Why High Levels Of “good” Cholesterol May Not Be Enough

What the research is about

High-density lipoprotein (HDL), often called “good cholesterol,” is known for its role in protecting against atherosclerosis. For many years, the amount of cholesterol carried by HDL in the blood-measured as the HDL cholesterol level-has therefore been considered an important indicator of cardiovascular health.

Recent studies, however, suggest that what matters most may not be how much cholesterol HDL carries, but how well HDL works. One important function of HDL is its ability to remove excess cholesterol that has accumulated in blood vessels. This function is known as cholesterol efflux capacity, or CEC. Measuring CEC may provide a more accurate assessment of the risk of atherosclerosis and heart attack than measuring HDL cholesterol levels alone.

Conventional CEC measurement, however, requires complex procedures involving cultured cells and radioactive materials. These requirements have made it difficult to use CEC measurement in routine hospital testing. To address this problem, a research team led by Professor Ryunosuke Ohkawa, Associate Professor Taishi Yonetsu, and third-year doctoral student Tsunehiro Miyakoshi at Institute of Science Tokyo (Science Tokyo) has developed the immobilized liposome-bound gel beads (ILG) method. This cell-free method provides a safe, simple, and accurate way to measure CEC.

Why this matters

The researchers measured CEC using the ILG method in 61 patients with coronary artery disease. They also used optical coherence tomography, or OCT-a technique that uses near-infrared light to produce high-resolution images of the inside of blood vessels-to examine atherosclerotic plaques, which are deposits of lipids and other substances in artery walls.

The results showed that patients with larger, lipid-rich plaques had lower CEC. By contrast, HDL cholesterol levels showed no significant differences. This suggests that measuring how well HDL functions can reveal information that cannot be obtained from HDL cholesterol levels alone.

Previous studies had already shown that CEC is associated with atherosclerosis. However, this demonstrates for the first time an association between CEC measured using a simple, cell-free method and coronary artery plaques observed directly in patients. The findings suggest that the ILG method could help identify atherosclerosis risk that may be difficult to detect using conventional blood tests.

What’s next

If the ILG method is adopted as a clinical test, it may help detect atherosclerosis risk at an earlier stage than current lipid tests. It could also be used to identify patients who should undergo detailed imaging to check for plaques that are more likely to cause heart attacks, or to evaluate the effectiveness of new drugs designed to improve HDL function.

The research team plans to validate the method in larger groups of patients, with the aim of developing it into a test that can be used routinely in hospitals.

Comment from the researcher

What matters is not only how much “good” cholesterol there is, but also how well it works. In this study, we showed that a simple method for measuring HDL function may provide a clue to identifying high-risk atherosclerosis. We hope to develop it into a test that enables earlier detection of atherosclerosis in more people.

(Ryunosuke Ohkawa, Professor, Department of Clinical Bioanalysis and Molecular Biology, Institute of Science Tokyo)

Professor Ryunosuke Ohkawa

Associate Professor Taishi Yonetsu

Doctoral student Tsunehiro Miyakoshi

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