Implementation of a multidisciplinary approach to diagnosis and management of familial hypercholesterolaemia (FH) in Wales: The role of the FH specialist nurse

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

“…Of the 24 included studies, 16 were conducted in Europe (England [24,25,30,34,35,41], Wales [28], Belgium [45], Denmark [22,42], Latvia [32], the Netherlands [40], Norway [33], Spain [29], Malta [39], Estonia [21]), one from Australia [23], three in the Americas (North America [27,37], Brazil [31]), one in New Zealand [36], two in Asia (India [38], Hong Kong [26]), and one in South Africa [44]. All studies used an observational design to assess the outcome measures.…”

“…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. Contact could be made through a range of approaches, including postal invitation, telephone, in person or a combination of approaches.…”

“…Contact could be made through a range of approaches, including postal invitation, telephone, in person or a combination of approaches. In the studies using either a direct or combination strategy which reported the type of person that reached out to the relatives, a nurse was used in seven studies [23,24,[29][30][31]36,40] compared to only single studies reporting using either a genetic counsellor [28] or an outpatient clinician [22]. Forward cascade testing was used in the majority of included studies (23 studies), with the remaining study using reverse cascade testing [42].…”

“…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]. A further eight studies used clinical assessment based on either SB [24,30], DCLN [32,…”

“…For the 16 studies using genetic testing for confirmation of FH, testing of only the LDLR gene was performed in three studies [36,38,40], testing of LDLR and APOB genes was performed in two studies [33,35], testing of LDLR, APOB and PCSK9 genes was performed in eight studies [21,23,26,27,29,31,37,41], and testing of LDLR, APoB, PCSK9, and LDLRAP1 genes was performed in one study [44]; the genes considered in the remaining two studies were unclear [25,28].…”