In this study, both anemia and chronic kidney disease were highly prevalent among HF patients discharged from two university hospitals and independently associated with an increased risk of dying in the hospital or of being readmitted within 30 days. The association between CKD, anemia and these outcomes (inhospital mortality and readmission) in HF patients has not been reported previously. Most studies have focused only on survival after hospital discharge as an outcome.
One study, in the framework of the SOLVD study, included only patients with left ventricular dysfunction. The risk of increased mortality associated with a 1% reduction in hematocrit was 2.7% [22
]. These results were comparable to another study conducted among Medicare beneficiaries in community hospitals in the US. In this latest study, patients with left ventricular diastolic dysfunction were also included as patients with left ventricular systolic dysfunction. The risk of death associated with a 1% reduction in hematocrit was 2% [23
]. In a new large recent study, among HF patients, chronic kidney disease and anemia were found independently to confer a twofold increased risk of death [25
]. Silverberg et al. recently reported that, in a randomized trial of 32 ambulatory HF patients with NYHA class III and IV and an hemoglobin < 12 g/dL, the correction of anemia was associated with an improved functional status and decreased hospitalization. However, the major limitation of this study was its small sample size and the fact that the randomization was not blinded [26
]. These observations suggest that anemia is a clinically important risk factor for death and readmission among heart failure patients, with or without CKD. The clinical implication of these findings for patients with HF is that failure to correct severe anemia among patients with CKD confers a preventable burden of reduced quality of life, while clinical trials have demonstrated that correction of anemia improved these measures. HF patients should be carefully examinated for presence of CKD and anemia and, if present, treated according to current evidence [27
]. Treating anemia among inpatients with HF and CKD may then reduce inhospital mortality and early readmission. However, currently no large clinical trials have been conducted to evaluate the effect of erythropoietin therapy on survival or readmission among patients suffering from HF and CKD.
In our study we found that, among HF patients, the prevalence of CKD was 25% among males and 20% among females respectively. However, by using this cut-point of a serum creatinine of ≥ 124 μmol/L for women and ≥ 133 μmol/L for men for defining CKD, we underestimated the true prevalence of CKD especially among elderly people. We choose these cut-points based on previous studies implemented in the USA [23
]. Reduced kidney function occurred frequently in patients with HF. Two studies have shown that creatinine clearance less than 60 ml/minute was present in 20 to 50% of HF patients [28
]. In another study, which included Medicare beneficiaries with heart failure hospitalized in community hospitals, 38% had CKD. In this cohort, the prevalence of CKD was 33% in females and 46% in males [23
]. Our results are similar to those found in these studies and show that CKD is highly prevalent among HF patients.
Interest in the relationship between HF and anemia is growing. Anemia commonly complicates HF (14–28% of patients depending on the cut off used) [30
] and is a potential exacerbating factor [31
]. In our study the prevalence of anemia (hemoglobin < 12 g/dL) among HF patients was 28%. In another study performed in one Swiss university hospital, the prevalence of anemia was 15% [13
]. Silverberg et al. showed that the prevalence of anemia increased with the severity of HF and reached almost 80% in those patients with a NYHA class IV [26
]. Anemia observed among individuals with HF is highly multi-factorial, but, a decreased renal function is a cause in numerous patients [32
Anemic patients with chronic renal failure should receive treatment with recombinant human erythropoietin (r-HuEPO, Eéoetin) to maintain hemoglobin levels over 11 g/dL with an acceptable target of 12 to 12.5 g/dL, according to recommendations from the European practice guideline for management of anemia in patients with chronic renal failure [33
] and the National Kidney Foundation K/DOQI clinical practice guidelines for anemia of chronic kidney disease [27
]. Benefits of adequate hemoglobin levels had been established in patients undergoing dialysis, and are supposed to be relevant also in CKD patients. In addition, anemic patients should receive iron supplementation in order to maintain serum ferritin levels above 100 μg/L and transferrin saturation above 20%.
This study had a number of limitations. It is an observational study based on information available in medical records. The chart abstraction process was implemented in each hospital by different persons with different education and backgrounds, although with similar training. Then, in one hospital the entire medical chart was available to the abstractors, whereas in the other only the electronic discharge letter, laboratory findings and reports from cardiology testing were available. In addition, the quality of medical records and completeness of information may also vary between centers. Incorrect information may have led to some misclassification bias. Further this study was conducted on an opportunity sample of two hospitals, making the generalisibility of results uncertain. Then, we excluded patients with valvular heart disease and acute myocardial infarction, because it was our intent to focus on a homogenous group of individuals with established heart failure. However, we agree that the issue of anemia and outcomes in both of these patient groups is important. Further, we were not able to exclude other causes of anemia, including the presence of iron, folate and vitamin B12 deficiencies, dilutional anemia, and the anemia of chronic diseases different from CKD, as explanations for anemia observed in this population and perhaps, to account for some potential confounders. Then, given the relative high number of elderly patients in the study population and that these patients may have CKD even with normal creatinine value; we underestimated the true prevalence of CKD. Finally, we acknowledge that we were not able to measure others risk factors associated with epo-resistance such as immune activation. We will consider measuring it in future studies. However, we would like to emphasis that the concerns about ACEI and anemia should not keep physicians from using ACE inhibitors in their management of heart failure.