Soluble TNFα receptor type I and hepcidin as determinants of development of anemia in the long-term follow-up of heart failure patients

Martínez-Ruiz, Ana; Tornel-Osorio, Pedro L.; Sánchez-Más, Jesús; Pérez-Fornieles, Joaquín; Vı́lchez, Juan Antonio; Martı́nez-Hernández, Pedro; Pascual-Figal, Domingo A.

doi:10.1016/j.clinbiochem.2012.05.011

Cited by 12 publications

(9 citation statements)

References 19 publications

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“…In heart failure, the assessment of iron deficiency is complicated by the fact that such patients often have a systemic inflammatory state, 44 which enhances the production of hepcidin in the liver ( Figure ) 45 . Circulating levels of hepcidin are increased in patients with heart failure 9,46,47 in proportion to the activation of proinflammatory pathways, 48–51 and the increase retards the entry of iron from the gastrointestinal tract and from macrophages, leading to a state of functional iron deficiency (akin to the anaemia of chronic disease 49,52,53 ), which is resistant to oral iron supplementation, but can be responsive to treatment with intravenous iron 54 . Patients with heart failure can suffer from either absolute iron depletion or the functional iron deficiency of chronic inflammation, or both 8,18,44,46–56 .…”

Section: Changes In Iron Homeostasis Proteins In Patients With Heart ...mentioning

confidence: 99%

How can sodium–glucose cotransporter 2 inhibitors stimulate erythrocytosis in patients who are iron‐deficient? Implications for understanding iron homeostasis in heart failure

Packer

2022

European J of Heart Fail

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Many patients with heart failure have an iron‐deficient state, which can limit erythropoiesis in erythroid precursors and ATP production in cardiomyocytes. Yet, treatment with sodium–glucose cotransporter 2 (SGLT2) inhibitors produces consistent increases in haemoglobin and haematocrit, even in patients who are iron‐deficient before treatment, and this effect remains unattenuated throughout treatment even though SGLT2 inhibitors further aggravate biomarkers of iron deficiency. Heart failure is often accompanied by systemic inflammation, which activates hepcidin, thus impairing the duodenal absorption of iron and the release of iron from macrophages and hepatocytes, leading to a decline in circulating iron. Inflammation and oxidative stress also promote the synthesis of ferritin and suppress ferritinophagy, thus impairing the release of intracellular iron stores and leading to the depletion of bioreactive cytosolic Fe2+. By alleviating inflammation and oxidative stress, SGLT2 inhibitors down‐regulate hepcidin, upregulate transferrin receptor protein 1 and reduce ferritin; the net result is to increase the levels of cytosolic Fe2+ available to mitochondria, thus enabling the synthesis of heme (in erythroid precursors) and ATP (in cardiomyocytes). The finding that SGLT2 inhibitors can induce erythrocytosis without iron supplementation suggests that the abnormalities in iron diagnostic tests in patients with mild‐to‐moderate heart failure are likely to be functional, rather than absolute, that is, they are related to inflammation‐mediated trapping of iron by hepcidin and ferritin, which is reversed by treatment with SGLT2 inhibitors. An increase in bioreactive cytosolic Fe2+ is also likely to augment mitochondrial production of ATP in cardiomyocytes, thus retarding the progression of heart failure. These effects on iron metabolism are consistent with (i) proteomics analyses of placebo‐controlled trials, which have shown that biomarkers of iron homeostasis represent the most consistent effect of SGLT2 inhibitors; and (ii) statistical mediation analyses, which have reported striking parallelism of the effect of SGLT2 inhibitors to promote erythrocytosis and reduce heart failure events.

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Section: Changes In Iron Homeostasis Proteins In Patients With Heart ...mentioning

confidence: 99%

How can sodium–glucose cotransporter 2 inhibitors stimulate erythrocytosis in patients who are iron‐deficient? Implications for understanding iron homeostasis in heart failure

Packer

2022

European J of Heart Fail

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“…To diagnose ID in HF and other conditions one would have to measure the iron parameters serum iron, serum transferrin, %Transferrin Saturation (%TSat), and serum ferritin [ 114 , 115 , 116 , 117 , 118 ] in any patient suspected of having ID and not just measure them in those with anemia.. The two commonly used tests that are used to detect ID are %TSat and serum ferritin.…”

Section: Diagnosis and Treatment Of Idmentioning

confidence: 99%

“…There is no test that can predict very accurately the degree of response to IV iron in HF or RF or in other inflammatory conditions with great accuracy [ 114 , 115 , 116 , 117 , 118 ]. Some suggest that analysis of the soluble transferrin receptor best reflects unmet cellular iron requirements and is the most accurate measurement for predicting the severity of the ID and the response to IV iron [ 116 ]. Others suggest the use of various red cell parameters such as the percentage of microcytic erythrocytes or hypochromic erythrocytes, or the level of hemoglobin in reticulocytes and mature red blood cells [ 117 , 118 ].…”

Section: Diagnosis and Treatment Of Idmentioning

confidence: 99%

Is Correction of Iron Deficiency a New Addition to the Treatment of the Heart Failure?

Silverberg

Wexler²,

Schwartz

2015

IJMS

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Anemia is present in about 40% of heart failure (HF) patients. Iron deficiency (ID) is present in about 60% of the patients with anemia (about 24% of all HF patients) and in about 40% of patients without anemia (about 24% of all HF patients). Thus ID is present in about half the patients with HF. The ID in HF is associated with reduced iron stores in the bone marrow and the heart. ID is an independent risk factor for severity and worsening of the HF. Correction of ID with intravenous (IV) iron usually corrects both the anemia and the ID. Currently used IV iron preparations are very safe and effective in treating the ID in HF whereas little information is available on the effectiveness of oral iron. In HF IV iron correction of ID is associated with improvement in functional status, exercise capacity, quality of life and, in some studies, improvement in rate of hospitalization for HF, cardiac structure and function, and renal function. Large long-term adequately-controlled intervention studies are needed to clarify the effect of IV iron in HF. Several heart associations suggest that ID should be routinely sought for in all HF patients and corrected if present. In this paper we present our approach to diagnosis and treatment of iron deficiency in heart failure.

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“…However, the physiopathology of anaemia in these patients is still not very well understood and is thought to be a complex and multifactorial process (Anand, 2008). Patients with CHF who became anaemic had higher levels of hepcidin (Martinez-Ruiz, et al, 2012).…”

Section: Hepcidin: An Endogenous Cytoprotective Agent In Cardiovascular Pathophysiology and Possible Therapeutic Targets?mentioning

confidence: 96%

The iron-regulatory hormone hepcidin: A possible therapeutic target?

Rochette

Gudjoncik

Guenancia

et al. 2015

Pharmacology & Therapeutics

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Soluble TNFα receptor type I and hepcidin as determinants of development of anemia in the long-term follow-up of heart failure patients

Cited by 12 publications

References 19 publications

How can sodium–glucose cotransporter 2 inhibitors stimulate erythrocytosis in patients who are iron‐deficient? Implications for understanding iron homeostasis in heart failure

How can sodium–glucose cotransporter 2 inhibitors stimulate erythrocytosis in patients who are iron‐deficient? Implications for understanding iron homeostasis in heart failure

Is Correction of Iron Deficiency a New Addition to the Treatment of the Heart Failure?

The iron-regulatory hormone hepcidin: A possible therapeutic target?

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