Faculty Bibliography

BACKGROUND: Increased iron stores are associated with greater cardiovascular risk in postmenopausal women. Oral contraceptive pill (OCP) use decreases the volume of menstrual blood loss and increases iron stores, but the link between OCP use, iron stores and cardiovascular risk in premenopausal women has not been characterized. STUDY DESIGN: We conducted a cross-sectional study of 23 healthy OCP users to determine the association between type and duration of OCP exposure, iron stores, and vascular endothelial function [flow-mediated dilation (FMD) in the brachial artery]. RESULTS: Median duration of OCP use was 45 months. FMD in the brachial artery was significantly associated with progestin type used (estranes/gonanes vs. drospirenone) and duration of OCP use (both p<.05) but not iron stores. In multivariate analysis, progestin type was the only independent predictor of FMD. CONCLUSIONS: Use of OCP containing drospirenone was independently associated with greater FMD in the brachial artery and, thus, a potentially more favorable cardiovascular risk profile, when compared with use of OCP containing estranes/gonanes

Background- Iron deficiency has been proposed as a potential therapeutic target in heart failure, but its prevalence and association with anemia and clinical outcomes in community-dwelling adults with heart failure have not been well characterized. Methods and Results- Using data from the Third National Health and Nutrition Examination Survey, we evaluated the associations between iron deficiency, hemoglobin, C-reactive protein (CRP), and all-cause and cardiovascular mortality in 574 adults with self-reported heart failure. Iron deficiency was defined in both absolute and functional terms as a ferritin level <100 mug/L or between 100 and 299 mug/L if the transferrin saturation was <20%. Iron deficiency was present in 61.3% of participants and was associated with reduced mean hemoglobin (13.6 versus 14.2 g/dL, P=0.007) and increased mean CRP (0.95 versus 0.63 mg/dL, P=0.04). Over a median of 6.7 years of follow-up, there were 300 all-cause deaths, 193 of which were from cardiovascular causes. In age- and sex-adjusted Cox proportional hazards models, hemoglobin, CRP, and transferrin saturation but not iron deficiency were significantly associated with all-cause and cardiovascular mortality. In multivariate models, hemoglobin remained an independent predictor of cardiovascular mortality, whereas CRP remained an independent predictor of both all-cause and cardiovascular mortality. Conclusions- Iron deficiency is common in heart failure and is associated with decreased hemoglobin and increased CRP. In multivariate analysis, hemoglobin was associated with cardiovascular mortality while CRP was associated with both all-cause and cardiovascular mortality. Iron deficiency was not associated with all-cause or cardiovascular mortality in this cohort

Diabetic patients with coronary artery disease (CAD) are more likely to develop heart failure (HF) than nondiabetic patients, but the mechanism responsible is unclear. Evidence suggests that infarct size and accompanying remodeling may not explain this difference. We used cardiac magnetic resonance (CMR) imaging to compare degree of left ventricular (LV) myocardial scar and remodeling in diabetic and nondiabetic patients with CAD. We evaluated 85 patients (39 diabetic, 46 nondiabetic) who underwent coronary angiography showing obstructive CAD and CMR imaging within 6 months of each other. Myocardial scar was measured by late gadolinium enhancement on CMR imaging and was graded according to spatial and transmural extents on a semiquantitative scale. More diabetic than nondiabetic patients had HF (69% vs 43%, p <0.03); however, groups did not differ in total scar burden (0.94 +/- 0.60 vs 1.17 +/- 0.74, p = NS), spatial extent of scar, or extent of transmural scar. Diabetes remained an independent predictor of HF after adjustment for CAD and other variables. LV ejection fraction (36 +/- 12% vs 37 +/- 14%, p = NS) and end-diastolic volume (215 +/- 56 vs 217 +/- 76 ml, p = NS) were similar for diabetic and nondiabetic patients, respectively. In conclusion, although diabetic patients with CAD had a higher prevalence of HF than nondiabetic patients, there was no difference in myocardial scar, LV volume, or LV ejection fraction. These findings support the theory that mechanisms other than extent of myocardial injury and negative remodeling play a significant role in the development of HF in diabetic patients with CAD

Iron-deficiency anemia is common in patients with heart failure (HF), but the optimum diagnostic tests to detect iron deficiency and the treatment options to replete iron have not been fully characterized. Recent studies in patients with HF indicate that intravenous iron can rapidly replenish iron stores in patients having iron-deficiency anemia, with resultant increased hemoglobin levels and improved functional capacity. Preliminary data from a subgroup analysis also suggest that supplemental intravenous iron therapy can improve functional capacity even in those subjects without anemia. The mechanisms responsible for this observation are not fully characterized, but may be related to beneficial effects of iron supplementation on mitochondrial respiration in skeletal muscle. The long-term safety of using intravenous iron supplementation in HF populations is not known. Iron is a known pro-oxidant factor that can inhibit nitric oxide signaling and irreversibly injury cells. Increased iron stores are associated with vascular endothelial dysfunction and increased risk of coronary heart disease events. Additional clinical trials are needed to more fully characterize the therapeutic potential and safety of intravenous iron in HF patients