Improving the identification of patients with a genetic diagnosis of familial hypercholesterolaemia in primary care: A strategy to achieve the NHS long term plan

Abstract

Background and aims: We aimed to validate a nurse-led process using electronic health records to identify those at risk of familial hypercholesterolaemia (FH) for genetic diagnosis in primary care. Methods: Those at risk of FH were identified using searches developed and refined locally and implemented in primary care by a trained nurse; they were invited for further assessment and genetic testing if indicated. Family members at risk of FH were identified and invited for cascade testing. Results: In total 94,444 patient records were screened (expected prevalence of FH (1 in 250); 377). Of 176 records which already had a diagnostic for FH, 15 had been genetically confirmed and one was undergoing DNA testing. A further 572 (0.61%) were identified as high risk of FH. After desktop screening, 113 (15%) were invited for further assessment. Of these, 73 individuals attended the primary care clinic (64%) of whom 61 (54%) underwent proband genetic testing. Pathogenic variants were detected in 22 cases (36%) and variants of unknown significance in a further 4 cases; a total of 26 probands (43%) were therefore referred for family cascade testing. Conclusions: An optimised FH identification pathway, based on the NICE CG71 recommendations for systematic searching of primary care electronic health records, can be deployed successfully in primary care settings.

Applying implementation science to improve care for familial hypercholesterolemia

“…Four studies implemented the existing clinical diagnostic criteria into their healthcare system electronic health records (EHRs) as a screening tool to identify previously unrecognized individuals with FH. Similar rates of individuals requiring additional diagnostic screening for FH were found: 1 in 245 (7468/1 831 658) met the Make Early Diagnoses Prevent Early Deaths (MEDPED) criteria [20], 1 in 150 (303/45 123) met the Simon Broome (SB) Criteria [21], and 1 in 183 (269/49 321) [21] and 1 in 119 (351/41 937) [22] met the Dutch Lipid Clinic Network Criteria (DLCN). The screening positive rate for FH was higher, 1 in 5 (84/469), when the DLCN criteria were applied to EHRs of those with known severe hypercholesterolemia [23].…”

“…The screening positive rate for FH was higher, 1 in 5 (84/469), when the DLCN criteria were applied to EHRs of those with known severe hypercholesterolemia [23]. Diagnostic evaluation for FH in individuals identified by these EHR screening initiatives found 18–36% met clinical criteria [21–23]. However, the percentage of these individuals with a genomic risk variant for FH ranged from 25 to 68% depending on the study [20,21,23] meaning that using genetics as the sole indicator for a diagnosis of FH would miss many individuals who met clinical diagnostic criteria.…”

Real-world utilization of guideline-directed genetic testing in inherited cardiovascular diseases

“…Other approaches have also been proposed. In 2021, Birnbaum et al ( 20 ) and Ingoe et al ( 23 ) demonstrated increased diagnosis of FH and utilization of genetic testing after system-wide scanning of the EHR to identify patients at high risk; and Soper et al ( 59 ) described a genomic screening program that identified individuals with variants in TTR , none of whom had a previous diagnosis of hereditary transthyretin amyloidosis. Adopting implementation science frameworks and practices may also facilitate the uptake of guideline-directed genetic testing.…”

A Scoping Review of Approaches for the Detection and Management of Familial Hypercholesterolaemia in Primary Care

“…Some strategies included specialist nurse (n=2) and specialist lipidologist (n=3) involvement in the review process. Specialist nurses triaged potential FH cases for genetic testing and also independently screened for FH index cases 27,28 .…”