Prevalence of anemia and effects on mortality in patients with heart failure

doi:10.1016/j.ahj.2004.08.039

American Heart Journal

Volume 149, Issue 3, March 2005, Pages 391-401

https://doi.org/10.1016/j.ahj.2004.08.039 Get rights and content

Background

In patients with chronic kidney disease, the adverse cardiovascular effects of anemia have been well established. New data are emerging to suggest anemia may represent an important treatable cause of cardiac morbidity and mortality in patients with heart failure. To improve the understanding of the problem of anemia in heart failure, it is important to assess the factors that influence the prevalence of anemia and to assess the consistency of the association of anemia and mortality in various populations of patients with heart failure.

Methods

A systematic review of the literature was conducted by performing detailed searches of MEDLINE and EMBASE, searching the bibliographies of the articles retrieved during the database search, and conferring with heart-failure experts involved in clinical trials.

Twenty-eight publications from 26 studies that evaluated anemia prevalence with or without effects on mortality in patients with heart failure were identified. The definition of anemia used in each study was tabulated along with pertinent patient characteristics, the prevalence of anemia, and the association between anemia and mortality.

Results

Anemia is common among patients with heart failure. The prevalence of anemia increases with increasing severity of heart failure, declining renal function, and increasing age. Anemia is consistently associated with poorer survival in all patient populations, but there are substantial differences in the patient populations and definition of anemia.

Conclusions

To clarify the prognostic relationship of anemia in patients with heart failure, a standard definition of anemia should be adopted accounting for the menopausal status of women. Age, severity of heart failure, evaluation of kidney function, important comorbidities, and use of angiotensin-converting-enzyme inhibitors should be included, and correctable causes of anemia should be excluded. Inclusion of these factors should allow better definition of the relationship between anemia and prognosis in patients with heart failure.

Section snippets

Search strategy

This systematic review of the literature was designed to identify and review studies evaluating the prevalence and prognostic import of anemia in patients with heart failure. The search included the US National Library of Medicine database (MEDLINE) and the Excerpta Medica database (EMBASE). The bibliographies of the articles retrieved during the database search were also individually reviewed for articles matching the search criteria. The MEDLINE search included articles from January 1966

Results

Twenty-six studies from 28 publications reported the prevalence of anemia in patients with heart failure and included a total of 203 600 patients. Three studies evaluated Medicare populations, 6 studies evaluated patients discharged from hospital, 10 studies evaluated outpatient populations, and 7 studies included patients from clinical research studies (Table I).5., 6., 7., 9., 10., 11., 12., 13., 14., 15., 16., 17., 18., 19., 20., 21., 22., 23., 24., 25., 26., 27., 28., 29. The definitions of

Discussion

The prevalence of anemia in patients with heart failure varies enormously among studies. This marked variation is due to a number of factors, including differences in the definition of anemia, substantial differences in populations studied, a lack of information about correctable causes of anemia, and no control for differences in true anemia vs anemia due to hemodilution.

An important factor limiting the assessment of the prevalence of anemia is the lack of a uniform definition of anemia. Any

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Current evidence regarding iron status and mortality risk among patients with diabetes is limited. This study aimed to evaluate association of iron indices with all-cause and cause-specific mortality risk among patients with diabetes.
The current study included 2080 (with ferritin data), 1974 (with transferrin saturation (Tsat) data), and 1106 (with soluble transferrin receptor (sTfR) data) adults with diabetes from NHANES 1999–2018. Death outcomes were obtained from National Death Index through December 31, 2019. Cox proportional hazards models were employed to calculate hazard ratios and 95% confidence intervals for mortality.
Association with all-cause mortality was demonstrated to be J-shaped for serum ferritin (P_nonlinearity < 0.01), U-shaped for Tsat (P_nonlinearity < 0.01) and linear for sTfR (P_linearity < 0.01). Ferritin 300–500 ng/mL possessed lower all-cause mortality risk than ferritin ≤ 100 ng/mL, 100–300 ng/mL, and > 500 ng/mL. Tsat 25–32 % showed a protective effect on all-cause mortality risk compared with Tsat ≤ 20 %, 20–25 %, and > 32 %. Individuals with sTfR < 4 mg/L were associated with a lower risk of all-cause mortality than those with higher sTfR.
Moderate levels of serum ferritin (300–500 ng/mL), Tsat (25 %–32 %) and a lower concentration of sTfR (< 4 mg/L) identified adults with diabetes with lower all-cause mortality risk, adding novel modifiers to diabetes management.
Guidelines for Continuing Medical Education - Anemia in the elderly
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Influence of the degree of anaemia on the prognosis of older adults with heart failure (SPAN-HF study)
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Evaluar si un valor óptimo de hemoglobina sostenido en los 3 meses posteriores al ingreso por descompensación de insuficiencia cardíaca (IC) reduce la morbimortalidad durante los 12 meses posteriores a un ingreso por IC aguda.
Estudio retrospectivo de los 1408 pacientes mayores de 65 años incluidos en el registro RICA divididos en 3 grupos: sin anemia (grupo A), anemia recuperada (grupo B) y anemia persistente (grupo C), según los niveles de hemoglobina en el ingreso y a los 3 meses tras el alta. Se construyeron curvas de Kaplan-Meier, comparando los grupos mediante la prueba de log-rank y se realizó un modelo de regresión de Cox para analizar la supervivencia.
Se incluyeron 578 (41,1%), 299 (21,2%) y 531 (37,7%) en los grupos A, B y C, respectivamente. Registramos un total de 768 muertes y reingresos. Hubo 23 (4%), 12 (4%) y 49 (9,2%) (p = 0,001) individuos que fallecieron debido a la IC, y 154 (27%), 73 (24%) y 193 (36%) (p < 0,001) reingresaron por esta patología, respectivamente. Los pacientes con anemia persistente tuvieron un riesgo superior de fallecimiento (RR: 1,29; IC95% de 1,04-1,61; p = 0,024) o reingreso (1,92; IC95% de 1,16-3,19; p = 0,012) por IC.
La anemia persistente en los meses posteriores a un ingreso por IC aumenta la morbimortalidad en el año posterior.
To assess whether a sustained optimal haemoglobin value in the 3 months after admission for heart failure (HF) decompensation reduces morbidity and mortality during the 12 months after admission for acute HF.
Retrospective study of the 1408 patients older than 65 years included in the RICA registry divided into 3 groups: no anaemia (group A), recovered anaemia (group B), and persistent anaemia (group C), according to haemoglobin levels on admission, and 3 months after discharge. Kaplan-Meier curves were constructed, comparing the groups using the log-rank test and a Cox regression model was performed to analyse survival.
578 (41.1%), 299 (21.2%) and 531 (37.7%) were included in groups A, B and C, respectively. We recorded a total of 768 deaths and readmissions. There were 23 (4%), 12 (4%) and 49 (9.2%), (p = .001) individuals who died due to HF and 154 (27%), 73 (24%) and 193 (36%) (P < .001) admissions for this pathology, respectively. Patients with persistent anaemia had a higher risk of death (RR 1.29, 95% CI 1.04-1.61, P = .024) or readmission (1.92, 95% CI 1.16-3, 19; P = .012) due to HF.
Persistent anaemia in the months after admission for HF increases morbidity and mortality in the subsequent year.
Lack of Association Between Anemia and Intrinsic Left Ventricular Diastolic Function or Cardiac Mechanics in Heart Failure With Preserved Ejection Fraction
2018, American Journal of Cardiology
Citation Excerpt :
Therefore, it becomes important to consider other factors which may contribute to the poorer outcomes seen in anemic HFpEF patients. Numerous large-scale studies have shown that anemia is associated with worse outcomes in HF3,4,14; but, the pathophysiology of anemia in the HF syndrome remains somewhat poorly understood. It has been hypothesized that anemia in HF results mainly from insufficient erythropoietin production from chronic kidney disease5; iron deficiency from malnutrition and inflammation-mediated impaired iron retention27; and hemodilution from renal sodium retention and activation of the renin-angiotensin-aldosterone system.26
Anemia is associated with a poor prognosis in heart failure with preserved ejection fraction (HFpEF), but the reasons underlying this association are unclear. Previous studies have reported an association between anemia and diastolic dysfunction. However, these studies used volume- and flow-dependent indexes of diastolic dysfunction. We hypothesized that in HFpEF, anemia is more closely associated with volume status and not markers of intrinsic myocardial dysfunction. We prospectively studied 419 outpatients in a systematic HFpEF program, all of whom underwent hemoglobin measurement and comprehensive echocardiography. Longitudinal, radial, and circumferential strain were also measured in 311 patients. We defined anemia as hemoglobin <12g/dL in women and <13g/dL in men. Linear and Cox regression analyses were used to determine the association between anemia and echocardiographic/strain variables and adverse outcomes, respectively. Over half (224/419 [53%]) of the HFpEF patients had anemia. Anemia was associated with volume (preload)-dependent markers of diastolic dysfunction including echocardiographic E/A (p = 0.004) and E/e′ ratio (p = 0.014) and elevated right heart pressures such as right atrial pressure (p = 0.002) and pulmonary artery systolic pressure (p<0.001). Anemia was not associated with markers of intrinsic myocardial dysfunction such as lateral e′ (p = 0.16) and septal e′ (p = 0.65) velocities or echocardiographic strain parameters (p > 0.05 for all comparisons). Anemia was associated with the combined outcome of cardiovascular hospitalization or death (hazard ratio = 1.50 [95% confidence interval 1.20, 1.88]; p < 0.001). In conclusion, anemia in HFpEF is associated with markers of volume status and not intrinsic markers of myocardial dysfunction.
Anemia and the Risk of Life-threatening Ventricular Tachyarrhythmias from the Israeli Implantable Cardioverter Defibrillator Registry
2017, American Journal of Cardiology
Anemia was shown to be associated with increased risk for adverse events in patients with heart failure (HF). However, there are limited data on the association between anemia and the risk for ventricular arrhythmias (VAs) in patients with an implantable cardioverter defibrillator (ICD). The present study population comprised 2,352 patients who were enrolled and prospectively followed up in the Israeli ICD Registry. The risk for a first appropriate ICD shock for VA was assessed by the presence of anemia, categorized at the lower tertile of hemoglobin distribution (≤12 g/dL [n = 753]). Patients who had anemia displayed higher risk clinical characteristics including older age, more advanced HF symptoms, and atrial fibrillation (p <0.01 for all). Kaplan-Meier survival analysis showed that at 2.5 years of follow-up the rate of appropriate shocks was significantly higher in patients with low (11%) versus high (6%) hemoglobin (log-rank p <0.005). Multivariate analysis showed that anemia was independently associated with a significant 56% increased risk for first appropriate ICD shock (p <0.026). When hemoglobin was assessed as a continuous measure, each 1 g/dL reduction in hemoglobin was independently associated with a significant 8% increased risk for first appropriate shock (p <0.03). Anemia was also associated with increased risk for all-cause mortality (hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.4 to 2.27], p <0.001), HF hospitalizations or death (HR 1.78, 95% CI 1.48 to 1.13, p <0.001), but not with inappropriate ICD shocks (HR 1.24, 95% CI 0.70 to 2.21, p = 0.47). In conclusion, our findings suggest that the presence of anemia in patients with ICD is associated with increased risk for VA during long-term follow-up.
The association between in-hospital hemoglobin changes, cardiovascular events, and mortality in acute decompensated heart failure: Results from the ESCAPE trial
2016, International Journal of Cardiology
Citation Excerpt :
Changes in hemoglobin (Hb) during index heart failure admission are frequently encountered [1,2]. This could be secondary to repeated blood withdrawals, complications of central venous catheter insertions or procedures performed during hospital admission, and fluid/electrolytes imbalance resulting in hemodilution [3-18]. It is unknown whether these acute changes in Hb during hospital admission have any prognostic effects on clinical outcomes in patients with acute decompensated heart failure (ADHF).
The effect of acute changes of hemoglobin during index heart failure admission on long-term outcomes remains unknown.
We examined 433 patients enrolled in the ESCAPE trial.
Of the 433 patients, 324 (75%) had baseline and discharge hemoglobin available for analysis. Of those, 64 (20%) had at least 1 g/dL drop of hemoglobin by time of discharge. Compared to patients without hemoglobin changes (g/dL), patients with hemoglobin drop were older (59 vs. 55, p = 0.011), had lower systolic BP (mm Hg) (99 vs. 106, p = 0.017), lower sodium (mg/dL) (136 vs. 137 (mg/dL), p = 0.025), higher BUN (mg/dL) (37 vs. 26, p < 0.001), higher creatinine (mg/dL) (1.6 vs. 1.3, p < 0.001) and higher hospital length of stay (10 days vs. 6 days, p = < 0.001). Higher hemoglobin drop was observed in the pulmonary artery catheter (PACs) (vs. clinical care) randomized arm of the trial (2 g/dL: 10% versus 3%, p = 0.010; 3 g/dL: 5% versus 0%, p = 0.005). After adjustments, a drop of hemoglobin with at least 1 g/dL was associated with increased mortality risk (Adjusted HR 2.38, p = 0.003) and higher hemoglobin concentrations by the time of discharge was associated with lower mortality rate (Adjusted HR 0.79, p = 0.003). PACs insertion was not associated with adverse clinical outcomes by quartiles of % change of hemoglobin. However, PACs use was an independent predictor of hemoglobin drop during heart failure admission (Adjusted OR: Hb Drop 1 g/dL: 1.88, p = 0.043; Hb Drop 2 g/dL: 3.6 p = 0.025).
In-hospital decrease in hemoglobin is independently associated with increased long-term mortality and hospital length of stay in ADHF. The ideal hemoglobin levels in ADHF patients should be investigated and the insertion of PACs to direct therapy should be weighed against bleeding risks.

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: Support for this literature review and preparation of the manuscript provided by Amgen Inc.

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Curriculum in CardiologyPrevalence of anemia and effects on mortality in patients with heart failure

Background

Methods

Results

Conclusions

Section snippets

Search strategy

Results

Discussion

J. Am. Coll. Cardiol.

Am. J. Cardiol.

J. Am. Coll. Cardiol.

Am. J. Med.

J. Am. Coll. Cardiol.

Lancet

Int. J. Cardiol.

Int. J. Cardiol.

Am. J. Cardiol.

Lancet

J. Am. Coll. Cardiol.

J. Am. Coll. Cardiol.

Int. J. Cardiol.

J. Card. Fail.

Am. Heart J.

Am. J. Clin. Nutr.

Am. J. Clin. Nutr.

U.S. Census Bureau population estimates for July 1, 1996

Curriculum in Cardiology
Prevalence of anemia and effects on mortality in patients with heart failure