Blood Test Looks for Type of Cell That Breaks Away From Artery Walls
By Brenda Goodman, MA
WebMD Health News
Reviewed by Louise Chang, MD
March 21, 2012 -- A new blood test could one day give doctors a critical head start on heart attacks, a small new study suggests.
The test looks for cells that normally line the insides of blood vessels. When those cells, called endothelial cells, start to build up in the blood, researchers say they may be an early indicator of trouble.
"When they start to leak and slough off into the blood, that's a really bad sign. They do that over the course of a few days to a couple of weeks before a heart attack occurs," says researcher Eric J. Topol, MD, a professor of genomics and director of the Scripps Translational Science Institute in La Jolla, Calif.
"As they continue to slough off, they basically create a crack [in an artery wall]. A blood clot forms to seal the crack. That's what causes a heart attack," Topol says.
In recent years, doctors have developed a new understanding of heart attacks.
They once thought that arteries clog for the same reason that drain pipes do. Gunk like cholesterol that flows through them gradually sticks to the inside walls, hardening over time and narrowing the artery opening. That's a process called stenosis, and that kind of buildup sometimes does lead to chest pain and heart attacks.
But more often, scientists believe heart attacks happen for a different reason: soft plaques.
Soft plaques are collections of liquid fats and debris that build up hidden away inside artery walls, almost like pimples.
When the layer of cells containing the plaque starts to thin, the plaque can break open. A blood clot forms in response to the plaque rupture. The clot is often what blocks the artery, causing a heart attack.
The problem with soft plaques is that they are hard to detect and may not cause any symptoms.
Indeed, 50% of men and 64% of women who die suddenly of heart attacks have had no previous symptoms of heart disease, according to the American Heart Association.
"Clearly the ability to predict plaque rupture and [heart attack] is one of the most difficult situations that we have in heart disease," says Barry Kaplan, MD, vice chairman of cardiology at North Shore University Hospital in Manhasset, N.Y. and Long Island Jewish Medical Center in New Hyde Park, N.Y.
Kaplan reviewed the study for WebMD but was not involved in the research.
The new test uses tiny, protein-coated magnets to pull circulating endothelial cells (CECs), which are normally rare, out of a blood sample.
Similar technology is used in a test for cancer patients. That test identifies circulating tumor cells, which are also rare. In cancer, the test is meant to help doctors and patients determine how aggressive a tumor may be or whether it is responding to treatment.
Study researcher Mark C. Connelly, PhD, director of cellular research at Veridex, the company that makes the test, declined to speculate on how much the experimental blood test might cost if it's used for heart attacks.
Researchers gave the test to 50 patients who were having major heart attacks that could be confirmed by changes to their heart's electrical rhythms and to key levels of enzymes that are indicators of heart damage.
They also gave the test to 44 blood donors who reported being free of any chronic disease.
Heart attack patients had levels of CECs that were more than four times higher than the levels seen in healthy blood donors.
There were other important differences, too. Under a microscope, the CECs seen in heart attack patients were larger and appeared to be stuck together in clusters, whereas the CECs in healthy people were smaller and appeared more often as single cells.
The study is published in the journal Science Translational Medicine.
Experts who were not involved in the study say the results are intriguing, but note that much more work is needed before such a test could be used to predict heart attacks.
"This is an interesting observation, but it fails to demonstrate that finding these cellular patterns in blood during stable, asymptomatic phases of [heart] disease actually will predict the future risk of a heart attack," says Prediman K. Shah, MD, director of the division of cardiology at Cedars-Sinai Medical Center in Los Angeles. Shah also directs atherosclerosis research at Cedars-Sinai.
"That's a fundamental flaw of the study. Maybe that will be their next study, but that's going to be a hard study to do," says Shah, noting that such a study would require following thousands of patients at risk for heart attack, rather than testing people who've already had one.
Other experts agree that the test has potential but needs more research.
"I think the key word is potential," says Suzanne Steinbaum, MD, a preventive cardiologist who directs the division of women and heart disease at Lenox Hill Hospital in New York City. "We're really looking at people who've already had heart attacks. Their theory is that if we can see these cells in people before they have a heart attack, can we really diagnose those that are at risk?"
If the test checks out in future studies, Steinbaum says it could have a major impact. "I think it would change the face of how we manage heart disease, in general. It's exciting to think about."
Until researchers get more answers, Kaplan says there are important things patients can do to reduce their risk of a plaque rupture.
"Number one is not smoking. The second is to keep cholesterol levels very low, particularly in patients who we know have coronary disease," he says.
"We know from studies that keeping cholesterol very low with diet and with statins decreases the risk of plaque rupture," Kaplan says.
The study was co-authored by doctors and scientists from Scripps Health; STSI; TSRI; Veridex, LLC (a Johnson & Johnson company), the manufacturer of the test used in the study; Palomar Health; and Sharp HealthCare. Funding came from a $2 million grant from the National Institutes of Health.
SOURCES: Damani, S. Science Translational Medicine, March 21, 2012. Eric J. Topol, MD, professor of genomics; director of the Scripps Translational Science Institute, La Jolla, Calif. Barry Kaplan, MD, vice chairman of cardiology North Shore University Hospital in Manhasset and Long Island Jewish Medical Center in New Hyde Park, N.Y. Mark C. Connelly, PhD, director of cellular research and development, Veridex, Raritan, N.J. Prediman K. Shah, MD, director, Division of Cardiology, director, Atherosclerosis Research, Cedars-Sinai Medical Center, Los Angeles, Calif. Suzanne Steinbaum, MD, director, Women and Heart Disease, Lenox Hill Hospital, New York, N.Y.©2012 WebMD, LLC. All Rights Reserved.
With the success of recent research in the area of genetics, doctors have been looking forward to bringing personalized treatment to their mesothelioma patients. By identifying specific genetic mutations, or biomarkers, within tumors doctors can target treatment according to the patient’s unique characteristics. For example, crizotinib has been found to be an effective drug for treating non-small cell lung cancer patients with tumors that express the abnormal anaplastic lymphoma kinase (ALK) gene. However, according to researchers in Great Britain, treatment based on genetic markers could fail due to genetic diversity within each tumor.
Personalized care has been touted as offering treatment options that might not otherwise have been considered. Personalized care also optimizes the potential for success of the treatment. Mesothelioma, an asbestos-caused cancer, currently has limited treatment options, but genetic science has promised to allow physicians to tailor treatment to individual patients based on their genetic makeup.
According to an article published in the New England Journal of Medicine (NEJM), though, genetic tests can be misleading. Depending on where on a tumor a biopsy is conducted, or whether it is from the primary or secondary tumor, the results could lead a physician down an incorrect path.
The researchers from the London Research Institute report that most often only one biopsy sample is taken to drive the course of treatment. But after they mapped the “genetic changes or faults in different regions of the same tumor” they believe physicians could miss the gene they had hoped to find to guide the patient’s treatment with just a single test.
The researchers analyzed kidney cancer tumors with samples taken from different regions of the primary tumor as well as biopsies from organs where the cancer had metastasized. They found that nearly 70% of the biomarkers differed across samples. This led them to conclude that these differences “may present major challenges to personalized-medicine and biomarker development.”
“We’ve known for some time that tumors are a patchwork of faults, but this is the first time we’ve been able to use cutting-edge genome sequencing technology to map out the genetic landscape of a tumor in such exquisite detail,” said Charles Swanton of University College London’s cancer institute who led the study.
In an editorial responding to the article, Dan Longo, MD, Deputy Editor of the NEJM, suggested the findings are a stark difference to the “overoptimism” in the field. He added that the drive toward personalized medicine may be more difficult than previously thought.
The researchers do not want the study to dampen enthusiasm for using genetically targeted therapies, however, they point out the focused treatment could become more costly. Mesothelioma advocates, although disappointed in the fact that personalized medicine may be more challenging, are encouraged that the findings now suggest physicians conduct multiple tests prior to subscribing to a particular treatment.