Improving Familial Hypercholesterolemia Index Case Detection: Sequential Active Screening from Centralized Analytical Data

Abstract

The majority of familial hypercholesterolemia index cases (FH-IC) remain underdiagnosed and undertreated because there are no well-defined strategies for the universal detection of FH. The aim of this study was to evaluate the diagnostic yield of an active screening for FH-IC based on centralized analytical data. From 2016 to 2019, a clinical screening of FH was performed on 469 subjects with severe hypercholesterolemia (low-density lipoprotein cholesterol ≥220 mg/dL), applying the Dutch Lipid Clinic Network (DLCN) criteria. All patients with a DLCN ≥ 6 were genetically tested, as were 10 patients with a DLCN of 3–5 points to compare the diagnostic yield between the two groups. FH was genetically confirmed in 57 of the 84 patients with DLCN ≥ 6, with a genetic diagnosis rate of 67.9% and an overall prevalence of 12.2% (95% confidence interval: 9.3% to 15.5%). Before inclusion in the study, only 36.8% (n = 21) of the patients with the FH mutation had been clinically diagnosed with FH; after genetic screening, FH detection increased 2.3-fold (p < 0.001). The sequential, active screening strategy for FH-IC increases the diagnostic yield for FH with a rational use of the available resources, which may facilitate the implementation of FH universal and family-based cascade screening strategies.

Coronary lesion complexity in patients with heterozygous familial hypercholesterolemia hospitalized for acute myocardial infarction: data from the RICO survey

“…Moreover, genetic testing was not performed to confirm FH in the present study. In another recent study, a genetic diagnosis was obtained in 57 of 84 patients with DLCN ≥6 (67.9%) [39]. However, the procedure used to calculate the probability of FH with the adapted Dutch lipid Clinic criteria is widely used in routine clinical practice.…”

Applying implementation science to improve care for familial hypercholesterolemia

“…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]. Diagnostic evaluation for FH in individuals identified by these EHR screening initiatives found 18–36% met clinical criteria [21–23].…”

“…Diagnostic evaluation for FH in individuals identified by these EHR screening initiatives found 18-36% met clinical criteria [21][22][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.…”

Implementation of a biochemical, clinical, and genetic screening programme for familial hypercholesterolemia in 26 centres in Spain: The ARIAN study

“…Over the last decade, considerable interest has been shown in the identification of patients with FH by using analytical records from community laboratories ( Bell et al, 2014 ; Kirke et al, 2015 ; Mirzaee et al, 2019 ). There are limited data in Spain on the use and benefits of centralised analytical data screening in testing for FH ( Gutiérrez-Cortizo et al, 2021 ; Sabatel-Pérez et al, 2021 ).…”