Prevalence and factors associated with iron deficiency among patients hospitalized with acute decompensated heart failure at Mbarara regional referral hospital, southwestern Uganda

Prevalence and factors associated with iron deficiency among patients hospitalized with acute decompensated heart failure at Mbarara regional referral hospital, southwestern Uganda | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prevalence and factors associated with iron deficiency among patients hospitalized with acute decompensated heart failure at Mbarara regional referral hospital, southwestern Uganda Abdi Salat Noor, Fardous Charles Abeya, Anthony Muyingo, Angus K Nightingale, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7425258/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background Iron deficiency is one of the most common comorbidities occurring among heart failure patients. Iron deficiency in heart failure is an independent predictor of heart failure outcomes. Data are scarce regarding its prevalence in our setting especially among patients presenting with acutely decompensated heart failure. Methods A nested cross-sectional study was conducted at MRRH including patients hospitalized with acute decompensated heart failure. Simple proportions were used for the prevalence of iron deficiency among patients hospitalized with ADHF, while multivariate logistic regression was used for associated factors, reporting adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results A total of 150 participants were enrolled. The median age was 54 years, with IQR of 40–67. The majority had NYHA functional class III [91 patients (60.7%)] and IV 38 patients (25.3%) respectively. The median systolic blood pressure was 114 (IQR 102–133), Hb 12.8g/dl (IQR11.5-14.1), NT-proBNP 9685 (IQR 2534–20631) and eGFR 53.5 (IQR 37.1–68.7). The median LV ejection fraction was 36.9 IQR (30–54), regarding etiology of HF, majority had dilated cardiomyopathy 44.9%. Comorbidities included Hypertension (85%), HIV (22%), diabetes mellitus (10.7%), and 11% had history of alcohol consumption. The prevalence of iron deficiency was 56 % (95% CI 47.7–64.1). In multivariate logistic regression, factors associated with iron deficiency among patients hospitalized with ADHF were; the presence of congestion (fluid overload) like pedal edema on physical examination aOR 3.197 ( 95% CI: 1.015–10.076; P = 0.047) and hs-CRP above 3mg/l aOR 7.982 ( 95% CI: 2.514–25.343; P < 0.001). Conclusion Our study shows that more than 50% of the patients with acute decompensated heart failure are iron deficient. The factors we found independently associated with ID are a high serum level of high-sensitivity CRP and evidence of congestion like pedal edema at admission. We recommend screening of patients hospitalized with ADHF for iron deficiency and thereafter targeted therapy to improve HF outcomes. Acute decompensated heart failure iron deficiency Figures Figure 1 Introduction Heart failure (HF) is a serious health issue, and about 64.3 million people in the world suffer from it, with a highly variable epidemiology both within and between nations ( 1 ). HF is a chronic syndrome and causes frequent hospitalizations leading to high healthcare costs both for the patient and the healthcare system ( 2 ). In sub-Saharan Africa (SSA), HF is responsible for up to 7% of all patients admitted to the internal medicine hospital wards whereas in specialized cardiac centers, it is responsible for more than 30% of hospitalizations ( 3 ). In one systematic review by Agbor et al about the etiologies of heart failure ( 4 ), cardiomyopathies made up 21.4% of all heart failure cases, making them the second-leading cause of HF after hypertensive heart disease at 39.2%. In hospitals across Africa, a frequent reason for admission among patients with heart illnesses is acute decompensated heart failure (ADHF), ( 5 ) and ADHF patients have an increased risk of poor clinical outcomes ( 6 – 8 ). Approximately 30% of all HF patients have iron deficiency ( 9 ). Iron deficiency is among the heart failure co-morbidities linked to bad outcomes but if treated, morbidity, mortality, and New York Heart Association (NYHA) class improve significantly ( 10 ). Iron deficiency is a significant reason for anemia occurring in HF ( 11 ), and in HF patients, the occurrence of anemia is a poor prognostic factor, which necessitates correction to ameliorate cardiac function decompensation or the adverse development of organ failure. One study in Uganda showed that, among HF patients at Mulago Hospital, anemia had a high prevalence of 64.3% and the in-hospital mortality that was found in that study was higher by a significant margin of 10% among patients with anemia compared to the patients who did not have anemia ( 12 ). Several factors contribute to iron deficiency among heart failure patients, including the disease's consequences such as inadequate nutritional intake, intestinal edema, drug interactions brought on by polypharmacy, and polymorbidity ( 13 ). There is also an association between functional iron deficiency and systemic pro-inflammatory status among HF patients ( 14 ). A pro-inflammatory state increases hepcidin levels, leading to iron sequestration in stores, and therefore a decrease in the amount of iron available to carry out hematopoiesis ( 14 ). In high-income countries (HIC), iron deficiency prevalence among heart failure lies between 14% and 73% depending on the nature of the study participants and the kind of criteria used for diagnosis ( 15 ). Iron deficiency in HF is often under-diagnosed because most times, anemia is not evident clinically. Moreover, anemia may not even be present at all, since it requires a particular time frame to manifest following the occurrence of iron deficiency (ID). A study done by Martens showed that iron deficiency was prevalent in 53% of the participants, mostly those with reduced left ventricular function, while anemia was demonstrated in only 36% ( 16 ). Some trials have been done involving the administration of intravenous iron to treat iron deficiency in patients who have heart failure with reduced left-ventricular ejection fraction (LVEF), and these demonstrated benefits in outcomes about patients, including improvement in the New York Heart Association (NYHA) class, improvement in the 6-minute walking distance, a better quality of life and reduced hospitalization rates ( 17 , 18 ). There is insufficient data in our setting, in Uganda and Africa regarding iron deficiency among heart failure patients, especially those hospitalized with acute decompensation. Therefore, we purposed to determine the prevalence of iron deficiency and the factors associated with it among acutely decompensated heart failure patients in Mbarara Regional Referral Hospital. METHODS Study Design and setting This was a hospital-based, a nested cross-sectional study conducted at medical ward of Mbarara Regional Referral Hospital (MRRH), a tertiary public and teaching hospital located in Mbarara City, southwestern Uganda. Eligibility Criteria In this study we used participants enrolled in the ECADU (Epidemiology of Cardiac Dysfunction in Sub-Saharan Africa: Heart Failure Registry of HIV infected and HIV uninfected persons in Uganda and Zambia). ECADU study was a prospective cohort study that recruited patients hospitalised with acute decompensated heart failure as identified by a healthcare provider. It aimed at comparing the clinical characteristics and predictors of outcomes among heart failure patients with HIV and those without HIV. ECADU study included adults (aged ≥ 18 years) hospitalised with ADHF and exlude patients with chronic lung disease or chronic liver disease and had no signs and symptoms of heart failure. Sample size During the study period 271 patients were hospitalized with acute decompensated heart failure. We used the finite population formula to determine how many of the 271 patients were needed to answer the study’s objectives. For our study, we used a 95% confidence interval, and thus a Z = 1.96, an expected prevalence of 76% from a study done in India by Sharma et al, thus a p = 0.76, a margin of error of 5%, thus e = 0.05, and N = 271, Feeding this numbers into the formula: $$\:n=\frac{\frac{{1.96}^{2}X0.76(1-0.76)}{{0.05}^{2}}}{1+\frac{{1.96}^{2}X0.76(1-0.76)}{{O.05}^{2}X271}}=137$$ The estimated sample size came to 137 patients. However, since the ECADU study had recruited 150 patients, we include all these in the study. Study Procedures and Study Variables Patients who were eligible provided a written informed consent. A trained study nurse and study investigator collected data on demographics, lifestyle behaviors (alcohol, smoking), comorbidities (including diabetes, HIV, chronic kidney disease and history of gastrointestinal bleeding, peptic ulcer disease (PUD), and use of medication for PUD were also obtained. Menstrual history for women in child bearing age was obtained). Clinical examination parameters were obtained: NYHA (New York Heart Association) class of heart failure; systolic and diastolic blood pressure, pulse rate, absence or presence of an irregular pulse, raised jugular venous pressure, hepatojugular reflux, apex beat, apical or parasternal heave, third/or fourth heart sound, ascites, and ankle edema were obtained. Echocardiographic images for: left ventricular ejection fraction, valvular abnormalities. Blood was drawn for serum creatinine, urea, electrolytes, lipid profile, complete blood count, NT-proBNP, high sensitive C-reactive protein, and iron studies. Clinical Measurements Blood pressure was measured using a validated Sinocare AES-U181 device. Anthropometric measurements included weight, height, BMI. Electrocardiogram (ECGs) was recorded using the PC ECG 2.1 SEMIP 1.5 system. Echocardiograms were performed using HD7 XE Diagnostic ultrasound system, China. We measured left ventricular ejection fraction, heart chamber sizes, valve stenosis or regurgitation and the possible underlying etiology. Venous blood was analyzed for complete blood count using a Sysmex ®XN-550 automated hematology analyzer; serum creatinine, Hs-CRP, NT-proBNP, blood urea nitrogen which was done using a Huma Star 200® biochemistry analyzer. Measurement of serum Iron, transferrin and transferrin saturation (TSAT) were done using Abbot Architect c: 8200 machine. Serum iron levels below 13 µmol per liter and Transferrin saturation (TSAT) below 20% was used to establish the diagnosis of iron deficiency. These parameters have sensitivity of 94% and specificity of 88% (Grote Beverborg et al., 2018). Statistical analysis Data were captured in REDCap and exported to STATA version 17. Categorical variables were summarized as percentages, and as frequencies, whereas continuous and normally distributed variables were summarized as mean and standard deviations, and median plus interquartile ranges were utilized for skewed data. Prevalence of iron deficiency was expressed in proportion and percentage. Bivariate and multivariate logistic regression was performed to determine factors associated with iron deficiency among patients hospitalized with acute decompensated heart failure. Variables with p < 0.05 or biological relevance were included in multivariable models. Significance was set at p < 0.05. Results Participant Recruitment and Baseline Characteristics From June 2022 through to November 2023, a total of 216 patients admitted for decompensated CHF were screened. Of these, 25 declined to consent, 28 had end stage chronic kidney disease, 10 had chronic obstructive pulmonary disease, and 3 had normal cardiac echocardiograph. Ultimately 150 participants were enrolled into the study. The clinical, demographic and laboratory characteristics for the 150 study participants are shown in Table 1. The median age was 54 years IQR (40-67). Majority of the participants had admission NYHA functional classes III (60.7%) and IV (25.3%) respectively. The median systolic blood pressure was 114 (IQR 102-133), median Hb 12.8g/dl (IQR11.5-14.1). Majority of the participants had congestion; median NT-proBNP 9685 (IQR 2534-20631). The median eGFR 53.5 (IQR 37.1-68.7). The median LV ejection fraction was 36.9 IQR (30-54), regarding etiology of HF, majority had dilated cardiomyopathy 44.9%, hypertensive heart disease 19.7% and valvular heart disease/Rheumatic heart disease 18%. About 44% of the participants had history of prior hospitalization for heart failure. Comorbidities included Hypertension (85%), HIV (22%), diabetes mellitus (10.7%), and 11% had history of alcohol consumption. The Prevalence of Iron Deficiency Iron deficiency was defined as Serum iron levels below 13 µmol per liter and a transferrin saturation (TSAT) below 20%. Out of the 150 patients who presented with acutely decompensated heart failure that were analyzed for iron deficiency, 84 (56%) had iron deficiency with a 95% confidence interval (95% CI 47.7- 64.1). Factors Associated with Iron Deficiency In multivariable analysis (Table 2), presence of pedal edema on physical examination (aOR 3.20; 95% CI 1.02-10.08; P =0.047) and hs-CRP above 3mg/l (aOR 7.98; 95% CI (2.51-25.34); P <0.001) were found to be significantly associated with iron deficiency. Although not statistically significant, trends toward factors associated with iron deficiency were observed in NYHA class III and IV (OR 5.09; 95% CI 1.76-14-79; p= 0.003) and NT-proBNP >2000pg/mL (OR 3.63; 95% CI 1.61-8.19; p=0.002). Discussion In our study, we found that the prevalence of iron deficiency among patients hospitalized with acute decompensated heart failure was high at 56%, and was significantly associated with elevated high-sensitive C-reactive protein and presence of pedal edema on physical examination. The observed prevalence is high and underscores the burden of this high-risk factor for heart failure hospitalization and outcomes. The prevalence of iron deficiency in our study was similar to the multicenter European study which demonstrated a prevalence of 58% (21) and also a study done in Germany and Switzerland (RAID-HF registry) which showed a prevalence of 54.7% (22). The similarity in the prevalence is likely due to advanced heart failure class (NYHA III & IV) requiring hospitalization. Another study done in 46 centers in France among hospitalized patients with acute decompensated chronic HF showed a higher prevalence of iron deficiency 69-75% (28). The difference in this could be explained by patient population difference where the median age in our study is 54 years IQR (40-67) whereas in the French study the patients were older mean age among women and men was 74.8 ±12 and 81.2 ± 11.4 respectively (28). The elderly are more at risk of malnutrition and gastrointestinal blood loss due to the increased risk of GI malignancies associated with increasing age (23). At the same time over 40% of the patients in the French study were on either aspirin or oral anticoagulant which may have increased their risk of GI blood loss leading to increased iron deficiency whereas in our study antiplatelet and anticoagulant use was limited to 10% of our study population. The prevalence of iron deficiency in our study is higher than the one found among HF patients in Tanzania by Makubi et al. (15) which was 49%. This could be explained by the test done in our study to define iron deficiency, iron levels <13umol/l and TSAT <20% which has a sensitivity of 94% and a specificity of 88% to determine iron deficiency in HF (Grote Beverborg et al., 2018); whereas the study done in Tanzania did not do iron studies but rather used RBC indices of mean corpuscular volume <80 and mean corpuscular hemoglobin concentration <330 g/l to define iron deficiency in patients with heart failure as such this could explain the variation in the prevalence of iron deficiency among heart failure patients (24). In our study, high hsCRP levels and the presence of fluid overload signs like positive pedal edema were significantly associated with iron deficiency. The association between fluid overload and iron deficiency may be due to gut edema leading to malabsorption (13). Sandek et, al also observed that the permeability of the intestines and absorption ability is been modified in patients with chronic heart failure (25). The finding of high hs-CRP being independently associated with iron deficiency is consistent with the fact that heart failure is considered a chronic inflammatory condition (26) and chronic inflammation leads to increases in acute phase reactant levels like C-reactive protein, ferritin & hepcidin (26). Hepcidin for example attaches to the membrane transporter known as ferroportin, and this will induce the internal translocation of the ferroportin and subsequent degradation. This leads to a reduction in the duodenal absorption of iron from the gut and also reduces the release of iron from the body storage sites including the reticulo-endothelial cells and the hepatocytes. This results in a state of functional iron deficiency (27). Conclusion and Our study shows that 56% of the patients with acute decompensated heart failure are iron deficient. The factors that were found to be independently associated with iron deficiency were increased serum level of high-sensitivity CRP and evidence of congestion like pedal edema at admission. Recommendation This study points out the importance of screening patients with acute decompensated heart failure for iron deficiency on admission. We recommend that further studies be done on the relationship between iron deficiency and mortality among patients presenting with acute decompensated heart failure. Strengths To our knowledge, this is the first study conducted in Uganda to assess for iron deficiency in patients hospitalized for acute heart failure decompensation using TSAT and serum Iron. The study population was relatively homogeneous similar to most resource limited settings which enhances the generalizability of the findings to individuals with acute heart failure decompensation. Limitations The study has limitations, including its cross-sectional design, which limits the ability to infer causality, and the single-center nature of the study may restrict the generalizability of the findings. We were not able to measure other markers of iron metabolism such as ferritin level and soluble transferrin receptor test. Abbreviations ADHF: Acute Decompensated Heart Failure hs-CRP: highly sensitive C - Reactive Protein ESC: European society of cardiology ESR: Erythrocyte Sedimentation Rate HF: Heart failure HFA: Heart Failure Association HFSA: Heart Failure Society of America HFrEF: Heart failure with reduced ejection fraction HICs: High-Income Countries JHFS: Japanese Heart Failure Society LMICs: Low- and Middle-Income Countries LVSD: Left Ventricular Systolic Dysfunction NYHA: New York Heart Association TSAT: Transferrin Saturation Declarations Ethical Approval Ethical approval for this study was obtained from the Mbarara University of Science and Technology Research Ethics Committee (MUST-REC) under reference number MUST-2023-1168; MUST REC 05/02-20, Uganda national council for science and technology (UNCST) HS788ES, University of Virginia IRB for Health Sciences and Research IRB-HSR-21894 Administrative clearance was granted by Mbarara Regional Referral Hospital. The study was conducted in accordance with the ethical principles of the collaborative Institutional Training Initiative (CITI program) for Good Clinical Practice guidelines and applicable local regulations. ‘Clinical trial number: not applicable’ Acknowledgments We thank the study team, hospital administration, and the patients who participated in this study. Author contributions ASN, FCA, AM, MS, and OS, AN, contributed to the conception and design of the study. ASN, FCA, conducted data collection and, performed the data analysis. ASN also drafted the initial manuscript. FCA, MS, ASN, LM, were responsible for funding acquisition. All authors critically reviewed, revised, and approved the final version of the manuscript. Competing interests The authors declare that they have no competing interests. Consent to publish All authors consented to publish this work. Availability of data and materials The datasets used during this study are available from the corresponding author upon reasonable request. Source of Funding Research reported in this manuscript was supported by University of Virginia department of Internal Medicine and Global Health. The content is solely the responsibility of the authors and doesn’t necessarily represent the official views of the National Institutes of Health. References James SL, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet. 2018;392(10159):1789–858. Rocha BML, Cunha GJL, Menezes Falcão LF. The Burden of Iron Deficiency in Heart Failure. J Am Coll Cardiol. 2018 Feb;71(7):782–93. Kengne AP, Dzudie A, Sobngwi E. 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PMID: 25065368 Tables Table 1 and 2 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1and2.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 06 Oct, 2025 Editor invited by journal 08 Sep, 2025 Editor assigned by journal 05 Sep, 2025 Submission checks completed at journal 05 Sep, 2025 First submitted to journal 21 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7425258","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":530461188,"identity":"b961c36e-164c-40ff-8a6f-2bcc5f4e006c","order_by":0,"name":"Abdi Salat Noor","email":"","orcid":"","institution":"Mbarara University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Abdi","middleName":"Salat","lastName":"Noor","suffix":""},{"id":530461190,"identity":"4359d9e3-f9f5-40a8-b17e-0ac5ff804a26","order_by":1,"name":"Fardous Charles 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1","display":"","copyAsset":false,"role":"figure","size":112004,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePrevalence of iron deficiency with and without Anemia\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7425258/v1/e0b5c3681df54eea89597497.png"},{"id":93807011,"identity":"039adf05-7a0c-4e5b-970f-51b5b935fdf0","added_by":"auto","created_at":"2025-10-17 18:26:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":701501,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7425258/v1/8f53f35c-b632-4d89-8d19-edfaecd7fdf8.pdf"},{"id":93805620,"identity":"182edf33-e7d4-4c42-bfa0-e0d74c33568a","added_by":"auto","created_at":"2025-10-17 18:02:12","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":51600,"visible":true,"origin":"","legend":"","description":"","filename":"Table1and2.docx","url":"https://assets-eu.researchsquare.com/files/rs-7425258/v1/3fe01a49a2273ccefc1a7872.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prevalence and factors associated with iron deficiency among patients hospitalized with acute decompensated heart failure at Mbarara regional referral hospital, southwestern Uganda","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHeart failure (HF) is a serious health issue, and about 64.3\u0026nbsp;million people in the world suffer from it, with a highly variable epidemiology both within and between nations (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). HF is a chronic syndrome and causes frequent hospitalizations leading to high healthcare costs both for the patient and the healthcare system (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn sub-Saharan Africa (SSA), HF is responsible for up to 7% of all patients admitted to the internal medicine hospital wards whereas in specialized cardiac centers, it is responsible for more than 30% of hospitalizations (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn one systematic review by Agbor et al about the etiologies of heart failure (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e), cardiomyopathies made up 21.4% of all heart failure cases, making them the second-leading cause of HF after hypertensive heart disease at 39.2%.\u003c/p\u003e\u003cp\u003eIn hospitals across Africa, a frequent reason for admission among patients with heart illnesses is acute decompensated heart failure (ADHF), (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) and ADHF patients have an increased risk of poor clinical outcomes (\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eApproximately 30% of all HF patients have iron deficiency (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Iron deficiency is among the heart failure co-morbidities linked to bad outcomes but if treated, morbidity, mortality, and New York Heart Association (NYHA) class improve significantly (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Iron deficiency is a significant reason for anemia occurring in HF (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e), and in HF patients, the occurrence of anemia is a poor prognostic factor, which necessitates correction to ameliorate cardiac function decompensation or the adverse development of organ failure.\u003c/p\u003e\u003cp\u003eOne study in Uganda showed that, among HF patients at Mulago Hospital, anemia had a high prevalence of 64.3% and the in-hospital mortality that was found in that study was higher by a significant margin of 10% among patients with anemia compared to the patients who did not have anemia (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eSeveral factors contribute to iron deficiency among heart failure patients, including the disease's consequences such as inadequate nutritional intake, intestinal edema, drug interactions brought on by polypharmacy, and polymorbidity (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). There is also an association between functional iron deficiency and systemic pro-inflammatory status among HF patients (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). A pro-inflammatory state increases hepcidin levels, leading to iron sequestration in stores, and therefore a decrease in the amount of iron available to carry out hematopoiesis (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). In high-income countries (HIC), iron deficiency prevalence among heart failure lies between 14% and 73% depending on the nature of the study participants and the kind of criteria used for diagnosis (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Iron deficiency in HF is often under-diagnosed because most times, anemia is not evident clinically. Moreover, anemia may not even be present at all, since it requires a particular time frame to manifest following the occurrence of iron deficiency (ID). A study done by Martens showed that iron deficiency was prevalent in 53% of the participants, mostly those with reduced left ventricular function, while anemia was demonstrated in only 36% (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Some trials have been done involving the administration of intravenous iron to treat iron deficiency in patients who have heart failure with reduced left-ventricular ejection fraction (LVEF), and these demonstrated benefits in outcomes about patients, including improvement in the New York Heart Association (NYHA) class, improvement in the 6-minute walking distance, a better quality of life and reduced hospitalization rates (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThere is insufficient data in our setting, in Uganda and Africa regarding iron deficiency among heart failure patients, especially those hospitalized with acute decompensation. Therefore, we purposed to determine the prevalence of iron deficiency and the factors associated with it among acutely decompensated heart failure patients in Mbarara Regional Referral Hospital.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Design and setting\u003c/h2\u003e\u003cp\u003eThis was a hospital-based, a nested cross-sectional study conducted at medical ward of Mbarara Regional Referral Hospital (MRRH), a tertiary public and teaching hospital located in Mbarara City, southwestern Uganda.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eEligibility Criteria\u003c/h3\u003e\n\u003cp\u003eIn this study we used participants enrolled in the ECADU (Epidemiology of Cardiac Dysfunction in Sub-Saharan Africa: Heart Failure Registry of HIV infected and HIV uninfected persons in Uganda and Zambia). ECADU study was a prospective cohort study that recruited patients hospitalised with acute decompensated heart failure as identified by a healthcare provider. It aimed at comparing the clinical characteristics and predictors of outcomes among heart failure patients with HIV and those without HIV. ECADU study included adults (aged\u0026thinsp;\u0026ge;\u0026thinsp;18 years) hospitalised with ADHF and exlude patients with chronic lung disease or chronic liver disease and had no signs and symptoms of heart failure.\u003c/p\u003e\n\u003ch3\u003eSample size\u003c/h3\u003e\n\u003cp\u003eDuring the study period 271 patients were hospitalized with acute decompensated heart failure. We used the finite population formula to determine how many of the 271 patients were needed to answer the study\u0026rsquo;s objectives. For our study, we used a 95% confidence interval, and thus a Z\u0026thinsp;=\u0026thinsp;1.96, an expected prevalence of 76% from a study done in India by Sharma et al, thus a p\u0026thinsp;=\u0026thinsp;0.76, a margin of error of 5%, thus e\u0026thinsp;=\u0026thinsp;0.05, and N\u0026thinsp;=\u0026thinsp;271,\u003c/p\u003e\u003cp\u003eFeeding this numbers into the formula:\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:n=\\frac{\\frac{{1.96}^{2}X0.76(1-0.76)}{{0.05}^{2}}}{1+\\frac{{1.96}^{2}X0.76(1-0.76)}{{O.05}^{2}X271}}=137$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe estimated sample size came to 137 patients. However, since the ECADU study had recruited 150 patients, we include all these in the study.\u003c/p\u003e\n\u003ch3\u003eStudy Procedures and Study Variables\u003c/h3\u003e\n\u003cp\u003ePatients who were eligible provided a written informed consent. A trained study nurse and study investigator collected data on demographics, lifestyle behaviors (alcohol, smoking), comorbidities (including diabetes, HIV, chronic kidney disease and history of gastrointestinal bleeding, peptic ulcer disease (PUD), and use of medication for PUD were also obtained. Menstrual history for women in child bearing age was obtained). Clinical examination parameters were obtained: NYHA (New York Heart Association) class of heart failure; systolic and diastolic blood pressure, pulse rate, absence or presence of an irregular pulse, raised jugular venous pressure, hepatojugular reflux, apex beat, apical or parasternal heave, third/or fourth heart sound, ascites, and ankle edema were obtained. Echocardiographic images for: left ventricular ejection fraction, valvular abnormalities. Blood was drawn for serum creatinine, urea, electrolytes, lipid profile, complete blood count, NT-proBNP, high sensitive C-reactive protein, and iron studies.\u003c/p\u003e\n\u003ch3\u003eClinical Measurements\u003c/h3\u003e\n\u003cp\u003eBlood pressure was measured using a validated Sinocare AES-U181 device. Anthropometric measurements included weight, height, BMI. Electrocardiogram (ECGs) was recorded using the PC ECG 2.1 SEMIP 1.5 system. Echocardiograms were performed using HD7 XE Diagnostic ultrasound system, China. We measured left ventricular ejection fraction, heart chamber sizes, valve stenosis or regurgitation and the possible underlying etiology.\u003c/p\u003e\u003cp\u003eVenous blood was analyzed for complete blood count using a Sysmex \u0026reg;XN-550 automated hematology analyzer; serum creatinine, Hs-CRP, NT-proBNP, blood urea nitrogen which was done using a Huma Star 200\u0026reg; biochemistry analyzer. Measurement of serum Iron, transferrin and transferrin saturation (TSAT) were done using Abbot Architect c: 8200 machine.\u003c/p\u003e\u003cp\u003eSerum iron levels below 13 \u0026micro;mol per liter and Transferrin saturation (TSAT) below 20% was used to establish the diagnosis of iron deficiency. These parameters have sensitivity of 94% and specificity of 88% (Grote Beverborg et al., 2018).\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eData were captured in REDCap and exported to STATA version 17. Categorical variables were summarized as percentages, and as frequencies, whereas continuous and normally distributed variables were summarized as mean and standard deviations, and median plus interquartile ranges were utilized for skewed data. Prevalence of iron deficiency was expressed in proportion and percentage. Bivariate and multivariate logistic regression was performed to determine factors associated with iron deficiency among patients hospitalized with acute decompensated heart failure. Variables with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 or biological relevance were included in multivariable models. Significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eParticipant Recruitment and Baseline Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom June 2022 through to November 2023, a total of 216 patients admitted for decompensated CHF were screened. Of these, 25 declined to consent, 28 had end stage chronic kidney disease, 10 had chronic obstructive pulmonary disease, and 3 had normal cardiac echocardiograph. Ultimately 150 participants were enrolled into the study.\u003c/p\u003e\n\u003cp\u003eThe clinical, demographic and laboratory characteristics for the 150 study participants are shown in Table 1. The median age was 54 years IQR (40-67). Majority of the participants had admission NYHA functional classes III (60.7%) and IV (25.3%) respectively. The median systolic blood pressure was 114 (IQR 102-133), median Hb 12.8g/dl (IQR11.5-14.1). Majority of the participants had congestion; median NT-proBNP 9685 (IQR 2534-20631). The median eGFR 53.5 (IQR 37.1-68.7).\u003c/p\u003e\n\u003cp\u003eThe median LV ejection fraction was 36.9 IQR (30-54), regarding etiology of HF, majority had dilated cardiomyopathy 44.9%, hypertensive heart disease 19.7% and valvular heart disease/Rheumatic heart disease 18%. About 44% of the participants had history of prior hospitalization for heart failure. Comorbidities included Hypertension (85%), HIV (22%), diabetes mellitus (10.7%), and 11% had history of alcohol consumption.\u003c/p\u003e\n\u003cp id=\"_Toc172802463\"\u003e\u003cstrong\u003eThe Prevalence of Iron Deficiency\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIron deficiency was defined as Serum iron levels below 13 \u0026micro;mol per liter and a transferrin saturation (TSAT) below 20%. Out of the 150 patients who presented with acutely decompensated heart failure that were analyzed for iron deficiency, 84 (56%) had iron deficiency with a 95% confidence interval (95% CI 47.7- 64.1).\u0026nbsp;\u003c/p\u003e\n\u003cp id=\"_Toc172802464\"\u003e\u003cstrong\u003eFactors Associated with Iron Deficiency\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;In multivariable analysis (Table 2), presence of pedal edema\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eon physical examination (aOR 3.20; 95% CI 1.02-10.08; P =0.047) and hs-CRP above 3mg/l (aOR 7.98; 95% CI (2.51-25.34); P \u0026lt;0.001) were found to be significantly associated with iron deficiency. Although not statistically significant, trends toward factors associated with iron deficiency were observed in NYHA class III and IV (OR 5.09; 95% CI 1.76-14-79; p= 0.003) and NT-proBNP \u0026gt;2000pg/mL (OR 3.63; 95% CI 1.61-8.19; p=0.002).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our study, we found that the prevalence of iron deficiency among patients hospitalized with acute decompensated heart failure was high at 56%, and was significantly associated with elevated high-sensitive C-reactive protein and presence of pedal edema on physical examination.\u003c/p\u003e\n\u003cp\u003eThe observed prevalence is high and underscores the burden of this high-risk factor for heart failure hospitalization and outcomes.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThe prevalence of iron deficiency in our study was similar to the multicenter European study which demonstrated a prevalence of 58%\u0026nbsp;(21)\u0026nbsp;and also a study done in Germany and Switzerland (RAID-HF registry) which showed a prevalence of 54.7%\u0026nbsp;(22). The similarity in the prevalence is likely due to advanced heart failure class (NYHA III \u0026amp; IV) requiring hospitalization.\u003c/p\u003e\n\u003cp\u003eAnother study done in 46 centers in France among hospitalized patients with acute decompensated chronic HF showed a higher prevalence of iron deficiency 69-75% (28). The difference in this could be explained by patient population difference where the median age in our study is 54 years IQR (40-67) whereas in the French study the patients were older mean age among women and men was 74.8\u0026nbsp;\u0026plusmn;12 and 81.2\u0026nbsp;\u0026plusmn;\u0026nbsp;11.4 respectively (28). The \u0026nbsp;elderly are more at risk of malnutrition and gastrointestinal blood loss due to the increased risk of \u0026nbsp;GI malignancies associated with increasing age \u0026nbsp;(23). At the same time over 40% of the patients in the French study were on either aspirin or oral anticoagulant which may have increased their risk of GI blood loss leading to increased iron deficiency whereas in our study antiplatelet and anticoagulant use was limited to 10% of our study population.\u003c/p\u003e\n\u003cp\u003eThe prevalence of iron deficiency in our study is higher than the one found among HF patients in Tanzania by Makubi et al.\u0026nbsp;(15)\u0026nbsp;which was 49%. This could be explained by the test done in our study to define iron deficiency, iron levels \u0026lt;13umol/l and TSAT \u0026lt;20% which has a sensitivity of \u0026nbsp;94% \u0026nbsp; and a specificity of 88%\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eto determine iron deficiency in HF (Grote Beverborg et al., 2018); whereas the study done in Tanzania did not do iron studies but rather used RBC indices of mean corpuscular volume \u0026lt;80 and mean corpuscular hemoglobin concentration \u0026lt;330 g/l to define iron deficiency in patients with heart failure as such this could explain the variation in the prevalence of iron deficiency among heart failure patients\u0026nbsp;(24).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn our study, high hsCRP levels and the presence of fluid overload signs like positive pedal edema were significantly associated with iron deficiency. The association between fluid overload and iron deficiency may be due to gut edema leading to malabsorption \u0026nbsp;(13). Sandek et, al also observed that the permeability of the intestines and absorption ability is been modified in patients with chronic heart failure\u0026nbsp;(25).\u003c/p\u003e\n\u003cp\u003eThe finding of high hs-CRP being independently associated with iron deficiency is consistent with the fact that heart failure is considered a chronic inflammatory condition\u0026nbsp;(26)\u0026nbsp;and chronic inflammation\u0026nbsp;leads to increases in acute phase reactant levels like C-reactive protein, ferritin\u0026nbsp;\u0026amp; hepcidin (26).\u003c/p\u003e\n\u003cp\u003eHepcidin for example attaches to the membrane transporter known as ferroportin, and this will induce the internal translocation of the ferroportin and subsequent degradation. This leads to a reduction in the duodenal absorption of iron from the gut and also reduces the release of iron from the body storage sites including the reticulo-endothelial cells and the hepatocytes. This results in a state of functional iron deficiency\u0026nbsp;(27).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion and\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur study shows that 56% of the patients with acute decompensated heart failure are iron deficient. The factors that were found to be independently associated with iron deficiency were increased serum level of high-sensitivity CRP and evidence of congestion like pedal edema at admission.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRecommendation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study points out the importance of screening patients with acute decompensated heart failure for iron deficiency on admission. We recommend that further studies be done on the relationship between iron deficiency and mortality among patients presenting with acute decompensated heart failure.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrengths\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;To our knowledge, this is\u0026nbsp;the first study conducted in Uganda to assess for iron deficiency in patients hospitalized for acute heart failure decompensation using TSAT and serum Iron.\u0026nbsp; The study population was relatively homogeneous similar to most resource limited settings which enhances the generalizability of the findings to individuals with acute heart failure decompensation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study has limitations, including its cross-sectional design, which limits the ability to infer causality, and the single-center nature of the study may restrict the generalizability of the findings. We were not able to measure other markers of iron metabolism such as ferritin level and soluble transferrin receptor test.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eADHF: Acute Decompensated Heart Failure\u003c/p\u003e\n\u003cp\u003ehs-CRP: highly sensitive C - Reactive Protein\u003c/p\u003e\n\u003cp\u003eESC: European society of cardiology\u003c/p\u003e\n\u003cp\u003eESR: Erythrocyte Sedimentation Rate\u003c/p\u003e\n\u003cp\u003eHF: Heart failure\u003c/p\u003e\n\u003cp\u003eHFA: Heart Failure Association\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHFSA: Heart Failure Society of America\u003c/p\u003e\n\u003cp\u003eHFrEF: Heart failure with reduced ejection fraction\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHICs: High-Income Countries\u003c/p\u003e\n\u003cp\u003eJHFS: Japanese Heart Failure Society\u003c/p\u003e\n\u003cp\u003eLMICs: Low- and Middle-Income Countries\u003c/p\u003e\n\u003cp\u003eLVSD: Left Ventricular Systolic Dysfunction\u003c/p\u003e\n\u003cp\u003eNYHA: New York Heart Association\u003c/p\u003e\n\u003cp\u003eTSAT: Transferrin Saturation\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval for this study was obtained from the Mbarara University of Science and Technology Research Ethics Committee (MUST-REC) under reference number MUST-2023-1168; MUST REC 05/02-20, Uganda national council for science and technology (UNCST) HS788ES, University of Virginia IRB for Health Sciences and Research IRB-HSR-21894 Administrative clearance was granted by Mbarara Regional Referral Hospital. The study was conducted in accordance with the ethical principles of the collaborative Institutional Training Initiative (CITI program) for Good Clinical Practice guidelines and applicable local regulations. \u0026lsquo;Clinical trial number: not applicable\u0026rsquo;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the study team, hospital administration, and the patients who participated in this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eASN, FCA, AM, MS, and OS, AN, contributed to the conception and design of the study. ASN, FCA, conducted data collection and, performed the data analysis. ASN also drafted the initial manuscript. FCA, MS, ASN, LM, were responsible for funding acquisition. All authors critically reviewed, revised, and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors consented to publish this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used during this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSource of Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResearch reported in this manuscript was supported by University of Virginia department of Internal Medicine and Global Health. The content is solely the responsibility of the authors and doesn\u0026rsquo;t necessarily represent the official views of the National Institutes of Health.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJames SL, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990\u0026ndash;2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet. 2018;392(10159):1789\u0026ndash;858. \u003c/li\u003e\n\u003cli\u003eRocha BML, Cunha GJL, Menezes Falc\u0026atilde;o LF. The Burden of Iron Deficiency in Heart Failure. J Am Coll Cardiol. 2018 Feb;71(7):782\u0026ndash;93. \u003c/li\u003e\n\u003cli\u003eKengne AP, Dzudie A, Sobngwi E. Heart failure in sub-Saharan Africa: a literature review with emphasis on individuals with diabetes. Vasc Health Risk Manag. 2008;4(1):123\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eAgbor VN, Essouma M, Ntusi NA, Nyaga UF, Bigna JJ, Noubiap JJ. Heart failure in sub-Saharan Africa: a contemporaneous systematic review and meta-analysis. Int J Cardiol. 2018;257:207\u0026ndash;15. \u003c/li\u003e\n\u003cli\u003eSliwa K, Mayosi BM. Recent advances in the epidemiology, pathogenesis and prognosis of acute heart failure and cardiomyopathy in Africa. Heart. 2013;99(18):1317\u0026ndash;22. \u003c/li\u003e\n\u003cli\u003eAdams Jr KF, Fonarow GC, Emerman CL, LeJemtel TH, Costanzo MR, Abraham WT, et al. Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J. 2005;149(2):209\u0026ndash;16. \u003c/li\u003e\n\u003cli\u003eBenjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. Heart Disease and Stroke Statistics\u0026mdash;2017 Update: A Report From the American Heart Association. Circulation [Internet]. 2017 Mar 7 [cited 2024 Aug 9];135(10). Available from: https://www.ahajournals.org/doi/10.1161/CIR.0000000000000485\u003c/li\u003e\n\u003cli\u003eSolomon SD, Desai AS. Acute Heart Failure. J Am Coll Cardiol. 2017 Jun;69(25):3040\u0026ndash;1. \u003c/li\u003e\n\u003cli\u003eSinger CE, Vasile CM, Popescu M, Popescu AIS, Marginean IC, Iacob GA, et al. Role of iron deficiency in heart failure\u0026mdash;clinical and treatment approach: An overview. Diagnostics. 2023;13(2):304. \u003c/li\u003e\n\u003cli\u003eJankowska EA, Tkaczyszyn M, Suchocki T, Drozd M, Von Haehling S, Doehner W, et al. Effects of intravenous iron therapy in iron‐deficient patients with systolic heart failure: a meta‐analysis of randomized controlled trials. Eur J Heart Fail. 2016 Jul;18(7):786\u0026ndash;95. \u003c/li\u003e\n\u003cli\u003eYeo TJ, Yeo PSD, Ching‐Chiew Wong R, Ong HY, Leong KTG, Jaufeerally F, et al. Iron deficiency in a multi‐ethnic Asian population with and without heart failure: prevalence, clinical correlates, functional significance and prognosis. Eur J Heart Fail. 2014 Oct;16(10):1125\u0026ndash;32. \u003c/li\u003e\n\u003cli\u003eKuule JK, Seremba E, Freers J. Anaemia among patients with congestive cardiac failure in Uganda\u0026ndash;its impact on treatment outcomes. S Afr Med J [Internet]. 2009 [cited 2024 Aug 9];99(12). Available from: https://www.ajol.info/index.php/samj/article/view/50878\u003c/li\u003e\n\u003cli\u003eHughes CM, Woodside JV, McGartland C, Roberts MJ, Nicholls DP, McKeown PP. Nutritional intake and oxidative stress in chronic heart failure. Nutr Metab Cardiovasc Dis. 2012;22(4):376\u0026ndash;82. \u003c/li\u003e\n\u003cli\u003eSilverberg DS, Wexler D, Schwartz D. Is correction of iron deficiency a new addition to the treatment of the heart failure? Int J Mol Sci. 2015;16(6):14056\u0026ndash;74. \u003c/li\u003e\n\u003cli\u003eMakubi A, Roberts DJ. Investigation and treatment for iron deficiency in heart failure: the unmet need in Lower and Middle Income Countries. Br J Haematol. 2017 Jun;177(6):896\u0026ndash;904. \u003c/li\u003e\n\u003cli\u003eMartens P, Nijst P, Verbrugge FH, Smeets K, Dupont M, Mullens W. Impact of iron deficiency on exercise capacity and outcome in heart failure with reduced, mid-range and preserved ejection fraction. Acta Cardiol. 2018 Mar 4;73(2):115\u0026ndash;23. \u003c/li\u003e\n\u003cli\u003eGraham FJ, Pellicori P, Ford I, Petrie MC, Kalra PR, Cleland JGF. Intravenous iron for heart failure with evidence of iron deficiency: a meta-analysis of randomised trials. Clin Res Cardiol. 2021 Aug;110(8):1299\u0026ndash;307. \u003c/li\u003e\n\u003cli\u003eJankowska EA, Tkaczyszyn M, Suchocki T, Drozd M, von Haehling S, Doehner W, et al. Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials. Eur J Heart Fail. 2016;18(7):786\u0026ndash;95. \u003c/li\u003e\n\u003cli\u003eGrote Beverborg N, Klip IjT, Meijers WC, Voors AA, Vegter EL, Van Der Wal HH, et al. Definition of Iron Deficiency Based on the Gold Standard of Bone Marrow Iron Staining in Heart Failure Patients. Circ Heart Fail. 2018 Feb;11(2):e004519. \u003c/li\u003e\n\u003cli\u003eGraham FJ, Masini G, Pellicori P, Cleland JGF, Greenlaw N, Friday J, et al. Natural history and prognostic significance of iron deficiency and anaemia in ambulatory patients with chronic heart failure. Eur J Heart Fail. 2022 May;24(5):807\u0026ndash;17. \u003c/li\u003e\n\u003cli\u003eEnjuanes C, Klip IjT, Bruguera J, Cladellas M, Ponikowski P, Banasiak W, et al. Iron deficiency and health-related quality of life in chronic heart failure: results from a multicenter European study. Int J Cardiol. 2014;174(2):268\u0026ndash;75. \u003c/li\u003e\n\u003cli\u003eWienbergen H, Pfister O, Hochadel M, Michel S, Bruder O, Remppis BA, et al. Usefulness of iron deficiency correction in management of patients with heart failure [from the registry analysis of iron deficiency-heart failure (RAID-HF) registry]. Am J Cardiol. 2016;118(12):1875\u0026ndash;80. \u003c/li\u003e\n\u003cli\u003eJoosten E, Meeuwissen J, Vandewinckele H, Hiele M. Iron status and colorectal cancer in symptomatic elderly patients. Am J Med. 2008;121(12):1072\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eTkaczyszyn M, Com\u0026iacute;n‐Colet J, Voors AA, Van Veldhuisen DJ, Enjuanes C, Moliner‐Borja P, et al. Iron deficiency and red cell indices in patients with heart failure. Eur J Heart Fail. 2018 Jan;20(1):114\u0026ndash;22. \u003c/li\u003e\n\u003cli\u003eSandek A, Bauditz J, Swidsinski A, Buhner S, Weber-Eibel J, Von Haehling S, et al. Altered Intestinal Function in Patients With Chronic Heart Failure. J Am Coll Cardiol. 2007 Oct;50(16):1561\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eBegum S, Latunde-Dada GO. Anemia of inflammation with an emphasis on chronic kidney disease. Nutrients. 2019;11(10):2424. \u003c/li\u003e\n\u003cli\u003eNemeth E, Ganz T. Regulation of Iron Metabolism by Hepcidin. Annu Rev Nutr. 2006 Aug 1;26(1):323\u0026ndash;42. \u003c/li\u003e\n\u003cli\u003eCohen-Solal A, Damy T, Terbah M, Kerebel S, Baguet JP, Hanon O, Zannad F, Lapperche T, Leclercq C, Concas V, Duvillie L, Darne B, Anker S, Mebazaa A. High prevalence of iron deficiency in patients with acute decompensated heart failure. Eur J Heart Fail.2014 sept; 16(9):984-91. doi: 10.1002/ejhf.139. Epub 2014 Jul 28. PMID: 25065368\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 and 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Acute decompensated heart failure, iron deficiency","lastPublishedDoi":"10.21203/rs.3.rs-7425258/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7425258/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eIron deficiency is one of the most common comorbidities occurring among heart failure patients. Iron deficiency in heart failure is an independent predictor of heart failure outcomes. Data are scarce regarding its prevalence in our setting especially among patients presenting with acutely decompensated heart failure.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA nested cross-sectional study was conducted at MRRH including patients hospitalized with acute decompensated heart failure. Simple proportions were used for the prevalence of iron deficiency among patients hospitalized with ADHF, while multivariate logistic regression was used for associated factors, reporting adjusted odds ratios (aOR) with 95% confidence intervals (CI).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 150 participants were enrolled. The median age was 54 years, with IQR of 40\u0026ndash;67. The majority had NYHA functional class III [91 patients (60.7%)] and IV 38 patients (25.3%) respectively. The median systolic blood pressure was 114 (IQR 102\u0026ndash;133), Hb 12.8g/dl (IQR11.5-14.1), NT-proBNP 9685 (IQR 2534\u0026ndash;20631) and eGFR 53.5 (IQR 37.1\u0026ndash;68.7). The median LV ejection fraction was 36.9 IQR (30\u0026ndash;54), regarding etiology of HF, majority had dilated cardiomyopathy 44.9%. Comorbidities included Hypertension (85%), HIV (22%), diabetes mellitus (10.7%), and 11% had history of alcohol consumption. The prevalence of iron deficiency was 56\u003cb\u003e%\u003c/b\u003e (95% CI 47.7\u0026ndash;64.1). In multivariate logistic regression, factors associated with iron deficiency among patients hospitalized with ADHF were; the presence of congestion (fluid overload) like pedal edema on physical examination aOR 3.197 ( 95% CI: 1.015\u0026ndash;10.076; P\u0026thinsp;=\u0026thinsp;0.047) and hs-CRP above 3mg/l aOR 7.982 ( 95% CI: 2.514\u0026ndash;25.343; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eOur study shows that more than 50% of the patients with acute decompensated heart failure are iron deficient. The factors we found independently associated with ID are a high serum level of high-sensitivity CRP and evidence of congestion like pedal edema at admission. We recommend screening of patients hospitalized with ADHF for iron deficiency and thereafter targeted therapy to improve HF outcomes.\u003c/p\u003e","manuscriptTitle":"Prevalence and factors associated with iron deficiency among patients hospitalized with acute decompensated heart failure at Mbarara regional referral hospital, southwestern Uganda","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-17 18:02:07","doi":"10.21203/rs.3.rs-7425258/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2025-10-06T07:15:24+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-08T06:42:15+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-05T10:35:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-05T10:34:22+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2025-08-21T10:35:30+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"49ae6c9f-65e3-4ac2-b9b5-3b1ba7097ae9","owner":[],"postedDate":"October 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-10-17T18:02:07+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-17 18:02:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7425258","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7425258","identity":"rs-7425258","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}