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In a recent Finnish study, ferritin was suggested to be an independent risk factor for acute myocardial infarction. This study suggested that high levels of iron stores might thus be atherogenic and possibly explain partly the sex difference in the incidence of ischemic heart disease.A randomly selected group (n=2036), men and women aged 25 to 74 years, were examined between June and September 1983. All classic risk factors for coronary artery disease were measured as well as basic hematologic parameters and the parameters of iron metabolism, ie, iron, total iron-binding capacity (TIBC), and ferritin. During the follow-up for 8.5 years, 81 subjects experienced acute myocardial infarction (63 men and 18 women). The differences in the iron parameters between men and women were almost exclusively seen in ferritin values (198 μg/L in men and 91 μg/L in women), whereas small differences were seen in TIBC. The Cox proportional hazards model was used to estimate the contribution of independent variables to the risk of myocardial infarction. TIBC was found to be a strong independent negative risk factor in men (RR=0.95; 95% CI, 0.92 to 0.98), whereas ferritin (RR=0.999; 95% CI, 0.997 to 1.001) or other iron parameters had no significant predictive power. Each increase in TIBC of 1 μmol/L was associated with a 5.1% decrease in the risk of myocardial infarction. The classic major risk factors, ie, blood pressure, smoking, total cholesterol, and high-density lipoprotein, had significant independent correlation with myocardial infarction. When Cox multivariate analysis was carried out on both sexes combined, TIBC was still an independent negative risk factor, and the logarithmic transform of ferritin had a weak negative correlation but was not statistically significant. Sex was in this group still a very strong risk factor after taking into account all classic risk factors as well as the parameters of iron metabolism.This study suggests that transferrin, measured as TIBC, is an independent negative risk factor for myocardial infarction. Other parameters of iron metabolism, including ferritin, were not found to contribute to the risk.