FOR RELEASE: 4 p.m. ET, Monday May 17, 1999
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American Heart Association journal report: Cholesterol carriers better predictors than cholesterol for second heart attack
DALLAS, May 18 -- Two proteins that carry cholesterol in the blood may provide a better way to measure heart attack risk than the usual cholesterol blood test, report researchers in today's Circulation: Journal of the American Heart Association.
"Because the two proteins are more sensitive heart disease risk detectors than cholesterol, they may identify more individuals at risk and one day replace cholesterol testing," says the study's lead author, Arthur J. Moss, M.D., professor of medicine (cardiology) at the University of Rochester Medical Center, Rochester, N.Y.
The association between the proteins -- apolipoprotein (apo) A-1 and apolipoprotein (apo) B -- and heart attack risk held true even in the presence of heart disease risk factors including, smoking, diabetes, high blood pressure and high blood levels of cholesterol.
(Apo) A-1 and apo B carry cholesterol in the bloodstream. Apo B is a cholesterol donor, while apo A-1 is a cholesterol scavenger.
Researchers also identified a third protein, D-dimer, which was associated with heart attack risk. D-dimer is a breakdown product in the blood when clots form. Elevated levels of D-dimer indicate excess clotting or coagulation activity in the blood.
Individuals with the blood protein profile of low apo A-1, high apo B, and high D-dimer levels were eight times more likely than others in the study to experience a second heart attack within two years, Moss says. Patients with an abnormal blood level of only one of these proteins were twice as likely to experience another heart attack within two years.
When apo B levels are high, apo B deposits cholesterol on the inside surface of the plaque. Then it moves into the plaque, thereby increasing the size of the fatty deposit. Ordinarily, apo A-1 would pick up these cholesterol deposits before they enter the plaque. However, if apo A-1 levels are low, the process does not go as expected. Instead, the cholesterol accumulates and forms plaque, a fatty deposit that can block blood vessels. As the plaque accumulation increases, it stresses the coating that usually keeps the plaque in place. If sufficiently weakened, the coating ruptures and forms a blood clot, thus triggering a heart attack or stroke.
"Individuals with high apo B, low apo A-1, and high D-dimer levels are at increased risk for rupture of plaque with subsequent blockage of the blood vessel, which can result in a heart attack, " says Moss.
He adds, "One can think of this clotting tendency as the opposite of hemophilia, a condition characterized by a tendency for excessive bleeding because of a faulty clotting mechanism. In high-risk heart disease patients, an excess clotting tendency contributes to blockage of the blood vessel."
In the study, researchers measured the three proteins and 11 other blood factors in 1,045 people who had already experienced recurrent heart attack. Eighty-one of these individuals had a second heart attack and 25 of them died. Among the patients studied, only the three proteins -- apo A-I, apo B, and D-dimer -- were associated with an increased risk of heart attack.
A direct association existed between D-dimer and heart attack risk, with a doubling of risk occurring in people with levels in the top fourth (above 650 nanograms per milliliter). As for the other proteins, the doubling of risk was seen only in those with the lowest fourth apo A-1 levels (below 101 milligrams per deciliter) and the highest fourth apo B levels (more than 140 mg per deciliter).
The results support continued use of cholesterol-lowering drugs in patients at risk for second heart attacks, Moss says. These drugs apparently not only help reduce the risk of plaque rupture, but also reduce clotting tendency.
"Diet, exercise and drug treatment can favorably alter the concentration of these proteins, so it is important for at-risk patients to continue to follow the guidelines of the American Heart Association," Moss says. In addition, anticoagulant drugs, including aspirin, are recommended for the treatment of patients with heart disease. These reduce clotting activity.
The protein tests, which can be performed in standard clinical laboratories, may become routine in the future, Moss says.
Co-authors are Robert Goldstein, M.D.; Victor Marder, M.D.; Charles Sparks, M.D.; David Oakes, Ph.D.; Henry Greenberg, M.D.; Harvey Weiss, M.D.; Wojciech Zareba, M.D., Ph.D.; Mary Brown, M.S.; Chang-Seng Liang, M.D.; Edgar Lichstein, M.D.; William Little, M.D.; John Gillespie, M.D.; Lucy Van Voorhees, M.D.; Ronald Krone, M.D.; Monty Bodenheimer, M.D; Judith Hochman, M.D.; Edward Dwyer, Jr., M.D.; Rohit Arora, M.D.; Frank Marcus, M.D.; Luc Miller Watelet, Ph.D.; and Robert Case, M.D.
NR 99-1039 (Circ/Moss)
Media advisory: Dr. Moss can be reached at (716) 275-5391. (Please do not publish phone number.)
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