• Vascular Annual Meeting^®
• Registration
• Hotel Reservations
• Schedule-at-a-Glance
• Program-in-Detail
• Wednesday, June 9 - Postgraduate Courses Day
• Thursday, June 10
• Friday, June 11
• Saturday, June 12
• Sunday, June 13
• International Attendee Information
• General Information
• New in 2010
• Call for Abstracts
• Speaker Information
• Exhibitor Information
• Alumni Association Information
• Future Meeting Dates
• 2009 Meeting Information
• Contact Us

Home > Vascular Annual Meeting^® > LB6. Iron Storage, Inflammatory Biomarkers, and...

LB6. Iron Storage, Inflammatory Biomarkers, and Mortality in Stable Peripheral Arterial Disease: a Substudy of the Iron and Atherosclerosis (FeAST) Trial

Ralph G. DePalma1,2, Virginia W. Hayes2,  Bruce K. Chow3, Galina Shamayeva3, Patricia E. May2, Leo R. Zacharski4  1Department of Veterans Affairs, Washington, DC; 2VA Sierra Nevada Health Care System, Reno, NV; 3VA Palo Alto Health Care System, Menlo Park, CA; 4VA New England Health Care System, White River Junction, VT

OBJECTIVES: This research aimed to define relationships between iron storage and inflammatory biomarkers in cohort of 100 participants at the VA Sierra Nevada Health Care System (SNHCS) with peripheral arterial disease (PAD). A prospective randomized single blind clinical trial entering 1,277 cancer-free patients with advanced peripheral arterial disease (PAD) from 24 participating VA hospitals (VA Cooperative Study #410, The Iron and Atherosclerosis Study (FeAST)) tested the hypothesis that iron in excess of physiologic requirements contributes to atherosclerosis. Patients were randomized to calibrated iron reduction by graded phlebotomy or control groups. The primary outcome was all cause mortality and the secondary outcome death plus non-fatal myocardial infarction and stroke. Data on cardiovascular disease (CVD) outcomes and on the occurrence of new cancer diagnosis and cancer-specific mortality were collected prospectively and analyzed by intent-to-treat. In the main study population iron reduction resulted in a significant age-related improvement in primary and secondary (CVD) as well as cancer mortality. Levels of ferritin correlated with inflammatory biomarkers during the SHNHC substudy.

METHODS: Approval was obtained to measure cytokines IL 6, TNFa, receptors 1 and 2, IL 2, IL 10 and high sensitivity C reactive protein (hs CRP)at entry and at 6-monthly follow-up intervals on 100 participants followed over the 6-year study duration. We explored relationships between iron status (ferritin levels) and inflammatory markers at entry and during follow-up in this subset of FeAST participants.

RESULTS: The average age at entry was 67+/-9 yrs in both the main and substudy participants. Clinical and laboratory parameters at entry were comparable in participants randomized to iron reduction (n = 51) and control (n = 49). At baseline 53 entrants receiving statins trended lower mean ferritin levels (114.06 ng/ml; CI 93.43–134.69) compared to 47 participants not receiving statins (mean 127.6 ng/ml; CI 103.21-152.02) (p=NS)  During the study interval 31 additional subjects started on statins. Longitudinal analysis using all follow-up data showed that after adjusting for the phlebotomy treatment effect, statin has a significant effect on the reduction of ferritin (-29.78 ng/ml) with a Cohen effect size of -0.47 (t=2.33, p=0.0123).  Mean follow-up ferritin levels were higher in 23 participants that died compared to the 77 survivors (132 vs 86.3 ng/ml p= 0050. Mean follow-up IL-6 levels were higher in the 23 participants that died compared to the 77 survivors (p =0.03). Pearson correlations showed significant relationships between levels of ferritin and IL-6 (p =0.002) and hsCRP (p = 0.04).

CONCLUSIONS: These data support the hypothesis that iron catalyzed oxidative stress may contribute to inflammation in patients with PAD.

AUTHOR DISCLOSURES: R.G. DePalma, None; V.W. Hayes, None; B.K. Chow, None; G. Shamayeva, None; P.E. May, None; L.R. Zacharski, None.