HDL Does Not Protect Some Chronically Ill Patients from Heart Disease

Cardiovascular disease researchers have found that HDL, the so-called "good cholesterol,” does not play a protective role in individuals with some types of inflammatory disorders, diabetes, chronic renal failure, or coronary heart disease.

Current wisdom maintains that high levels of total cholesterol and LDL-cholesterol increase risk of heart disease while high levels of HDL are protective and, by removing cholesterol from cholesterol-loaded arterial macrophages, reduce heart attack risk.

However, a paper published in the December 2008 issue of The FASEB Journal has revised the role of HDL, especially in individuals with various types of chronic illness.

In normal individuals, the main HDL protein, apolipoprotein A-I (Apo A-I), has an amphipathic structure suited for transport of lipids. It readily interacts with the ATP-binding cassette transporter ABCA1, the SR-B1 scavenger receptor, and activates the enzyme lecithin-cholesterol acyl transferase (LCAT), which is critical for HDL maturation. It also has antioxidant and anti-inflammatory properties, along with the HDL-associated enzymes paraoxonase, platelet activating factor acetylhydrolase (PAF), and glutathione peroxidase. Regarding the HDL lipid moiety, an atheroprotective role has been recognized for lysosphingolipids, particularly sphingosine-1-phosphate (S1P).

Reviewing the latest studies on HDL, the authors found that all of HDL's atheroprotective functions disappear from the dysfunctional plasma HDLs of subjects with systemic inflammation, coronary heart disease, diabetes, and chronic renal disease. They highlighted the emerging notion that the quality of the HDL particles has more predictive power than their quantity. This has stimulated further exploration of the HDL proteome, already revealing unsuspected pro- or anti-atherogenic proteins and peptides associated with HDL.

"For many years, HDL has been viewed as good cholesterol and has generated a false perception that the more HDL in the blood, the better,” said first author Dr. Angelo Scanu, professor of biochemistry and molecular biology at the University of Chicago (IL, USA). "It is now apparent that subjects with high HDL are not necessarily protected from heart problems and should ask their doctor to find out whether their HDL is good or bad.”

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