Radio Signals Give New Spectrum For Cholesterol Lipoprotein Readings

July 09, 1998

DALLAS, July 10 -- A new laboratory test can detect levels of 15 different blood cholesterol-containing particles called lipoproteins, an advance that will help paint a clearer picture of a person's risk of heart disease than the cholesterol blood tests now used, scientists say.

Blood cholesterol tests help determine if a person has elevated cholesterol, a major risk factor for heart disease. In general, the higher the blood level of low-density lipoprotein (LDL), the "bad" cholesterol, the higher the person's risk of heart attack. However, the new study found that certain sizes of lipoproteins -- particles that package cholesterol, enabling it to be transported -- are not as dangerous as others. And, surprisingly, the study found that the "good" cholesterol, high-density lipoprotein (HDL), is not always protective.

"It's not cholesterol, per se, that's really important, but the size and type of lipoproteins that count in predicting disease," says James Otvos, Ph.D., developer of the test and professor of biochemistry, North Carolina State University, Raleigh.

By providing a more accurate reading of lipoproteins, physicians can better match their therapies to the person's heart disease risk. In the future, the test could provide a person with a "lipoprotein subclass profile," that would help determine which treatments would work best, according to study's lead author, David Freedman, Ph.D., senior epidemiologist, U.S. Centers for Disease Control and Prevention in Atlanta.

The different subclasses of lipoprotein can be detected easily with the new testing technology that employs proton nuclear magnetic resonance (NMR) spectroscopy. NMR measures and records a radio signal emitted by the lipoprotein and other blood fats transported in the bloodstream. The radio signals vary according to the size of the particles. A computer unscrambles the signals and determines the contribution made by each subclass and its concentration in the blood sample.

Commenting on the research, Sidney Smith, M.D., past president of the American Heart Association, says, "We have a large number of patients in whom we have needed this type of information because their cholesterol levels are pretty much in the normal range and yet they continue to have heart problems in spite of treatment. So when I look at this study, I see promise. This machine may help us manage patients with atherosclerosis, but I also see some areas that need further work. The study was only in men, it was in a relatively small number." The study, in this month's Arteriosclerosis, Thrombosis and Vascular Biology: Journal of the American Heart Association, included 158 men who had diagnostic coronary arteriography to assess possible blockages in their coronary arteries, the blood vessels leading to the heart. Most of the men, who were an average age of 63 years, had chest pain. Blood samples were taken and NMR spectroscopy measured levels of three cholesterol subclasses: very low-density lipoprotein (VLDL), LDL and HDL. LDL obstructs blood vessels while HDL is regarded as "good" because it helps remove LDL from the blood. VLDL transports triglycerides in the bloodstream.

Otvos says even though the same types of blood fats (primarily cholesterol and triglycerides) are found in the blood, it is lipoprotein size and shape that makes the individual signals distinguishable. "It's analogous to bells of a different size ringing with different tones and frequencies even though they are made of the same metal," he says.

Researchers found more heart disease in individuals with high levels of large VLDL and small HDL particles. Men with high levels of either of these subclasses were three to four times more likely to have extensive heart disease than the other men. This risk increased to 15-fold among men with high levels of small HDL and large VLDL. However, men with higher levels of intermediate size HDL particles were protected, reports Freedman.

Although high levels of small LDL particles initially appeared to be an important predictor of disease, the association became much weaker after the men's triglyceride levels and HDL were taken into account. Despite HDL's good reputation, the laboratory tests showed that men with above average levels of small HDL particles were three to four times more likely to have heart disease than those with below average levels. In contrast, men with higher levels of intermediate-sized HDL had a 70 percent reduced risk.

Although NMR equipment is expensive, the tests on a blood sample can be done in minutes, compared to the many hours needed for the techniques now used to separate subclasses of blood fats. Researchers predict the new test will cost about the same as standard testing. When the NMR spectroscopy method was compared to standard methods of measuring the different blood cholesterol subclasses, there was no difference other than the time required to measure the subclasses and it took only a few minutes.

Other laboratory procedures, such as gradient gel electrophoresis, (which separates the particles based on their molecular density), take several days, says Otvos. "The new test provides analyses rapidly because it does not require the physical separation of blood components," he adds. With standard cholesterol lipoprotein testing, some individuals are underdiagnosed and some are overdiagnosed. "Some may be judged at higher risk than they really are," he says. "There are plenty of examples of individuals who have identical levels of total cholesterol, LDL and HDL but have very different risks of coronary artery disease."

For years physicians have been perplexed as to why heart disease develops in some individuals with low cholesterol levels while some with very high levels don't. The individual variations within the LDL and HDL may help explain this paradox. "The hope is that this new test will go a step further in predicting who will develop heart disease and who won't," says Freedman.

Co-authors are Elias J. Jeyarajah, M.S., North Carolina State University, Raleigh; Joseph J. Barboriak, Sc.D., Milwaukee Veterans Administration Medical Center, Milwaukee; and Alfred J. Anderson, M.S., and John A. Walker, M.D., St. Luke's Hospital, Milwaukee.
NR 98-4910 (Arterio/Freedman)
Media advisory: Dr. Otvos can be reached at (919) 515-5724. Dr. Freedman can be reached by phone at (770) 488-6016. (Please do not publish numbers.)

American Heart Association

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