Normal, healthy circulating endothelial cells, left, are smaller and… (Scripps Translational…)
Doctors are one step closer to a simple test that could predict whether a patient is about to have a heart attack — by using a blood sample to detect cells that have sloughed off of damaged blood vessel walls.
The finding, published Wednesday in the journal Science Translational Medicine, could potentially address "the greatest unmet need" facing cardiologists, said lead author Dr. Eric Topol, a cardiologist at the Scripps Translational Science Institute in San Diego. Though physicians can easily detect a heart attack that's already underway, every year tens of thousands of patients walk away from the doctor's office after having passed a stress test, only to suffer a devastating heart attack within a few weeks.
Topol called the phenomenon the "Tim Russert syndrome," referring to the newsman who died of a heart attack in 2008, weeks after undergoing a stress test with apparently normal results.
"When someone is having the real deal, we know that," Topol said. "The real question is, is something percolating in their artery? We'd like to prevent the heart attack from happening," or mitigate its effects with drugs.
The new technique involves tracking a type of cell in the blood called a circulating endothelial cell.
Endothelial cells create a wrapper that lines the inside of blood vessels. When the vessel is damaged, endothelial cells break away and enter the bloodstream.
Healthy people have very few of these circulating cells. But a person with mild cholesterol buildup can develop a crack in an artery wall that disrupts the lining and sends them into the blood.
A heart attack occurs when an area of plaque ruptures in an artery, forming a blood clot that blocks blood flow to the heart, resulting in heart tissue damage.
Ruptures resulting from mild cholesterol buildups can lead to particularly deadly heart attacks, said Dr. Douglas Zipes, a cardiologist at the Indiana University School of Medicine in Indianapolis, because patients with such blockages are often asymptomatic, and — unlike people with larger blockages — are unlikely to have developed new blood vessels that can help bypass the obstruction.
Knowing that the endothelial lining has been damaged before a blood clot grows might allow physicians to predict onset of a heart attack or stroke, said Zipes, who was not involved in the study.
Scientists reported the detection of circulating endothelial cells in heart attack patients in 1999 but didn't have the technology at that time to isolate the cells and properly study them. Newer tools allowed the Scripps team, working with a variety of institutions in the San Diego area, to examine the cells more closely.
The team studied blood samples from 50 patients with confirmed heart attacks and 44 healthy control patients. First they established that the heart attack patients had more circulating endothelial cells in their blood — 19 cells per milliliter, on average, versus four in healthy individuals.
The researchers next explored whether there were differences between the circulating endothelial cells of healthy people and those of heart attack patients. There were: Cells from the heart attack group were clustered together and large, and had multiple nuclei (organelles in the cell that hold the DNA).
Topol attributed the bizarre appearance of the cells to the effects of profound inflammation in the damaged arteries.
"These cells shouldn't be in the blood. If you have them, you have trouble lurking," he said.
Cardiologists not involved in the study said they were excited by the findings.
"We do prostate tests, we do cholesterol tests," said Zipes. "Perhaps we should have [circulating endothelial cell] tests too, in people at risk."
Dr. Robert Harrington, a professor of medicine at Duke University, added that the research is helping scientists understand the biology of heart attacks. But he cautioned that more study was needed to flesh out and confirm the results, and to prepare a test for patients. The methods presented in the Scripps research may be too complicated for use in a doctor's office or an emergency room, he said.
One key detail yet unknown is how long before a heart attack the circulating endothelial cells appear.
"Is it a day before? A week before? That would be good to understand," Harrington said.
Topol said research into the abnormal cells had allowed his team to obtain a genetic signature for them. That should help development of a simple blood test, he added, perhaps within a couple of years.