Suppression of erythropoiesis in patients with chronic heart failure and anaemia of unknown origin: evidence of an immune basis

Okonko, Darlington O.; Marley, Stephen B.; Anker, Stefan D.; Poole‐Wilson, Philip A.; Gordon, Myrtle Y.

doi:10.1016/j.ijcard.2011.11.081

Cited by 24 publications

(18 citation statements)

References 41 publications

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“…Inflammatory biomarkers, as indicated by previous evidence, can provide important prognostic information for HF [43]. On the other hand, it is widely accepted that inflammation inhibits erythrocyte maturation and accelerates the migration of reticulocytes into the peripheral circulation, thereby increasing RDW [44]–[46]. Indeed, the positive relationships between RDW and inflammatory indices have also been documented [30], [47], [48].…”

Section: Discussionmentioning

confidence: 85%

Prognostic Value of Red Blood Cell Distribution Width for Patients with Heart Failure: A Systematic Review and Meta-Analysis of Cohort Studies

et al. 2014

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AimsMultiple studies have investigated the prognostic role of red blood cell distribution width (RDW) for patients with heart failure (HF), but the results have been inconsistent. The aim of the present study was to estimate the impact of RDW on the prognosis of HF by performing a systematic review and meta-analysis.Methods and ResultsThe Embase, PubMed, and Web of Science databases were searched up to November 16, 2013 to identify eligible cohort studies. The quality of each study was assessed using the Newcastle-Ottawa Scale (NOS). The association between RDW, either on admission or at discharge, and HF outcomes (all-cause mortality [ACM], heart transplantation, cardiovascular mortality, and rehospitalization, etc.) were reviewed. The overall hazard ratio (HR) for the effect of RDW on ACM was pooled using a random-effects model, and the publication bias was evaluated using funnel plots and Eggers' tests. Seventeen studies, with a total of 18288 HF patients, were included for systematic review. All eligible studies indicated that RDW on admission and RDW at discharge, as well as its change during treatment, were of prognostic significance for HF patients. The HR for the effect of a 1% increase in baseline RDW on ACM was 1.10 (95% confidence interval: 1.07–1.13), based on pooling of nine studies that provided related data. However, publication bias was observed among these studies.ConclusionsHF patients with higher RDW may have poorer prognosis than those with lower RDW. Further studies are needed to explore the potential mechanisms underlying this association.

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Section: Discussionmentioning

confidence: 85%

Prognostic Value of Red Blood Cell Distribution Width for Patients with Heart Failure: A Systematic Review and Meta-Analysis of Cohort Studies

et al. 2014

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“…Finally, ALAS2 is known to be positively regulated by erythropoietin (EPO) in erythroblasts (33) and EPO levels are often elevated in HF patients due to the underlying anemia (34). EPO receptor was previously shown to be expressed in the human heart (35), suggesting that cardiomyocytes may respond to EPO signaling.…”

Section: Resultsmentioning

confidence: 99%

“…The significance of these findings in the context of failing hearts remains to be determined. Despite elevated EPO levels, HF patients were found to be resistant to EPO signaling in promoting hematopoiesis (34), but it remains unknown whether the sensitivity of cardiomyocytes to EPO stimulation is also altered.…”

Section: Discussionmentioning

confidence: 99%

Heme Levels Are Increased in Human Failing Hearts

Khechaduri

Bayeva

Chang

et al. 2013

Journal of the American College of Cardiology

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Objectives The goal of this study was to characterize the regulation of heme and non-heme iron in human failing hearts. Background Iron is an essential molecule for cellular physiology, but in excess it facilitates oxidative stress. Mitochondria are the key regulators of iron homeostasis through heme and iron-sulfur cluster synthesis. Since mitochondrial function is depressed in failing hearts and iron accumulation can lead to oxidative stress, we hypothesized that iron regulation may also be impaired in heart failure (HF). Methods We measured mitochondrial and cytosolic heme and non-heme iron levels in failing human hearts retrieved during cardiac transplant surgery. In addition, we examined the expression of genes regulating cellular iron homeostasis, heme biosynthetic pathway, and microRNAs that may potentially target iron regulatory networks. Results While cytosolic non-heme iron levels were reduced in HF, mitochondrial iron content was maintained. Moreover, we observed a significant increase in heme levels in failing hearts, with corresponding feedback inhibition of the heme synthetic enzymes and no change in heme degradation. The rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), was significantly upregulated in HF. Overexpression of ALAS2 in H9c2 cardiac myoblasts resulted in increased heme levels, and hypoxia and erythropoietin treatment increased heme production through upregulation of ALAS2. Finally, increased heme levels in cardiac myoblasts were associated with excess production of reactive oxygen species and cell death, suggesting a maladaptive role for increased heme in HF. Conclusions Despite global mitochondrial dysfunction, heme levels are maintained above baseline in human failing hearts.

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“…Thus, a possible explanation for the associations between AF or RBBB and the increased levels of hemoglobin is that increased blood levels of hemoglobin may reflect increased erythropoiesis which results from subclinical tissue hypoperfusion caused by AF or RBBB in an apparently normal heart. In contrast, patients with chronic heart failure are frequently anemic despite elevated endogenous EPO levels due to EPO resistance which results from impaired EPO-induced signal transduction (15) and a suppression of erythropoiesis by heart failure-related inflammation (16). EPO induces positive inotropic and lusitropic effects in the murine and human myocardium (17).…”

Section: Discussionmentioning

confidence: 99%

Atrial Fibrillation (AF) and Complete Right Bundle Branch Block (RBBB) Are Independently Associated with Increased Hemoglobin Levels in Apparently Healthy Subjects

Oda

Aizawa

2013

Intern. Med.

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Objective The associations between atrial fibrillation (AF) or complete right bundle branch block (RBBB) and other laboratory tests have not been examined sufficiently in healthy populations. Methods These associations were examined with multivariable logistic regression analyses using data from 6,381 apparently healthy subjects including 46 subjects with AF and 100 subjects with RBBB. Results The mean age, body mass index (BMI), hemoglobin, the prevalence of male sex and a history of coronary heart disease (CHD) were significantly higher in subjects with AF or RBBB than without. The odds ratio (OR) (95% confidence interval (CI)) of AF was 1.62 (1.28-2.05) p<0.0001 for each 1 g/dL increment of hemoglobin and 1.07 (0.36-3.21) p=0.90 and 4.32 (1.29-14.43) p=0.017, respectively for the second and the third tertiles of hemoglobin compared with the first tertile after adjusting for sex, age, BMI, CHD, and other confounding covariates. The OR (95% CI) of RBBB was 1.53 (1.32-1.77) p<0.0001 for each 1 g/dL increment of hemoglobin and 2.53 (1.06-6.00) p=0.036, 3.10 (1.12-8.61) p=0.030, and 4.03 (0.91-17.82) p=0.066, respectively, for the second, third, and fourth quartiles of hemoglobin compared with the first quartile after adjusting for sex, age, BMI, CHD, and other confounding covariates. Conclusion An increased blood levels of hemoglobin was independently associated with AF and RBBB after adjusting for sex, age, BMI, CHD, and other confounding covariates in apparently healthy subjects.

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Suppression of erythropoiesis in patients with chronic heart failure and anaemia of unknown origin: evidence of an immune basis

Cited by 24 publications

References 41 publications

Prognostic Value of Red Blood Cell Distribution Width for Patients with Heart Failure: A Systematic Review and Meta-Analysis of Cohort Studies

Prognostic Value of Red Blood Cell Distribution Width for Patients with Heart Failure: A Systematic Review and Meta-Analysis of Cohort Studies

Heme Levels Are Increased in Human Failing Hearts

Atrial Fibrillation (AF) and Complete Right Bundle Branch Block (RBBB) Are Independently Associated with Increased Hemoglobin Levels in Apparently Healthy Subjects

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