Abstract
Background Familial Hypercholesterolaemia (FH) is a greatly underdiagnosed and treatable genetic lipid disorder which significantly increases risk of premature cardiovascular disease. The prevalence of monogenic FH is thought to be 1 in 250–350. The NHS Long Term Plan aims to increase FH detection to at least 25% over 5 years in collaboration with primary care, supported by the NHS genomics programme.
Aim This systematic review evaluates systematic screening methods for FH in adults aged ≥18 years in primary care.
Method Seven databases [Cochrane, PubMed, Ovid, CINAHL, ProQuest, Web of Science, Scopus], four clinical trial registries [ISRCTN, ANZCTR, Clinicaltrials.gov, WHO-ICTRP] and relevant grey literature [OpenGrey] from March 2020 to May 2023 were searched. Only studies including adults were eligible. Risk of bias was assessed using ROBINS-I.
Results 831 records were screened. No randomised, controlled studies were identified. From full-text review, five eligible non-randomised studies out of 57 (6.90%) were identified. The included studies all used automated FH case-identification from electronic medical records (EMR) and were high quality studies with a moderate risk of bias. Narrative synthesis reported outcomes which included three algorithmic studies, with a pooled detection rate, DR 14.4% (95%CI 11.67–16.62), one supervised Machine Learning [Ensemble] study, DR 15.5% (95%CI 15.47–15.53) and one study utilising a hybrid diagnostic EMR model and/or FH genotype confirmation DR 25.0% (95%CI 16.30–35.8). No adverse effects were reported in these studies.
Conclusion Incorporating automated case-finding from EMR with clinical follow-up in primary care can enhance FH identification. Pathways incorporating genotyping showed the best detection rate.