ApoB: a better marker for heart disease risk than "bad" cholesterol

American Heart Association
Tuesday, 28 October 2003

A cholesterol component called apolipoprotein B may be more strongly linked to several heart disease risk factors than the LDL cholesterol for which millions of Americans are screened each year, researchers report in today's rapid access issue of Circulation: Journal of the American Heart Association.

The National Cholesterol Education Program (NCEP) and the American Heart Association recommend therapy to reduce heart disease risk based on blood levels of low-density lipoprotein (LDL) cholesterol. It is considered "bad" cholesterol because it contributes to the buildup of atherosclerotic plaque in artery walls.

This study indicates that apolipoprotein B (apoB) may be a better predictor of cardiovascular disease risk. It's the first study to explore LDL and apoB levels in an ethnically diverse population, said Steve Haffner, M.D., professor of medicine at the University of Texas Health Science Center, San Antonio, and co-author of the study.

LDL carries most of the cholesterol in the blood, but LDL particles come in various sizes. Research has shown that small, dense LDL particles are more often associated with atherosclerosis than large, "fluffy" LDL particles. Current cholesterol tests measure LDL indirectly, by measuring the cholesterol portion of the LDL molecule rather than its protein portion. This does not gauge the size or number of LDL particles. However, measuring apoB, which is a component of the protein portion of LDL, indicates the number of LDL particles. That can indicate whether a patient's cholesterol profile has more of the small, dense and dangerous sort, Haffner said.

The researchers examined 1,522 people in the Insulin Resistance Atherosclerosis Study, which examined links between abnormal blood sugar metabolism and the development of heart and blood vessel disease. It included African-Americans, Hispanics and non-Hispanic whites. All of them had high levels of triglycerides, components of total cholesterol that often occur along with low levels of high-density lipoproteins (HDL), the so-called "good" cholesterol carrier. HDL helps keep cholesterol from accumulating in the artery walls.

The researchers divided the participants into several groups according to their LDL and apoB levels. Participants were examined for a range of cardiovascular disease risk factors such as abdominal obesity, the inflammatory marker C-reactive protein, clotting factors fibrinogen and plasminogen activator inhibitor-1, insulin concentrations and the thickness of the lining of the carotid (neck) arteries that lead to the brain (an easily visualized marker for thickening of the vessels throughout the body).

Of the people studied, 942 met the criteria for treatment based on LDL levels. Eighty five percent of that group (801) also had elevated apoB. Of the 580 participants who did not fit the LDL profile for treatment, 25 percent (147) had elevated apoB.

The results were consistent across ethnic groups, Haffner said.

Researchers noted that a total of 288 people in the study group (19 percent) would have a different treatment recommendation if apoB were used to guide treatment rather than LDL.

Researchers said they were most concerned about the 147 people with normal LDL and elevated apoB. They were more likely to have abdominal obesity, high blood insulin levels and clotting factors compared to people with high LDL and normal apoB levels. All of these factors also contribute to the metabolic syndrome.

"These patients don't just have a cholesterol problem, they have an insulin-glucose metabolism problem," said co-author Allan D. Sniderman, a professor of medicine at McGill University, Montreal in Canada. "This is the first study to my knowledge that ties the abnormal insulin-glucose metabolism to high triglycerides with high apoB."

He noted that LDL is still an important marker for heart disease risk.

"We are not proposing that we should throw out LDL cholesterol testing. But we're going beyond LDL cholesterol and we're getting more precise," Sniderman said. "The question is which parameter should you rely on: the one that tells you the most (apoB) or the one that you've been using the longest (LDL)."

Testing apoB may also be a good way to determine whether cholesterol-lowering drugs are working. The test is now standardized, accurate, inexpensive and does not require fasting, as does the LDL-C test, he said.

The American Heart Association does not currently recommend apoB testing. However, Association spokesperson Alice Lichtenstein noted: "This is an important observation and needs to be considered carefully in light of prior data to determine whether current guidelines should be modified to recommend routinely measuring apoB levels in high risk individuals."

Canada began recommending the apoB test in its national guidelines about two years ago and is currently updating the country's guidelines for lipids (blood fats) and diabetes to include the apoB test, he said.

Other co-authors are Ken Williams, M.S.; Naveed Sattar, M.D.; Ralph D'Agostino Jr., M.D. and Lynne E. Wagenknecht, Ph.D.

The study was partly funded by the National Heart, Lung, and Blood Institute.

For more information, or to contact American Heart Association, see their website at: www.americanheart.org