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Familial hypercholesterolemia: a missed opportunity in preventive medicine

Nature Clinical Practice Cardiovascular Medicine volume 4, pages 404–405 (2007)Cite this article

Familial hypercholesterolemia (FH) is caused by a codominantly inherited defect in the synthesis or function of the LDL receptor (LDLR) that reduces the catabolism of LDL particles and markedly increases plasma cholesterol concentrations.1 The population prevalence of heterozygous FH is at least 1 in 500, and could be as high as 1 in 50 in communities with a 'founder gene', such as the Christian Lebanese. More than 1,000 LDLR mutations have been identified to date. Patients with FH have an increased incidence of atherosclerotic cardiovascular disease (CVD), particularly coronary artery disease (CAD).2 When left untreated, FH confers a 100-fold excess risk of CAD in young men. Women with FH are also at a substantial risk of CAD, but the risk is lower than that for men and, on average, women develop the disease 10 years later.2 Lifestyle measures, including fat-modified diets, and pharmacotherapy, particularly with statins, can substantially decrease the risk of CAD.2 Despite impressive advances in our understanding of the pathophysiology of FH, over 80% of patients with FH in Western countries go undetected,3 and this easily diagnosed disorder remains a major challenge for preventive medicine. We urge that this challenge be met by the transformation of existing nihilism into a rigorous and cost-efficient strategy for detecting and treating FH.

FH fulfils all the WHO criteria for disease screening.1 Relatives of probands can and must be screened for FH before they develop clinical CVD, but this seldom occurs in current clinical practice.4,5 The most cost-effective approach is undoubtedly 'cascade screening' of first-degree relatives of index cases.6 Identifying index cases is fundamental to the success of such programs, but at present there are no internationally agreed criteria for the diagnosis of FH. We favor the Dutch Lipid Clinic Network Criteria, in which a score is derived from the LDL cholesterol level, the family and personal history of premature CVD, and the presence of tendon xanthomas or corneal arcus.3 All patients with a history of premature CVD should be screened for FH, but regrettably this is not practiced regularly at present.4,5

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References

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Authors and Affiliations

  1. GF Watts is Professor of Medicine and Head of Internal Medicine and the Lipid Disorders Clinic at the Royal Perth Hospital and the University of Western Australia, Perth,

    Gerald F Watts

  2. B Lewis is a Visiting Professor in the Department of Medicine, and DR Sullivan is a Consultant, Clinical Associate Professor and Head of the Lipid Clinic at the Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia.,

    Barry Lewis & David R Sullivan

Authors
  1. Gerald F Watts
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  2. Barry Lewis
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  3. David R Sullivan
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Correspondence to Gerald F Watts.

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Competing interests

GF Watts and DR Sullivan have acted as consultants and received honoraria for educational lectures and advisory board membership from AstraZeneca, Merck, Pfizer, Sanofi-Aventis, and Solvay. B Lewis declared he has no competing interests.

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Watts, G., Lewis, B. & Sullivan, D. Familial hypercholesterolemia: a missed opportunity in preventive medicine. Nat Rev Cardiol 4, 404–405 (2007). https://doi.org/10.1038/ncpcardio0941

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