Physicians' Academy for Cardiovascular Education

Incorporation of genetic testing increases rates of diagnosis for FH

Incorporation of genetic testing significantly increases the number of individuals diagnosed with familial hypercholesterolemia

Literature - Brown EE, Byrne KH, Davis DM et al., - J Clin Lipidol. 2020. doi: 10.1016/j.jacl.2020.02.006.

Introduction and methods

Familial hypercholesterolemia (FH) is typically due to pathogenic variants in APOB, LDLR, PCSK9, and LDLRAP1 and is characterized by elevated LDL-c levels. Patients are at high risk of developing atherosclerotic CVD [1-3]. There are multiple diagnostic criteria for FH, such as the US Make Early Diagnoses Prevent Early Deaths Program Diagnostic Criteria (US MEDPED), Simon Broome criteria and Dutch Lipid Clinic Network (DLCN) criteria [4-7]. US MEDPED takes into account total cholesterol levels and family history of FH. Simon Broome and DLCN criteria also consider physical signs of FH, personal or family history of premature coronary artery disease or hyperlipidemia, and a positive genetic test result. A consensus statement published in the Journal of American Collage of Cardiology (JACC) concerning the utilization of genetic testing for FH recommends genetic testing in adults with LDL persistently ≥250 mg/dL (regardless of family history), in adults with LDL-c persistently ≥190 mg/dL (with family history of hyperlipidemia or premature CAD), and in adults with LDL-c persistently ≥160 mg/dL (with family history of hyperlipidemia and either a personal or family history of premature CAD) [8]. However, even with these criteria and recommendations, FH remains underdiagnosed. A possible explanation for underdiagnosis could be that genetic testing is not incorporated into evaluations. This study compared diagnosis rate before and after genetic testing.

A total of 134 adults were included in the analysis who were seen at the Advanced Lipid Disorders Clinic at the John Hopkins Hospital for FH evaluation and who underwent genetic testing. Pediatric patients and individuals with homozygous FH were excluded. US MEDPED, Simon Broom and DLCN criteria were applied to each patient before and after genetic testing. Genetic testing included sequencing and deletion duplication analysis of APOB, LDLR, PCSK9, and LDLRAP1 genes.

Main results


Depending on the criteria used (US MEDPED, Simon Broome or DLCN), incorporation of genetic testing identified 11-14 additional patients with FH, compared to classification based only on clinical criteria. This suggests that family history and a patient’s phenotype alone may not be sufficient for diagnosis of FH.


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Find this article online at J Clin Lipidol.

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