Iron: Protector or Risk Factor for Cardiovascular Disease? Still Controversial

Abstract

Iron is the second most abundant metal in the Earth’s crust. Despite being present in trace amounts, it is an essential trace element for the human body, although it can also be toxic due to oxidative stress generation by the Fenton reaction, causing organic biomolecule oxidation. This process is the basis of numerous pathologies, including cardiovascular diseases (CVD). The relationship between iron and cardiovascular disease was proposed in 1981 by Jerome Sullivan. Since then, numerous epidemiological studies have been conducted to test this hypothesis. The aim of this review is to present the main findings of the chief epidemiological studies published during the last 32 years, since Sullivan formulated his iron hypothesis, suggesting that this element might act as a risk factor for cardiovascular disease. We have analyzed 55 studies, of which 27 supported the iron hypothesis, 20 found no evidence to support it and eight were contrary to the iron hypothesis. Our results suggest that there is not a high level of evidence which supports the hypothesis that the iron may be associated with CVD. Despite the large number of studies published to date, the role of iron in cardiovascular disease still generates a fair amount of debate, due to a marked disparity in results.

A comparison of the cardiometabolic profile of black South Africans with suspected non-alcoholic fatty liver disease (NAFLD) and excessive alcohol use

“…The association of SBP with iron in our study, and its link to metabolic syndrome, is also supported by previous reports in the literature (DeBoer et al, 2012;Houschyar et al, 2012;Rajapurkar et al, 2012). There is also evidence for the higher serum iron levels, its association with oxidative stress (Muñoz-Bravo, Gutiérrez-Bedmar, Gómez-Aracena, García-Rodríguez, & Navajas, 2013), and the increased severity of atherosclerosis and coronary artery disease (Bagheri et al, 2013).…”

Iron Together with Lipid Downregulates Protein Levels of Ceruloplasmin in Macrophages Associated with Rapid Foam Cell Formation

“…The reason is probably that people focus on the association between CVD and systemic iron status. The parameters tested generally include serum ferritin, iron, and hepcidin 30) . CVD, in the case of atherosclerosis, may display a focal iron deposition or accumulation in atherosclerotic plaques rather than a systemic iron overload.…”

Iron concentrations in atherosclerotic plaque and serum in patients with carotid atherosclerosis

“…On the other hand, excess iron could be harmful because it is able to catalyse the formation of highly reactive oxygen and hydrogen radicals when present in the unbound state. Transition metal ions, established catalysts of protein, lipid and DNA oxidation, are present at elevated levels in human atherosclerotic plaques, and in some animal models, consistent with the hypothesis that metal ions contribute to both plaque formation and its destabilization (19,21,23), though the role of metal ions remains controversial (16,29).…”

“…On the other hand, excess iron could be harmful because it is able to catalyse the formation of highly reactive oxygen and hydrogen radicals when present in the unbound state. Transition metal ions, established catalysts of protein, lipid and DNA oxidation, are present at elevated levels in human atherosclerotic plaques, and in some animal models, consistent with the hypothesis that metal ions contribute to both plaque formation and its destabilization (19,21,23), though the role of metal ions remains controversial (16,29).Epidemiological studies have reported an increased incidence of cardiovascular disease (CVD) in subjects with overt iron overload (7,8,19). Recent studies on cardiovascular evaluation and outcome in high-versus low-frequency blood donors have demonstrated improvements in surrogate markers of vascular health such as decreased oxidative stress, and…”