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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