HDL – a difficult friend

Abstract

High-density lipoprotein (HDL) is an attractive target for antiatherogenic drug therapy because of the inverse association between HDL cholesterol and cardiovascular risk as well as many potentially antiatherogenic functions. However, controversial data from inborn errors of human HDL metabolism and genetic animal models as well as the frequent confounding of low HDL cholesterol with other proatherogenic conditions in the population have complicated the proof of a causal relationship between HDL cholesterol and atherosclerosis. Because HDLs form a very heterogenous class of lipoproteins which differ in protein and lipid composition, it is increasingly accepted that the quality rather than quantity of HDL is relevant for its atheroprotective activity. As a consequence, protein or lipid or functional biomarkers are postulated to be better biomarkers than HDL cholesterol to assess and monitor the cardiovascular risk exerted by disturbed HDL metabolism and to estimate the benefit of any therapeutic intervention. In addition, novel therapeutics are searched which either improve HDL metabolism, mimic HDL function or cure the regulatory network underlying disturbed HDL metabolism and function. Beyond better biomarkers of HDL functionality and metabolism early clinical endpoint studies are needed to assess the therapeutic benefit of any novel HDL-modifying therapy.