Anemia, erythropoietin and iron in heart failure

In this thesis, two comorbidities have been studied that are very prevalent in patients with heart failure. Both comorbidities exacerbate the already low oxygen transport in these patients: anemia and iron deficiency. It is known that both anemia and iron deficiency have profound effects on the quality of life and prognosis of patients with heart failure. Because of that, both are considered interesting targets of treatment. Anemia is often treated using erythropoietin (EPO) injections. The benefits hereof are limited while it bears the risk of severe side effects. I show that one fourth of patients with heart failure does not respond well to EPO, and that it is difficult to predict which patients this will be. Additionally, I show that subjects from the general population, who produce high EPO levels, have more cardiovascular risk factors and are at increased risk of developing heart failure.
In part two, I constructed a reliable definition for iron deficiency using the gold standard of bone marrow iron staining as a reference. Using these bone marrow iron stainings, I studied different causes of iron deficiency. I showed that these distinct forms have diverse consequences for patients with regard to symptoms and prognosis. In human cardiac muscle cells, I induced iron deficiency which caused cells to have an impaired contraction and relaxation. This could be almost fully restored after the supplementation of iron. Finally, I used genetic data to provide evidence that a higher iron storage protects from the development of coronary artery disease.