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Published on: October 12, 2017
High-density lipoprotein functionality in coronary artery disease
Constantine E Kosmas1, Georgios Christodoulidis, Jeh-wei Cheng
1Zena and Michael A. Wiener Cardiovascular Institute (CEK), Icahn School of Medicine at Mount Sinai, New York, New York; Department of Internal Medicine (GC), Winthrop University Hospital, Mineola, New York; Department of Medicine (JWC, SL), Emory University School of Medicine, Atlanta, Georgia; and St. Francis Hospital-The Heart Center (TJV), Division of Cardiology, Center of Advanced Cardiac Therapeutics, Roslyn, New York.
Insights
High-density lipoprotein (HDL) function, not just levels, is key for cardiovascular health. Cholesterol efflux capacity is a vital measure of HDL
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
- Atherosclerosis Research
Background:
- High-density lipoprotein (HDL) is traditionally linked to cardiovascular protection.
- Epidemiological studies show an inverse relationship between HDL levels and coronary artery disease risk.
- Emerging evidence suggests high HDL levels may not always be protective, highlighting the need to assess HDL functionality.
Purpose of the Study:
- To explore the shift in focus from HDL concentration to HDL functionality in cardiovascular risk assessment.
- To investigate HDL heterogeneity and its impact on biological and functional properties.
- To evaluate cholesterol efflux capacity as a metric for HDL functionality and its association with coronary artery disease.
Main Methods:
- Review of epidemiological data and recent scientific evidence.
- Analysis of HDL particle heterogeneity and functional properties.
- Evaluation of cholesterol efflux capacity as a measure of HDL functionality.
Main Results:
- HDL functionality, rather than concentration, is crucial for assessing cardiovascular risk.
- Cholesterol efflux capacity from macrophages is a strong indicator of HDL functionality.
- Cholesterol efflux capacity shows an inverse relationship with angiographically documented coronary artery disease risk.
Conclusions:
- Improving HDL quality and function is a potential therapeutic target for cardiovascular disease.
- Assessment of HDL function, particularly cholesterol efflux capacity, offers valuable insights into atheroprotection.
- Understanding HDL functionality is essential for refining strategies against cardiovascular events.
Abstract:
The role of high-density lipoprotein (HDL) in cardiovascular atheroprotection is well established. Epidemiological data have clearly demonstrated an inverse relationship between HDL levels and the risk for coronary artery disease, which is independent of the low-density lipoprotein levels. However, more recent data provide evidence that high HDL levels are not always protective and that under certain conditions may even confer an increased risk. Thus, a new concept has arisen, which stresses the importance of HDL functionality, rather than HDL concentration per se, in the assessment of cardiovascular risk. HDL functionality is genetically defined but can also be modified by several environmental and lifestyle factors, such as diet, smoking or certain pharmacologic interventions. Furthermore, HDL is consisted of a heterogeneous group of particles with major differences in their structural, biological and functional properties. Recently, the cholesterol efflux capacity from macrophages was proven to be an excellent metric of HDL functionality, because it was shown to have a strong inverse relationship with the risk of angiographically documented coronary artery disease, independent of the HDL and apolipoprotein A-1 levels, although it may not actually predict the prospective risk for cardiovascular events. Thus, improving the quality of HDL may represent a better therapeutic target than simply raising the HDL level, and assessment of HDL function may prove informative in refining our understanding of HDL-mediated atheroprotection.
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