Elsevier

International Journal of Cardiology

Volume 205, 15 February 2016, Pages 6-12
International Journal of Cardiology

The impact of iron deficiency and anaemia on exercise capacity and outcomes in patients with chronic heart failure. Results from the Studies Investigating Co-morbidities Aggravating Heart Failure

https://doi.org/10.1016/j.ijcard.2015.11.178Get rights and content

Abstract

Anaemia and iron deficiency (ID) are important co-morbidities in patients with chronic heart failure (HF) and both may lead to reduced exercise capacity.

Methods

We enrolled 331 out-patients with stable chronic HF (mean age: 64 ± 11 years, 17% female, left ventricular ejection fraction [LVEF] 35 ± 13%, body mass index [BMI] 28.5 ± 5.2 kg/m2, New York Heart Association [NYHA] class 2.2 ± 0.7, chronic kidney disease 35%, glomerular filtration rate 61.7 ± 20.1 mL/min). Anaemia was defined according to World Health Organization criteria (haemoglobin [Hb] < 13 g/dL in men, < 12 g/dL in women). ID was defined as serum ferritin < 100 μg/L or ferritin < 300 μg/L with transferrin saturation (TSAT) < 20%. Exercise capacity was assessed as peak oxygen consumption (peak VO2) by spiroergometry and 6-minute walk test (6MWT).

Results

A total of 91 (27%) patients died from any cause during a mean follow-up of 18 months. At baseline, 98 (30%) patients presented with anaemia and 149 (45%) patients presented with ID. We observed a significant reduction in exercise capacity in parallel to decreasing Hb levels (r = 0.24, p < 0.001). In patients with anaemia and ID (n = 63, 19%), exercise capacity was significantly lower than in patients with ID or anaemia only. Cox regression analysis showed that after adjusting for NYHA, age, hsCRP and creatinine anaemia is an independent predictor of mortality in patients with HF (hazard ratio [HR]: 0.56, 95% confidence interval [CI]: 0.33–0.97, p = 0.04).

Conclusion

The impact of anaemia on reduced exercise capacity and on mortality is stronger than that of ID. Anaemia remained an independent predictor of death after adjusting for clinically relevant variables.

Introduction

Anaemia and iron deficiency (ID) are prevalent in patients with chronic heart failure (HF) and their presence may, but does not necessarily overlap. Both anaemia and ID are associated with worse symptoms and adverse clinical outcomes [1]. In the last decade, there has been an enormous interest in the subject of ID and anaemia and their management in patients with HF. Many questions with regard to the role and therapy of the two clinical entities have not been answered to date. Komajda et al. [2] showed a prevalence of anaemia of 15.9% and an incidence of 14.2% over one year. Importantly, hospitalized HF patients with anaemia showed a 43% higher risk of death than non-anaemic patients [2]. In general, anaemic patients are older, more often female and present with hypertension and chronic kidney disease [3]. In addition, it needs to be acknowledged that anaemia may be the cause of HF or may contribute to its progression and to the patients' clinical deterioration. The prevalence of ID is high – even in the absence of anaemia – in patients with chronic HF. Although ID can be easily diagnosed using two biomarkers (serum ferritin and transferrin saturation, TSAT), it remains underdiagnosed in patients with HF [4]. Thus, ID remains undertreated even though patients may benefit symptom-wise.

The aetiology of anaemia in HF is a matter of ongoing debate. Using hospital discharge codes, Ezekowitz et al. [5] showed that absolute ID was found in only 21% of patients discharged from hospital with a main diagnosis of HF. However, 58% of the remaining patients were diagnosed with anaemia of chronic disease in which iron cannot be mobilized due to an inflammatory cascade being active [5]. Most iron in the body is bound to haemoglobin (Hb), thus it is important to differentiate between ID with normal Hb and ID anaemia. The differential diagnosis of the different forms of anaemia is rather complex and ID and anaemia are important factors that limit patients' exercise capacity and can be used as predictors of unfavourable outcomes [6], [7], [8], [9]. Therefore the influence of anaemia and ID on exercise capacity and outcomes is of outstanding interest in patients with HF.

The aim of this study was to examine the impact of anaemia and ID on exercise capacity as assessed by spiroergometry testing and by the six minute walk test using data from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). SICA-HF is a multi-national, pathophysiological observation study into HF and its co-morbidities [10]. Using these data, we also assessed the prevalence of anaemia and ID in patients with HF along with their influence on mortality.

Section snippets

Methods

We analysed data of subjects enrolled into SICA-HF between February 2010 and March 2014 at participating center in Berlin (Charité Medical School, Campus Virchow-Klinikum) and Wroclaw (Laboratory for Applied Research on Cardiovascular System, Medical University Wroclaw). We included 331 patients who were followed until death or until April 2014 when the follow-up was censored. All subjects provided written informed consent at enrolment, and the local ethics committees approved the protocol. The

Results

A total of 331 out-patients with stable chronic HF were enrolled. Their baseline characteristics are presented in Table 1. Their medication and co-morbidities are presented in Table 2. Patients were predominantly male with a mean age of 64 ± 11 years ranging from 24 to 88 years. The left ventricular ejection fraction (LVEF) ranged from 10 up to 70% with a mean of 34.7 ± 13% and a median of 31% (interquartile range, 25–40%). A total of 70 patients (34%) were found with LVEF ≥ 40% and 253 patients

Discussion

In our cohort of patients with chronic HF, the prevalence of anaemia was 30% and that of ID was 45%. We found the presence of ID and/or anaemia to be strongly associated with decreased exercise capacity. Exercise capacity decreased with ID and worsened even further in patients who were also anaemic (Fig. 2). The maximum oxygen uptake as a quantitative value was directly correlated with the Hb value (Fig. 3). The association between exercise capacity and Hb is stronger in anaemic patients, and

Conclusion

Anaemia is an important comorbidity in patients with chronic HF and important determining factor of exercise capacity. ID anaemia worsened exercise capacity to a larger extent than anaemia or ID alone. Regardless of whether or not patients had ID, or the severity of HF, the presence of anaemia showed a significant association with mortality after adjustment for confounding factors.

Conflict of interest

Stephan von Haehling has been a paid consultant to Thermo Fisher Scientific, Solartium Dietetics, Professional Dietetics, Pfizer, Respicardia and Vifor Pharma; he has received payment from the Heart Failure Association of the European Society of Cardiology to develop educational presentations and travel support from Novartis Pharma; his institution has received a research grant from Vifor Pharma. Stefan Anker has been a paid consultant to Amgen, Bosch Healthcare, Professional Dietetics,

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