Journal
CURRENT OPINION IN LIPIDOLOGY
Volume 28, Issue 5, Pages 414-418Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOL.0000000000000446
Keywords
cardiovascular risk; cholesterol efflux capacity; HDL; HDL particle concentration; HDL proteomics
Funding
- National Institutes of Health [HL112625, HL108897, P30 DK17047, P01 HL092969, T32 HL007828]
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Purpose of review Epidemiological and clinical studies link low levels of HDL cholesterol (HDL-C) with increased risk of atherosclerotic cardiovascular disease (CVD). However genetic polymophisms linked to HDL-C do not associate consistently with CVD risk, and randomized clinical studies of drugs that elevate HDL-C via different mechanisms failed to reduce CVD risk in statin treated patients with established CVD. New metrics that capture HDL's proposed carchoprotectwe effects are therefore urgently needed. Recent findings Recent studies demonstrate cholesterol efflux capacity (CEC) of serum HDL (serum depleted of cholesterol rich atherogenic lipoproteins) is an independent and better predictor of incident and prevalent CVD risk than HDL-C. However, it remains unclear whether therapies that increase CEC are cardioprotective. Other key issues are the impact of HDL-targeted therapies on HDL particle size and concentration and the relationship of those changes to CEC and cardioprotection. Summary It is time to end the clinical focus on HDLC and to understand how HDL's function, protein composition and size contribute to CVD risk. It will also be important to link variations in function and size to HDL-argeted therapies. Developing new metrics for quantifying HDL function, based on better understanding HDL metabolism and macrophage CEC, is critical for achieving these goals.
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