Tomi-Pekka Tuomainen , research fellow a, Riitta Salonen , senior clinical research fellow a, Kristiina Nyyssouml;nen , clinical biochemist a, Jukka T Salonen , academy professor of Academy of Finland a a Research Institute of Public Health University of Kuopio 70211 Kuopio Finland Correspondence to: Professor Salonen Accepted 15 November 1996

Introduction Mild iron deficiency has been hypothesised to reduce risk of heart disease risk,1 while a high concentration of body iron has been suggested as a risk factor for myocardial infarction.1 2 Menstruation in women and voluntary blood donations are the most important causes of blood loss and thus modulators of stores of body iron. We prospectively investigated the association of donating blood with the risk of acute myocardial infarction in a random population sample of middle aged men.

Patients, methods, and results We investigated the incidence of acute myocardial infarctions in participants in the Kuopio ischaemic heart disease risk factor study.3 During 1984-9 we carried out baseline examinations of 2682 (83%) of the 3235 men aged 42, 48, 54, or 60 whom we had invited. We obtained data on the subjects' donating blood by record linkage to files of the local Red Cross office. We registered and verified all myocardial infarctions, definite or possible, between the baseline examinations and the end of 1992.2 The mean follow up time was 5.5 years, and, with multiple infarctions, we considered only the first. We used Cox's proportional hazard's analyses to compare the occurrence of cardiac events in blood donors and in non-donors. In the 24 months before the baseline examinations 153 (5.7%) of the 2682 participants had donated blood. During follow up, one (0.7%) of the donors experienced an acute myocardial infarction compared with 226 (9.8%) of the 2529 non-donors (P<0.001 for difference). Table 1) shows that, in a multivariate model adjusted for the main coronary risk factors, the blood donors' risk of acute myocardial infarction was 86% less than that of the non-donors (relative risk 0.14, 95% confidence interval 0.02 to 0.97, P=0.047). Additional adjustment for a large number of measurements of medical history, health state, health practices, and psychosocial characteristics attenuated this association only marginally. Table 1 Coronary risk factors in 153 male blood donors and 2529 non-donors and relative risks for acute myocardial infarction (values are means (SD) unless stated otherwise) View this table:

Comment This is the first study to report a reduced risk of coronary events in male blood donors. The mechanism through which donating blood reduces the risk of coronary events could be the depletion of body iron stores. Such depletion could decrease the amount of injury promoting iron in the myocardium, alter the activity of iron dependent enzymes, increase plasma antioxidative capacity, and decrease lipid peroxidation in both the circulation and in vessel walls.1 2 4 5 There is experimental, clinical, and epidemiological support for high iron stores increasing the risk of coronary events and atherosclerotic progression.4 5 The lack of consistency in epidemiological studies is probably explained by large variability in estimates of iron stores and iron intake and by the diversity of study outcomes.5 We suggest that the loss of iron associated with giving blood might be the reason for the observed risk reduction. However, voluntary blood donors seem to be generally more health conscious and more healthy than those who do not donate blood, and this may have caused self selection bias. In our study the association between donating blood and reduced risk for myocardial infarction was weakened but remained significant after adjustment for the main coronary risk factors. Our finding needs to be confirmed in other prospective population studies, and investigation of the impact of iron depletion on atherosclerotic progression or coronary events is necessary to test the above theory.

Acknowledgments We thank Kimmo Ronkainen for carrying out the data analyses and Professor Jaakko Tuomilehto for providing the FINMONICA AMI registry data.

Footnotes Funding The study was supported by the Academy of Finland and the Ministry of Education of Finland.

Competing interests None.