Diabetes Forecast

Meet LDL's Partner in Plaque

ApoB puts the "bad" in bad cholesterol

By Erika Gebel, PhD ,

Look out LDL cholesterol: There's a new villain in town. Not that LDL's bad reputation is being challenged; far from it. But, especially for people with diabetes, measuring the amount of the protein "apoB" in the blood provides extra—and possibly superior—insight into cardiovascular disease. A consortium of diabetes experts convened by the American Diabetes Association has just released a statement encouraging doctors to test their patients who are on cholesterol- lowering therapy for apoB.

When people think of LDL, usually cholesterol comes to mind. But technically, the cholesterol is just one part of a larger fat and protein cluster called either simply LDL or the LDL "particle." LDL, or low-density lipoprotein, circulates in the blood, increasing the risk of cardiovascular disease. High-density lipoprotein, or HDL, on the other hand, also carries fats in the blood but has a different makeup than LDL; having more of it seems to reduce cardiovascular risk. So that's why your doctor wants you to raise your HDL and lower your LDL.

And yet, in several large clinical trials, apoB predicted heart attacks and disease better than LDL cholesterol. But why, if it's not the cause? Well, in a sense, apoB is what puts the "bad" in bad cholesterol. Cholesterol itself isn't innately good or bad, it's just one molecule: four adjacent polygons and a greasy tail. In fact, it has many useful effects, such as making cell linings or being a building block for hormones and some vitamins. Whether cholesterol is "good" HDL or "bad" LDL depends not on its structure, but on the company it keeps. Cholesterol found with apoB becomes bad.

A boatload of bad news

LDL cholesterol and a crew of other water-averse fat moblecules gel around apoB, forming something like a microscopic oil droplet: the LDL particle. Such particles are like boats that sail the bloodstream, collecting and delivering their cargo throughout the body. There are several particle types, including the "good" HDL particle, which carries HDL cholesterol and has a different protein at its helm. ApoB is the protein captain of the LDL particle.

LDL particles carry the heaviest cholesterol load and deal mostly in distributing it to cells, which use the cholesterol for a variety of essential life processes. HDL particles, by contrast, retrieve overstock cholesterol from cells. When cells overload on LDL particles, they gum up with cholesterol, causing the formation of arterial plaques that can hinder blood flow, sometimes leading to the clots that precipitate heart attacks and strokes.

The LDL cholesterol level gives doctors a general idea of how many LDL particles are around. "Guideline after guideline, LDL is the first thing to check," says Barbara Howard, PhD, of the MedStar Research Institute and one of seven authors on the lipoprotein consensus statement. But it's not perfect, because LDL particles carry varying amounts of cholesterol. For example, two small LDL particles could carry the same amount of cholesterol as one large particle. According to the LDL cholesterol level, the cardiovascular risk is the same for these two scenarios. However, since risk is related directly to LDL particle number, a person with more, though smaller, particles is at greater risk than a person with fewer, though larger, particles.

People with diabetes have a preponderance of small LDL particles, for reasons not fully understood. And that means that looking only at LDL cholesterol will tend to underestimate cardiovascular risk. Measuring the apoB gives doctors and patients an edge. Unlike the varying cholesterol quantities, LDL particles have only one apoB molecule each. So, measuring the apoB lets doctors count LDL particles and get a better sense of the actual cardiovascular risk.

Yet checking apoB is a bit more expensive and less common than testing for LDL cholesterol. For diabetes patients, though, the extra effort and cost may be well worth it, some experts say. "It is people with diabetes who … are at the highest risk" for cardiovascular complications, says Howard. For them, she says, doctors should measure all that they can to assess risk. "That is where apoB comes in."

According to Howard, the test was recently made available at all Veterans Affairs hospitals. "It's become cheaper and better standardized in many places, though not in all places," she says. Meaning that apoB may finally make a name for itself—even if it is a "bad" one.

The New Math

A consensus statement from diabetes experts recommends the following targets for people with diabetes:

  • ApoB: less than 90 mg/dl

(If you have cardiovascular disease [CVD] or an additional risk factor for CVD: less than 80 mg/dl)

  • LDL cholesterol: less than 100 mg/dl

(If you have CVD or an additional risk factor: less than 70 mg/dl)

Ideal values for HDL and triglycerides:

  • HDL cholesterol:

women: more than than 50 mg/dl
men: more than 40 mg/dl

  • Triglycerides: less than 150 mg/dl


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