Approach to the Patient with Extremely Low HDL-Cholesterol

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.

Undetectable HDL Cholesterol in a Patient with Flu-Like Illness

“…By these criteria, low HDL-C occurs in a substantial fraction of the population, and is associated with diverse environmental and genetic factors. Very low HDL-C occurs in at most a few percent of the population and has a much narrower range of causes (2 ). It may possibly occur in patients with very high triglycerides (Ͼ500 mg/dL or Ͼ5.65 mmol/L), but more typically such patients have HDL-C in the low range, and the current patient had only a modest increase in triglycerides.…”

“…It is a negative risk factor presumably because of its role as the acceptor of free cholesterol efflux from peripheral cells. Production of the HDL particle requires synthesis of its major protein component, apolipoprotein (apo) A-I, as well as lipid metabolism pathways that require the ATP-binding cassette transporter A1 (ABCA1), lipoprotein lipase, and lecithin-cholesterol acyltransferase (LCAT) (2 ). In the context of coronary risk, concentrations above 60 mg/dL (1.55 mmol/L) are considered optimal, whereas concentrations below 40 mg/dL (1.03 mmol/L) are considered "low" (conferring increased risk).…”

“…Known acquired causes for low and possibly very low HDL-C include some malignancies, severe sepsis, and other systemic illnesses that cause increased interleukin (IL)-10, and certain drugs, including anabolic steroids, fibrates, and thiazolidinediones (2,4,5 ). None of these applied to the patient under discussion, except perhaps for the possibility of increased IL-10 production as discussed in the next paragraph.…”

“…The patient also had a lipid panel drawn (presumably because it was a visit to his family physician who ordered this as a routine) and was found to have an undetectable concentration of HDL cholesterol (HDL-C). 2 Other laboratory data are summarized in Table 1.…”

Current Treatment of Dyslipidemia: Evolving Roles of Non-Statin and Newer Drugs

“…with these mutations, despite extremely low levels of HDL-C that led investigators to expect profound atherosclerosis, no consistent premature CHD was apparent [10,11]. Although still incomplete, the lack of genetic evidence argues against the HDL hypothesis.…”