EFFECT OF REDUCTION OF IRON STORES ON VASCULAR …



EFFECT OF REDUCTION OF IRON STORES ON VASCULAR AND CANCER OUTCOMES IN PATIENTS WITH PERIPHERAL ARTERIAL DISEASE (PAD): VA COOPERATIVE STUDY #410, THE IRON AND ATHEROSCLEROSIS STUDY (FEAST)

L.R. Zacharski1,2, B.K. Chow3,4, G.Shamayeva3,4, P.W. Lavori3,4

1VA Medical Center, White River Jct., Vermont and Department of Medicine, 2Dartmouth Medical School, Lebanon, New Hampshire, 3Palo Alto CSPCC, Palo Alto, California, 4VA Medical Center, Palo Alto, California, USA

Age-related iron accumulation has been implicated in cardiovascular and cancer risk through iron-catalyzed free radical damage. Effects of iron reduction by phlebotomy were tested in a 6-year, controlled clinical trial in 1,277 cancer-free PAD patients. Overall differences between iron reduction and control groups for all cause mortality or death plus non-fatal myocardial infarction (MI) and stroke were not statistically significant. However, graded improvement in outcomes by age quartile was statistically significant for death plus non-fatal MI and stroke (p = 0.004). Benefits from iron reduction occurred in the youngest age quartile for both all cause mortality (p = 0.02) and death plus non-fatal MI and stroke (p < 0.001). Age analyzed as a continuous variable was significantly associated with improved outcome for both endpoints (p = 0.04 and 0.001 respectively). Iron reduction resulted in a 37% lower incidence of new cancer (p = 0.025), reduced cancer risk on Kaplan-Meier (p = 0.036) and Cumulative Incidence (p = 0.019) analysis, and reduced cancer-specific (p = 0.003) and all-cause (p = 0.009) mortality in patients diagnosed with cancer. Minimal cancer risk occurred with follow-up ferritins below about 60 ng/ml. Reduced cancer risk with iron reduction occurred within 6 months follow-up regardless of age. Ferritin levels found commonly in adults are associated with disease risk while levels characteristic of childhood and pre-menopausal women (below about 60 ng/ml) carry reduced risk. Findings suggest strategies for non-toxic, low-cost, population-based disease prevention and treatment.

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