based on the genetic test result: According to the EAS consensus statement initiation of statin treatment in children at the age of 8-10 is recommended on the basis of a positive genetic test result or strong clinical arguments including LDL-C 4135 mg/dl (43.5 mmol/l). The EAS expert panel advises to offer lipoprotein apheresis in children with homozygous FH.…”

Elucigene FH20 and LIPOchip for the diagnosis of familial hypercholesterolaemia: a systematic review and economic evaluation.

“…Of the 15 studies, three (four reports) reported Elucigene FH20, [36][37][38] five (six reports) evaluated LIPOchip, [39][40][41][42][43] four reported LDL-C compared with genetic analysis [44][45][46][47] and three reported ageand gender-specific LDL-C for cascade testing of relatives. [48][49][50] We did not identify any studies reporting a combination of the index tests, that is Elucigene FH20 and LIPOchip.…”

“…In the studies by Starr and colleagues 49 and Mabuchi and colleagues 46 a genetically tested cohort of relatives was recruited to study the test performance of age-and gender-specific LDL-C cut-offs and a cut-off of 4 mmol/l, which is the minimum cut-off required by Simon Broome criteria respectively. In the study by Starr and colleagues, clinically diagnosed index cases based on the Dutch criteria (the Netherlands) and a combination of lipid levels, clinical characteristics and family history (Norway and Denmark) were included, whereas the study by Mabuchi and colleagues 46 included clinically diagnosed index cases based on TC (≥ 5.9 mmol/l and < 12.9 mmol/l) with tendon xanthomata or primary hypercholesterolaemia with/without tendon xanthomata in a family with FH patients among first-degree relatives.…”

“…In the study by Wiegman and colleagues 50 the participants were children. In the studies by Starr and colleagues 49 and Widhalm and colleagues 47 the participants were a mixture of adults, adolescents and children, whereas in the study by Civeira and colleagues 44 they were adults and adolescents. The remaining seven studies 36,[38][39][40][41][42]48 (six abstracts and one full text) did not specify whether the participants (index patients or relatives) were adults, children or adolescents.…”