Feasibility and cost of FH cascade screening in Belgium (BEL-CASCADE) including a novel rapid rule-out strategy

Abstract

Background: Familial hypercholesterolaemia (FH) is underdiagnosed in most countries. We report our first experience from a national pilot project of cascade screening in relatives of FH patients. Methodology: Participating specialists recruited consecutive index patients (IP) with Dutch Lipid Clinic Network (DLCN) score 6. After informed consent, the relatives were visited by the nurses to collect relevant clinical data and perform blood sampling for lipid profile measurement. FH diagnosis in the relatives was based on the DLCN and/or MEDPED FH (Make-Early-Diagnosis-to-Prevent-Early-Deaths-in-FH) criteria. Results: In a period of 18 months, a total of 127 IP (90 with definite FH and 37 with probable FH) were enrolled in 15 centres. Out of the 270 relatives visited by the nurses, 105 were suspected of having FH: 31 with DCLN score >8, 33 with DLCN score 5-8 and 41 with MEDPED FH criteria. In a post-hoc analysis, another set of MEDPED FH criteria established in the Netherlands and adapted to Belgium allowed to detect FH in 51 additional relatives. Conclusion: In a country with no national FH screening program, our pilot project demonstrated that implementing a simple phenotypical FH cascade screening strategy using the collaboration of motivated specialists and two nurses, allowed to diagnose FH in 127 index patients and an additional 105 of their relatives over the two-year period. Newly developed MEDPED FH cutoffs , easily applicable by a nurse with a single blood sample, might further improve the sensitivity of detecting FH within families.

Effectiveness of cascade testing strategies in relatives for familial hypercholesterolemia: A systematic review and meta-analysis

“…The direct method of cascade testing contact in relatives was used in 11 studies [22,24,27,29,31,35,36,38,40,42,44], and a further eight studies used an indirect method [21,25,26,[32][33][34]37,43]. The remaining five studies used a combination of direct and indirect methods [23,28,30,39,41], where the decision regarding which method was used was decided by the index case.…”

“…Forward cascade testing was used in the majority of included studies (23 studies), with the remaining study using reverse cascade testing [42]. Fourteen of the included studies reported the extent of cascade; the majority cascaded to second degree relatives (eight studies [21,22,26,31,35,38,40,43]), with only five studies cascading to first degree [24,27,32,39,44] and one study cascading to third degree [23].…”

“…The majority of included studies confirmed FH diagnosis in the index cases using genetic testing (14 studies [21,23,[25][26][27][28][29]31,33,[36][37][38]40,41], nine studies confirmed FH diagnosis in the index cases using clinical assessment based either on SB (four studies [24,30,34,35], DCLN (three studies [32,39,43], or study-specific criteria (serum cholesterol ≥8 mmol/L and LDL cholesterol ≥ 6 mmol/L and family history of hypercholesterolemia [22]; apolipoprotein B: apolipoprotein A-1 ratio >97th centile or apolipoprotein B > 99th centile, and LDL cholesterol >95th centile and no secondary causes for raised cholesterol [42]); and one study stated diagnosis was based on either genetic or clinical criteria but did not provide additional details [44]. For the relatives, genetic confirmation of FH was used in the majority of studies (15 studies, [21,23,[25][26][27][28][29]31,33,[36][37][38]40,41,46].…”

“…For the relatives, genetic confirmation of FH was used in the majority of studies (15 studies, [21,23,[25][26][27][28][29]31,33,[36][37][38]40,41,46]. A further eight studies used clinical assessment based on either SB [24,30], DCLN [32,39], MEDPED [34], combination of DCLN and MEDPED [43], or study-specific criteria (serum cholesterol ≥ 7 mmol/L [22]; LDL cholesterol >95th centile [42]). The final study used genetic testing or clinical assessment based on SB criteria depending on which arm of the trial the proband had been randomized to Ref.…”

“…The majority of studies were rated as having a moderate risk of bias; only three studies had a high methodological quality score [23,32,43] and two studies were rated with low methodological quality [36,37] (Supplementary Table S2). The reasons for lower methodological quality were primarily related to less clarity regarding consecutive inclusion of participants (Question 4) and incomplete inclusion of participants (Question 5).…”