HDL metabolism in context: looking on the bright side.
OBJECTIVE
To review new data concerning HDL metabolism and cardiovascular disease, the concept of HDL 'functionality', and HDL kinetics in the metabolic syndrome.


RESULTS
HDL-apoA-I and apoA-II may be better predictors of cardiovascular disease than HDL-cholesterol. Cholesteryl ester transfer protein inhibition with torcetrapib does not benefit cardiovascular disease; whether this is related to 'congestion' of HDL transport or a specific off-target vasopressor effect remains unclear. Accelerated catabolism of HDL particles in metabolic syndrome could be due to increased hepatic secretion of apoB and apoC-III, hepatic steatosis, and low plasma adiponectin. The role of serum amyloid A and homocysteine is uncertain. In metabolic syndrome, therapies that could favourably alter HDL transport include weight loss, fish oils, higher dose statins, and fibrates; 'balancing feedback' may offset reduced catabolism of HDL, fenofibrate being the only agent hitherto shown to increase apoA-I production.


CONCLUSIONS
Elevating HDL-apoA-I and apoA-II may be a more important therapeutic objective than increased HDL-cholesterol. Recent studies underscore the potential value of studying HDL functionality, particularly in the metabolic syndrome. Reverse cholesterol transport can only be reliably probed at present by studying the kinetics of HDL particles or apolipoproteins; new methods are needed for investigating cellular and whole body cholesterol turnover. In metabolic syndrome, HDL-raising therapies have differential impact on HDL kinetics, the optimal endpoint being to increase transport and concentration with unchanged or accelerated catabolism.
Watts
Gerald F
GF
Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia. Gerald.watts@uwa.edu.au
Barrett
P Hugh R
PH
Chan
Dick C
DC
D052242:Adiponectin / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism; D007700:Kinetics
D052242:Adiponectin; D008076:Cholesterol, HDL; D006710:Homocysteine