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Screening
for Vulnerable Plaque: Not Ready for Prime Time
By
TCTMD
Tuesday, October 14, 2008
By TCT Daily Staff
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Traditional risk
factor-based screening to identify vulnerable patients fails
miserably, contended Morteza Naghavi, MD, of the Society for
Heart Attack Prevention and Eradication (SHAPE) in Houston,
and proponent of the SHAPE guidelines that recommend
screening asymptomatic people.
Cardiologists face two major
problems, Naghavi said. One is obtaining an accurate risk
assessment for apparently healthy people. He illustrated the
dilemma by pointing to the different fates of a
cigar-smoking, overweight Winston Churchill and the runner
Jim Fixx, who was very fit. Churchill did not suffer a major
event until age 90, while Fixx died of a massive MI at age
53. |
The other problem involves patients who do not respond to treatment,
as illustrated by the case of the late journalist Tim Russert.
To make his point about risk stratification, Naghavi proposed a
thought experiment: Take a group of patients who arrive at the ER
with no prior MI, CAD, diabetes, or other symptoms. Turn back the
clock 24 hours, and run them through the existing NCEP guidelines
for risk stratification, and only about 12% fall into the high-risk
category and about half would not even qualify for treatment.
Approximately 70% of people would have been categorized as low risk,
Naghavi said.
This kind of analysis inspired the SHAPE task force to focus on
combining functional assessments with structural assessments, such
as the evidence-based coronary calcium score and carotid intima
medial thickness measurement. This approach is better able to
identify people who are most vulnerable, said Naghavi. "You identify
the disease and you treat based on the severity of the disease," he
added.
There is growing evidence from IVUS and a variety of other imaging
techniques that local disease in asymptomatic people often causes
trouble, Naghavi said. "Should we wait? Or should we do something
about it?" he asked.
Finally, Naghavi lamented the relative lack of awareness of and
economic support for screening for cardiovascular disease, which is
the number one killer in the United States, ahead of cancer and
accidental deaths combined. Yet the federal budget allocates about
$1,000 per patient for cancer screening compared to just $50 per
patient for cholesterol and blood pressure screening.
Broadening the understanding of vulnerable plaque
According to Bernard De Bruyne, MD, PhD, of the Cardiovascular
Center in Aalst, Belgium, screening for vulnerable plaque is
"premature, too costly, and unproven." Nonetheless, he said, he
believes in the concept of vulnerable plaque. People who are at high
risk and not being protected by optimal medical treatment should be
targeted for treatment of local plaque. But, he emphasized, we are
still a long way from accurate identification of such plaque and
even farther from identification to effective treatment.
To begin with, the definition of "vulnerable plaque" is very loose,
De Bruyne said, and many aspects of the phenemenon are
underappreciated. For example, many people believe that thin cap
fibroatheroma is the only pathological substrate for acute
thrombotic occlusion. But there are many other culprits, he
observed. For example, erosion of an atheroma is responsible for up
to 30% of cases of ACS in women and diabetics. Another misconception
is that vulnerable plaque is mostly non-stenotic and hemodynamically
insignificant, he said. But there is good reason to suspect that in
many patients with AMI, the stenosis is not benign. In a recent
study in which careful quantitative coronary angiography was
performed on patients with ACS, the vast majority were found to have
significant stenosis underneath their thrombus. It is important to
realize that these lesions induce a gradient, said De Bruyne, and
that over time this force can contribute to plaque fatigue and
rupture. In addition, when the lesion encroaches on the lumen, an
area of low shear stress develops around the lesion that promotes
plaque destabilization. In short, De Bruyne said, there is
"cross-talk" among the hemodynamic, rheological, and biological
contributors to vulnerable plaque.
The noninvasive technique that has been most used to assess
vulnerable plaque is virtual histology, De Bruyne said. Recent
promising results with an inhibitor of progression of the necrotic
core in the IBIS 2 (Integrated Biomarker and Imaging) study do not
mean that virtual histology is anywhere near being a reliable
surrogate for clinical endpoints — but it is a step in the right
direction, he said. Noninvasive techniques are critical to
unraveling the natural history of vulnerable plaque, which remains
largely unknown.
It is also crucial to match imaging data with clinical outcomes. And
then, of course, to find effective treatment, which means proving
that local treatment is safer and more effective than the best
medical therapy available. Unfortunately, with mild stenosis, the
rate of events is typically low, so that achieving a favorable
treatment-to-benefit ratio may be difficult.
Despite his many caveats, however, in a nod to Naghavi’s project, De
Bruyne said he keeps a copy of the SHAPE guidelines on his desk when
seeing patients.
Disclosures:
Dr. Naghavi reports being a founder and shareholder of Endothelix
Inc. and Volcano Corp.
Dr. De Bruyne reports no relevant conflicts of interest.
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