A Test That Could Predict Heart Attacks

March 2014

One in three people who have a heart attack die before reaching the hospital. However, it's hard to know your risk of having an attack – even moments before one occurs.

At The Scripps Research Institute (TSRI), a team led by Associate Professor Peter Kuhn has developed a new test that could identify patients who are at high risk of having a heart attack in the upcoming days or weeks. They could then be given a potentially life-saving treatment to prevent the heart attack from occurring.

Peter Kuhn

TSRI Associate Professor Peter Kuhn

"There are plenty of other ways to suggest that you are at long-term risk of a heart attack, and there are good ways of diagnosing that you have just had a heart attack – but what we don't have is the ability to say, 'You will very likely have a heart attack in the next three weeks and we need to do something about this now,'" said Dr. Kuhn.

Cells known as endothelial cells line the walls of the arteries, and these cells have been strongly linked to ongoing heart attacks when circulating in the bloodstream. The new test works by looking for these circulating endothelial cells (CECs). They are thought to arrive in the blood stream when diseased plaque that has built up in arteries ruptures and ulcerates, causing inflammation. This damage can cause blood clots to form, which prevents blood from flowing through the arteries and ultimately results in a heart attack.

The TSRI team has developed a new "fluid biopsy" test, called the High-Definition Circulating Endothelial Cell (HD-CEC) assay, that can identify CECs in a patient's bloodstream. The team used it on the blood samples of 79 patients who had recently experienced a heart attack at the time of sampling. For comparison, they also used the assay on two control groups, which consisted of 25 healthy patients and seven patients undergoing treatment for vascular disease. The technique successfully distinguished the patients undergoing treatment for a recent heart attack from those in the healthy control group.

"The goal of this paper was to establish evidence that these circulating endothelial cells can be detected reliably in patients following a heart attack and do not exist in healthy controls – which we have achieved," said Dr. Kuhn. "Our results were so significant relative to the healthy controls that the obvious next step is to assess the usefulness of the test in identifying patients during the early stages of a heart attack."

The assay was able to identify CECs by their morphological features and their reactions with specific antibodies. The cells were shown to be significantly elevated in the heart attack patients compared to the healthy controls and were detected with high sensitivity and high specificity.

The researchers also compared their results with a commercially available test, called CellSearch®, which has previously been approved by the U.S. Food and Drug Administration (FDA) to enumerate circulating tumor cells in cancer patients. The team's new HD-CEC test showed a higher specificity for CECs compared to CellSearch® because it used a direct analysis method. "Our assay effectively analyzes millions of cells, which is more work but guarantees that you are analyzing all of the potential cells," said Dr. Kuhn.

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