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.
Highlights
Familial hypercholesterolemia (FH) is the genetic disorder most frequently associated with premature atherosclerotic cardiovascular disease (ASCVD) [1] due to lifelong elevated levels of low-density lipoprotein cholesterol (LDL-C)
We considered ASVCD whenever medical records included a clinical diagnosis of non-thromboembolic stroke, peripheral artery disease (PAD), or ischemic heart disease, both stable and acute coronary syndrome (ACS)
Genetic tests were performed in all patients with Dutch Lipid Clinic Network (DLCN) ≥ 6 as well as 10 patients with
Summary
Familial hypercholesterolemia (FH) is the genetic disorder most frequently associated with premature atherosclerotic cardiovascular disease (ASCVD) [1] due to lifelong elevated levels of low-density lipoprotein cholesterol (LDL-C). Despite international recommendations in FH clinical and genetic diagnosis [10], the main problem is the lack of clearly defined screening strategies for the identification of FH index cases in the general population, as well as insufficient genetic test availability [20]. This is why diagnosis is currently performed either after the development of clinical ASCVD or after the fortuitous detection of abnormally high LDL-C levels. The majority of patients with FH remain underdiagnosed and undertreated [21]
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