North Carolina State University News Services Campus Box 7504 Raleigh, NC 27695 (919) 515-3470
Media Contacts:
Dr. James Otvos, 919/515-5724 or [email protected]
Tim Lucas, News Services, 919/515-3470 or [email protected]
Carole Bullock, American Heart Association, 214/706-1279
July 20, 1998
New Test More Accurately Measures Risk of Heart Disease, Study Finds
FOR IMMEDIATE RELEASE
A North Carolina State University biochemist has developed a blood test that allows doctors to assess a person's risk of heart disease more accurately than before, according to a new study published this month in the American Heart Association journal Arteriosclerosis, Thrombosis and Vascular Biology.
The test can detect 15 different subclasses of cholesterol-containing lipoproteins found in blood. Lipoproteins are particles that package cholesterol, allowing it to be transported in the blood.
"This is the first test that can measure many different sizes of lipoproteins. Before this, we could measure the quantity of ëgood' and ëbad' cholesterol in a person's blood, but not the quality -- the different sizes and types of it. Now we can," says the test's inventor, Dr. James D. Otvos, professor of biochemistry at NC State and a co-author of the study.
That new capability is important, he says, because "it's not cholesterol, per se, that's really important, rather it's the size and type of lipoproteins that count in predicting disease. There are plenty of examples of individuals who have identical levels of total cholesterol, bad cholesterol and good cholesterol, but have very different risks of coronary artery disease."
Blood cholesterol tests are used to help determine if a person has elevated cholesterol, a major risk factor for heart disease. In general, the higher the blood level of the "bad" cholesterol, low-density lipoprotein (LDL), the higher the risk of a heart attack.
However, using Otvos's new technology, medical researchers have found that certain sizes of LDL are not as dangerous as others. They also have found that not all types of high-density lipoprotein (HDL), the so-called "good" cholesterol, are protective.
The patented technology uses proton nuclear magnetic resonance (NMR) spectroscopy to measure and record radio signals emitted by lipoproteins in the bloodstream. A computer unscrambles the radio signals and determines which subclasses of lipoproteins are present and in what concentrations. This is possible, Otvos says, because different sizes of lipoproteins produce distinguishably different radio signals.
By providing a more accurate analysis of cholesterol lipoproteins, Otvos' test could help physicians match therapies to a patient's heart-disease risk, says the study's lead author, Dr. David Freedman, senior epidemiologist at the Centers for Disease Control and Prevention. Eventually, he says, the test could be used to produce a "lipoprotein subclass profile" for each patient.
In the study, blood samples were taken from 158 men who underwent diagnostic coronary arteriography to assess potential blockages in the blood vessels leading to their heart. NMR spectroscopy was used to measure levels of three types of cholesterol in their blood: LDL, HDL and VLDL -- very low-density lipoproteins. LDL obstructs blood vessels while HDL is regarded as "good" because it helps remove LDL. VLDL transports triglycerides in the blood.
Researchers found more heart disease in individuals with high levels of large VLDL and small HDL particles. Men with above-average 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 the 27 men with high levels of both large VLDL and small HDL particles. In contrast, men with higher levels of intermediate-sized HDL had a 70 percent reduced risk of disease.
High levels of small LDL initially appeared to be an indicator of high risk of heart disease. However, this association became much weaker when researchers took the levels of HDL and triglycerides into account.
NMR technology is able to perform the tests in minutes, Otvos says, compared to hours or days needed for other forms of testing which separate particles by molecular density or diameter. "Our test is faster because it doesn't require any physical separation of blood components," he says.
Equally important is the more detailed knowledge the tests provide. For years, doctors have been puzzled why heart disease develops in some patients with low cholesterol levels while it doesn't develop in some with very high levels of cholesterol. The different sizes and shapes of LDL and HDL -- which are impossible to distinguish using routine lipid testing -- 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," Freedman says.
Co-authors in the study are Elias J. Jeyarajah of Raleigh, a doctoral student at NC State; Dr. Joseph J. Barboriak of the Milwaukee (Wis.) Veterans Administration Medical Center; and Alfred J. Anderson and Dr. John A. Walker of St. Luke's Hospital in Milwaukee. Funding came from the National Institutes of Health and the Medical Research Service of the Department of Veterans Affairs.
Lipomed Inc. of Raleigh has rights to commercialize Otvos' technology.
-- lucas --
NOTE TO EDITORS: An abstract of the AHA journal paper appears on the following page. For a copy of the article, call (214) 706-1173. For a video release about the study, call Carol Floyd Massey at the AHA at (214) 706-1397. Dr. Freedman can be reached at (770) 488-6016.
"The Relation of Lipoprotein Subclasses as Measured by Proton Nuclear Magnetic Resonance Spectroscopy to Coronary Artery Disease"
Published July 10, 1998, in Arteriosclerosis, Thrombosis and Vascular Biology, a journal of the American Heart Association
Authors: D.S. Freeman, Centers for Disease Control and Prevention; J.D. Otvos and E.J. Jeyarajah, NC State University; J.J. Barboriak, Milwaukee Veterans Administration Medical Center; and A.J. Anderson and J.A. Walker, St. Luke's Hospital of Milwaukee.
ABSTRACT: Although each of the major lipoprotein fractions is composed of various subclasses that may differ in atherogenicity, the importance of this heterogeneity has been difficult to ascertain owing to the labor-intensive nature of subclass measurement methods. We have recently developed a procedure, using proton nuclear magnetic resonance (NMR) spectroscopy to simultaneously quantify levels of subclasses of very low density (VLDL), low density (LDL) and high density (HDL) lipoproteins; subclass distributions determined with this method agree well with those derived by gradient-gel electrophoresis. The objective of the current study of 158 men was to examine whether NMR-derived lipoprotein subclass levels improve the prediction of arteriographically documented cororary artery disease (CAD) when levels of lipids and lipoproteins are known. We found that a global measure of CAD severity was positively associated with levels of large VLDL and small HDL particles, and inversel! y associated with intermediate-sized HDL particles; these associations were independent of age and the standard lipid measurments. At comparable lipid and lipoprotein levels, for example, men with relatively high (higher than the median) levels of either small HDL or large VLDL particles were 3 to 4 times more likely to have extensive CAD than were the other men; the 27 men with high levels of both large VLDL and small HDL were 15 times more likely to have extensive CAD than were men with low levels. In contrast, adjustment for levels of triglycerides or HDL cholesterol greatly reduced the relation of small LDL particles to CAD. These finding suggest that large VLDL and small HDL particles may play important roles in the development of occlusive disease and that their measurement, which is not possible with routine lipid testing, may lead to more accurate risk assessment.
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