What is the role of plasma lipoproteins in the pathophysiology of low HDL cholesterol (hypoalphalipoproteinemia)?

Updated: May 21, 2021
  • Author: Vibhuti N Singh, MD, MPH, FACC, FSCAI; Chief Editor: George T Griffing, MD  more...
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Plasma lipoproteins are macromolecular complexes of lipids and proteins that are classified by density and electrophoretic mobility. The structure of all lipoproteins is the same. The nonpolar lipids (ie, cholesterol ester, triglycerides [TGs]) reside in a core surrounded by more polar components (eg, free cholesterol, phospholipids, proteins). The proteins, termed apolipoproteins, play an important role in lipoprotein metabolism.

The major apolipoproteins of high-density lipoprotein (HDL) are alpha lipoproteins (ie, apolipoprotein A-I [apo A-I], apo A-II, apo A-IV), which are soluble and can move between different classes of lipoproteins. The beta lipoproteins are structural, are never complexed with HDL, and remain throughout the metabolism of the lipoproteins with which they are associated. Apo B-450 is associated with chylomicrons and their remnants, and apo B-100 is associated with low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), VLDL remnants, and intermediate-density lipoprotein.

HDL plays a major role in reverse cholesterol transport, mobilizing cholesterol from the periphery to promote return to the liver. In the general population, lower-than-normal HDL cholesterol levels are closely correlated with coronary heart disease (CHD); the risk of a coronary event is thought to increase 2% for every 1% decrease in HDL cholesterol. However, extreme HDL deficiencies caused by rare autosomal recessive disorders, including familial hypoalphalipoproteinemia (HA), familial lecithin-cholesterol acetyltransferase (LCAT) deficiency, and Tangier disease, do not always correlate with more frequent CHD. [7, 8]

Results from the Framingham Heart Study offspring cohort, where 3590 individuals without known cardiovascular disease were studied from 1987 to 2011, found that cardiovascular risk was not only associated with high-density lipoprotein cholesterol but also was associated with a combination HDL levels and levels of low-density lipoprotein cholesterol and triglycerides. [9, 10]

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