2 Evidence review and recommendations: case-finding 2.5 Evidence statements 2.5.1 Clinical evidence statement Low to very low quality evidence from: 2 studies with 405 people found that direct cascade testing had a range of diagnostic yields for identification of clinically defined FH of 6 to 59%, with a number needed to test of 2 for the Simon Broome criteria and 17 for the Dutch Lipid Network Criteria (DLCN). 2 studies with 776 people found that indirect cascade testing had a range of diagnostic yields for identification of clinically defined FH of 30.5 to 37.9%, with a number needed to test of 3 for the Medped criteria and 3 for other non-standardised diagnostic criteria used to diagnose FH. 2 studies with 1,879 people found that a combination of indirect and direct cascade testing had a range of diagnostic yields for identification of clinically defined FH of 14.7 to 57.5%, with a number needed to test of 5 for the Simon Broome criteria and 2 for DLCN. 2.5.1.2 Cascade testing - genetic diagnosis Moderate to very low quality evidence from: 5 studies with 7,144 people found that direct cascade testing had a median diagnostic yield for identification of genetically defined FH of 37.5% (range 11.4 to 51.4%), with a number needed to test of 3 (range 2 to 9). 1 study with 1,805 people found that indirect cascade testing had a diagnostic yield for identification of genetically defined FH of 44.8%, with a number needed to test of 3. 1 study with 642 people found that direct and indirect cascade testing had a diagnostic yield of 55.9%, with a number needed to test of 2. 2 studies with 2,910 people found that unknown methods of cascade testing had a diagnostic yield range of 32.8 to 33.9% with a number needed to test of 3. Cascade testing – uptake rate Low to very low quality evidence from: 3 studies with 1,557 people found a median uptake rate for index individuals for direct cascade testing of FH of 84.1% (range 69.1 to 98.9%). 2 studies with 626 people found uptake rates for relatives of index individuals for direct cascade testing of FH ranging from 84.1 to 98.9%. 1 study with 2,474 people found an uptake rate for relatives of index individuals for indirect cascade testing of FH of 73.0%. 1 study with 2,292 people foumd an uptake rate for relatives of index individuals for both indirect and direct cascade testing of FH of 65.2%. 2.5.1.3 Primary care electronic databases Very low to moderate quality evidence was found from 6 studies which used distinct methods of case finding within primary care. The studies varied as to whether DLCN or Simon Broome criteria were used, and whether the scores were verified. Four studies with 339,642 people found that searching primary care electronic databases had a median diagnostic yield for identification of FH of 0.178% (range 0.083 to 3.9%), with a number needed to test of 563 (range 116 to 1,250) using the Simon Broome (n=2) or DLCN (n=3) criteria. Five studies with 34 5,182 people found that electronic search criteria & GP review had a median diagnostic yield for identification of FH of 14.16% (range 1.27 to 29.4%), with a number needed to test of 10 (range 4 to 35) using Simon Broome (n=1) or DLNC (n=5) criteria. From 3 studies with 676 people, genetic testing had a median diagnostic yield for identification of genetically defined FH of 13% (range 0.014% to 37.90%), with a number needed to test of 7 (range 3 to 69). The most relevant study to UK clinical practice used an informatics tool to identify cases of possible FH (diagnostic yield 0.05%, number needed to test = 2,013), then had targeted case-finding; a nurse assessed people at risk of FH, but not yet screened (overall diagnostic yield 22.2%, number needed to test = 5). Primary care -uptake rate Low quality evidence from 1 study with 2,762 people had an uptake rate from primary care searches of index individuals with FH of 26%. 2.5.1.4 Secondary care electronic databases Pathology databases Very low quality evidence from: 3 studies of 85,616 people found that case finding of FH through pathology databases had a median diagnostic yield for identification of clinically defined FH of 8.5% (range 1.2 to 9.2%), with a number needed to test (DLCN) of 12 (range 11 to 398) and a number needed to test of 27 using Simon Broome criteria. 3 studies with 641 people found that case finding of FH through pathology databases had a median diagnostic yield for identification of genetically defined FH of 26.7% (range 12.9 to 30.4%) and a number needed to test of 4 (range 3 to 8). 2 studies with 4,517 people had an uptake rate of 13.2% for people at increased CV risk attending clinical assessment, and 61.6% for those at high risk of FH attending specialist review. Lipid clinics/registries Very low quality evidence from: 4 studies with 1,343 people found that case finding of FH through lipid clinics or registries had a median diagnostic yield for identification of clinically defined FH of 51.0% (range 33.5 to 87.8%), with a number needed to test of 2 for DLCN criteria, and a number needed to test of 2 for both Simon Broome and Medped criteria. 6 studies with 1,955 people found that case finding of FH through lipid clinics or registries had a median diagnostic yield for identification of genetically defined FH of 33.3% (range 10.9 to 51.0%), with a number needed to test of 3 (range 2 to 9). No studies reported uptake rate of testing through lipid clinics or registries. Coronary units/ MINAP Moderate to low quality evidence from: 4 studies with 12,331 people found that case finding of FH through coronary care units or using the MINAP database had a median diagnostic yield for identification of clinically defined FH of 5.9% (range 1.2 to 14.3%), with a number needed to test of 37 for DLCN and 19 for Simon Broome criteria. 1 study with 231 people found that case finding of FH through coronary care units or using the MINAP database had a median diagnostic yield for identification of genetically defined FH of 1.23%, with a number needed to test of 77. 35 1 study with 231 people found that uptake rate for DNA testing in coronary units is 50.1%. Screening programs Very low quality evidence from: 2 studies with 19,768 people found that case finding of FH through screening programs had a diagnostic yield for identification of clinically defined FH ranging from 0.001 to 0.145%, and a number needed to test ranging from 991 to 1,262. 3 studies with 10,432 people found that case finding of FH through screening programs had a median diagnostic yield for identification of genetically defined FH of 17.0% (range 0.4 to 57.0%), and a median number needed to test of 6 (range 2 to 273). 1 study with 189 people found that case finding of FH through screening programs had an uptake rate of 43.4%. In document Familial hypercholesterolaemia: identification and management. Evidence reviews for case-finding, diagnosis and statin monotherapy (Page 33-35)
