May 13, 1996

New Heart Disease Tests Detect Recently Discovered Risks -- Article by Jeffery Kahn

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BERKELEY, CA  Closing the gap between heart disease research findings and medical care, Ernest Orlando Lawrence Berkeley National Laboratory has entered into a partnership to make state-of-the-art cardiovascular risk testing available to the public.

Berkeley Lab has signed an agreement with a private company, Berkeley HeartLab, which will commercialize a panel of blood cholesterol tests that has not been available to the public up until now. Developed by the national laboratory, this panel detects the presence of traits recently discovered to be associated with an increased risk of atherosclerosis and heart disease. Cardiovascular disease, which accounts for 35 to 40 percent of all deaths in the U.S., is the country's leading cause of death.

Because it identifies a range of abnormalities, the new test series will allow physicians to better select appropriate therapies to halt progression of the disease. Some disease patterns respond to diet and lifestyle changes whereas others do not. In certain cases, treatment with cholesterol lowering drugs is advisable.

Berkeley Lab -- where researchers first isolated lipoproteins in 1949 -- is one of the world's premier research labs in this field. The Lab was the first to identify subclasses of lipoproteins and to determine that the ratio of high density to low density lipoproteins is a strong indicator of heart disease risk. More recently, researchers here discovered a trait called "Pattern B." Found in 30 percent of adult men and 15 percent of post-menopausal women, Pattern B can triple an individual's risk of heart attack and cardiovascular disease.

Berkeley Lab Director Charles V. Shank noted that, more often than not, current cholesterol tests do not identify individuals who will develop heart disease. "This next generation of cardiovascular tests will screen for newly discovered risk factors. It has the potential to save many, many lives," said Shank.

Dr. Ronald Krauss, who heads Berkeley Lab's Cholesterol Research Center, says the new screening panel not only will benefit individuals but also will accelerate research progress.

"In terms of heart care," said Krauss, "this $3.8 million five-year contract will help us continue our efforts to identify and understand the genetic and metabolic factors that predispose individuals to cardiovascular disease. Our long term goal is to develop a panel of genetic tests that can be administered in childhood to identify risks."

Berkeley Lab will be able to refine its assays and develop additional diagnostic tools through access to Berkeley HeartLab test results, family medical histories, and the results of follow-up treatment of participants. Researchers will have the opportunity to further correlate traits identified during testing with the response to diet and other therapies. Over the long term, Berkeley Lab will build a database of large, at-risk families with shared traits. This database will help narrow the search for yet more definitive genetic markers of heart disease risk.

Currently, the typical blood lipoprotein analysis (aimed at assessing cardiovascular risk) is confined to total cholesterol, low-density lipoprotein cholesterol (LDL or bad cholesterol), high-density lipoprotein cholesterol (HDL or good cholesterol), and triglycerides. Risk factors identified by this series include elevated LDL levels and HDL values below 35 mg/dl.

The new lipid analyses, which health providers around the country can make available to patients through arrangement with the Berkeley HeartLab, consists of the above series plus these six additional tests:

  • LDL Particle Size -- Individuals have a mix of different sized LDL particles. LDL size patterns and the coronary risk associated with them are influenced by genetic factors. However, that risk can be modified by treatment. The LDL particle size test classifies people as predominantly small LDL (Pattern B) as versus predominantly large LDL (Pattern A). Pattern B dramatically increases risk and is found in an estimated 40 to 50 percent of heart disease patients. Individuals with Pattern B can reduce their risks significantly by reducing their dietary intake of fat. Conversely, healthy Pattern A individuals experience little benefit or even adverse effects from low fat diets.
  • Lp(a) -- Lp(a) is an LDL particle with an abnormal protein called (a) attached. Elevated Lp(a) levels increase the risk of heart disease three-fold and are not detected in routine blood work.
  • HDL Subclassification -- HDL particles likewise vary, with this test identifying HDL subclasses and their distribution. This information can help predict whether efforts to raise HDL levels in a particular patient -- through weight loss, exercise, and/or estrogen administration -- are more or less likely to be successful.
  • Apolipoprotein A-1 -- Apo A-1 is one of several proteins attached to the HDL particle. It may be a better predictor of heart disease risk than HDL levels.
  • Apolipoprotein E -- Apo E exists in normal and abnormal genetic forms. By identifying the form, this test indicates whether an individual is prone to develop excess blood lipids or has inherited an increased risk of heart disease independent of other know factors.
  • Apolipoprotein B-100 -- Apo B is a single protein attached to the LDL particle. This assay provides a more accurate indication of the relative number of LDL particles than does a standard LDL cholesterol blood test.

Because these tests are still considered investigative, physicians who receive the results will be able to consult with Dr. Krauss and the researchers at Berkeley Lab's Cholesterol Research Center. Physicians will then provide information about the clinical significance of the tests and the most appropriate and effective follow-up program for each patient.

Berkeley Lab conducts unclassified scientific research for the U.S. Department of Energy. It is located in Berkeley, California and is managed by the University of California.

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