Epidemiological associations between iron and cardiovascular disease and diabetes

Abstract

Disruptions in iron homeostasis are linked to a broad spectrum of chronic conditions including cardiovascular, malignant, metabolic, and neurodegenerative disease. Evidence supporting this contention derives from a variety of analytical approaches, ranging from molecular to population-based studies. This review focuses on key epidemiological studies that assess the relationship between body iron status and chronic diseases, with particular emphasis on atherosclerosis ,metabolic syndrome and diabetes. Multiple surrogates have been used to measure body iron status, including serum ferritin, transferrin saturation, serum iron, and dietary iron intake. The lack of a uniform and standardized means of assessing body iron status has limited the precision of epidemiological associations. Intervention studies using depletion of iron to alter risk have been conducted. Genetic and molecular techniques have helped to explicate the biochemistry of iron metabolism at the molecular level. Plausible explanations for how iron contributes to the pathogenesis of these chronic diseases are beginning to be elucidated. Most evidence supports the hypothesis that excess iron contributes to chronic disease by fostering excess production of free radicals. Overall, epidemiological studies, reinforced by basic science experiments, provide a strong line of evidence supporting the association between iron and elevated risk of cardiovascular disease and diabetes. In this narrative review we attempt to condense the information from existing literature on this topic.

The Case for an Estrogen-iron Axis in Health and Disease

“…Furthermore, a Women's Health Initiative (WHI) primary prevention trial has recommended that HRT should not be initiated/continued for primary prevention of CHD [78]. This is consistent with the observation that iron overload is a risk factor in cardiovascular disease [79][80][81][82][83] and our hypothesis that E2 exacerbates iron overload [30][31][32][33][34].…”

Alterations of protein expression in serum of infants with intrauterine growth restriction and different gestational ages

“…High TF levels in the serum of IUGR neonates may result in iron excess, generally considered to contribute to chronic disease by free radical production. Epidemiological and experimental studies, strongly support the association between iron and a higher risk of cardiovascular disease and diabetes [41], both adult conditions related to IUGR. Abundant proteins, upregulated in "Very Preterm" IUGR exclusively at birth, included five albumins, involved in transport of bile acids, salts and small organic anions.…”

HFE p.C282Y gene variant is associated with varicose veins in Russian population

“…The increase in serum iron concentration has been shown in chronic venous insufficiency patients in comparison with healthy controls [44][45][46]. There is epidemiologic evidence of a relationship between the level of iron and cardiovascular diseases [47][48][49]. Most clinical cases of iron overload in populations of European origin are carriers of the p.282Y HFE variant (rs1800562 A allele) [50].…”