News Release

Clotting protein may be link to heart disease

Peer-Reviewed Publication

American Heart Association

DALLAS, Oct. 3 – A little known clotting protein called fibrinogen may be the missing link between heart disease risk factors, such as smoking and high cholesterol, and heart attacks, according to a study in today’s Circulation: Journal of the American Heart Association.

Fibrinogen, a protein produced in the liver, has a pivotal role in the formation of blood clots. A number of factors -– particularly cigarette smoking – increase fibrinogen levels. Higher levels are also seen with advancing age, obesity, physical inactivity and diabetes. Elevated cholesterol is also associated with high fibrinogen, and genetic factors play a role as well.

When subjects in a prior study were divided into three groups, participants with the highest fibrinogen levels were shown to have a 2.3-fold greater risk of coronary disease and heart attack than those in the lowest third.

Here, researchers used a newly developed test called FIF (Functional Intact Fibrinogen) to check fibrinogen levels in 2,632 participants in the Framingham Offspring Study – a continuation of the famed Framingham Heart Study begun more than 50 years ago.

“We not only found fibrinogen levels to be higher in people with heart disease but it also seems to be a common pathway by which other risk factors cause heart disease,” says one of the study’s authors Geoffrey H. Tofler, M.D. a former associate professor at Harvard Medical School, now a professor of cardiology at Royal North Shore Hospital in Sydney, Australia.

Tofler and other scientists at Harvard Medical School and Boston University also measured fibrinogen using an older procedure known as the Clauss Method, in which fibrinogen in a blood sample is converted to fibrin, then timed to determine how long it takes a clot to form. The FIF test, by contrast, uses an antibody, which produces a specific reaction from fibrinogen. This new method may be more adaptable for measuring fibrinogen levels in large populations.

“While our study doesn’t necessarily prove that fibrinogen should be tested routinely as part of a standard physical examination, it does support the argument that measuring fibrinogen provides useful information for assessing an individual patient’s risk,” says Tofler.

“If I’m uncertain about what level of therapy a patient requires -– whether someone should be given a cholesterol-lowering drug, for example – finding high fibrinogen would tend to make me take a more aggressive approach in treatment,” he adds. “Conversely, finding low or normal fibrinogen would reassure me.”

Tofler emphasizes that it’s important for the public to know that the dangers represented by high fibrinogen levels can be reduced in many cases by quitting smoking, losing weight, becoming more physically active and lowering cholesterol through dietary changes and/or medication.

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This work was funded in part by the National Institutes of Health and American Biogenetic Sciences.

Co-authors are James J. Stec, B.S.; Halit Silbershatz, Ph.D.; Travis H. Matheney, MLA; Patrice Sutherland, B.S.; Izabela Lipinska, Ph.D.; Joseph M. Massaro, Ph.D.; Peter F. W. Wilson, M.D.; James E. Muller, M.D.; and Ralph B. D’Agostino, Sr., Ph.D.

NR00-1175 (Circ/Tofler)

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