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Progress in the care of common inherited atherogenic disorders of apolipoprotein B metabolism

Nature Reviews Endocrinology volume 12, pages 467–484 (2016)Cite this article

Subjects

Key Points

  • Familial hypercholesterolaemia, familial combined hyperlipidaemia and elevated lipoprotein(a) are inherited disorders of apo B-100 metabolism that are frequently encountered in clinical lipidology

  • Each of these inherited hyperlipidaemias markedly accelerates the onset of atherosclerotic cardiovascular disease (ASCVD)

  • To prevent premature ASCVD, these disorders must be accurately diagnosed and treated in index patients and at-risk family members

  • The supplementation of established lipid-lowering therapies with newly developed biological agents will be important for managing the most severe hyperlipidaemias, but long-term safety and cost-effectiveness need to be demonstrated

  • The promotion of public and clinical awareness of these disorders, and the establishment and maintenance of appropriate patient registries, are essential to facilitate research and improve clinical care

Abstract

Familial hypercholesterolaemia, familial combined hyperlipidaemia (FCH) and elevated lipoprotein(a) are common, inherited disorders of apolipoprotein B metabolism that markedly accelerate the onset of atherosclerotic cardiovascular disease (ASCVD). These disorders are frequently encountered in clinical lipidology and need to be accurately identified and treated in both index patients and their family members, to prevent the development of premature ASCVD. The optimal screening strategies depend on the patterns of heritability for each condition. Established therapies are widely used along with lifestyle interventions to regulate levels of circulating lipoproteins. New therapeutic strategies are becoming available, and could supplement traditional approaches in the most severe cases, but their long-term cost-effectiveness and safety have yet to be confirmed. We review contemporary developments in the understanding, detection and care of these highly atherogenic disorders of apolipoprotein B metabolism.

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Figure 1: Proposed diagnostic protocol for cascade testing individuals for familial hypercholesterolaemia.
Figure 2: Algorithms for managing patients with familial hypercholesterolaemia.
Figure 3: Algorithm for managing patients with familial combined hyperlipidaemia.
Figure 4: Algorithm for the future management of patients with hyper-Lp(a).

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Authors and Affiliations

  1. School of Medicine and Pharmacology, The University of Western Australia, PO Box X2213, Perth, 6847, Western Australia, Australia

    Katrina L. Ellis, Amanda J. Hooper, John R. Burnett & Gerald F. Watts

  2. Centre for Genetic Origins of Health and Disease, The University of Western Australia and Curtin University, 35 Stirling Highway, Crawley, Perth, 6009, Western Australia, Australia

    Katrina L. Ellis

  3. PathWest Laboratory Medicine WA, Royal Perth Hospital and Fiona Stanley Hospital Network, Perth, Western Australia, Australia

    Amanda J. Hooper & John R. Burnett

  4. School of Pathology and Laboratory Medicine, The University of Western Australia, 35 Stirling Highway, Crawley, Perth, 6009, Western Australia, Australia

    Amanda J. Hooper

  5. Department of Cardiology, Lipid Disorders Clinic, Royal Perth Hospital, Wellington Street, Perth, Western Australia, Australia

    John R. Burnett & Gerald F. Watts

Authors
  1. Katrina L. Ellis
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  2. Amanda J. Hooper
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  3. John R. Burnett
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  4. Gerald F. Watts
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Contributions

All authors researched data for the article, contributed to discussion of the content, wrote the article and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Gerald F. Watts.

Ethics declarations

Competing interests

G.F.W. has received research grants and advisory board honouraria from Amgen and Sanofi. The other authors declare no competing interests.

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FURTHER INFORMATION

ClinicalTrials.gov

PowerPoint slides

Supplementary information

Supplementary information S1 (table)

Dutch Lipid Clinic Network Score for making a diagnosis of familial hypercholesterolaemia in an index patient. (PDF 332 kb)

Supplementary information S2 (box)

Indications for measuring lipoprotein(a) (PDF 68 kb)

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Ellis, K., Hooper, A., Burnett, J. et al. Progress in the care of common inherited atherogenic disorders of apolipoprotein B metabolism. Nat Rev Endocrinol 12, 467–484 (2016). https://doi.org/10.1038/nrendo.2016.69

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