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Review
. 2012 Oct;97(10):3399-407.
doi: 10.1210/jc.2012-2185.

Approach to the patient with extremely low HDL-cholesterol

Daniel J Rader  1 , Emil M deGoma
Affiliations
Review

Approach to the patient with extremely low HDL-cholesterol

Daniel J Rader et al. J Clin Endocrinol Metab. 2012 Oct.

Abstract

Patients with extremely low high-density lipoprotein-cholesterol (HDL-C) pose distinct challenges to clinical diagnosis and management. Confirmation of HDL-C levels below 20 mg/dl in the absence of severe hypertriglyceridemia should be followed by evaluation for secondary causes, such as androgen use, malignancy, and primary monogenic disorders, namely, apolipoprotein A-I mutations, Tangier disease, and lecithin-cholesterol acyltransferase deficiency. Global cardiovascular risk assessment is a critical component of comprehensive evaluation, although the association between extremely low HDL-C levels and atherosclerosis remains unclear. Therapeutic interventions address reversible causes of low HDL-C, multiorgan abnormalities that may accompany primary disorders and cardiovascular risk modification when appropriate. Uncommon encounters with patients exhibiting extremely low HDL-C provide an opportunity to directly observe the role of HDL metabolism in atherosclerosis and beyond the vascular system.

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Figures

Fig. 1.
Fig. 1.
HDL metabolism and monogenic extremely low HDL-C disorders. ABC, ATP-binding cassette transporter; CETP, cholesteryl ester transfer protein; LDL-R, LDL receptor. [Reproduced from E. M. Degoma and D. J. Rader: Novel HDL-directed pharmacotherapeutic strategies. Nat Rev Cardiol 8:266–277, 2011 (4) with permission. © Nature Publishing Group.]
Fig. 2.
Fig. 2.
Physical examination findings in monogenic extremely low HDL-C disorders. Patients with apoA-I deficiency may manifest xanthomas (A) and mild corneal clouding (B). [Reproduced from E. J. Schaefer et al.: Marked HDL deficiency and premature coronary heart disease. Curr Opin Lipidol 21:289, 2010 (19), with permission. © Lippincott Williams & Wilkins.] The hallmark physical findings in Tangier disease are enlarged yellow-orange tonsils (C). [Reproduced from T. Sampietro et al.: Images in cardiovascular medicine. Tangier disease in severely progressive coronary and peripheral artery disease. Circulation 119:2741, 2009 (26), with permission. © American Heart Association.] Patients with LCAT deficiency exhibit age-dependent corneal opacification. Eyes from a 32-yr-old patient (D) and a 67-yr-old (E) patient are shown. [Reproduced from A. von Eckardstein: Differential diagnosis of familial high density lipoprotein deficiency syndromes. Atherosclerosis 186:231, 2006 (16), with permission. © Elsevier.]
Fig. 3.
Fig. 3.
Two-dimensional gel electrophoresis of monogenic extremely low HDL-C disorders. A composite is shown of the HDL gel patterns observed in a normal subject, a homozygote with apoA-I deficiency, a Tangier patient, and an individual with LCAT deficiency. [Reproduced from E. J. Schaefer et al.: Marked HDL deficiency and premature coronary heart disease. Curr Opin Lipidol 21:289–297, 2010 (19) with permission. © Lippincott Williams & Wilkins.]
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