Iron and coronary artery disease

                Several circumstances have supported although not always through scientific experimentation, the hypothesis that there is a correlation between the concentration of iron in the body and coronary artery disease (CAD).  Such circumstances include the observation that women have less tendency to suffer from heart disease, or that Asians have relatively lower incidence of death caused by heart disease (Sullivan, 1981). Laufer (1990) observes the existence of high concentration of iron as well as high concentration of serum cholesterol at the same time in both men and women, supporting such correlation. True enough, a correlation of 0.55 has been reported in one study by Lauffer (1990) between hepatic iron stores and mortality from ischemic heart disease.  These instances, however it shows correlation, do not necessarily signify causal relation. Other factors yet undiscovered, as well as the existence of other causative factors may in the future show such relationship with CAD. Meanwhile, scientists try to establish a direct causal relationship by arriving at several possible explanations and testing these explanations.

            According to Laufer (1990), the contribution of iron to CAD happens at two critical stages of the disease. The first is during atherogenesis. In theory as well as in the laboratory, iron has been shown to be a strong oxidant that is capable of catalyzing the oxidation of low-density lipoproteins (LDL). The foundations of atherosclerotic lesions require the oxidation of LDLs in the walls of the artery in order to attract macrophages. The second critical stage is during reperfusion injury when ischemic events trigger the formation of oxygen free radicals. These, in theory provide an explanation on its role in atherogenesis but such role however remains uncertain in vivo (Laufer, 1990).

            Going back to the correlation observed by Laufer (1990) that high liver iron and high cholesterol concentration occur simultaneously in men and women, Fields, et. al. (1993) said that there may be a correlation between high iron stores and hypercholesterolemia but high iron stores alone cannot possibly induce hypercholesterolemia alone. Studies show that increased lipid peroxidation and hypercholesterolemia are exhibited both when rats are fed a diet that is high in iron and low both in ?-tocopherol and ?-carotene, and rats fed a diet that is low in Selenium and treated with a free-radicall generator (Fields, 1999). Copper deficiency also showed increased free-radical generation and increased blood cholesterol concentration (Fields, 1999). Meanwhile, zinc-deficiency is said to induce oxidative damage in tissues (Disilvestro and Blostein-Fujii, 1997), although the existence of antagonistic relationship between zinc and iron cannot be denied. This implies that atherogenesis and thus, CAD develops when reactive-oxygen generators exist in a suppressed antioxidant status and not necessarily a result of high iron concentration in blood and in the liver (Fields, et. al., 1993; Fields, 1999).

            The strong epidemiological evidence that relates iron and CAD may be available but until the real mechanism of iron-induced CAD is discovered, the scientific community is limited to speculations on oxidation-related explanations. After all, the availability of iron at peroxidation sites remain unclear (Burt, Walliday and Powell, 1993). According to Burt, Walliday and Powell (1993), if it is true that iron has an important role in the development of CAD, high rates of CAD should be observed in patients homozygous and heterozygous for hematochromatosis. It appears that no substantial evidence of that exists at present and therefore, the actual relationship between iron and CAD is still subject to mere speculations.

References

Burt, M., Halliday, J., Powell, L. (1993). Iron and coronary heart disease. British Medical Journal, 307:575-576.

DiSilvestro, R. and Blostein-Fujii, A. (1997). Moderate zinc deficiency in rats enhances lipoprotein oxidation in vitro. Free Radicals in Biology and Medicine, 22:739–742.

Fields M., Lewis, C., Lure,  M., Burns, W. and Antholine, W.(1993) Low dietary iron prevents free radical formation and heart pathology of copper-deficient rats fed fructose. Proceedings of the Society for Experimental Biology and Medicine, 202:225–231.

Fields, M. (1999). Invited Commentary: Role of Trace Elements in Coronary Artery Disease. British Journal of Nutrition, 81, 85–86.

Lauffer, R. (1990). Iron stores and the international variation in mortality from coronary artery disease. MedHypotheses, 35:96-102.

Sullivan, J. (1981). Iron and the sex difference in heart disease risk. Lancet, i:12934.

 

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