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NHLBI Refines Test for Good Cholesterol Function
Routine blood tests at the doctor’s office measure the amount of good and bad cholesterol in the body. Research has shown though that measuring how well high-density lipoprotein (HDL)—or “good cholesterol”—functions can better predict heart disease risk. New NIH research is now bringing such testing closer to clinical use.
HDL cholesterol removes extra cholesterol from the arteries by gobbling up early-forming plaque and transporting it to the liver for disposal. Excess plaque in the arteries can narrow blood vessels and impede blood flow, leading to heart attacks and stroke. When HDL cholesterol works well, heart disease risks are reduced.
To date, measuring HDL function has been limited to research labs. The test involves harvesting cells in the lab and can take days to process.
Researchers at the National Heart, Lung and Blood Institute (NHLBI) have developed a diagnostic test that could enable large-scale testing. The cell-free test could be easily replicated in labs, automated to process larger samples and provide readings in about an hour.
“This is going to quicken the pace of basic research,” said Dr. Edward Neufeld, a scientist in NHLBI’s Lipoprotein Metabolism Laboratory who, along with Dr. Masaki Sato, developed the test. “It increases the number of samples you can study. It increases the number of experiments you can do.”
Importantly, they have shown in clinical studies their test can predict cardiovascular disease risk better than HDL concentrations, currently used to assess such risk. They published these findings in the Journal of Clinical Investigation.
To perform the test, a person’s plasma, which contains HDL, is separated from their blood. The plasma is added to donor particles coated with a lipid mixture that resembles plaque, and a fluorescent-tagged phospholipid that can only be removed by HDL. The fluorescent signal obtained by HDL is then measured. A brighter signal reflects optimal HDL lipid removal function. A dim light indicates reduced function.
The test is still years away from potential use in a medical setting, but it holds promise for physicians looking to gather additional information that could help inform their treatment decisions. NIH has now patented the test and will work with an outside company to purchase the rights to license and manufacture the diagnostic material.
Basic research over many years has led to advances and novel discoveries in lipoprotein research. Statins, which lower levels of LDL—“the bad”—cholesterol, were developed decades ago. Despite ongoing research into HDL cholesterol, therapeutic advances so far haven’t followed.
“Someday we may have a drug that modulates HDL and turns out to be beneficial, but right now we don’t have that,” said NHLBI Senior Investigator Dr. Alan Remaley.
Neufeld said, “This [research] could open up new opportunities to gain further insights, such as with drug development, that have been difficult to achieve.”