Association of myocardial infarction with dietary and body iron
ACP J Club. 1993 Jan-Feb;118:20. doi:10.7326/ACPJC-1993-118-1-020
Salonen JT, Nyyssönen K, Korpela H, et al. High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. Circulation. 1992 Sep;86:803-11.
To study the association of body iron (serum ferritin) and dietary iron intake with the risk for acute myocardial infarction in middle-aged men.
Cohort followed for a mean of 3 years (Kuopio Ischaemic Heart Disease Risk Factor Study).
Community in eastern Finland.
A random sample of men aged 42, 48, 54, or 60 years, who had no symptomatic coronary heart disease, enrolled between March 1984 and December 1989. Heart disease was defined as a history of myocardial infarction or angina pectoris, or the use of nitroglycerine ≥ 1 time per week. 1931 men were enrolled and followed.
Assessment of risk factors
Blood samples for ferritin measurement were taken after abstinence from alcohol for 3 days and from smoking and eating for 12 hours. Dietary iron was calculated from a 4-day food diary. A history of heart disease, angina, hypertension, and tobacco and iron supplement use were assessed using questionnaires.
Main outcome measures
Multinational and national data bases provided information on myocardial infarctions. For multiple end points, the first myocardial infarction was used.
51 men had myocardial infarctions (9 fatal and 42 nonfatal). When adjusted for all risk factors, men with serum ferritin ≥ 200 µg/L had a relative risk for myocardial infarction of 2.2 (95% CI 1.2 to 4.0) compared with men who had a serum ferritin < 200 g/L. This risk was the same for both smokers and nonsmokers. A 1% increase in serum ferritin was associated with an approximately 2.4% increase in the risk for acute myocardial infarction after adjustment for other risk factors. For each milligram of iron ingested daily, the risk for acute myocardial infarction increased 5%. The strongest risk factors for myocardial infarction in a multivariable model were pack-years smoked and serum ferritin. The association between serum ferritin and risk for myocardial infarction was stronger among men with high levels of low-density lipoprotein (LDL) cholesterol (≥ 5 mmol/L) than among men with lower levels (< 5 mmol/L).
A high stored-iron (serum ferritin) level was a risk factor for myocardial infarction in men, especially when serum cholesterol was increased.
Sources of funding: Finnish Academy and the Ministry of Education of Finland.
For article reprint: Dr. J.T. Salonen, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland. FAX 358-71-162936.
Iron is a potential oxidant of LDL, and growing evidence shows that oxidative modification may increase the atherogenic effects of LDL (1). Salonen and colleagues' observation that the increased risk for coronary heart disease associated with total body iron and dietary iron was highest when both ferritin and LDL were increased is consistent with this hypothesis.
The study is well designed and the analysis is appropriate. The increased risk associated with elevated serum ferritin, however, is modest—about 2-fold—and the lower limit of the confidence interval falls very close to 1. It is important to replicate these findings in other populations because mean ferritin levels were relatively high in this study and the incidence of coronary heart disease in this region is among the highest in the world. More information about whether patients had inflammatory conditions that may have influenced both ferritin level and risk for coronary heart disease would have been useful. Moreover, it is not clear whether a low serum ferritin level is protective because the observed trend appears to be primarily caused by the increased risk for those in the upper 25% of ferritin levels (> 200 g/L). Sullivan (2) has speculated that low iron levels may account for the low risk for coronary heart disease in premenopausal women, but estrogen may have a protective effect that is independent of menstruation (3).
Clinicians should not use ferritin yet to screen for coronary heart disease risk. This association needs confirmation, appropriate interventions need to be defined, and the cost of testing is not trivial. With trials under way to investigate whether antioxidants such as β-carotene or vitamin E can prevent heart disease, future treatment options may be developed. Until then, these findings remind us that preventing heart disease does not begin and end with cholesterol screening.
David Atkins, MD, MPH
Susan R. Hecbert, MD, PhD Cardiovascular Health Research Unit Seattle, Washington, USA