One option for a more complete profile
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Are fully automated tests for the direct measurement of low-density lipoprotein cholesterol the way to go?
Atherotech thinks so. The Birmingham, Ala.-based company promotes
its test as a sizable improvement over the routine calculation approach
because it offers direct LDL measurement as opposed to traditional
measurement, which calculates LDL based on directly measured total
cholesterol, HDL, and triglycerides, or the Friedewald equation.
"The problem with the Friedewald LDL is that it gives you a falsely
low LDL. The higher the triglycerides, the more falsely low this
calculated LDL gets. Most clinicians know that when the triglycerides
are 400, they don’t even report an LDL anymore," says Richard Lanman,
MD, chief medical officer for Atherotech. "But what most doctors
don’t realize is that at 200, there still might be five to 10 percent
falsely low calculated LDL results."
Atherotech’s VAP II (vertical auto profile) technology measures
two characteristics of lipoproteins—density and cholesterol
content—using a combination of ultracentrifugation and spectrophotometry.
The technology was developed in the early to mid-1990s, says Dr.
Lanman, and is innovative for its ability to measure the cholesterol
in seven HDL subclasses, four LDL subclasses, and three very-low-density
Dr. Lanman reports that the PROCAM study (Prospective Cardiovascular
Münster Study) has found that adding direct measurement of LDL (as
the VAP II does), adding also Lp(a), and including family history
of premature heart disease in traditional testing can increase the
detection rate to 83 percent. By including information on the size
and density of LDL particles, 90 percent is closer to the mark,
Small/dense LDL particles are more atherogenic than just having
a high LDL cholesterol reading, he says, noting that half the men
who have heart attacks have a small/dense LDL—a fact that
would not be revealed by a traditional lipid panel. "If you know
the LDL particles are small and dense, you can add 15 to 20 percent
to the detection rate over the 30-year-old traditional lipid panel,"
The VAP test includes measures of the remnant lipoproteins IDL
(intermediate-density lipoprotein) and VDL3
(small/dense VLDL). These particles also are highly atherogenic.
ATP III mentions that Lp(a) and remnant lipoproteins may be an emerging
risk factor to help guide treatment decisions. "If you combine several
key risk markers—direct LDL, Lp(a), small/dense LDL pattern,
IDL, HDL2—you can raise
your ability to detect risk to 90 percent from 50 percent with the
traditional panel," Dr. Lanman says.
For people with an indication for a comprehensive evaluation of
heart disease risk, this should be the test of choice, he adds.
"The people we’re studying are the very patients whose calculated
LDLs would be falsely low because of triglycerides, so they are
being underdetected and undertreated."
But the test could also be valuable for people at age 20 who have
no apparent risk factors. "A lot of heart scans won’t be positive
until relatively late in the development of atherosclerosis," says
Dr. Lanman. "So let’s say you’re 20 and want to know how seriously
you should diet and exercise. With your VAP panel, you might find
an abnormality and know you’re at higher risk. It’s a very inexpensive
way to understand who needs to get serious about diet and lifestyle."
Herbert Naito, PhD, of the Veterans Affairs Medical Center, Cleveland,
believes the new cutpoints for HDL in the ATP III report are important.
"But I think where we have a misunderstanding going on in the medical
community is the role of triglycerides and LDL cholesterol in ruling
out metabolic disease," he says. "I think it’s very important and
very complicated, and the medical community has misunderstood it
and not used the tests accurately." Atherotech’s system, he adds,
addresses that measure because it guides clinicians through the
process of ruling out metabolic syndrome, a prediabetes-like condition.
Atherotech doubled and redoubled in size last year as it began
marketing its commercialized version of the test, which has been
scaled down to make the cost comparable to a traditional lipid panel.
The test is covered by Medicare at a payment of about $49 per panel
and under a national agreement with Blue Cross Blue Shield at $68.