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

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


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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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.

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Correspondence to Gerald F. Watts.

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

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