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HDL: a question of quantity or quality? - ESC Congress 2016- Rome (2016-08-29)

Until recently it was undisputed dogma that high-density lipoprotein cholesterol (HDL-C) has solely atheroprotective properties. This notion was based on population studies and meta-analyses showing an association of high HDL-C plasma levels with a decreased risk for cardiovascular disease.

Recently, however, this view has been challenged, mainly by clinical studies showing that HDL-C levels predicted cardiovascular death only in individuals without CAD.

HDL particles can be divided in various sub-fractions or subpopulations depending on their size, composition, density, charge and physiological function. This heterogeneity is a result of the varying contents of lipids and proteins of the respective LDL particles in which size and density show an inverse correlation. According to density, HDL particles can be classified as HDL2, which are large and less dense, and as HDL3, which are small and dense.

The major atheroprotective effect of HDL is thought to be associated with its function in reverse cholesterol transport. Anti-inflammatory, anticoagulant and antioxidative effects have also been described.

The anti-inflammatory and antioxidant effects are brought about by PON-1, whereas the anticoagulant properties of HDL seem to be related to its ability to reduce platelet activation and decrease expression of tissue factor.

These atheroprotective effects are lost in dysfunctional HDL.
Current knowledge on the transition from functional to dysfunctional HDL is still fragmentary and mainly based on in vitro findings.
However, it is generally believed that systemic inflammation seen in pathologies such as metabolic syndrome, diabetes, CAD and infections contribute to the conversion of HDL-C from an antiatherogenic to a proatherogenic molecule.

In summary, the controversy of the atheroprotective role of HDL-C fuelled by conflicting clinical data might be explained by the fact that the exact function of HDL-C and thus its role in the development of cardiovascular pathologies depends not so much on its quantity but more on its lipid and protein composition, with the small dense fraction having the highest antiatherogenic activity.

It thus seems likely that the concept of dysfunctional HDL-C will lead to assays with greater sensitivity and specificity and will shape future therapies, which will not only be based on quantitative but more so on qualitative modifications to change or modulate functions of HDL-C.

For more information
HDL: a question of quantity or quality?
ESC Congress News 2016 - Rome, Italy, 29 Aug 2016