To the Editor: The iron-heart hypothesis postulated a primary protective effect of iron depletion against ischemic heart disease.1 The report of the Iron (Fe) and Atherosclerosis Study (FeAST) by Dr Zacharski and colleagues2 had 2 key limitations as a general test of the idea: it was a trial of secondary prevention, and the iron-reduction protocol fell short of achieving full iron depletion.
Exploratory post hoc analyses suggested that reducing iron stores may improve outcomes for people with symptomatic but stable peripheral arterial disease if iron reduction is begun before age 60 years (unadjusted hazard ratio for the primary outcome, 0.47; 95% confidence interval, 0.24-0.90). The study findings would support a trial designed to test the original hypothesis using full iron depletion (defined as the absence of storage iron without significant iron-deficiency anemia), particularly among patients in this subgroup.
Zheng et al3 reported that frequent volunteer blood donors with a median serum ferritin value of 17 ng/mL had significantly better endothelial function than casual donors with a median value of 52 ng/mL. The participants in FeAST who were randomized to undergo iron reduction experienced a decrease in mean serum ferritin value from 122.5 ng/mL to 79.7 ng/mL.2 This suggests that improved outcomes could be associated with reductions of storage iron beyond those achieved in FeAST.
Before FeAST, ethical concerns put much greater weight on the risks of iron removal than on potential benefits.4 Limited iron reduction in FeAST reflected concern over the safety of iron removal in patients with peripheral arterial disease.5 Phlebotomy was apparently safe for participants randomized to undergo iron reduction, with the only adverse events associated with the 3141 reported phlebotomy episodes being 6 cases of “minor vasovagal events.” Lack of statistically significant cardiovascular benefit in older FeAST participants may have been attributable to the small amount of stored iron removed.2 In future trial designs, consideration should be given to the risk of failing to detect a large benefit because of inadequate treatment.
Financial Disclosures: None reported.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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