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Familial Hypercholesterolaemia in the Era of Genetic Testing

  • Cardiovascular Genomics (TL Assimes, Section Editor)
  • Published:
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Abstract

Familial hypercholesterolaemia (FH) is a relatively common autosomal dominant genetic condition leading to premature ischaemic vascular disease and mortality if left untreated. Currently, a universal consensus on the diagnostic criteria of FH does not exist but the diagnosis of FH largely relies on the evaluation of low density lipoprotein-cholesterol (LDL-C) levels, a careful documentation of family history, and the identification of clinical features. Diagnosis based purely on lipid levels remains common but there are several limitations to this method of diagnosis both practically and in the proportion of false-negatives and false-positives detected, resulting in substantial under-diagnosis of FH. In some countries, diagnostic algorithms are supplemented with genetic testing of the index case as well as genetic and lipid testing of relatives of the index case. Such "cascade" screening of families following identification of index cases appears to not only improve the rate of diagnosis but is also cost-effective. Currently, we observe a great variation in the excess mortality among patients with FH, which likely reflects a combination of additional genetic and environmental effects on risk overlaid on the risk associated with FH. Current accepted drug therapies for FH include statins and PSCK9 inhibitors. Further work is required to evaluate the cardiovascular disease risk in patients with genetically diagnosed FH and to determine whether a risk-based approach to the treatment of FH is appropriate.

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Authors and Affiliations

  1. Department Metabolic Medicine/Chemical Pathology, Lister Hospital, Stevenage, SG1 4AB, UK

    D. P. Hughes & A. Viljoen

  2. Department Metabolic Medicine/Chemical Pathology, Guy’s & St Thomas’ Hospitals, St Thomas’ Hospital, Lambeth Palace Road, London, SE1 7EH, UK

    A. S. Wierzbicki

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Correspondence to A. Viljoen.

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Conflict of Interest

A. Viljoen reports personal fees and other from AstraZeneca, personal fees and other from Merck Sharpe & Dohme, personal fees, non-financial support and other from Novo Nordisk, personal fees, non-financial support and other from Sanofi-Aventis, personal fees from Janssen, other from Amgen, and personal fees and other from Takeda.

A.S. Wierzbicki reports being a clinical trial investigator for Merck Sharp & Dohme, and for Amgen, and part of the clinical trial registry for Chiesi, D.P. Hughes declares that he has no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Cardiovascular Genomics

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Hughes, D.P., Viljoen, A. & Wierzbicki, A.S. Familial Hypercholesterolaemia in the Era of Genetic Testing. Curr Cardiol Rep 18, 42 (2016). https://doi.org/10.1007/s11886-016-0723-z

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