Impact of body iron status on myocardial perfusion, left ventricular function, and angiographic morphologic features in patients with hypercholesterolemia

Background Previous studies have shown that the effects of iron stores on atherogenesis through promotion of free radical formation and low-density lipoprotein (LDL) oxidation largely depend on the state of hypercholesterolemia (HCL) in animal models. A synergistic association of serum ferritin and LDL cholesterol with the risk of myocardial infarction has also been observed in humans. Methods We sought to assess the relationship of serum iron parameters to myocardial perfusion and wall motion abnormalities and to the extent of angiographic coronary artery disease (CAD) in patients with HCL. Sixty-eight male patients (mean age 58 ± 9 years) with hypercholesterolemia (LDL cholesterol >130 mg/dL) who had never been treated and 52 normocholesterolemic male subjects of similar age underwent coronary angiography and exercise technetium-99m sestamibi gated single-photon emission computed tomography imaging within 10 days. Results Serum ferritin had a significant correlation with the perfusion index (r = 0.70, P < .001), the reversibility index (r = 0.68, P < .01), and the wall motion index (r = 0.54, P < .05), whereas a relatively weak correlation was observed between total iron binding capacity and perfusion index (inversely) (r = −0.59, P < .01) in patients with HCL. Iron parameters were not associated with either perfusion or wall motion indices in the normocholesterolemic group. Stepwise multiple regression analysis confirmed these results. Ferritin was a strong determinant of perfusion in patients with HCL only (β = .55, P = .002). Iron parameters were not related to the angiographic extent of CAD as defined by angiographic vessel or extent score in either group. Conclusions Our data suggest that increased iron stores are closely associated with a greater extent and severity of perfusion and functional abnormalities but not with the angiographic extent of CAD in patients with HCL. Enhanced iron-mediated oxidative stress and LDL peroxidation may contribute to the hypercholesterolemia-related endothelial dysfunction and cause further impairment of myocardial perfusion and wall motion. (Am Heart J 2002;143:257-64.)