Increasing HDL-cholesterol and prevention of atherosclerosis: A critical perspective

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Atherosclerosis Research

Background:

• The link between high-density lipoprotein (HDL) and atherosclerosis is intricate, differing from the clearer association with low-density lipoprotein (LDL).
• Low HDL-cholesterol levels are linked to atherosclerotic disease, but this association is often indirect, reflecting higher concentrations of triglyceride-rich lipoproteins.
• HDL functionality, particularly its role in reverse cholesterol transport, is crucial for preventing atherosclerosis.

Purpose of the Study:

• To elucidate the complex relationship between HDL and atherosclerosis.
• To differentiate between HDL quantity and HDL functionality in the context of atherosclerotic disease.
• To inform therapeutic strategies for atherosclerosis prevention targeting HDL.

Main Methods:

• Review and analysis of existing literature on HDL, LDL, triglyceride-rich lipoproteins, and atherosclerosis.
• Examination of the mechanisms of reverse cholesterol transport mediated by HDL.
• Evaluation of the impact of HDL quantity versus HDL function on atherosclerotic progression.

Main Results:

• Low HDL-cholesterol is an indicator, not a direct cause, of atherosclerosis, often correlating with increased triglyceride-rich lipoproteins.
• HDL's functional capacity, including reverse cholesterol transport, is a key factor in atherosclerosis prevention.
• The concentration of HDL-cholesterol and the functionality of the HDL system are not always directly correlated.

Conclusions:

• Therapeutic approaches for atherosclerosis should focus on either reducing triglyceride-rich lipoproteins (which may raise HDL-cholesterol) or enhancing HDL functionality.
• Simply elevating HDL-cholesterol levels without improving HDL function or reducing triglyceride-rich lipoproteins is unlikely to prevent atherosclerosis effectively.
• Future treatments should consider both HDL quantity and quality for optimal cardiovascular protection.