Electronic health record-based facilitation of familial hypercholesterolaemia detection sensitivity of different algorithms in genetically confirmed patients

Abstract

Familial hypercholesterolaemia (FH) is a disorder of LDL-cholesterol clearance, resulting in increased risk of cardiovascular disease. Recently, we developed a Dutch Lipid Clinic Network (DLCN) criteria-based algorithm to facilitate FH detection in electronic health records (EHR). In this study, we investigated the sensitivity of this and other algorithms in a genetically confirmed FH population. All patients with a healthcare insurance-related coded diagnosis of ‘primary dyslipidaemia’ between 2018-2020 were assessed for genetically confirmed FH. Data were extracted at the time of genetic confirmation of FH (T1) and during the first visit in 2018-2020 (T2). We assessed the sensitivity of algorithms on T1 and T2 for DLCN ≥ 6 and compared to other algorithms (FAMCAT, MEDPED, and Simon Broome [SB]) using EHR-coded data and using all available data (i.e., including non-coded free text). 208 patients with genetically confirmed FH were included. The sensitivity (95% CI) on T1 and T2 with EHR-coded data for DLCN ≥ 6 was 19% (14-25%) and 22% (17-28%), respectively. When using all available data, the sensitivity for DLCN ≥ 6 was 26% (20-32%) on T1 and 28% (22-34%) on T2. For FAMCAT, the sensitivity with EHR-coded data on T1 was 74% (67-79%) and 32% (26-39%) on T2, whilst sensitivity with all available data was 81% on T1 (75-86%) and 45% (39-52%) on T2. For MEDPED and SB, using all available data, the sensitivity on T1 was 31% (25-37%) and 17% (13-23%), respectively. The FAMCAT algorithm had significantly better sensitivity than DLCN, MEDPED, and SB. FAMCAT has the best potential for FH case-finding using EHRs.

Familial Hypercholesterolemia: Pitfalls and Challenges in Diagnosis and Treatment

“…In line with all of the above mentioned findings are the results of several studies, showing significant variability in the accuracy of clinical algorithms in those with genetically confirmed FH [ 33 , 34 ]. One extreme example represents the analysis by Mohammadnia et al .…”

“…One extreme example represents the analysis by Mohammadnia et al . [ 33 ], who demonstrated that the sensitivity of currently available scores for the clinical FH diagnosis in subjects, positive for FH gene mutations is only modest, being 9% for DLCN 6, 17% for SB and 31% for MEDPED. Within another clinical cohort, analyzing genomic sequence and clinical data from 50,726 individuals from the Geisinger Health System, showed that only 24% out of 215 carriers of a FH variant met criteria for definite or probable clinical FH.…”