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High density lipoproteins (HDLs) and atherosclerosis; the unanswered questions
Philip Barter1, John Kastelein, Alistair Nunn
1Cardiovascular Investigation Unit, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia. philip.barter@adelaide.edu.au
Insights
High density lipoprotein-cholesterol (HDL-C) predicts lower coronary heart disease (CHD) risk, but how HDL prevents atherosclerosis and if HDL-raising therapies are effective remains unclear.
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
- Preventive Cardiology
Background:
- High density lipoprotein-cholesterol (HDL-C) is a strong negative predictor of premature coronary heart disease (CHD).
- Evidence suggests HDLs protect against atherosclerosis development, though mechanisms are uncertain.
- HDL comprises various subpopulations with potentially distinct cardioprotective roles.
Purpose of the Study:
- To review current knowledge on HDL's role in atherosclerosis and CHD prevention.
- To identify critical unanswered questions regarding HDL function and therapeutic interventions.
- To evaluate the efficacy of HDL-C-raising strategies for CHD prevention.
Main Methods:
- Review of human prospective population studies on HDL-C and CHD.
- Analysis of human and animal intervention studies on HDL and atherosclerosis.
- Synthesis of evidence on lifestyle and pharmacological interventions affecting HDL-C.
Main Results:
- Consistent association between higher HDL-C and reduced CHD risk.
- Evidence supporting HDL's anti-atherosclerotic properties.
- Uncertainty regarding specific HDL subpopulations' protective effects and intervention efficacy.
Conclusions:
- HDL-C is a key factor in cardiovascular health.
- Further research is urgently needed to elucidate HDL mechanisms and optimize therapeutic strategies.
- Caution is advised before widespread implementation of HDL-C-raising therapies for CHD prevention.
Abstract:
The concentration of high density lipoprotein-cholesterol (HDL-C) has been found consistently to be a powerful negative predictor of premature coronary heart disease (CHD) in human prospective population studies. There is also circumstantial evidence from human intervention studies and direct evidence from animal intervention studies that HDLs protect against the development of atherosclerosis. HDLs have several documented functions, although the precise mechanism by which they prevent atherosclerosis remains uncertain. Nor is it known whether the cardioprotective properties of HDL are specific to one or more of the many HDL subpopulations that comprise the HDL fraction in human plasma. Several lifestyle and pharmacological interventions have the capacity to raise the level of HDL-C, although it is not known whether all are equally protective. Indeed, despite the large body of information identifying HDLs as potential therapeutic targets for the prevention of atherosclerosis, there remain many unanswered questions that must be addressed as a matter of urgency before embarking wholesale on HDL-C-raising therapies as strategies to prevent CHD. This review summarises what is known and highlights what we still need to know.