Identification of coronary artery stenoses and poststenotic blood flow patterns using a miniature high-frequency epicardial transducer.
Authors: M J Kern
Journal: Circulation (1994)

disease.However, on certain points the analysis and discussion are incomplete.The abstract version of the study4 should have been cited, noting that the conclusions drawn in the abstract differed substan- tially from those in the full paper.1The abstract did not include data on the significant association of heme iron intake with myocardial infarction.Only the negative evidence based on total iron intake was presented.The peer-reviewed version included data on total and heme iron intake and drew conclusions that strongly support the iron theory.Documenting omission of the positive findings is particularly important in this case because the abstract was given prominence as the subject of a news release from the American Heart Association.5Despite allusions to the heme iron intake data in the news release, the published abstract was widely interpreted as evidence against the iron theory.Pub- lishing only the negative evidence4 and omitting the interesting and important positive evidence1 have added confusion to the debate and may have inappropriately discouraged research on iron and heart disease.The iron theory, in focusing on protective effects of iron depletion, does not stipulate a necessary relation between heart disease and dietary iron.The key hypothesis concerns the relation between heart disease and iron in the body, not necessarily iron in the diet.Dietary iron intake is obviously the source of stored iron in the body.However, stored iron may be absent in the face of very high levels of intake if there is regular blood loss, eg from menstruation, frequent blood donation, or daily use of aspirin.The authors note correctly that "oxidative stress can free iron from ferritin."1However, they miss the point of the iron theory2,3 in suggesting that an oxidative stress may be required for stored iron to have any adverse effect.Free iron cannot be released from ferritin if there is no ferritin present.The absence of ferritin iron is inherently benign.In its absence, in a clinical state of iron depletion, even severe oxidative stresses cannot mobilize free iron from storage.The authors fail to cite evidence from animal exper- iments suggesting that removal of stored iron has a potent antioxi- dant effect in vivo.6-10Free iron liberated from stored iron may be required for many of the adverse effects of an oxidative stress.The lack of association of heme iron intake with risk of coronary bypass surgery (CABG) does not invalidate the association of heme iron intake with myocardial infarction.As a "coronary event," the CABG must be carefully distinguished from spontaneous myocar- dial infarction.Indications for CABG are defined by practitioner consensus, whereas myocardial infarctions are produced by still incompletely defined pathologic processes.There are as yet no reliable criteria for identifying individual asymptomatic subjects who will go on to experience myocardial infarction.Lack of associ- ation of heme iron intake with CABG also does not exclude an important role for iron in atherogenesis.Much more research on the specific role of iron in atherogenesis is needed.Very little is known about the kinetics of iron-catalyzed low density lipoprotein (LDL) oxidation in vivo.It may be that very small quantities of stored iron are enough for substantial promotion of LDL oxidation in vivo, ie that nearly complete iron depletion is required for LDL protection.There are also potential mechanisms of iron-promoted atherogenesis that may not directly involve mediation by free radicals.Monocyte-macrophage proliferation in atherosclerotic le- sions could be regulated in part by stored iron level.This cell type is of central importance in atherogenesis and also in iron metabo- lism.Perhaps very small amounts of stored iron are enough for maximal stimulation of monocyte-macrophage proliferation within atherosclerotic plaques.