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RENEGADE ANTIBODIES
HELSINKI- The discovery of high levels of renegade antibodies in the blood of heart attack victims sheds new light on the role of immunological factors in the development of heart attacks, according to a new Finnish study. In recent years, much research effort has been directed a the potential link between a type of antibody called antiphospholipid antibodies and heart attack. Until now, the data has been conflicting with some studies showing an apparent link and others not. However, all previous studies have involved patients who have already had heart disease or who had experienced heart attacks. The current Finnish study is the first to look for the antibodies in a healthy population. The new data come from a large study of cholesterol lowering medications in the Finnish population called the Helsinki Heart Study. The researchers measured levels of one anti-phospholipid antibody, the anti-cardiolipin antibody, in the middle-aged male participants at the beginning of the study and throughout its five year course. One hundred and forty men out of the study population of 4,081 had heart attacks during the study. Subsequent analysis revealed that patients with the highest levels of aCL antibodies had twice the risk of heart attack as other patients. This was true even after accounting for other risk factors such as age, smoking, blood pressure and cholesterol levels. "This is the first prospective study demonstrating the clinical importance of a high level of anti-cardiolipin (aCL) antibodies as a predictor of heart attack," notes Outi Vaarala, M.D., University of Helsinki, Finland. The researchers also observed that smoking doubled the risk of heart attack. The risk of having a heart attack was more than five times as high in patients who both smoked and had aCL antibodies. The researchers also observed that aCL antibodies appeared to cross-react with antibodies to oxidized LDL (low density lipoprotein), often called the "bad" cholesterol. LDL molecules and cardiolipin, the phospholipid component to which aCL antibodies react, have numerous structural similarities. The combined effect of the two antibodies appears to exacerbate the development of coronary thrombosis, notes Dr. Vaarala. The phospholipids targeted by the aCL antibodies are an essential component of the membranes of all cells in the body. Phospholipids are also important factors in blood coagulation. The researchers hypothesize that antibodies directed against the phospholipids interfere with coagulation, contributing to clotting, leading ultimately to heart attacks. "We conclude that immunological factors are important in the development of heart attacks. Right now we don't know what to do if you have high levels of aCL antibodies. This new finding may lead to new tests and new treatments in the future," said Dr. Vaarala. Anti-cardiolipin antibodies were first discovered in the blood of patients with the autoimmune disease systemic lupus. People with this disease have a high incidence of clotting, atherosclerosis and heart attack. The same antibodies are seen transiently during many infections and in association with several prescription drugs. The next stage in research will be to determine if the antibodies play a direct role in blood clot formation, reflect some kind of chronic infection, or both. Dr. Vaarala's study appeared in Circulation, 1/1/95, v.91, n.1., pp 23-27.
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