Abstract 3358: Resistance to Endogenous Erythropoietin Predicts Survival in Anemic Heart Failure Patients
Background In response to hypoxia the kidney produces erythropoietin (EPO). Elevated levels of EPO are observed in patients with chronic heart failure (CHF) and are related to an impaired outcome. However it is unknown whether these EPO-levels are adequate for the degree of anemia and how the adequacy of EPO levels relates to prognosis.
Methods Therefore, we studied 240 CHF patients (96% were in NYHA functional class III). The adequacy of EPO levels was assessed by an observed-predicted ratio. A value <0.9 indicates inadequate low EPO levels (=blunted EPO-response), whereas >1.1 indicates inappropriate high EPO levels (=EPO resistance). Group comparisons were therefore made between
low EPO responders n = 30
normal EPO responders n = 25
EPO-resistance n = 22. Anemia was defined according to the WHO definition (males and postmenopausal females Hemoglobin (Hb) < 3.0 g/dL and premenopausal females Hb < 12.0 g/dL). The primary endpoint was mortality.
Results During a median follow up of 3.8 years, 98 patients died (41.4% mortality rate). EPO levels were an independent predictor of mortality, also adjusted for hemoglobin levels (HR 1.013, 95%CI [1.007–1.018], p=0.001). Anemia was present in 77 (32%) patients. Inadequate low EPO levels were observed in 30 anemic patients (39%) and related to renal failure (glomerular filtration rate < 30 ml/min/1.73m2 (p<0.009). EPO resistance was present in 22 anemic patients (29%) and was associated with a significant higher mortality rate compared to patients with a normal EPO response and a low EPO response, 72.7% vs 34.8% and 40.0% respectively (p=0.012 and p=0.021, respectively). EPO resistance was an independent predictor of an increased mortality risk in Cox regression analyses adjusted for variables with p<0.10 in the univariate analysis including age, sex and high sensitive CRP; HR 2.63 95%CI [1.12– 6.17], p=0.026, whereas a low EPO response was not associated with an impaired outcome; HR 1.12 95% CI [0.45–2.79], p=0.81, compared to normal EPO responders.
Conclusion EPO resistance is common in CHF patients and is associated with a high mortality.