BACKGROUND: Immune mechanisms have been suggested to play an important role in the development of coronary atherosclerosis and its thrombotic complications. We evaluated the predictive value of the levels of various serum immunoglobulin classes in middle-aged men at increased risk of myocardial infarction. METHODS: Using nested case-control design and logistic regression analysis, we estimated the association between serum immunoglobulins and the risk of coronary end points (nonfatal or fatal myocardial infarction or sudden cardiac death) in dyslipidemic men (levels of non-high-density lipoprotein cholesterol >5.2 mmol/L [>201 mg/dL]) participating in the Helsinki Heart Study. The cases consisted of 135 subjects in whom a coronary end point occurred during the 5-year observation period of the study, and the controls were 135 subjects who did not suffer coronary end points during this period. Levels of IgA, IgE, IgG, and IgM were determined in serum samples collected at study entry. RESULTS: Levels of IgA, IgE, and IgG, but not IgM, were significantly higher in cases than in controls. After adjustment for other risk factors, such as age, smoking, and blood pressure, the risk of coronary disease showed a significant relation to the levels of IgA, IgE, and IgG. The risk in the highest quartile of each distribution as compared with the lowest quartile was 2.2-fold for IgA (95% confidence interval, 1.0-4.5), 2.8-fold for IgE (1.3-5.9), and 2.8-fold for IgG (1.3-5.9). Hypertriglyceridemia and a low level of high-density lipoprotein cholesterol were associated with increased risk of a coronary end point only if the levels of IgA, IgE, or IgG were also elevated. CONCLUSION: Elevated levels of IgA, IgE, and IgG are associated with myocardial infarction and cardiac death in men with dyslipidemia. The present data suggest that, for dyslipidemia to cause coronary atherothrombosis, an immune response reflected by elevated levels of these immunoglobulin classes is an important determinant.