Effect of Rosuvastatin on Hemoglobin Levels in Patients With Anemia and Low‐Grade Inflammation: A Post Hoc Analysis of the JUPITER Trial

1483 2011 51 1483-1487 T anemia of chronic disease (ACD) affects app­ roximately 3% of adults over age 65 and often occurs in patients with inflammatory conditions such as rheumatoid arthritis, inflammatory bowel disease, lupus, and chronic infection. One of the primary mechanisms underlying ACD is a functional iron deficiency caused by immune­mediated changes in iron homeostasis. These changes are regulated by the peptide hormone hepcidin whose expression is increased during inflammation, infection, and iron overload but suppressed by anemia and hypoxia. High levels of circulating hepcidin create an iron­ restricted environment by decreasing intestinal abs­ orption of iron and preventing the release of iron stored in macrophages. Pharmacologic interventions that lower hepcidin levels could have therapeutic value in the treat­ ment of ACD. Both hepcidin and C­reactive protein (CRP) expression are thought to be induced by interleukin­6 (IL­6) during inflammation. In a phase III trial in rheumatoid arthritis patients, it was observed that patients treated with an experimental IL­6 receptor inhibitor plus methotrexate had lower CRP levels and increased hemoglobin concentra­ tions at 24 weeks relative to patients on placebo plus methotrexate. HMG CoA reductase inhibitors (stat­ ins) are also known to reduce CRP levels, possi­ bly through interference with the IL­6 signaling pathway. Therefore, it is possible that statins may also reduce hepcidin levels. This hypothesis is sup­ ported by a randomized study of 40 patients with end­stage renal disease which found that patients assigned to receive fluvastatin had lower serum levels of prohepcidin, a hepcidin precursor, than patients assigned to receive placebo. We hypothesized that in patients with ACD, stat­ ins would decrease hepcidin levels and raise hemo­ globin concentrations. We explored this hypothesis in a post hoc analysis of a large randomized, placebo­ controlled trial of rosuvastatin in patients with moder­ ate inflammation. We assessed the effects of ros u vastatin therapy on hemoglobin concentrations among patients with anemia at baseline.