IVD Technology Magazine
IVDT Article Index

Originally published September, 1998

IVD Technology News

New heart disease marker on the way?

In the search for a benchmark of heart disease risk, cholesterol levels have long been the marker of choice. But researchers are hot on the trail of new markers that may prove to be even better indicators of impending heart disease.

Current tests measure total cholesterol and can further quantify the levels of both "good" high-density lipoproteins (HDL) and "bad" low-density lipoproteins (LDL). But clinicians have long questioned the utility of such measurements as indicators of disease. "The majority of people who have heart attacks have what is considered normal cholesterol," says Ishwarlal Jialal, PhD, an associate professor of pathology at the University of Texas (UT) Southwestern Medical Center (Dallas).

Now, results of a UT study conducted by Jialal and his colleagues suggest that a form of cholesterol called remnant-like particle (RLP) lipoproteins may hold the key to risk assessment for coronary artery disease. Of the 86 men included in the study, the 63 with symptoms of heart disease had 33% higher levels of RLP than the 23 control subjects.

The connection between RLP and arteriosclerosis was discovered to be especially close for patients with Type III dyslipidemia, a genetic disease that elevates RLP and LDL cholesterol levels and causes severe arteriosclerosis. In the UT study, RLP levels in these patients were found to be 24 times higher than in the healthy control subjects.

To measure RLP levels, the investigators used an RLP cholesterol assay developed by Japan Immunoresearch Labs (Takasaki, Japan). The assay uses antihuman apo A-1 and apo B-100 monoclonal antibodies in an immunoaffinity sepharose gel. When 5 µl of human serum is mixed with the gel, the antibodies bind all apo B–containing lipoproteins and HDL forms of cholesterol. After a 2-hour incubation, the gel is allowed to settle in the reaction tube. The remaining supernatant is highly enriched for remnant lipoproteins, or RLPs.

Jialal and his colleagues then ran the RLP supernatant in a peroxidase-based cholesterol assay using a Cobas Mira S autoanalyzer (Roche Diagnostic Systems, Montclair, NJ). Since the gel removed all other forms of cholesterol, cholesterol levels in the supernatant represent RLP levels.

The RLP assay is currently approved for use by physicians in Japan. A UT spokesperson says that the assay has been submitted to FDA and is expected to be approved sometime this fall.—Gary Woo