FEAST substudy: Higher ferritin levels linked with increased inflammation biomarkers

Ferritin levels were also higher in patients who died during follow-up.

Issue: August 2009

Increased ferritin levels were associated with increased inflammation in patients with peripheral arterial disease, according to results from an analysis.

FEAST studied the relationship between iron storage and inflammatory biomarkers. They enrolled 1,277 patients with PAD and evaluated a cohort of 100 patients for the analysis. Patients were randomly assigned to calibrated iron by graded phlebotomy group (n=51) or a control group (n=49). The primary outcome was all-cause mortality, with a secondary outcome of death plus nonfatal MI and stroke. The researchers also monitored cytokines interleukin-6, TNF alpha, receptors 1 and 2, IL-2, IL-10 and high-sensitivity CRP levels at entry and again at six months.

According to the results of the analysis, 53 entrants who were assigned to statins at baseline trended toward lower ferritin levels (mean 114.06 ng/mL) compared with 47 patients who were not assigned to statins (mean 127.6 ng/mL). A longitudinal analysis revealed that after adjusting for the phlebotomy treatment effect, statins had an effect on the reduction of ferritin levels (–29.78 ng/mL). Mean ferritin levels were higher in the 23 patients who died during follow-up vs. the 77 survivors (132 ng/mL vs. 86.3 ng/mL). The researchers also reported that mean IL-6 levels were higher in the patients who died vs. the survivors (P=.03).

“We may consider recommending blood donation by men and nonmenstruating women,” said Ralph G. DePalma, MD, national director of surgery for the Department of Veterans Affairs in Washington, D.C., and a professor of surgery at the Uniformed Services University of the Health Sciences in Bethesda, Md. “We may also consider reduction of iron intake, red meat and iron supplementation in food, and certainly these results provide biological support of more trials of robust iron reduction in younger individuals.” – by Eric Raible

For more information:

DePalma RG. #LB6. Presented at: Vascular Annual Meeting; June 11-14, 2009; Denver.

The association between iron metabolism and inflammation is intriguing. However, dealing with data presented in abstracts is fraught with difficulty because often some of the important methodological issues cannot be described due to the limitations on space. This study, attempting to link inflammatory markers and ferritin levels, is a good example. Ferritin levels and values of IL-6, and as might be expected, CRP (since IL-6 is thought to be the proximate stimulus for increases in CRP), were associated with adverse events, the former even after correcting for the beneficial effects of phlebotomy and statin use. Was the same correction done for the inflammatory markers? Are there other important covariants that should or perhaps have been taken into account? A large number of inflammatory markers were measured. To what extent might one expect one or the other to be abnormal in a small cohort? The abstract says that the values used in the analysis were “follow-up” values. Does that mean the follow-up values for each person were averaged? What was done to patients who were censured?

It may well be that all the i’s will be dotted and t’s crossed in the manuscript, but scientific rigor dictates that we should see that before we accept the concept that these markers are associated or particularly, the concept that they may be causally related. Nonetheless, the apparent association is intriguing.

– Allan S. Jaffe, MD

Cardiology Today Editorial Board member