Jon VanZile
Friday, March 9, 2007

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A number of research companies have introduced new cholesterol tests that promise to revolutionize the way we measure and treat cholesterol — a breakthrough that may help identify many more potential heart attack victims.

Researchers now say the tests commonly used to measure cholesterol — widely considered the most important risk factor for heart disease that can be improved by lifestyle changes — are flawed.

For years, doctors have relied on a standard lipid panel, a blood test that measures lipid levels, to provide a risk analysis.

A typical lipid panel measures "good" HDL cholesterol, "bad" LDL cholesterol, total cholesterol, and triglycerides.

While these numbers are helpful, the tests often miss many people who are at risk for a heart attack. The tests also underestimate heart attack risk because of shortcomings in the way these numbers are calculated.

For example, a standard cholesterol test does not directly measure LDL, which is probably the most important single number in a cholesterol panel.

"The standard lipid panel often underestimates LDL, especially in people with high triglycerides," according to lipid researcher Kris Kulkarni, Ph.D., director of laboratory and research for Atherotech, Inc., in Birmingham, Ala. "Patients may be misclassified and undertreated."

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These new tests focus on lipoproteins, or the individual packages that actually carry cholesterol through the blood. The best way to think of lipoproteins is to think of them as vehicles, while the cholesterol molecules are passengers. Some of the vehicles are buses; some are sleek cars; some pick up passengers and some drop off passengers; and some are reckless drivers.

"A good example is the guy who has a heart attack even though he has a 'normal' lipid profile," said Dr. William Davis, a cardiologist with the Wisconsin Heart Hospital in Milwaukee, Wis. "He's told it's genetic, but it's really not. When you do a lipoprotein analysis, it's obvious what's wrong. It's very rare that there's not a discernible, correctable reason for heart disease."

A few measures in particular have gained attention for their ability to better predict heart disease. The LDL particle number is especially promising. This number tells a physician how many actual LDL particles are present in the blood, with no regard for their size or how much cholesterol is on each particle.

In some recent studies, LDL particle number has been the best overall predictor of heart attack risk, even better than age, race, or any lipid number, according to Michelle Turenne, director of professional advocacy for LipoScience, Inc., in Raleigh, N.C.

"We used to think that small LDL particles were more dangerous because they were small and could pierce the artery," Turenne said. "But it's not that they're small. It's that there's so many of them." Like a lottery, more LDL particles increase the odds of at least some cholesterol traveling into the artery wall and causing heart disease.

Besides LDL particle number, two other proteins have attracted attention for their ability to better predict heart disease risk.

Apolipoprotein B, or apoB, is a component of LDL cholesterol. In general, there is one apoB molecule for every LDL particle, meaning that researchers can indirectly figure out the LDL particle count by measuring apoB. Many studies have shown that apoB is superior to LDL when predicting heart attack risk.

On the other hand, apolipoprotein A-1, or apoA, is the main component of protective HDL cholesterol.

One emerging consensus is that the apoB/apoA ratio is a much better indicator for heart attack risk than standard cholesterol measurements because it provides a very accurate picture of the balance of good and bad cholesterol in the blood.

Here are the three most important new lipoprotein tests:

The Nuclear Magnetic Resonance (NMR) Test

Among these, the NMR test is likely to emerge as the "gold standard" of lipoprotein testing, according to Dr. Davis. "This is the same test as the magnetic resonance imaging [MRI] doctors use to diagnose diseases," said Dr. Davis. "It's just a smaller version. You can put blood into it and directly analyze the blood proteins." The NMR test measures LDL particle number, HDL and other lipids directly.

"It's very simple," says Turenne, who noted that her company has performed more than 2 million NMR blood tests since its introduction. "Studies have shown that LDL particle number is two to three times more strongly correlated to coronary events than LDL cholesterol, non-HDL cholesterol, and apoB."

In addition to identifying people who should be treated, the NMR test can also identify people who do not need to be treated so aggressively. In one recent study of diabetics, up to 25 percent of patients were being overtreated for cholesterol problems when in fact their LDL particle count was within normal ranges.

"I think the NMR provides a precision of diagnosis many times higher," said Dr. Davis. "Where it's especially helpful is among people who have somewhat low HDL and somewhat high triglycerides. For example, a man has HDL of 45 and triglycerides of 150. This would be normal by conventional definitions, but when you do a lipoprotein analysis, you find he has flagrant lipid abnormalities."

The Vertical Auto Profile (VAP) Test

The VAP test, developed by Atherotech, Inc., of Birmingham, Ala., offers the ability to test for lipo(a), as well as intermediate density lipoprotein (IDL) and actual LDL. Lipo(a) is an inherited trait that is closely linked to elevated risk for heart attack. Kulkarni estimates that his company performs 80,000 to 90,000 VAP tests every month.

One drawback to the VAP, according to Dr. Davis, is its inability to calculate the apoB/apoA ratio, as well as its inability to directly measure LDL particle number.

Gel Electrophoresis

The third lipoprotein test is known as gel electrophoresis. The test is offered by Berkeley HeartLab, Inc., in California. This test, which uses proprietary measurement techniques, offers additional insight to guide treatment by separating lipoproteins into seven subclasses of HDL.

The LDL and HDL gel testing is offered as part of a comprehensive baseline for CVD risk that reports 11 different test results and includes significant risk biomarkers such as Apo B, Lp (a), and Lp-PLA2.

"You can't just pin your hat on one biomarker and get an accurate picture of what's going on with any one patient," said Bruce Sadownick, director of marketing for Berkeley HeartLab. "By using a comprehensive panel, you have a much better chance of catching someone who needs intervention." One major issue with any new diagnostic test involves insurance and ability to pay for it. While all of these tests offer clearly superior information to a standard lipid panel, they are not all covered by insurance. The best way to see if an individual test is covered is to call your insurance company before undergoing the test.

© NewsMax 2007. All rights reserved.

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