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B. de Valk, MD; J. J. M. Marx, MD, PhD

Arch Intern Med. 1999;159:1542-1548.

Objective  To review the epidemiological and experimental data concerning iron and the development of atherosclerosis and ischemic heart disease.

Data Sources  The English-language literature was searched from 1981 through 1998 manually and using MEDLINE and Current Contents. Important references in the articles that were found were also included in this review.

Results  There is growing epidemiological evidence for a relationship between iron levels and cardiovascular disease. Some experimental data support the role of iron in the process of lipid peroxidation, the first step in the formation of atherosclerotic lesions. Macrophages and endothelial cells are involved in this process, but the exact mechanism and the sites of the interactions between these cells, iron, and low-density lipoprotein are still unknown.

Conclusions  Strong epidemiological evidence is available that iron is an important factor in the process of atherosclerosis. Epidemiological studies, eg, prospective follow-up studies in blood donors, may clarify the cardiovascular benefits of iron depletion. Knowledge of the molecular mechanism of iron-related cardiovascular disease is still limited. We speculate that catalytically active iron species modify low-density lipoprotein levels to interact with the macrophage oxidized low-density lipoprotein receptor. Both nontransferrin-bound plasma iron and hemoglobin are candidates for such interactions.

From the Department of Internal Medicine and Eijkman-Winkler Institute for Microbiology, Infectious Diseases, and Inflammation, University Hospital Utrecht, Utrecht, the Netherlands.

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