Iron Deficiency in Korean Patients With Heart Failure.

BACKGROUND: Although iron deficiency (ID) is an important and treatable risk factor for heart failure (HF), data on ID are scarce in Asian patients with HF. Therefore, we sought to determine the prevalence and clinical characteristics of ID in hospitalized Korean patients with HF. METHODS: In this prospective, multicenter cohort study, 461 patients with acute HF seen at five tertiary centers from January to November 2019 in Korea were enrolled. ID was defined as serum ferritin < 100 µg/L or ferritin 100-299 µg/L in combination with transferrin saturation < 20%. RESULTS: The patients' mean age was 67.6 ± 14.9 years, and 61.8% were male. Among total 461 patients, ID was present in 248 patients (53.8%). The prevalence of ID was significantly higher in women than in men (65.3% vs. 47.3%, P < 0.001). In a multivariable logistic regression analysis, the independent predictors of ID were female sex (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.47-3.30), valvular heart disease (OR, 2.10; 95% CI, 1.10-4.17), higher heart rate (OR, 1.10; 95% CI, 1.01-1.21), anemia (OR, 1.60; 95% CI, 1.07-2.40), and the use of clopidogrel (OR, 1.56; 95% CI, 1.00-2.45). Among women, the prevalence of ID did not significantly differ between younger and older women (< 65 years: 73.7% vs. ≥ 65 years: 63.0%, P = 0.222), those with low and high body mass index (BMI < 25 kg/m²: 66.2% vs. BMI ≥ 25 kg/m²: 69.6%, P = 0.703), or those with low and high natriuretic peptide (NP) levels (NP < median: 69.8% vs. NP ≥ median: 61.1%, P = 0.295). Only 0.2% patients with acute HF received intravenous iron supplementation in Korea. CONCLUSION: The prevalence of ID is high in hospitalized Korean patients with HF. Because ID cannot be diagnosed by clinical parameters, routine laboratory examinations are necessary to identify patients with ID. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04812873.

Prevalence of Iron Deficiency and Iron-Deficiency Anemia in US Females Aged 12-21 Years, 2003-2020.

This study examines prevalence of iron deficiency among females aged 12 to 21 years to inform future screening strategies for iron deficiency and iron-deficiency anemia.

Iron status of blood donors.

PURPOSE OF REVIEW: This review examines recent research on the prevalence and importance of iron deficiency in blood donors, and on efforts to mitigate it. RECENT FINDINGS: Premenopausal females, teenagers, and high-frequency donors are at the highest risk for donation-induced iron deficiency, in both high-resource and low-resource settings. The physiology relating iron stores to hemoglobin levels and low hemoglobin deferral is well elucidated in blood donor populations, yet the clinical effects attributable to iron loss in the absence of anemia are challenging to identify. Expanded adoption of ferritin testing is improving donor management but may cause decreases in the blood supply from temporary donor loss. The potential for personalized donor management is emerging with development of computational models that predict individual interdonation intervals that aim to optimize blood collected from each donor while minimizing low hemoglobin deferrals. SUMMARY: Measures to reduce iron deficiency are available that can be deployed on a standardized or, increasingly, personalized basis. Blood centers, regulators, and donors should continue to evaluate different tactics for addressing this problem, to obtain a balanced approach that is optimal for maintaining adequate collections while safeguarding donor health.

Criteria for Iron Deficiency in Patients With Heart Failure.

BACKGROUND: Guidelines on heart failure (HF) define iron deficiency (ID) as a serum ferritin <100 ng/mL or, when 100-299 ng/mL, a transferrin saturation (TSAT) <20%. Inflammation (common in HF) may hinder interpretation of serum ferritin. OBJECTIVES: This study sought to investigate how different definitions of ID affect its prevalence and relationship to prognosis in ambulatory patients with chronic HF. METHODS: Prevalence, relationship with patients' characteristics, and outcomes of various ID definitions were evaluated among patients with HF referred to a regional clinic (Hull LifeLab) from 2001 to 2019. RESULTS: Of 4,422 patients with HF (median age 75 years [range: 68-82 years], 60% men, 32% with reduced left ventricular ejection fraction), 46% had TSAT <20%, 48% had serum iron ≤13 µmol/L, 57% had serum ferritin <100 ng/mL, and 68% fulfilled current guideline criteria for ID, of whom 35% had a TSAT >20%. Irrespective of definition, ID was more common in women and those with more severe symptoms, anemia, or preserved ejection fraction. TSAT <20% and serum iron ≤13 µmol/L, but not guideline criteria, were associated with higher 5-year mortality (HR: 1.27; 95% CI: 1.14-1.43; P < 0.001; and HR: 1.37; 95% CI: 1.22-1.54; P < 0.001, respectively). Serum ferritin <100 ng/mL tended to be associated with lower mortality (HR: 0.91; 95% CI: 0.81-1.01; P = 0.09). CONCLUSIONS: Different definitions of ID provide discordant results for prevalence and prognosis. Definitions lacking specificity may attenuate the benefits of intravenous iron observed in trials while definitions lacking sensitivity may exclude patients who should receive intravenous iron. Prespecified subgroup analyses of ongoing randomized trials should address this issue.

Prevalence and Predictors of Iron Deficiency in Adolescent and Young Adult Outpatients: Implications for Screening.

Current screening guidelines may not be adequate to identify iron deficiency (ID) and iron deficiency anemia (IDA) in adolescent and young adults. Adolescent and young adult outpatients from 4 hospital-based clinics (N = 493) reported on diet, health, and bleeding, and had phlebotomy for iron and hematologic tests. We examined sex-specific factors associated with ID and IDA and ability of universal and risk factor-based screening using hemoglobin and hemoglobin plus ferritin to detect ID and IDA. Among females (n = 350), 34.6% had ID and 6.3% had IDA. Nearly 1 in 3 females with ID had no risk factors. Among males, 12.6% had ID; none had IDA. More than 1 in 3 males with ID did not have risk factors. Current screening approaches would have missed ID in 47% to 82% of females and 95% to 100% of males. ID was prevalent in both male and female adolescents and young adult outpatients. New approaches to screening for ID are needed to accurately evaluate iron status in this population.

Prevalence of Micronutrient Deficiencies and Relationship with Clinical and Patient-Related Outcomes in Pulmonary Hypertension Types I and IV.

BACKGROUND: Pulmonary hypertension (PH) is a rare progressive and lethal disease affecting pulmonary arteries and heart function. The disease may compromise the nutritional status of the patient, which impairs their physical performance. This study aimed to determine the prevalence of micronutrient deficiencies in pulmonary arterial hypertension (PAH) and chronic thrombo-embolic pulmonary hypertension (CTEPH) patients. METHODS: Eighty-one blood samples from a prospective observational cohort study were analyzed for concentrations of micronutrients and inflammation-related factors. The samples consisted of newly diagnosed (treatment-naive) PAH and CTEPH patients and patients treated for 1.5 years according to ERS/ESC guidelines. RESULTS: In the newly diagnosed group, 42% of PAH patients and 21% of CTEPH patients were iron deficient compared to 29% of PAH patients and 20% of CTEPH patients in the treatment group. Vitamin D deficiency occurred in 42% of the newly diagnosed PAH patients, 71% of the newly diagnosed CTEPH patients, 68% of the treated PAH patients, and 70% of the treated CTEPH patients. Iron levels correlated with the 6 min walking distance (6MWD). CONCLUSIONS: Iron and vitamin D deficiencies are highly prevalent in PAH and CTEPH patients, underlining the need for monitoring their status. Studies evaluating the effects of supplementation strategies for iron and vitamin D are necessary.

Perturbation of monocyte subsets in iron-deficient children - a shift to a pro-inflammatory state?

BACKGROUND: Iron deficiency anemia (IDA) is the most prevalent micronutrient deficiency in preschool children in developing countries including India. IDA is associated with immune perturbation, which is reflected in greater frequency of infections in these children. Recent research has shown three distinct monocyte subsets with distinct functions linked to infectious, inflammatory, and autoimmune diseases. These subsets have not been studied in children with IDA. OBJECTIVE: The aim of the study was to assess the percentage of monocyte population and the three subset populations in children with IDA and to compare the data with age-matched healthy controls. METHODS: Venous blood samples (5 mL) from 40 IDA children and 20 controls were collected after taking informed consent. Monocyte subpopulations were compared across the two groups. The outcome variables were calculated using Students Independent t-test or Mann-Whitney U test. P value of <0.05 was taken as significant. RESULTS: No significant difference was found in the absolute numbers as well as percentages of total monocytes between the control and case (study) group. Children in the IDA group showed a significant (p = 0.03) decrease in the nonclassical subset population when compared to the control group. CONCLUSION: This is the first study done on monocyte subsets in iron-deficient children. Decrease in nonclassical monocytes observed may be associated with a pro-inflammatory state and increased risk of inflammatory and auto immune diseases. Follow-up studies are needed to confirm these findings.

Nutrition, Inflammation, and the Gut Microbiota among Outpatients with Active Tuberculosis Disease in India.

India has the highest rates of tuberculosis (TB) globally and a high prevalence of malnutrition; however, the interplay between host nutritional status, inflammation, and the gut microbiome in active tuberculosis disease (ATBD) is less well-studied. We examined differences in gut microbial composition and diversity based on undernutrition and inflammation status among outpatients with ATBD at the time of treatment initiation. During this exploratory cross-sectional study, outpatients (N = 32) with ATBD (confirmed by Xpert MTB/RIF) were enrolled in anti-TB treatment initiated at a hospital in rural southern India. The 16S rRNA sequencing was used to assess the composition of the gut microbiome. We assessed multiple markers of nutritional status, including micronutrient status concentrations (vitamin D [25(OH)D], vitamin B12, ferritin), anthropometry (body mass index, mid-upper arm circumference, and height), and C-reactive protein (CRP), as indicators of inflammation. We found that 25(OH)D was positively associated with the relative abundance of Oscillospira spp., a butyrate-producing genus linked with anti-inflammation effects, and that ferritin was positively associated with Proteobacteria taxa, which have been associated with worse inflammation in other studies. Finally, we found a greater abundance of inflammation-associated taxa from the Proteobacteria phylum and lower alpha-diversity indices among those who were underweight or who had low mid-upper arm circumference or short stature. In summary, we found differences in the gut microbiota composition and diversity among those with undernutrition compared with those with adequate nutrition status at the time of initiation of treatment among patients with ATBD in India. Clinical implications of these findings will need to be examined by larger longitudinal studies.

Prevalence of Micronutrient Deficiencies among Preschool and School-Going Children in Flood-Hit Areas of Pakistan.

There is minimal literature regarding micronutrient deficiencies in flood-affected regions. In our study, we aimed to find the prevalence of micronutrient deficiencies (vitamin A, calcium, zinc, iron, and iodine) among preschool and school-age children in flood-hit areas of Khyber Pakhtunkhwa, Pakistan. In this cross-sectional study, a multi-stage sampling technique was used for the selection of 656 households. Serum micronutrient status was detected in the targeted population in the affected districts. The least significant difference test was used with analysis of variance to determine significant differences in nutrient contents in different areas. Of the total respondents, 90.8% of the children were calcium deficient, 88.3% were zinc deficient, 26.7% were iron deficient, 53.5% were vitamin A deficient, and 39.5% were had an iodine deficiency in flood-affected areas. A significant difference (P < 0.05) was found in different age groups of children for zinc (5.7-42.63 µg/dL) and urinary iodine (69.6-85.4 µg/L). The 10- to 12-year-old age group had a lower serum zinc concentration (5.7 µg/dL), whereas the 1- to 3-year-old age group had a lower urinary iodine concentration (69.6 µg/L) than other groups. There was no significant difference (P > 0.05) between male and female children and various age groups for calcium and iron status. Vitamin A levels were significantly (P < 0.05) different among different age groups (high in age group 4-6 years) and districts. Vitamin A concentration was lower in the Nowshera District, whereas serum iron and zinc were lower in the Dera Ismail Khan District. All the important micronutrients in the population of children were deficient in the flood-affected areas of Pakistan. Therefore, policymakers should implement potential prevention strategies, such as food security, school health nutrition, food fortification, nutrition in the first 1,000 golden days, nutrition knowledge, and awareness of the local population, to reduce the burden of micronutrients deficiencies in flood-affected areas.

Iron Deficiency Is a Risk Factor for Thyroid Dysfunction During Pregnancy: A Population-Based Study in Belgium.

Background: Iron deficiency affects thyroid hormone synthesis by impairing the activity of the heme-dependent thyroid peroxidase. The prevalence of iron deficiency is elevated particularly in pregnant women. This study aimed to investigate the effects of iron status on thyroid function in a nationally representative sample of mildly iodine-deficient pregnant women. Methods: The study population comprised a sample of pregnant women in Belgium during the first and third trimesters of pregnancy (n = 1241). Women were selected according to a multistage proportional-to-size stratified and clustered sampling design. Urine and blood samples were collected, and a questionnaire was completed face to face with the study nurse. Concentrations of free thyroxine (fT4), total thyroxine (T4), free triiodothyronine, thyrotropin (TSH), thyroglobulin (Tg), thyroid peroxidase antibodies, Tg antibodies, hemoglobin, serum ferritin (SF), soluble transferrin receptor, urinary iodine concentrations (UICs) were measured and body iron stores (BIS) were calculated. Results: Median UICs were 117 and 132 µg/L in the first and third trimesters of pregnancy, respectively (p < 0.05). The frequency of SF <15 µg/L was 6.2% in the first trimester and 39.6% in the third trimester of pregnancy (p < 0.05). UIC was a significant predictor of serum Tg concentrations (p < 0.01) but not of thyroid hormone or TSH concentrations. The frequency of fT4

Metabolic syndrome may be associated with a lower prevalence of iron deficiency in Ecuadorian women of reproductive age.

The present study aimed to assess the associations of the stages of Fe deficiency (Fe deficiency without anaemia (ID) and Fe-deficiency anaemia (IDA)) and anaemia with metabolic syndrome (MetS) in Ecuadorian women. A cross-sectional study was conducted in 5894 women aged 20-59 years, based on data from the 2012 Ecuadorian National Health and Nutrition Survey. The sample was stratified by age. A χ2 test was used to assess the possible associations of ID, IDA and anaemia with MetS. The prevalence ratio (PR) for each stage of Fe deficiency and anaemia was estimated considering women without MetS as a reference. The total prevalence of MetS, ID, IDA and anaemia was 32⋅3 % (se 0⋅6), 6⋅2 % (se 0⋅3), 7⋅1 % (se 0⋅3) and 5⋅0 % (se 0⋅3), respectively. In women aged 20-29, 30-39 and 40-49 years, MetS was associated with a lower prevalence of ID (PR (95 % CI; P-value)): 0⋅17 (0⋅06, 0⋅46; P < 0⋅001), 0⋅69 (0⋅48, 0⋅99; P = 0⋅044) and 0⋅44 (0⋅29, 0⋅67; P < 0⋅001), respectively. In women aged 50-59 years, MetS was associated with IDA and anaemia (PR (95 % CI; P-value)): 0⋅12 (0⋅02, 0⋅96; P = 0⋅026) and 0⋅22 (0⋅07, 0⋅64; P = 0⋅002), respectively. In conclusion, Ecuadorian women of reproductive age with MetS have a lower prevalence of ID compared with those without MetS. Furthermore, the MetS and IDA coexist at the population level. These findings require an analysis from a dietary pattern approach, which could provide key elements for developing public policies that simultaneously address all forms of malnutrition.

Associations of maternal characteristics and dietary factors with anemia and iron-deficiency in pregnancy.

OBJECTIVE: Anemia and iron deficiency during pregnancy influence maternal and fetal health, birth outcomes, and the risk of chronic disease in offspring. This study aimed to examine the association with sociodemographic, maternal factors, supplement use and dietary intakes, and anemia and iron deficiency in pregnancy. METHODS: A cross-sectional study was conducted on 165 pregnant women aged between 19 and 45 years who were interviewed, and dietary intake was assessed by 24-hours dietary recall, supplement records and food frequency questionnaire. Learning Vector Quantization feature selection method which is one of the machine learning techniques was used to extract important variables from sociodemographic, maternal, and dietary factors. RESULTS: The prevalence of anemia was 15.2% and prevalence of iron deficiency was 65.5%. Total intake of iron, phosphorus, vitamin B1 and B2 were importance factors for iron deficiency while age, number of births, use of folic acid supplement, dietary folate equivalent and total iron intake were importance factors for anemia. CONCLUSIONS: Maternal and dietary characteristics were the most crucial risk factors for anemia while dietary factors were the most important risk factor for iron deficiency in pregnancy. The development of anemia and iron deficiency is associated with the coexistence of many nutrient deficiencies.

Safety and Effectiveness of an Accelerated Intravenous Iron Administration Protocol in Hospitalized Patients With Heart Failure.

BACKGROUND: The ACC/AHA heart failure (HF) guidelines include a class IIb recommendation for intravenous (IV) iron replacement in patients with iron deficiency and New York Heart Association class II or III to improve functional status and quality of life. Several studies have addressed the use of IV iron formulations such as ferric carboxymaltose or iron sucrose in HF population; however, few studies focused on sodium ferric gluconate complex (SFGC). OBJECTIVES: To assess the safety and effectiveness of an IV SFGC administration protocol in patients hospitalized with HF. METHODS: A retrospective cohort study was conducted. We included patients admitted to the HF service from September 2017 to March 2018. The primary outcome was the frequency of adverse reactions. The secondary outcome was the odds of HF readmissions between the 2 groups (IV SFGC vs. control). RESULTS: Of the 123 patients, 70 received IV iron (SFGC group) and 53 did not receive IV iron (control group). Five (7%) patients of the 70 in the SFGC group experienced adverse events, which included hypotension (n = 2, 2.8%), fever (n = 2, 2.8%) and myalgia (n = 2, 2.8%). Nine (12.8%) and 18 (25.7%) were readmitted within 30 days and 6 months respectively. In the control arm, 5 (9.4%) and 14 (26.4%) were admitted within 30 days and 6 months respectively. The odds of HF readmission at 30 days [OR 1.4 (95% CI: 0.45, 4.5)] and at 6 months [OR 0.96 (95% CI: 0.43, 2.2)] were similar in those who did not receive IV iron compared to those who received IV iron. CONCLUSIONS: Sodium ferric gluconate complex given at an accelerated dosing schedule appears to provide a more efficient means to prescribe IV iron in the inpatient setting and is safe with a low frequency of hypotension, fevers, and myalgias.

Hypophosphatemia Is Common After Intravenous Ferric Carboxymaltose Infusion Among Patients With Symptomatic Heart Failure With Reduced Ejection Fraction.

Administration of intravenous ferric carboxymaltose (FCM) for iron-deficient patients suffering heart failure with reduced ejection fraction (HFrEF) has been associated with transient hypophosphatemia. We sought to investigate and model the effect of intravenous FCM on phosphate levels in iron-deficient patients with HFrEF. In this single-center retrospective study, serum phosphate levels, recorded for clinical reasons, were collected out to 60 days following intravenous FCM. Hypophosphatemia was defined as a nadir serum phosphate level <0.64 mmol/L. This was further categorized as severe (0.4 to <0.64 mmol/L) and extreme (<0.4 mmol/L). Factors associated with hypophosphatemia and change in serum phosphate over time were explored. Of 173 patients included, 47 (27%) experienced hypophosphatemia, 44 (25%) were classified as severe, and 3 (2%) extreme. Risk of hypophosphatemia was increased for patients with a creatinine clearance between 60 and <90 mL/min (odds ratio, 2.3; 95% confidence interval, 1.0-5.5), while <60 mL/min was protective. The median time to nadir in patients who experienced hypophosphatemia was 8 (interquartile range, 4-16) days, with a return to baseline levels at 6 weeks. Biochemically relevant hypophosphatemia is common following a single dose of intravenous FCM. The median time to nadir was 8 days, and creatinine clearance may influence phosphate levels following intravenous FCM. These observations support the need to increase awareness among clinicians administering intravenous FCM to iron-deficient patients with HFrEF.