Improper Protein Levels in Blood Make People 8 Times More Likely to Have Second Heart Attack

Blood proteins may be better predictors than cholesterol for heart attack risk, authors say - Results in Circulation

May 17, 1999

People who have improper blood levels of three key proteins are up to eight times more likely to have a second heart attack than people with the proper levels of those proteins, according to a University of Rochester study in today's issue of Circulation. Two of the proteins make cholesterol either "good" or "bad" while the third signals when blood is prone to excessive clotting. Physicians at Strong Memorial Hospital of the University of Rochester are already looking for the genes that create these proteins so they can be altered through gene therapy.

The study's authors conclude that concentrations of these proteins are a more important indicator of someone's risk of a second heart attack than their "good" or "bad" cholesterol levels. People in the study with high concentrations of one protein, apolipoprotein B (apo B), were nearly twice as likely to have a second heart attack as people with lower concentrations - regardless of what their cholesterol levels were. However, people with improper levels of all three proteins (apo A, apo B, and D-dimer) experienced an 8-fold increase in heart attack risk.

"In the past, doctors have tested patients' cholesterol levels to identify those at risk for heart attacks," explains lead author of the study Arthur J. Moss, M.D., professor of Medicine (Cardiology). "This study shows that testing a patient's cholesterol level won't give doctors the whole picture. Testing levels of these three proteins in the blood will make clear who is really at risk."

Moss is already working on finding the genes that give rise to these three proteins in the hopes of altering the genes to produce a healthier balance of the proteins. Though the study was conducted on people who already had had a heart attack, Moss says that improper levels of the three proteins likely signal an increased risk of heart attack in someone who has no history of heart disease.

How the Proteins Work

The three proteins come in two types: D-dimer, created when blood is prone to excessive clotting, and apo A and apo B, which carry cholesterol in the blood stream.

Apo A and apo B grab onto bits of cholesterol and steer them through the body. Apo A acts like a janitor, picking up cholesterol and other fats from blood vessels and tissues and taking them to the liver to be excreted. Apo B does just the opposite, sticking cholesterol and other fats against the walls of blood vessels, building harmful plaque. Too much plaque in an artery can choke blood flow, causing a heart attack. Essentially, there is no such thing as "good" or "bad" cholesterol, just cholesterol with either apo A or apo B carrying it. The danger of heart attack arises when there is too little apo A cleaning up, and too much apo B sticking cholesterol in the arteries, or a combination of the two problems.

Apo A and apo B do more than just carry cholesterol, which is why checking the levels of good and bad cholesterol doesn't tell the whole story. These two proteins also carry other fats, such as triglycerides, cleaning them up or depositing them the same way as with cholesterol. The third protein, D-dimer, is created when the blood is in a hypercoagulative state - a condition in which the blood clots too easily, such as in an artery narrowed by plaque deposits. Though D-dimer doesn't cause the clotting, it is a clear indicator of the hypercoagulative condition.

This study marks the first time the connection between cholesterol-carrying proteins and clotting proteins has been explored in relation to heart attack.

What this means for people with heart disease

"Understanding what makes someone more likely to have a heart attack opens doors to new therapies," explains Moss. "We're already investigating which genes are responsible for making these proteins so we can change the protein levels in the body and help prevent heart attacks. For the present, people should keep eating a healthy diet, exercise and use the medications their physician prescribes for them."

"If you've had a heart attack, if would be a good idea to get your levels of these proteins checked," says co-author of the study Charles E. Sparks, M.D., professor of Pathology and Laboratory Medicine at Strong Memorial Hospital at the University of Rochester. "Blood tests for all three proteins are already available through family physicians."

"This is very exciting," says Michael Ezekowitz, M.D., Ph.D., professor of Medicine (Cardiology) at Yale University. "Measuring these proteins may predict who really is in danger of a second heart attack."

The study was conducted over four years, enrolling 1,045 patients who had just recovered from a heart attack. Doctors tested the patients' blood for a variety of proteins, including apo A, apo B and D-dimer. Thirteen hospitals were involved in the study, which was funded entirely by the National Institutes of Health.

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