• Users Online: 408
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 2  |  Issue : 2  |  Page : 99-102

Iron deficiency in chronic systolic heart failure(indic study)


1 Department of Cardiology, All Institute of Medical Science, New Delhi, India
2 Department of Pharmacology, All Institute of Medical Science, New Delhi, India
3 Department of Cardiology, VMMC and Safdarjung Hospital, New Delhi, India

Date of Web Publication7-Oct-2016

Correspondence Address:
Praloy Chakraborty
Department of Cardiology, VMMC and Safdarjung Hospital, New Delhi - 110 029
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2395-5414.191524

Rights and Permissions
  Abstract 

Background: Chronic systolic heart failure (HF) is characterized by the left ventricular dysfunction, exercise intolerance and is associated with neurohormonal activation that affects several organs such as kidney and skeletal muscle. Anemia is common in HF and may worsen symptoms. Iron deficiency (ID) is also common in HF patients with or without anemia. Iron is the key cofactor in oxidative metabolism in skeletal muscle and the Krebs cycle. There is a paucity of data regarding iron metabolism in chronic systolic HF in India. Methods: IroN Deficiency In CHF study (INDIC) is an observational study that investigated forty chronic heart failure patients for the presence of ID. Serum ferritin (micrograms per liter), serum iron (micrograms per liter), total iron binding capacity (micrograms per liter), transferring (milligrams per deciliter), and transferrin saturation were measured to assess iron status. Results: There were 67.5% (27/40) patients who had ID with a mean serum ferritin level of 76.4 μg/L. Of the 27 iron deficient patients, 22 (55%) had an absolute ID, and 5 had a functional ID. Eight out of 27 of the iron deficient patients were anemic (20% of the total cohort, 30% of the iron deficient patients). Anemia was seen in 6 other patients, which was possibly anemia of chronic disease. There was a trend for more advanced New York Heart Association (NYHA) class (NYHA III and NYHA IV) patients with ID (37.4% vs. 30.77%, P = 0.697). Conclusion: In our study, ID was very common, affecting more than half of the patients with systolic HF. Absolute ID was the most common cause of ID and patients with ID had a tendency to have advanced NYHA class. Our study also demonstrated that ID can occur in the absence of anemia (iron depletion).

Keywords: Iron deficiency, IroN Deficiency In CHF study, New York Heart Association class


How to cite this article:
Verma S, Dua P, Saini A, Chakraborty P. Iron deficiency in chronic systolic heart failure(indic study). J Pract Cardiovasc Sci 2016;2:99-102

How to cite this URL:
Verma S, Dua P, Saini A, Chakraborty P. Iron deficiency in chronic systolic heart failure(indic study). J Pract Cardiovasc Sci [serial online] 2016 [cited 2019 Nov 18];2:99-102. Available from: http://www.j-pcs.org/text.asp?2016/2/2/99/191524


  Introduction Top


Chronic systolic heart failure (HF) is characterized by the left ventricular dysfunction, exercise intolerance and is associated with neurohormonal activation that affects several organs such as kidney and skeletal muscle. Although the remarkable advances in the management of chronic HF (CHF) have reduced CHF mortality, the morbidity associated with CHF remains a major problem. Patients with HF have considerable impairment of normal daily activities. Most of the patients report fatigue and dyspnea that adversely affect their quality of life.[1] Besides hemodynamic dysfunction, multiple other mechanisms may contribute to impaired exercise tolerance in patients with HF, including impaired oxygen delivery to the skeletal muscle during exercise.[2],[3] Anemia and iron deficiencies are common in HF, and both may worsen symptoms.[4] Iron deficiency (ID) may occur in HF patients with or without anemia. Iron is the key cofactor in oxidative metabolism in skeletal muscle and the Krebs cycle. Besides helping in erythropoiesis, it plays a key role in oxygen uptake, transport, and storage as well as in oxidative metabolism.[5] Traditionally, ID has been considered to have clinical consequences only in the presence of anemia. The reduced hemoglobin level is considered as the end result of depletion of iron stores. However, ID, even in the absence of anemia, attenuates aerobic performance and is accompanied by the reports of fatigue and exercise intolerance.[6] The repletion of iron in patients who have ID without HF improves cognitive, symptomatic, and exercise performance.[7] Recently, it has been recognized that patients with HF are prone to the development of ID due to multiple mechanisms. This can be due to the depletion of the iron store (absolute ID) due to dietary deficiency, low intake, and decreased absorption from gastrointestinal (GI) congestion or blood loss from GI tract.[8] Chronic inflammation, commonly observed in chronic HF, may also play a role. Inflammation causes reduced iron absorption and availability of iron recycled in the reticuloendothelial system (functional ID).[9],[10] A decreased iron status is associated with disease severity and is a strong and independent predictor of outcome.[11] The unfavorable outcome of ID in HF is irrespective of the presence of anemia and the severity of heart disease. It has been shown that the correction of ID with the use of intravenous iron in patients with chronic heart failure may result in clinical benefits, and the symptomatic benefit is similar in patients with anemia and those without anemia.[12] ID is the most common nutritional disorder in India and some population group (children, adolescent girls, and pregnant women) the prevalence more than 95%.[11] However, there is a paucity of data regarding iron metabolism in chronic systolic HF in India. Accordingly, IroN Deficiency In CHF study (INDIC) was designed as a pilot study to investigate the role of ID in chronic systolic HF in India.


  Methods Top


INDIC study is an observational study designed to investigate ID in HF. A total of forty HF patients who were clinically stable for at least 1 month, left ventricular ejection fraction (LVEF) <40%, signs and symptoms of HF for the last 6 months, and receiving optimal medical therapy were enrolled. All patients were recruited from the outpatient clinics of the All India Institute of Medical Sciences, New Delhi and VMMC and Safdarjung Hospital, New Delhi. Patients with a history of HF decompensation in the previous 1 month or a history of acute coronary syndrome or myocardial revascularization in the previous 3 months, or a history of any disease which could alter iron metabolism (CKD, malignancy, inflammatory disorder, or hematological disorders) or a history of therapy for anemia or iron therapy in the previous 12 months were excluded from the study. Details of functional status (The New York Heart Association [NYHA] class), cardiovascular risk factors, drug history, and LVEF were recorded. Hematologic indices were measured in venous blood collected in EDTA tubes. The following blood biomarkers reflecting iron status were measured: Ferritin (micrograms per liter), serum iron (micrograms per liter), total iron binding capacity (micrograms per liter), transferrin (milligrams per deciliter), and transferrin saturation (TSAT). A serum ferritin in the range of 30–300 µg/L was considered to be normal.

Definitions

Iron deficiency (ID) was defined as a (as per the European Society of Cardiology guidelines) ferritin level <100 µg/L or serum ferritin 100–299 µg/L in combination with a TSAT <20%.

Absolute ID was diagnosed as ferritin level <100 μg/L.

Functional ID was diagnosed as normal serum ferritin (serum ferritin 100–299 µg/L) in combination with a TSAT <20%.

Anemia was defined as hemoglobin <12 g/dL in women and <13 g/dL in men.

Statistical analysis

Continuous variables with a normal distribution (age, LVEF, hemoglobin, hematocrit, red blood cell, mean corpuscular volume [MCV], mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration, ferritin, and serum iron] were expressed as mean (x) with standard deviations. The inter-group differences were tested using Student's t-test. The categorical variables were expressed as numbers in percentages. The inter-group differences were tested using Chi-square tests. To explore the associations of ID and patient characteristics, univariable logistic regression was performed with variables for any association and to obtain odds ratios and 95% confidence intervals. A two-tailed P < 0.05 of will be considered statistically significant. All analyses were performed using STATA version 13.0 (StataCorp. 2013. Stata Statistical Software: Release 13. College Station, TX: StataCorp LP. Texas).


  Results Top


Baseline patient characteristics of the forty patients enrolled in the study are shown in [Table 1]. There were 67.5% (27/40) patients who had ID with a mean serum ferritin level of 76.4 µg/L. Of the 27 iron deficient patients, 22 (55%) had an absolute ID, and 5 had a functional ID. Eight out of 27 of the iron deficient patients were anemic (20% of the total cohort, 30% of the iron deficient patients) [Table 2]. Anemia was seen in 6 other patients, which was possibly anemia of chronic disease. Patients with ID tended to have more advanced NYHA class (NYHA III and NYHAIV) (37.4% vs. 30.77%, P = 0.697). None of the clinical variables were found to predict ID [Table 3].
Table 1: Baseline characteristics

Click here to view
Table 2: Hemoglobin and iron metabolism parameters

Click here to view
Table 3: Clinical variables associated with iron deficiency

Click here to view



  Discussion Top


In this study, we found that ID is very common in Indian patients with systolic HF, affecting more than half the HF population. Absolute ID was more common than functional ID and patients with ID tended to have more advanced NYHA class. This study also confirmed that biochemical ID can occur in the absence of anemia.

Iron is essential not only for erythropoiesis but also for several bioenergetic processes in the skeletal muscle and in the Krebs cycle. Hence, chronic ID may not only lead to anemia but, by itself, reduce exercise capacity and lead to problems, including fatigue, restless legs, memory loss, skin problems, etc. A vegetarian diet, GI losses, malabsorption, and various illnesses can be a cause of ID.

In recent years, the prevalence and prognosis of ID in chronic HF have received greater attention. There is no standard definition of ID in chronic HF, leading to a wide variation in reported prevalence. In a large observational study [13] ID was present in 37% of all systolic chronic HF patients. Another recent study, reported a prevalence of 61% among community-dwelling HF patients.[14] A study which assessed ID using bone marrow iron status, demonstrated that 73% of patients with advanced HF and anemia had depleted iron stores.[15] Nonetheless, the criteria most commonly used for detecting ID in chronic HF are a ferritin level <100 µg/L or ferritin 100–299 µg/L in combination with a TSAT <20%. Using this definition, an international pooled analysis demonstrated that the prevalence of ID was 50%.[11] In one study, 43% of anemic patients and 15% of nonanemic patients had ID. Another study found the prevalence of ID of 50% with 45.6% patients being nonanemic.[11],[12]

The mechanisms of ID are multifactorial. Functional ID may occur despite adequate iron stores, whereas iron stores are depleted in absolute ID. In our study, absolute ID was the most common cause of ID, which can be explained by wide prevalent nutritional ID in India along with defective absorption in HF. Many studies have shown that ID is associated with advanced symptoms.[11],[13],[16] Our study has also shown that patients with ID have a trend to have advanced NYHA Class. Besides being the component of hemoglobin, iron is an integral part of myoglobin and cellular respiratory chain complex. HF is a low-output state, and it requires a compensatory increase in the activity of myoglobin, hemoglobin, and respiratory chain complex for more efficient cellular utilization of oxygen. ID can compromise the function of the respiratory chain and can exacerbate the symptoms of HF even in the absence of anemia.[11]

In our study, ID was more prevalent in patients without anemia. This can be explained by the fact that anemia can occur in the absence of ID and ID anemia is the manifestation of most severe of ID (serum ferritin <15 µg/L and TSAT <10%); whereas, ID is defined as Serum ferritin <100 µg/L or TSAT <20%. Recent studies have found that different clinical characteristics have been associated with the disorder of iron metabolism in patients with HF. These include advance NYHA class, female sex, lower MCV, and anemia. However, our study failed to identify any independent predictors of ID. This might be related to the small size of our study population.

ID in India,[13],[14],[15],[16] is common, 62.9% of females below 50 years and 23.3% of males below 50 years have been reported in various surveys to be anemic. Poor Vitamin B12 availability in food, lack of iron and folic acid supplementation, and lack of natural sources of iron in a vegetarian diet are possible causes for ID anemia in India. Whether HF added to the burden of anemia is not possible to deduce from this study, but the high prevalence of ID provides an easily correctable factor for these patients. Oral supplementation is easy to provide and safe intravenous supplementation are now also available.[17],[18],[19],[20],[21]

Study limitations

There are several limitations in this study. First, the sample size was small, and there was no control group, so it is difficult to predict whether the ID is more prevalent in the HF group than the general population in India. A larger study that includes age- and sex-matched controls is required to address the above-mentioned concerns. Second, this is a cross-sectional study and long-term effect of ID on mortality and morbidity has not been addressed. Third, only data from a single measurement in time were available, so the present study cannot comment on the effects of changes in iron status over time. More studies with serial measurements of iron indices over time are warranted.


  Conclusion Top


ID is an emerging problem in chronic HF, affecting more than half of the patients in our study sample. A decreased iron status is associated with the tendency of adverse disease severity (as assessed by NYHA functional class).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Roger VL, Weston SA, Redfield MM, Hellermann-Homan JP, Killian J, Yawn BP, et al. Trends in heart failure incidence and survival in a community-based population. JAMA 2004;292:344-50.  Back to cited text no. 1
    
2.
Clark AL, Poole-Wilson PA, Coats AJ. Exercise limitation in chronic heart failure: Central role of the periphery. J Am Coll Cardiol 1996;28:1092-102.  Back to cited text no. 2
    
3.
Massie BM, Conway M, Rajagopalan B, Yonge R, Frostick S, Ledingham J, et al. Skeletal muscle metabolism during exercise under ischemic conditions in congestive heart failure. Evidence for abnormalities unrelated to blood flow. Circulation 1988;78:320-6.  Back to cited text no. 3
    
4.
Tang YD, Katz SD. Anemia in chronic heart failure: Prevalence, etiology, clinical correlates, and treatment options. Circulation 2006;113:2454-61.  Back to cited text no. 4
    
5.
Dunn LL, Suryo Rahmanto Y, Richardson DR. Iron uptake and metabolism in the new millennium. Trends Cell Biol 2007;17:93-100.  Back to cited text no. 5
    
6.
Haas JD, Brownlie T 4th. Iron deficiency and reduced work capacity: A critical review of the research to determine a causal relationship. J Nutr 2001;131:676S-88S.  Back to cited text no. 6
    
7.
Davies KJ, Maguire JJ, Brooks GA, Dallman PR, Packer L. Muscle mitochondrial bioenergetics, oxygen supply, and work capacity during dietary iron deficiency and repletion. Am J Physiol 1982;242:E418-27.  Back to cited text no. 7
    
8.
Alexandrakis MG, Tsirakis G. Anemia in heart failure patients. ISRN Hematol 2012;2012:246915.  Back to cited text no. 8
    
9.
Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005;352:1011-23.  Back to cited text no. 9
    
10.
Jankowska EA, von Haehling S, Anker SD, Macdougall IC, Ponikowski P. Iron deficiency and heart failure: Diagnostic dilemmas and therapeutic perspectives. Eur Heart J 2013;34:816-29.  Back to cited text no. 10
    
11.
Klip IT, Comin-Colet J, Voors AA, Ponikowski P, Enjuanes C, Banasiak W, et al. Iron deficiency in chronic heart failure: An international pooled analysis. Am Heart J 2013;165:575-82.  Back to cited text no. 11
    
12.
de Silva R, Rigby AS, Witte KK, Nikitin NP, Tin L, Goode K, et al. Anemia, renal dysfunction, and their interaction in patients with chronic heart failure. Am J Cardiol 2006;98:391-8.  Back to cited text no. 12
    
13.
WHO, UNICEF, and UNU, Iron Deficiency Anaemia: Assessment, Prevention and Control, A Guide for Programme Managers, WHO, UNICEF, UNU, Geneva, Switzerland; 2001. Availabel from: http://www.who.int/nutrition/publications/micronutrients/anaemia_iron_deficiency/WHO_NHD_01.3/en/index.html. [Last accessed 2016 Aug 28].  Back to cited text no. 13
    
14.
Zimmermann MB, Hurrell RF. Nutritional iron deficiency. Lancet 2007;370:511-20.  Back to cited text no. 14
    
15.
Baker RD, Greer FR, Committee on Nutrition American Academy of Pediatrics. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0–3 years of age). Pediatrics 2010;126:1040-50.  Back to cited text no. 15
    
16.
Arnold F, Parasuraman S, Arokiasamy P, Kothari M. Nutrition in India, in National Family Health Survey (NFHS-3) India 2005-06; 2009. Availabel from: http://www.rchiips.org/nfhs/nutrition_report_for_website_18sep09.pdf. [Last accessed on 2016 Jun 20].  Back to cited text no. 16
    
17.
Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009;361:2436-48.  Back to cited text no. 17
    
18.
Bolger AP, Bartlett FR, Penston HS, O'Leary J, Pollock N, Kaprielian R, et al. Intravenous iron alone for the treatment of anemia in patients with chronic heart failure. J Am Coll Cardiol 2006;48:1225-7.  Back to cited text no. 18
    
19.
Okonko DO, Grzeslo A, Witkowski T, Mandal AK, Slater RM, Roughton M, et al. Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC-HF: A randomized, controlled, observer-blinded trial. J Am Coll Cardiol 2008;51:103-12.  Back to cited text no. 19
    
20.
Toblli JE, Lombraña A, Duarte P, Di Gennaro F. Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency. J Am Coll Cardiol 2007;50:1657-65.  Back to cited text no. 20
    
21.
Usmanov RI, Zueva EB, Silverberg DS, Shaked M. Intravenous iron without erythropoietin for the treatment of iron deficiency anemia in patients with moderate to severe congestive heart failure and chronic kidney insufficiency. J Nephrol 2008;21:236-42.  Back to cited text no. 21
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
   Abstract
  Introduction
  Methods
  Results
  Discussion
  Conclusion
   References
   Article Tables

 Article Access Statistics
    Viewed1603    
    Printed58    
    Emailed0    
    PDF Downloaded193    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]