LETTERS TO THE EDITOR
Coronary atherosclerosis and body iron stores
Johann Auer, MD,
Robert Berent, MD,
Thomas Weber, MD and
Bernd Eber, MD
Department of Cardiology and Intensive Care, General Hospital Wels, Grieskirchnerstraße 42, A-4600 Wels, Austria
johann.auer{at}khwels.at
We read with great interest the study by Gaenzer et al. (1) in a recent issue of the Journal. The investigators studied associations between iron status and early functional and structural vascular abnormalities in patients with hereditary hemochromatosis and found that impaired endothelial function and increased intima-media thickness (IMT) may be associated with iron overload, with subsequent induction of oxidative stress. Gaenzer and colleagues suggested that iron-depletion therapy, which normalizes endothelial function, may reduce the increased risk of cardiovascular events.
A possible association between body iron status and the risk of coronary heart disease was first supported by findings from a Finnish study relating increased levels of both serum ferritin and dietary iron to an increased risk of myocardial infarction in men (2). It is believed that inflammation and oxidation are important mechanisms involved in the complex pathological process of atherogenesis (3). Free radical production is catalyzed and accelerated in the presence of iron (4) and this has been used as a possible explanation for the higher incidence of ischemic heart disease in young and middle-aged men compared to premenopausal women, as ferritin concentrations are three times higher in men than in premenopausal women (5). In contrast, more recently published data, like the studies by Aronow (6), Moore et al. (7), and Ascherio and colleagues (8), do not support the hypothesis of a relationship between serum ferritin and atherosclerosis risk.
It is noteworthy that the putative role of iron in the development of atherosclerosis is based primarily on clinical and epidemiological studies. However, only few reports investigating correlations between serum concentration of ferritin and anatomic diagnosis of coronary atherosclerosis assessed by coronary arteriography are available in the published data. We (9) could recently demonstrate that, in patients referred for coronary angiography, higher ferritin concentrations and transferrin-saturation levels (as measures of the amount of circulating iron available to tissues) are not associated with an increased extent of coronary atherosclerosis (as assessed angiographically). In that study (9), estimates of the relative risk of coronary heart disease for the quintile with the highest concentration of serum ferritin as compared with the lowest quintile were 0.83 (95% confidence interval, 0.63 to 1.24).
Another important point seems to be that all the iron indicators used to relate iron status to coronary artery disease (CAD) are affected by inflammation. As a result, an association between CAD and higher serum ferritin levels could be confounded by inflammation (10). A shortcoming of the study by Gaenzer et el. (1) is the lack of information on inflammatory markers such as C-reactive protein.
In summary, early functional and structural vascular abnormalities in patients with hereditary hemochromatosis may predict both extent of coronary atherosclerosis and the risk of cardiovascular events in this particular patient group, but in subjects without hereditary hemochromatosis our results and data from others do not support the hypothesis that body iron stores, as measured by serum ferritin and transferrin saturation, are related to the risk of CAD. In patients with hereditary hemochromatosis, enhancement of atherogenesis may involve additional mechanisms beyond iron.
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References
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1. Gaenzer H, Marschang P, Sturm W, et al. Association between increased iron stores and impaired endothelial function in patients with hereditary hemochromatosis. J Am Coll Cardiol. 2002;40:2189–2194[Abstract/Free Full Text]
2. Salonen JT, Nyyssonen K, Korpela H, et al. High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. Circulation. 1992;86:803–811[Abstract/Free Full Text]
3. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med. 1999;340:115–126[CrossRef][Medline]
4. McCord JM. Is iron sufficiency a risk factor in ischemic heart disease? Circulation. 1991;83:1112–1114[Free Full Text]
5. Colditz GA, Willett WC, Stampfer MJ, et al. Menopause and the risk of coronary heart disease in women. N Engl J Med. 1987;316:1105–1110[Medline]
6. Aronow WS. Serum ferritin is not a risk factor for coronary artery disease in men and women aged over 62 years. Am J Cardiol. 1993;72:347–348[CrossRef][Medline]
7. Moore M, Folsom AR, Barnes RW, et al. No association between serum ferritin and asyptomatic carotid atherosclerosis: the Atherosclerosis Risk In Communities (ARIC) study. Am J Epidemiol. 1995;141:719–723[Abstract/Free Full Text]
8. Ascherio A, Rimm EB, Giovannucci E, et al. Blood donations and risk of coronary heart disease in men. Circulation. 2001;103:52–57[Abstract/Free Full Text]
9. Auer J, Rammer M, Berent R, et al. Body iron stores and coronary atherosclerosis assessed by coronary angiography. Nutr Metab Cardiovasc Dis 2002;12:285–90
10. Finch CA, Huebers H. Perspectives in iron metabolism. N Engl J Med. 1982;306:1520–1528[Medline]
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