Body Iron Stores and Coronary Heart Disease (Editorial‪)‬

Over the past 20 years, the hypothesis that body iron stores are associated with risk of coronary heart disease (CHD) has generated extensive debate (1-4). This debate has intensified in the last 4 years after reports from three studies that carriers of the recently discovered HFE C282Y mutation commonly seen in hereditary hemochromatosis have significantly increased risk of CHD (5-9). Clinical trial has recently been proposed as the ultimate resolution to assess protective effects of iron depletion against CHD among C282Y heterozygotes (9). In this issue of Clinical Chemistry, Bozzini et al. (10) show that neither a biochemical marker (serum ferritin) nor a genetic marker (C282Y carrier status) of body iron stores was significantly associated with angiographically documented coronary atherosclerosis. Do increased body iron stores increase risk of CHD? Are individuals who are heterozygotes for the common C282Y mutation at especially high risk of CHD? Can iron depletion reduce the risk? These questions have important implications given the common practice of fortification of food and supplements with iron in industrialized countries and the high frequency of HFE C282Y carriers (~9% of them are of northern European descent) (11). Moreover, the "Oxidative Stress Theory" suggests that iron, as a potent catalytic agent, could promote formation of highly reactive oxygen species and lipid peroxidation, a crucial step in atherosclerosis (4). Thus, evaluation of the iron hypothesis for CHD will lead to advances in our understanding of its pathogenesis. To date, conflicting results have been reported from epidemiologic studies (4, 8, 9, 12-14) conducted in different countries and populations using different biochemical and genetic markers of body iron stores.