Apolipoprotein B may be more strongly linked to several heart disease risk factors than low-density lipoprotein cholesterol, according to an article in the October 28th rapid access issue of Circulation.

U.S. practice guidelines recommend therapy to reduce risk based on blood levels of low-density lipoprotein cholesterol. The current study, which is the first to explore both low-density lipoprotein cholesterol and apolipoprotein B in an ethnically diverse population, indicates that apolipoprotein B may be a better predictor of risk for cardiovascular disease, according to lead author Steven Haffner, M.D.

Current cholesterol tests measure low-density lipoprotein cholesterol indirectly, by measuring the cholesterol portion of the low-density particle rather than its protein portion. This does not actually assess the size or number of low-density lipoprotein particles. However, measurement of apolipoprotein B indicates the concentration of particles in the blood, and this may be a better measure for risk.

The researchers examined 1,522 people in the Insulin Resistance Atherosclerosis Study, which examined links between abnormal glucose metabolism and the development of cardiovascular disease. All participants had high levels of triglycerides.

Participants were divided into several groups according to their low-density lipoprotein and apolipoprotein B levels. All subjects were examined for a range of cardiovascular disease risk factors such as abdominal obesity, C-reactive protein, fibrinogen and plasminogen activator inhibitor-1, insulin concentration, and thickness of the carotid artery walls.

Of the people studied, 942 met criteria for treatment based on low-density lipoprotein cholesterol levels. In that group, 85 percent (801 people) also had elevated levels of apolipoprotein B. Of the 580 participants who did not fit the low-density lipoprotein profile for treatment, 25 percent (147 people) had elevated levels of apoplipoprotein B, findings that were consistent across ethnic groups (primarily Caucasian and African Americans).

In the article, the authors addressed concerns regarding the 288 people in the study (19 percent) who would have had a different treatment recommendation if apolipoprotein B were used to guide treatment--- especially the 147 people with normal low-density lipoprotein levels but elevated apolipoprotein B levels.

These 147 participants were more likely to have abdominal obesity, high blood insulin levels and clotting factors than were participants with high levels of low-density lipoprotein LDL and normal levels of apolipoprotein B, all three traits contributors to metabolic syndrome.

“These patients don’t just have a cholesterol problem, they have an insulin-glucose metabolism problem,” said coauthor Allan D. Sniderman, M.D. “This is the first study to my knowledge that ties the abnormal insulin-glucose metabolism to high triglycerides with high apoB.”

Sniderman noted that low-density lipoprotein is still an important marker for heart disease risk. “We are not proposing that we should throw out low-density lipoprotein cholesterol testing. But we’re going beyond low-density lipoprotein cholesterol and we’re getting more precise. The question is which parameter should you rely on: the one that tells you the most (apolipoprotein B) or the one that you’ve been using the longest (low-density lipoprotein cholesterol).”

Measurement of apolipoprotein B 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 low-density lipoprotein cholesterol test.

Although the American Heart Association does not currently recommend testing for apolipoprotein B, Canada recommended testing in its national guidelines about 2 years ago and is currently updating the country’s guidelines for lipids and diabetes to include testing for apolipoprotein B.