Iron Deficiency in Pulmonary Arterial Hypertension: A Deep Dive into the Mechanisms

Quatredeniers, Marceau; Mendes-Ferreira, Pedro; Santos‐Ribeiro, Diana; Nakhleh, Morad K.; Ghigna, Maria-Rosa; Cohen‐Kaminsky, Sylvia; Perros, Frédèric

doi:10.3390/cells10020477

Cited by 27 publications

(25 citation statements)

References 140 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous observations in patients with acute conditions, including acute exacerbation of chronic obstructive pulmonary disease, acute coronary syndrome, or acute HF, reported a prevalence of ID ranging between 20% and 80% [25][26][27]. In patients with chronic conditions, such as chronic heart failure, pulmonary arterial hypertension, or cancer, the prevalence of ID ranged between 30% and 50% [13,[28][29][30]. Therefore, our results fit into the range of ID prevalence described for other chronic conditions.…”

Section: Discussionmentioning

confidence: 99%

Iron Deficiency and Reduced Muscle Strength in Patients with Acute and Chronic Ischemic Stroke

Scherbakov

Sandek

Valentová

et al. 2022

JCM

View full text Add to dashboard Cite

(1) Introduction: Iron deficiency (ID) contributes to impaired functional performance and reduced quality of life in patients with chronic illnesses. The role of ID in stroke is unclear. The aim of this prospective study was to evaluate the prevalence of ID and to evaluate its association with long-term functional outcome in patients with ischemic stroke. (2) Patients and Methods: 140 patients (age 69 ± 13 years, BMI 27.7 ± 4.6 kg/m², mean ± SD) admitted to a university hospital stroke Unit, with acute ischemic stroke of the middle cerebral artery were consecutively recruited to this observational study. Study examinations were completed after admission (3 ± 2 days after acute stroke) and at one-year follow up (N = 64, 382 ± 27 days after stroke). Neurological status was evaluated according to the National Institute of Health Stroke Scale (NIHSS) and the modified Rankin scale (mRS). Muscle isometric strength of the non-affected limb was assessed by the maximum handgrip test and knee extension leg test. ID was diagnosed with serum ferritin levels ≤ 100 µg/L (ID Type I) or 100–300 µg/L if transferrin saturation (TSAT) < 20% (ID Type II). (3) Results: The prevalence of ID in acute stroke patients was 48% (N = 67), with about two-thirds of patients (N = 45) displaying ID Type I and one-third (N = 22) Type II. Handgrip strength (HGS) and quadriceps muscle strength were reduced in patients with ID compared to patients without ID at baseline (HGS: 26.5 ± 10.4 vs. 33.8 ± 13.2 kg, p < 0.001 and quadriceps: 332 ± 130 vs. 391 ± 143 N, p = 0.06). One year after stroke, prevalence of ID increased to 77% (p = 0.001). While an improvement of HGS was observed in patients with normal iron status, patients with ID had no improvement in HGS difference (4.6 ± 8.3 vs. −0.7 ± 6.5 kg, p < 0.05). Patients with ID remained with lower HGS compared to patients with normal iron status (28.2 ± 12.5 vs. 44.0 ± 8.6 kg, p < 0.0001). (4) Conclusions: Prevalence of ID was high in patients after acute stroke and further increased one year after stroke. ID was associated with lower muscle strength in acute stroke patients. In patients with ID, skeletal muscle strength did not improve one year after stroke.

show abstract

Section: Discussionmentioning

confidence: 99%

Iron Deficiency and Reduced Muscle Strength in Patients with Acute and Chronic Ischemic Stroke

Scherbakov

Sandek

Valentová

et al. 2022

JCM

View full text Add to dashboard Cite

show abstract

“…Furthermore, iron deficiency is involved in a circulus vitiosus in PAH. On one side, the upregulation of hepcidin in PAH leads to iron malabsorption, on the other side iron deficiency may counterfeit hypoxia, promoting pulmonary vasoconstriction leading to deterioration of the disease [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…While only 64% of the patients with > 2% hypochromic erythrocytes showed low ferritin levels and only 19% were diagnosed with anemia, a worse survival could be identified in this cohort. The variability of the definition of iron deficiency in different conditions can lead to controversial indication for iron supplementation [ 23 ], depending on functional iron deficiency of each individual patient. Thus, hypochromic erythrocytes could be a reliable parameter of iron homeostasis and outcome even in the absence of anemia.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of hypochromic erythrocytes in patients with pulmonary arterial hypertension

et al. 2021

View full text Add to dashboard Cite

Background Iron deficiency affects up to 50% of patients with pulmonary arterial hypertension (PAH) but iron markers such as ferritin and serum iron are confounded by several non-disease related factors like acute inflammation and diet. The aim of this study was to identify a new marker for iron deficiency and clinical outcome in PAH patients. Methods In this single-center, retrospective study we assessed indicators of iron status and clinical parameters specifying the time to clinical worsening (TTCW) and survival in PAH patients at time of initial diagnosis and at 1-year follow-up using univariable and multivariable analysis. Results In total, 150 patients were included with an invasively confirmed PAH and complete data on iron metabolism. The proportion of hypochromic erythrocytes > 2% at initial diagnosis was identified as an independent predictor for a shorter TTCW (p = 0.0001) and worse survival (p = 0.002) at initial diagnosis as well as worse survival (p = 0.016) at 1-year follow-up. Only a subset of these patients (64%) suffered from iron deficiency. Low ferritin or low serum iron neither correlated with TTCW nor survival. Severe hemoglobin deficiency at baseline was significantly associated with a shorter TTCW (p = 0.001). Conclusions The presence of hypochromic erythrocytes > 2% was a strong and independent predictor of mortality and shorter TTCW in this cohort of PAH patients. Thus, it can serve as a valuable indicator of iron homeostasis and prognosis even in patients without iron deficiency or anemia. Further studies are needed to confirm the results and to investigate therapeutic implications.

show abstract

“…However, non-enzymatic H 2 S production by red blood cells from L-cysteine and iron has been recently evidenced as a new source of circulating H 2 S under physiological conditions [59]. Interestingly, patients with severe PH exhibit iron deficiency [162]. Hypothetically, reduced iron levels could lead to a reduction of nonenzymatic H 2 S production by red blood cells and, consequently, decreased circulating H 2 S bioavailability in vascular tissues.…”

Section: H 2 S Significance and Perspectives In Phmentioning

confidence: 99%

Hydrogen Sulfide Metabolism and Pulmonary Hypertension

Roubenne

Marthan

Grand³

et al. 2021

Cells

View full text Add to dashboard Cite

Pulmonary hypertension (PH) is a severe and multifactorial disease characterized by a progressive elevation of pulmonary arterial resistance and pressure due to remodeling, inflammation, oxidative stress, and vasoreactive alterations of pulmonary arteries (PAs). Currently, the etiology of these pathological features is not clearly understood and, therefore, no curative treatment is available. Since the 1990s, hydrogen sulfide (H2S) has been described as the third gasotransmitter with plethoric regulatory functions in cardiovascular tissues, especially in pulmonary circulation. Alteration in H2S biogenesis has been associated with the hallmarks of PH. H2S is also involved in pulmonary vascular cell homeostasis via the regulation of hypoxia response and mitochondrial bioenergetics, which are critical phenomena affected during the development of PH. In addition, H2S modulates ATP-sensitive K+ channel (KATP) activity, and is associated with PA relaxation. In vitro or in vivo H2S supplementation exerts antioxidative and anti-inflammatory properties, and reduces PA remodeling. Altogether, current findings suggest that H2S promotes protective effects against PH, and could be a relevant target for a new therapeutic strategy, using attractive H2S-releasing molecules. Thus, the present review discusses the involvement and dysregulation of H2S metabolism in pulmonary circulation pathophysiology.

show abstract

Iron Deficiency in Pulmonary Arterial Hypertension: A Deep Dive into the Mechanisms

Cited by 27 publications

References 140 publications

Iron Deficiency and Reduced Muscle Strength in Patients with Acute and Chronic Ischemic Stroke

Iron Deficiency and Reduced Muscle Strength in Patients with Acute and Chronic Ischemic Stroke

Prognostic impact of hypochromic erythrocytes in patients with pulmonary arterial hypertension

Hydrogen Sulfide Metabolism and Pulmonary Hypertension

Contact Info

Product

Resources

About