Body Iron Stores and the Risk of Coronary Heart Disease

Sempos, Christopher T.; Looker, Anne C.; Gillum, Richard F.; Makuc, Diane M.

doi:10.1056/nejm199404213301604

Cited by 208 publications

(77 citation statements)

References 42 publications

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“…For instance, the observation that postmenopausal women receiving estrogen replacement therapy have a risk for CAD similar to that of premenopausal women (27) suggested that the determining factor for increased risk after menopause is a reduction in estrogen levels, rather than iron overload, as it had been previously supposed (1). In fact, in several of the epidemiological studies designed to assess the possible relation between body iron stores and atherosclerotic disease, no association was found, and even an inverse association was suggested in one of them (12). Moreover, supporting our findings is the recent demonstration that, in rabbits, iron overload decreases plasma cholesterol levels and the formation of an aortic arch lesion, suggesting that excess iron does not contribute to atherosclerosis (7).…”

Section: Resultsmentioning

confidence: 97%

“…To support this hypothesis, it has been experimentally observed that iron overload contributes to atherogenesis in rabbits (6); however, other investigators demonstrated that, in the same animal model, iron overload causes a decrease in plasma cholesterol levels as well as in the formation of lesions in the aortic arch (7). Similarly, whereas some epidemiological studies (8)(9)(10)(11) have found a positive association between CAD and clinical markers of iron overload, other reports have found either a negative association (12) or none at all (13,14). Thus, the iron hypothesis remains controversial.…”

Section: Introductionmentioning

confidence: 99%

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HFE gene mutations in coronary atherothrombotic disease

Calado

Franco

Pazin‐Filho

et al. 2000

Braz J Med Biol Res

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Although iron can catalyze the production of free radicals involved in LDL lipid peroxidation, the contribution of iron overload to atherosclerosis remains controversial. The description of two mutations in the HFE gene (Cys282Tyr and His63Asp) related to hereditary hemochromatosis provides an opportunity to address the question of the association between iron overload and atherosclerosis. We investigated the prevalence of HFE mutations in 160 survivors of myocardial infarction with angiographically demonstrated severe coronary atherosclerotic disease, and in 160 age-, gender-and race-matched healthy control subjects. PCR amplification of genomic DNA followed by RsaI and BclI restriction enzyme digestion was used to determine the genotypes. The frequency of the mutant Cys282Tyr allele was identical among patients and controls (0.022; carrier frequency, 4.4%), whereas the mutant His63Asp allele had a frequency of 0.143 (carrier frequency, 27.5%) in controls and of 0.134 (carrier frequency, 24.5%) in patients. Compound heterozygotes were found in 2 of 160 (1.2%) controls and in 1 of 160 (0.6%) patients. The finding of a similar prevalence of Cys282Tyr and His63Asp mutations in the HFE gene among controls and patients with coronary atherothrombotic disease, indirectly questions the possibility of an association between hereditary hemochromatosis and atherosclerosis.

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Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

HFE gene mutations in coronary atherothrombotic disease

Calado

Franco

Pazin‐Filho

et al. 2000

Braz J Med Biol Res

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“…However, despite initial reports that indicated possible associations between higher Fe marker levels and poor cardiovascular outcome in the general population (71), more robust epidemiologic studies did not show an increased risk for coronary heart disease with higher ISAT but, on the contrary, indicated a possible inverse association of Fe stores with overall and cardiovascular mortality in the general population (72,73). Similarly, recent studies in dialysis patients showed that a low, rather than a high, serum Fe is associated with higher death risk (74).…”

Section: The "Iron Apprehension"mentioning

confidence: 95%

The Fascinating but Deceptive Ferritin

Kalantar‐Zadeh

Kalantar‐zadeh

Lee

2006

Clinical Journal of the American Society of Nephrology

168

150

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Although the emergence of erythropoiesis-stimulating agents has revolutionized the anemia management of chronic kidney disease (CKD) in the past two decades, strategies to assess iron (Fe) status and to provide Fe supplementation have remained indistinct. The reported cases of hemochromatosis in dialysis patients from the pre-erythropoiesis-stimulating agent era along with the possible associations of Fe with infection and oxidative stress have fueled the "iron apprehension." To date, no reliable marker of Fe stores in CKD has been agreed on. Serum ferritin continues to be the focus of attention. Almost half of all maintenance hemodialysis patients have a serum ferritin >500 ng/ml. In this ferritin range, Fe supplementation currently is not encouraged, although most reported hemochromatosis cases had a serum ferritin >2000 ng/ml. The moderate-range hyperferritinemia (500 to 2000 ng/ml) seems to be due mostly to non-Fe-related conditions, including inflammation, malnutrition, liver disease, infection, and malignancy. Recent epidemiologic studies have shown that a low, rather than a high, serum Fe is associated with a poor survival in maintenance hemodialysis patients. In multivariate adjusted models that mitigate the confounding effect of malnutrition-inflammation, serum ferritin <1200 ng/ml and Fe saturation ratio in 30 to 50% range are associated with the greatest survival in maintenance hemodialysis patients. Although ferritin is a fascinating molecule, moderate hyperferritinemia is a misleading marker of Fe stores in patients with CKD. It may be time to revisit the utility of serum ferritin in CKD and ask ourselves whether its measurement has helped us or has caused more confusion and controversy.

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“…In this respect, it is of interest that in shorter term metabolically controlled studies, the dietary portfolio as used in the present study has been shown to reduce CRP (Jenkins et al, 2003b(Jenkins et al, , 2005a. Related to lower hemoglobin, lower serum iron and ferritin concentrations as markers of iron stores have also been suggested to be associated with reduced CHD risk (Sullivan, 1981) in some but not all studies (Sempos et al, 1994;Corti et al, 1997). Again, a link has been made with CRP, possibly stimulated by the pro-oxidant effect of iron (Williams et al, 2002).…”

Section: Discussionmentioning

confidence: 72%