Proteins predict heart attack in advance

By: Tiffany Ng

Posted: 12/4/08

Hopkins researchers have identified five proteins that are released when blood flow to the heart is severely decreased. These proteins could allow physicians to develop a test for an imminent heart attack in people with reduced blood flow, or ischemia.

The researchers, led by Jennifer Van Eyk of the Hopkins Proteomics Center, analyzed blood samples from patients before and after a bout of ischemia.

"We ran a mass spectrometry continuously for about six months," Van Eyk said, describing the extremely demanding and time-consuming process required to identify the proteins present in the blood. Mass spec determines the mass-to-charge ratio of the fragments of a compound, from which one can determine its exact composition.

In this case, the proteins found in pre- and post-ischemic blood were identified and their relative concentrations were compared. Of the thousands of different proteins present, they found five proteins in particular whose concentrations increased dramatically after the ischemia had occurred.

These five proteins are lumican, semenogelin, angiogenin, extracellular matrix protein and (deep breath) long palate, lung and nasal epithelium carcinoma-associated protein 1. These proteins are thought to have roles in tissue growth and immunity.

When ischemia occurs, time is of the essence. If left untreated, the reduced blood flow can result in permanent heart tissue damage, a potentially fatal heart attack, or in scientific terms, a myocardial infarction (MI). This occurs when part of the heart tissue dies from a lack of oxygen.

The detection of these proteins through a simple blood test could quickly and effectively alert EMTs or ER physicians to the condition of the patient, and what treatment is necessary. Oftentimes, when a patient experiences chest pain, an electrocardiogram (EKG) is not enough to determine whether the patient has already had a heart attack or is about to have one.

Furthermore, patients coming into the emergency room may be misdiagnosed. According to Van Eyk, "If you come in with chest pain, it could also be a pulmonary embolism or heartburn."

A blood test based on these five key proteins would provide clear answers to the severity of the patient's condition. Current tests use the release of troponin immediately prior to a heart attack to gauge its severity. "However, troponin is only found in the heart, and by the time it is found in the blood, the heart muscle is already injured," Van Eyk said.

Since the five proteins are released further in advance of a heart attack, before the release of troponin, this gives physicians more time to take preventative measures. "The impact in the emergency ward would be quite astounding," Van Eyk said. Physicians could intervene and administer blood thinners, check for additional blockages to the heart's blood vessels, or even perform surgery.

This test could also reduce the risk of a recurring heart attack. "After a few hours, the patient is released to go back home, but a percentage of people end up having another heart attack within 24 hours," Van Eyk said. A pre-troponin test would subdivide patients into groups to identify those at high risk so they can be monitored more closely.

Heart disease is the leading cause of death worldwide and is responsible for one in every three deaths in the United States. Heart disease refers to a very broad range of conditions including stroke, arrhythmia and ischemia. Heart attacks account for one in every five deaths in America.

The Hopkins scientists hope to expand their research to identify proteins that are associated with stroke. These findings will allow physicians to quantitatively judge the patient's risk for heart disease-related incidents, and improve the prognosis of patients suffering from heart disease.