Quintet of proteins could form new, early warning blood test before MI strikes

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NEW ORLEANS—Johns Hopkins biochemists have identified a mixed bag of five key proteins secreted into blood draining from the heart's blood vessels that may together or in certain quantities form the basis of a far more accurate early warning test than currently in use of impending MI in people with ischemia, according to data presented Sunday at the American Heart Association (AHA) Scientific Sessions.

“From the start, we knew that we were looking for rare, almost unique biomarkers that bore some direct relationship with ischemia,” according to study senior investigator and presenter Jennifer Van Eyk, PhD. She said the first step was to remove from the analysis common blood proteins, such as albumin and globulins, which left batches of 400 proteins for measure of any changes before and after ischemia.

The researchers found that only the five proteins were present in significantly increased amounts after ischemia occurred, with at least a doubling in the blood concentration, compared with those recorded during healthy blood flow. She reported that these were lumican, semenogelin, angiogenin, extracellular matrix protein and so-called long palate, lung and nasal epithelium carcinoma-associated protein 1.

Van Eyk said that the presence of all or even a selected set of the proteins in a rapid blood test could aid emergency paramedics and physicians during the critical 12- to 24-hour window before ischemia causes substantial heart tissue damage or death from MI.

A positive reading on a blood test incorporating the proteins, she said, could provide first responders with advance warning to take urgent action, such as using blood thinners like aspirin to prevent clotting, or performing cardiac catheterization to check for any more blockages in the blood vessels feeding the heart, which may in turn prompt more aggressive treatment.

“Our results lay the foundation for a first-of-a-kind, early-warning system that could save tens of thousands of people on the brink of a heart attack,” said Van Eyk, a professor at the Johns Hopkins University School of Medicine in Baltimore and its Heart and Vascular Institute. "People experiencing chest pain too often come to the emergency room, with subsequent EKG readings not showing any evidence that a heart attack has occurred, but still leaving open the question of whether or not a heart attack is imminent and about to happen or has already happened.”

Van Eyk said that people frequently have symptoms of chest pain, shortness of breath and dizziness, with pale or clammy skin coloring, while arterial blood is constricted but not yet closed. But these symptoms can “easily be mistaken for the more everyday, less-serious problems of heartburn, stomach cramps or gas.”

A new test based on the five proteins, she said, could provide a "more definitive answer" to the question "how serious is it?" much earlier than existing assays for heart attack, such as tests for troponin proteins I and T.

Van Eyk said commercially available tests for cardiac troponin, which is released into the blood in patterns for MI, provide results “too late to take preventive action and after some damage has already occurred.” Troponin lab tests also depend on the heart muscle dying first, which can take hours to detect. “So a negative reading is unreliable and can still mean that an ischemic problem is about to happen or has already happened,” she added.

The researchers plan to verify the presence of the five proteins in a larger study with at least 150 participants, and more than 1,000 blood samples. Simultaneously, they are planning further analysis of the proteins to map their molecular structures, so that an antibody can be identified to bind to one or several of the proteins, laying the basis for a blood test for ischemia, according to Van Eyk.