Fatigue and anaemia in patients with chronic heart failure
Abstract
Background:
Fatigue is common in patients with chronic heart failure (CHF) and has great impact on functional ability and daily activity. Although anaemia is associated with fatigue, the relationship between fatigue and anaemia is unclear in CHF. The aim of this study was to describe the fatigue experience and its relationship to haemoglobin (Hb) concentration and to evaluate its effect on health-related quality of life in an unselected hospitalised CHF population.
Methods:
Ninety three consecutive patients hospitalised with a diagnosis of CHF, enrolled in the EuroHeart Failure Survey, completed the Multidimensional Fatigue Inventory Scale (MFI-20). New York Heart Association (NYHA) functional class, quality of life and haemoglobin were also assessed.
Results:
Anaemia (Hb≤125 g/L) was found in 31 (33%) patients. The perception of fatigue differed significantly between patients with CHF and healthy individuals. Anaemic patients reported significantly more fatigue compared to non-anaemic patients. Decreased haemoglobin and higher NYHA class explained 30% of the variance in General Fatigue. Perceived fatigue was also inversely related to global health and quality of life.
Conclusion:
Our findings suggest that the subjective experience of fatigue in patients with CHF is associated with low haemoglobin concentration and reduced functional status after controlling for age and sex.
1. Introduction
Chronic heart failure (CHF) is recognized as a major health problem in Western countries 1,2. CHF is a complex syndrome affecting not only the cardiovascular system but also the musculoskeletal, renal, neuroendocrine and immune systems 3 and is associated with impaired quality of life and shortened life expectancy 4,5. Fatigue and breathlessness are the two most prevalent symptoms in CHF 6,7. There is some evidence showing that fatigue predicts worsening CHF and breathlessness is associated with increased risk for death 8.
Fatigue is a frequently reported symptom in patients with CHF and approximately 10–20% of new cases of heart failure report fatigue as the major presenting symptom 9. Fatigue and breathlessness are also the primary symptoms used in the New York Heart Association (NYHA) system for classifying functional limitation and disability in CHF 10. Fatigue and dyspnea are highly correlated 7. Whilst fatigue prevents subjects from pursuing activities, dyspnoea generally commences before fatigue once activity is initiated. Other symptoms associated with fatigue include nausea, loss of appetite and light-headedness 11.
The mechanisms responsible for the development of fatigue in patients with CHF are not well understood. There are several physiological alterations associated with CHF that could play an important role. Two such factors are impaired peripheral circulatory perfusion with reduced oxygen delivery and impaired muscle strength 9. Anaemia is associated with fatigue in cancer 12 and renal dysfunction 13. In CHF, mild to moderate anaemia has been reported in 10–60% of patients, depending on the population studied and the definition of anaemia used. Anaemia is associated with worse symptoms and is a prognostic factor for mortality 1415161718.
Since fatigue is a common symptom in both anaemia and CHF, the relationship between these conditions and their impact on the subjective experience of fatigue needs to be explored.
Little information on potential associations between haemoglobin values, fatigue and perception of quality of life is available. The aims of this study were: (1) to describe the fatigue experience and explore differences between men and women; (2) to investigate the relationship between fatigue and haemoglobin concentration; and (3) to evaluate the effect of fatigue on health-related quality of life in an unselected hospitalised CHF population.
2. Method
2.1. Patients
Patients hospitalised for exacerbation of symptoms or with a primary discharge diagnosis of CHF were screened for eligibility to participate in the study. Inclusion criteria were: patients with a new or previous clinical diagnosis of heart failure presenting with symptoms of heart failure (breathlessness or fatigue at rest or during exercise); ability to understand and speak Swedish; and a willingness to give informed consent. All patients were part of the EuroHeart Failure Survey 19. Exclusion criteria were disorientation in space or time and communicative limitations (e.g. loss of hearing and speech). All patients underwent routine clinical management. Patients without recorded haemoglobin levels or those who failed to complete the fatigue questionnaire were excluded from the analyses.
2.2. Study variables and instruments
Fatigue was measured with the Multidimensional Fatigue Inventory (MFI-20) a 20-item self-report questionnaire covering five dimensions of fatigue: General Fatigue, Physical Fatigue, Reduced Activity, Reduced Motivation and Mental Fatigue 20. General Fatigue includes general statements about fatigue such as “I am tired” and is sensitive to changes in circumstances. Physical Fatigue concerns physical sensations related to feelings of tiredness. Mental Fatigue pertains to cognitive functions, including difficulties to focus and concentrate. Reduced Motivation relates to lack of motivation and starting any activity. Reduced Activity refers to a consequence of fatigue, namely reduction in activity.
Respondents rate each of the 20 statements against a 5-point scale, to record how much each statement applies to them during the past few days. Item ratings are summed to dimension scores ranging between 4 and 20, where a higher score indicates a higher level of fatigue. The instrument has demonstrated good reliability and has been used in different patient populations undergoing radiotherapy. The Swedish version of the MFI showed good internal consistency (Chronbach's alpha 0.75–0.94) in a study measuring fatigue during radiotherapy 21. The internal consistency reliability of the MFI five subscales in this sample ranged from alpha 0.56–0.87. Since the instrument has not been used in a CHF population, reference values from a previous study in healthy individuals 22 were used for comparison with our fatigue scores.
The New York Heart Association (NYHA) functional classification system was used to categorize the degree of functional disability based on symptoms and activity limitations 10. Patients were also asked during admission to rate two additional items concerning their perceptions of overall health and quality of life on a 7-point scale (1=very poor to 7=very good). The items were obtained from the EuroHeart Failure Survey questionnaire.
Definitions of anaemia vary considerably 23 and there is no universally agreed definition of anaemia in CHF. In this study, anaemia was prospectively defined as a haemoglobin level of ≤125 g/L according to the National Kidney Foundation guidelines 24 for anaemia in men and postmenopausal women. Plasma haemoglobin concentrations, measured closest to admission, were analyzed in the hospital central laboratory.
2.3. Procedure
Patients were recruited from the EuroHeart Failure Survey, a prospective survey aimed at describing the quality of care among patients hospitalized with heart failure in 24 countries within the European Society of Cardiology 19. All patients admitted to the Department of Medicine of a large university hospital were screened over 12 weeks. Data for this study were collected from hospital records and patient interviews. The interviews were performed at the hospital. In order to standardize the data collection method and minimize missing data, the questionnaires were read to the patients by the first author and the project coordinator. The patients' haemoglobin levels were extracted from their medical records. NYHA functional class was assessed in conjunction with the interviews. The study was approved by the Research Ethics Committee of Göteborg University and all patients gave informed consent before inclusion.
2.4. Statistical analysis
SPSS statistical software, version 11.5 was used for the data analysis. Data are expressed as mean±SD and percent where appropriate. Ordinal and continuous variables were compared using t-test and ANOVA, followed by post hoc comparisons using Tukey's HSD procedure. Nominal and dichotomous variables were compared using X2. Multiple regression analysis was performed to examine the contribution of haemoglobin concentration, NYHA class, sex and age to the variance in the fatigue dimensions. Pearson's correlation coefficient (partial) was used to explore the relationship between fatigue experience and perception of overall health and quality of life, controlling for NYHA. All tests were two-tailed and statistical significance was set to p<0.05.
3. Results
The final study population consisted of 93 subjects (48 men and 45 women). The mean age was 74±12 years. Women were significantly older than men; mean 78±11 versus 71±11 years (p=0.001). Eighty-eight patients (95%) lived at home and 31 (69%) of the women lived alone, compared with 20 (42%) of the men. Most of the patients (88%) were retired and 54 (61%) had a relatively low level of education (compulsory school); only 8 patients (9%) had college or university as the highest educational level. NYHA functional class I/II/III/IV were 5/37/46/5, respectively. No significant differences between sex and age were observed for NYHA-class. The aetiology of heart failure was ischaemic heart disease in fifty-six patients (63%), of these, forty-six (82%) were reported to have had a myocardial infarction. Other causes of heart failure were dilated cardiomyopathy (7%) and valve disease (6%). Reported concomitant diseases were diabetes n=46 (50%), disabling stroke n=2 (2%), renal failure n=7 (8%) and respiratory disease n=16 (17%). No correlation was found between these conditions and the fatigue experience. Nor did we find any statistically significant differences between the proportion of concomitant diseases in the anaemic and non-anaemic groups of patients.
Patients reported significantly higher fatigue scores on all MFI-20 fatigue dimensions compared to healthy individuals (p≤0.001). Physical Fatigue was the subscale with the highest score in both the study sample and in the reference group of healthy subjects (Table 1). No differences in reported fatigue experience were found between men and women. When the subjects were divided into three age groups: ≤64 years (n=19), 65–79 years (n=39) and =80 years (n=35). The mean scores for the dimension Reduced Motivation for the group aged <64 years (7.8±4.0) and the group aged 65–79 (9.3±3.7) years were significantly (P≤0.01) lower than for the group aged >80 years (12.0±4.0). No other statistically significant difference was found between age and the other fatigue dimensions.
| MFI-20 scale | Total n=93 | Men n=48 | Women n=45 | Gender difference (p-value) | Reference values | Difference between CHF patients and reference groupsa,b(p-value) | |
|---|---|---|---|---|---|---|---|
| 74 years, range 62 (mean±SD) | 71 years, range 43 (mean±SD) | 78 years, range 62 (mean±SD) | 60–69 yearsa (mean±SD) | 70–79 yearsb (mean±SD) | |||
| General Fatigue | 14.5±4.6 | 14.3±4.6 | 14.8±4.7 | 0.617 | 7.8±6.8 | 6.4±5.0 | <0.001 |
| Physical Fatigue | 16.1±4.2 | 15.9±4.3 | 16.3±4.0 | 0.650 | 8.8±6.8 | 6.2±4.8 | <0.001 |
| Reduced Activity | 14.0±4.5 | 13.3±4.9 | 14.8±4.0 | 0.112 | 8.4±7.0 | 4.4±4.8 | <0.001 |
| Reduced Motivation | 10.0±4.2 | 9.2±4.2 | 10.9±4.0 | 0.550 | 5.0±4.8 | 3.2±3.4 | <0.001 |
| Mental Fatigue | 9.8±4.5 | 9.9±4.7 | 9.8±4.3 | 0.936 | 5.2±5.8 | 3.8±4.2 | <0.001 |
- a Reference values from a healthy population of women and men, aged a60–69 (n=181) and b70–79 (n=151) years 22.
The mean haemoglobin level was 133±21 g/L. No significant difference was found between men (135±19 g/L) and women (132±23 g/L). There was no interaction with age and no significant difference between NYHA class and haemoglobin levels. Anaemia, defined as a haemoglobin level ≤125 g/L, was found in 31 (33%) patients. The mean haemoglobin level in patients with anaemia was 110±14 g/L (114±11 g/L for men, n=15 and 107±17g/L for women, n=16). No statistical differences were found between anaemic and non-anaemic patients as to sex, age, and educational status and NYHA class or between anaemic and non-anaemic patients due to aetiology of heart failure. Anaemic patients reported significantly more fatigue compared with non-anaemic patients on all MFI-20 dimensions except Reduced Motivation, see Table 2. Severe anaemia (≤109 g/L) was found in 10 patients (3 men and 7 women) and moderate anaemia (110–125 g/L) in 21 patients (12 men and 9 women). No significant difference in reported fatigue was found between patients with moderate and severe anaemia.
| MFI-20 scale | Anaemic patients (n=31) mean±SD | Non-anaemic patients (n=62) mean±SD | p-value |
|---|---|---|---|
| General Fatigue | 16.8±3.4 | 13.4±4.8 | <0.01 |
| Physical Fatigue | 17.4±3.4 | 15.5±4.4 | <0.05 |
| Reduced Activity | 15.5±3.3 | 13.3±4.9 | <0.05 |
| Reduced Motivation | 10.5 ± 4.6 | 9.8±4.0 | NS |
| Mental Fatigue | 11.6±4.5 | 9.0±4.2 | <0.01 |
A multiple regression analysis was used to explore the relationship between the five dimensions of fatigue and NYHA class and haemoglobin levels, controlling for age and sex. We found that 30% of the variance in General Fatigue was explained by decreased haemoglobin level (β=−0.23) and higher NYHA classes (β=0.47), while 21% of the variance in Physical Fatigue and 8% of the variance in Reduced Activity were accounted for by a poorer (higher) NYHA class. There were no significant associations between Reduced Motivation, Mental Fatigue and NYHA class and haemoglobin values. The variance in Reduced Motivation was only significantly explained by age (r2=0.16).
The relationship between the fatigue experience and perceived global health and quality of life was explored and significant negative correlations, after controlling for NYHA class, were found see Table 3. Sex and age were unrelated to either perceived global health or quality of life.
| General Fatigue | Physical Fatigue | Reduced Activity | Reduced Motivation | Mental Fatigue | |
|---|---|---|---|---|---|
| Global health | −0.389** | −0.469** | −0.409** | −0.208 | −0.185 |
| Quality of life | −0.285** | −0.423** | −0.346** | −0.222* | −0.235* |
- * p=<0.05,
- ** p=<0.01.
4. Discussion
Compared with healthy individuals, patients with CHF experienced significantly higher levels of subjective fatigue as measured by the five subscales of the MFI-20. We found that 33% of the CHF patients in this study were anaemic; no differences were found between patients who were anaemic and those who were not anaemic with regard to age or sex, and there was no significant association between haemoglobin levels and NYHA class. We found a significant difference in the fatigue experience between the anaemic and non-anaemic patients, except for Reduced Motivation.
Physical fatigue and a general sensation of fatigue rather then mental fatigue seem to be dominant in patients with CHF. This is in line with the significant relationship we found with NYHA class, which assesses functional limitation due to fatigue and breathlessness. Although we found no significant sex related difference in fatigue scores, there was evidence for Reduced Motivation in the group ≥80 years. Since the women in our study were significantly older and overrepresented in this age group, one might assume that the women were less motivated than the men. Ekman and Ehrenberg 25 found good agreement between men's and women's descriptions of their experiences of fatigue; however, women showed greater variation than men in attributing fatigue to old age. Other studies confirm that many patients accept their condition as normal and perceive fatigue as a result of aging 11. This is one reason why patients do not seek medical attention for their fatigue 26. Our findings are consistent with previous studies 27,28 reporting no association between haemoglobin concentration and degree of CHF, as reflected by NYHA. However, other studies have reported a relationship between severity of symptoms and anaemia 16,18,29.
Symptoms of anaemia consist of fatigue, mild dyspnoea on exertion and occasionally palpitations 30. The fact that these symptoms overlap those of CHF (e.g., fatigue, dyspnea and palpitations) makes the evaluation of symptoms of anaemia in CHF patients challenging. Symptoms alone cannot be relied upon to indicate whether low haemoglobin values or poorer (higher) NYHA class are contributing to fatigue and functional limitations; however, there seems to be a difference in the characteristics of fatigue experience in anaemia versus CHF. Fatigue associated with restrictions in physical activity seemed to be more strongly related to poorer NYHA class, while fatigue related to lower haemoglobin values was characterized by a general sensation of tiredness, not necessarily combined with physical strain.
Since we found no association between NYHA class and anaemia, one can expect that both low haemoglobin values and deterioration in heart failure contributed independently to the fatigue experience in this study. After controlling for age and sex, we found that poorer NYHA class and decreased haemoglobin values predicted 30% of the variance in General Fatigue while NYHA class explained 21% of the variance in Physical Fatigue and 8% of the variance in Reduced Activity. Despite a significant correlation between General Fatigue and haemoglobin, these results indicate that haemoglobin values only partially explain subjectively experienced fatigue. It is therefore suggested that treatment and care of fatigued patients with CHF must involve all areas that might contribute to the experience.
One treatment strategy that may be of benefit to fatigued patients with CHF is the use of patient education programs on fatigue and coping strategies. Although there are no studies that have specifically assessed the effects of such programs on fatigue and its consequences, positive effects of patient education programs on self-care and normal daily activities have been reported 31. It would seem reasonable to expect that fatigue is responsible for a variety of limitations in self-care and coping with daily life for patients with CHF. It is well documented that non-adherence to treatment is common in patients with CHF 32, leading to repeated hospitalisations and unnecessary suffering for the patients themselves and high expenditure for the health care system.
The optimal target haemoglobin concentration for treatment has yet to be determined and further investigation of anaemia in patients with CHF is vital to answer this question 33. However, Silverberg et al. 17,34 found that when anaemia was corrected with erythropoietin and iron, the patients' functional status improved with reduced fatigue and shortness of breath, followed by improved health-related quality of life and a reduction in hospitalization.
We found that General Fatigue, Physical Fatigue and Reduced Activity were negatively correlated with global quality of life and general health perceptions, obtained from the EuroHeart Failure Survey questionnaire. Although it is well documented that health-related quality of life is moderate to low in patients with CHF 35,36, the contributions of fatigue are not well described in the literature. Since the experience of fatigue seems to strongly limit the ability to perform activities and impacts on daily life, one can assume that it also considerably affects wellbeing. Improving health-related quality of life is one of the major goals of therapy for patients with CHF and consequently fatigue must be a target for interventions.
4.1. Limitations
The MFI-20 fatigue scale has not been validated in heart failure patients. The present study was carried out in hospitalized patients who were probably more symptomatic than stable CHF patients in outpatient care. We therefore recommend that further investigations be carried out with the MFI-20 in patients with CHF. Another limitation was that the causes of anaemia, e.g. renal failure or iron deficiency, were not adequately established in our study. Such information could potentially help to clarify the relationship between anaemia and fatigue experience. Myocardial function was not documented as part of this study but all patients had a hospital based discharge diagnosis of CHF.
4.2. Conclusions
The experience of fatigue in patients with CHF is associated with low levels of haemoglobin and reduced functional status assessed according to the NYHA classification system. Anaemia constitutes a triad of subjective characteristics, i.e. fatigue, breathlessness and palpitations that need to be considered in the evaluation of patients with CHF. Prospective intervention trials aimed at correction of anaemia are needed to evaluate whether fatigue in these patients can be improved by treatment of anaemia.
