|Year : 2019 | Volume
| Issue : 1 | Page : 14-20
Iron-deficiency anemia as a risk factor for dyslipidemia in Egyptian patients
Maram M. M. Aboromia, Alyaa A El-Sherbeny, Emad A. Abd El-Hady MD
Department of Internal Medicine, Ain Shams University, Cairo, Egypt
|Date of Submission||13-Nov-2018|
|Date of Acceptance||25-Dec-2018|
|Date of Web Publication||27-Sep-2019|
Emad A. Abd El-Hady
10 Ahmed Saman Street, Makram Ebeid Street, Nasr City, Cairo, 11762
Source of Support: None, Conflict of Interest: None
Introduction Iron is an important component of some enzymes involved in hepatic lipid metabolism. Several factors such as increased erythropoiesis leading to increased cholesterol demand may lead to hypocholesterolemia combined with anemia.
Objective The aim of this study was to investigate the relationship between iron-deficiency anemia (IDA) and dyslipidemia in nonobese patients and to show the effect of iron therapy on their lipid profile.
Patients and methods This study was conducted on 60 nonobese individuals selected from Ain Shams University Hospital. It comprised 40 patients with IDA (equally divided according to sex), who were assessed initially and after receiving 3 months of oral iron therapy regarding lipid and iron profiles, in addition to 20 normal individuals without anemia as a control group. All patients were submitted to full history and clinical examination in addition to fasting lipid profile and iron study profile.
Results We found that patients with anemia especially male ones had higher lipid parameters compared with healthy nonanemic controls. However, after iron therapy, we found significant increase in hemoglobin (HB) levels and decrease in cholesterol, triglyceride, low-density lipoprotein, and very low-density lipoproteinlevels compared with pretherapy values. In patients with anemia, we found statistically significant negative correlations between the preiron therapy cholesterol levels on one hand and both of HB and ferritin on the other hand. Treatment of iron-deficiency corrected dyslipidemia significantly in the form of significant negative correlation between serum cholesterol level and HB.
Conclusion IDA may be associated with increased cholesterol levels. When a course of iron therapy is taken, significant beneficial changes in lipid profile may occur, but the exact mechanism is still unclear. As serum lipid profile is affected by many factors, hence the variations of lipid concentration in IDA may not be related to iron deficiency by itself.
Keywords: cholesterol, dyslipidemia, iron-deficiency anemia
|How to cite this article:|
Aboromia MM, El-Sherbeny AA, El-Hady EA. Iron-deficiency anemia as a risk factor for dyslipidemia in Egyptian patients. Egypt J Haematol 2019;44:14-20
|How to cite this URL:|
Aboromia MM, El-Sherbeny AA, El-Hady EA. Iron-deficiency anemia as a risk factor for dyslipidemia in Egyptian patients. Egypt J Haematol [serial online] 2019 [cited 2022 Jul 3];44:14-20. Available from: http://www.ehj.eg.net/text.asp?2019/44/1/14/268006
| Introduction|| |
Dyslipidemia refers to any abnormality of lipids in the blood and is usually associated with elevated levels of cholesterol and triglycerides (TGs). Of these, low-density lipoprotein (LDL) appears to be the most significant in terms of risk. In developed countries, most dyslipidemias are hyperlipidemias . Dyslipidemia can cause atherosclerosis predisposing for coronary artery disease (CAD) and peripheral artery disease . Hyperlipidemia can be related to hormonal diseases such as diabetes, hypothyroidism, Cushing syndrome, polycystic ovary syndrome, and metabolic syndrome. Central obesity or insulin resistance are risk factors for dyslipidemia and are commonly found in patients with these endocrine disorders .
Iron-deficiency anemia (IDA) is the world’s most widespread nutritional disorder and also the commonest cause of anemia occurring regardless of age, sex, and socioeconomic status, affecting both industrialized and developing countries. On a worldwide basis, WHO has estimated that approximately a third of the population has anemia with IDA . IDA is caused by insufficient dietary intake and absorption of iron, and/or iron loss from bleeding which can originate from a range of sources such as the intestine, uterus, or urinary tract. When the body has sufficient iron to meet its needs, the remainder is stored as ferritin complexes in all cells, but mostly in the bone marrow, liver, and spleen to be used later .
Iron has many functions in the body such as oxygen transport, enzymatic reaction, and neurotransmitter metabolism. So IDA is associated with changes in the mental and motor development, defects of immune system, cardiovascular diseases, and disruption of lipid profile. Plasma fatty acid metabolism and cell membrane composition are different in various iron states, for example, malnutrition in children is associated with decreased serum concentration of polyunsaturated fatty acid, as well as in vegetarian adults, low iron status disrupts fatty acid metabolism by decreasing the activities of Δ9, Δ6, and Δ5 desaturases .
The aim of this work is to investigate the relationship between IDA and dyslipidemia in nonobese patients and to show the effect of iron therapy on their lipid profile.
| Patients and methods|| |
This study was conducted on 60 nonobese individuals: 40 patients with IDA, being equally divided according to sex, and 20 normal age-matched and sex-matched nonanemic individuals as a control group. All 60 individuals were selected from the outpatient clinics of the internal medicine department in Ain Shams University hospital between January and June 2016, and all patients gave informed consent. The study was approved by the local ethics committee.
All patients were subjected to full history and clinical examination in addition to laboratory investigations, including fasting lipid profile [serum total cholesterol level, serum TG level, LDL, high-density lipoprotein (HDL), and very low-density lipoprotein (VLDL)], complete blood count, liver function tests (aspartate aminotransferase and alanine aminotransferase), serum creatinine, total iron-binding capacity (TIBC), serum ferritin using chemiluminescent technique, erythrocyte sedimentation rate, reticulocytic count (RC), as well as calculation of BMI [as the patient weight (kg) divided by the square of his height (m). Weight was measured in light clothing without shoes after emptying bladder. Height was measured as the distance from the top of the head to the bottom of the feet (no shoes)].
Obese patients (BMI>25 kg/m2); pregnant women; patients with renal failure or nephrotic syndrome and hepatic cirrhosis; patients with acute infectious diseases, any anemia except IDA, maternal lipid metabolism disorder, familial hyperlipidemia, diabetes mellitus, CAD, and cerebrovascular disease; and those receiving glucocorticoids, diuretics, and statins were excluded from the study.
All laboratory data of studied groups before and after iron therapy were statistically analyzed. The overall statistical comparison of different studied parameters between studied groups was done by using χ2-test for qualitative data, Student’s t-test for parametric data, and Mann–Whitney’s U-test for skewed data.
| Results|| |
This study was conducted on 60 individuals (patients) who were selected from the outpatient clinics of the internal medicine department in Ain Shams University hospital. They were divided into three groups:
- Group 1: 20 normal individuals with no IDA (control group).
- Group 2: 20 male nonobese patients with IDA
- Group 3:20 female nonobese patients with IDA
In this study, nonobese patients with dyslipidemia and IDA (groups 2 and 3) received oral iron therapy for 3 months in the form of iron capsules ‘Hematom’ once daily after launch, after which lipid and iron profiles were reassessed again.
[Table 1] showed that before iron therapy, patients had highly significant lower hemoglobin (HB) and highly significant higher cholesterol, TG, and VLDL in addition to significantly higher LDL than control group, as well as it showed significant improvement in patient group compared with control in such parameters after iron therapy, especially lipid profile.
|Table 1 Comparison between control on one hand and both patients groups regarding hemoglobin and lipid profile before and after iron therapy on the other hand|
Click here to view
[Table 2] shows the following:
- Before iron therapy, male patients had significant lower HB and HDL than female patients as well as highly significant higher levels of other lipid parameters (cholesterol, TG, LDL, and VLDL) than female patients.
- After iron therapy, male patients had significant lower HDL than female patients as well as highly significant higher levels of cholesterol, TG, and LDL than female patients.
|Table 2 Comparison between male and female patients regarding HB and lipid profile both before and after iron therapy|
Click here to view
[Table 3] showed highly significant improvement in patients regarding HB (being increased) and cholesterol, TG, LDL and VLDL (being decreased) after iron therapy.
|Table 3 Comparison between all patients regarding hemoglobin and lipid profile) before and after iron therapy|
Click here to view
[Table 4] showed highly statistically significant improvement after iron therapy regarding HB (being increased), as well as cholesterol, TG, LDL, and VLDL (being decreased) in both male and female patients.
|Table 4 Comparison between iron therapy effect on hemoglobin and lipid profile in both patient sexes (males and females)|
Click here to view
HB levels increased in both male and female patients almost to the same degree (13.92±0.55 and 13.82±0.71) respectively. Cholesterol, TG, and LDL levels decreased significantly in both male and female patients but still higher in male patients; however, VLDL level decreased significantly in both male and female patients almost to the same degree.
[Table 5] shows the following:
|Table 5 Correlation between different lipid parameters level and hemoglobin, ferritin, total iron-binding capacity, and reticulocytic count before and after iron therapy|
Click here to view
Before iron therapy:
- There was a significant indirect correlation between every parameter of lipid profile (cholesterol, TG, and LDL) on one hand and both HB and ferritin on the other hand.
- There was a significant direct correlation between every parameter of lipid profile (cholesterol, TG, and LDL) on one hand and both RC and TIBC on the other hand.
After iron therapy
- There was a significant indirect correlation between serum cholesterol level and HB, as well as between LDL and both HB and ferritin.
- There was a significant direct correlation between every parameter of lipid profile (cholesterol, TG, and LDL) on one hand and RC (in addition to negative correlation of TG with TIBC) ([Figure 1],[Figure 2],[Figure 3]).
|Figure 1 Correlation between TG and HB in all studied patients before therapy. HB, hemoglobin; TG, triglyceride.|
Click here to view
|Figure 2 Correlation between cholesterol and HB in all studied patients before therapy. HB, hemoglobin.|
Click here to view
|Figure 3 Correlation between LDL and HB in all studied patients before therapy. HB, hemoglobin; LDL, low-density lipoprotein.|
Click here to view
| Discussion|| |
IDA is the world’s most widespread nutritional disorder and also the commonest cause of anemia occurring worldwide . Dyslipidemia, along with other risk factors, such as smoking and hypertension, can cause atherosclerosis, predisposing to CAD, peripheral artery disease, and stroke .
Several factors such as plasma dilution, increased erythropoiesis leading to increased cholesterol demand, activation of macrophage system with the release of cytokines as well as increased uptake of cholesterol by the reticuloendothelial system may lead to hypocholesterolemia with anemia. Anemia thus may have a protective effect on lipid profile, thereby reducing the risk of CAD . The liver is the main site for interaction between lipid and iron metabolism as it is an important site for both these metabolic pathways. Iron is an important component of some enzymes and transporters involved in lipid metabolism, thereby exerting a direct effect on hepatic lipid metabolism. Iron in its ferrous form can generate free radicals, leading to oxidative stress and lipid peroxidation ,. The study in mice with increased hepatic iron store showed upregulation of several enzymes, including the rate-limiting enzyme of cholesterol biosynthesis ‘HMG-CoA reductase’. This fact suggests that hepatic iron loading increases liver cholesterol synthesis. So iron deficiency may lead to interference with lipid metabolism.
The aim of this study was to investigate the relationship of dyslipidemic changes in nonobese patients with IDA, and to detect the effect of iron therapy on lipid profile of such patients.
This study was conducted on 60 nonobese individuals who were selected from the outpatient clinics of the internal medicine department in Ain Shams University hospital. They were divided into three equal groups: a healthy nonanemic control group in addition to male and female patients with IDA. These male and female patients were subjected to 3 months of iron therapy in the form of iron capsules once daily, after which lipid and iron profiles were reassessed.
In our study, we found that patients with anemia had higher lipid parameters compared with healthy nonanemic controls. This is consistent with a study done by Verma et al.  and Nandyala et al.  who found that IDA in Indian adults was associated with abnormal serum lipid profile (with significant raised levels of both TG and VLDL cholesterol levels) as compared with healthy controls. However, Verma et al.  detected significantly lower levels of LDL cholesterol in those patients with anemia compared with healthy controls.
Antappanavar et al.  showed that TG and VLDL levels are elevated in the IDA compared with nonanemic patients, whereas lower levels of LDL cholesterol were found in patients with anemia. However, Sandeep et al.  observed lower levels of total cholesterol, HDL, LDL, VLDL, and TG levels in patients with anemia compared with healthy controls. Sandeep et al.  also demonstrated that although there were no significant differences in serum lipid concentrations between patients with moderate IDA and healthy controls, serum total cholesterol and TG level were significantly lower in severely anemic patients (HB <8.0 g/dl) compared with normal controls. They also showed that the reduced serum lipid levels returned to normal following iron supplementation. In the severely anemic patients, blood HB concentration was positively correlated with serum total cholesterol and TG concentrations. However, Yang et al.  reported higher levels of all lipoproteins and TG and lower HDL in IDA women. They also demonstrated that there was no significant difference when lipid values were separately compared with various types of anemia such as iron deficiency, megaloblastic, and hemolytic anemias which suggested that anemia per se rather than the type of anemia was responsible for lowered levels of lipoproteins in anemia.
Miri-Aliabad et al.  observed no statistically significant difference between control group and IDA group, with slightly increased, but not significant, TG and LDL levels observed in the IDA group compared with the control group. The control versus IDA groups lipid profile was as follows: TG (86.1±36.9 vs. 88.6±33.5 mg/dl), total cholesterol (151.7±28.7 vs. 148.9±29.2 mg/dl), LDL (78.4±29.1 vs. 88.1±22.6 mg/ dl), and HDL (54.2±13.1 vs. 52.5±10.1 mg/dl). They mentioned that disruption in carnitine metabolism and reduction of serum-free carnitine concentration were the reason for increased serum lipids. Finally, they concluded that there is a negative correlation between serum-free carnitine and total TG levels in iron-deficient patients . Although the study by Chopra et al.  showed that there was a direct association between both serum iron and ferritin levels and CAD risk factors, whether hypolipidemia found in diets deficient in energy, protein, and other nutrients (which are sometimes associated with IDA) has either protective effects in development of congenital heart disease is ambiguous .
In our study, before iron therapy, male patients had significant lower HB and significant higher lipid profile compared with female patients. In contrast, female patients had significant higher HDL than male patients. However, after iron therapy, we found significant increase in HB levels and decrease in cholesterol, TG, LDL, and VLDL levels as well as nonsignificant increase in HDL in both male and female patients compared with pretherapy values. HB levels increased significantly in both male and female patients almost to the same degree (13.92±0.55 and 13.82±0.71, respectively). Cholesterol, TG, and LDL levels decreased significantly in both male and female patients but were still higher in male patients (203.75±45.63 and 148.05±12.6 respectively; 156.6±41.45 and 115.1±10.3, respectively; and 128.85±36.48 and 69.95±5.28, respectively); however, VLDL level decreased significantly in both male and female patients almost to the same degree (30.7± 9.73 and 25.6± 7.12, respectively). These results are in agreement with those reported in India by Venkateshwarlu et al.  who found significant elevation in HB and ferritin levels and significant decrease in VLDL and TG levels in patients following iron therapy compared with pretherapy levels. Moreover, total cholesterol and LDL levels were found to be decreased but were not statistically significant.
In contrast, the study done by Choi et al. on young Korean girls with severe IDA reported low levels of TGs and total cholesterol, which returned to normal after the iron therapy. Moreover, Ozdemir et al.  investigated the relationship between IDA and lipid metabolism in premenopausal women. The mean levels of total cholesterol and LDL of anemic women was lower than those of nonanemic control patients. Despite increasing significantly after treatment of anemia, their levels were still lower than in the control participants. This hypothesized that low iron states in premenopausal women may exert an additional protective effect against atherosclerotic heart disease via lipid metabolism. Another study done by Narra et al.  found that all the subfractions of the lipid profile were significantly low in anemic cases compared with controls with the quantitative decrease directly correlated with the severity of anemia.
In patients with anemia, we found statistically significant negative correlations between the preiron therapy total cholesterol levels on one hand and both of HB and serum ferritin on the other hand. This was in contrast to the results of the study done in South Korea by Jong et al.  who investigated the effects of body iron depletion and iron supplementation on serum lipid concentrations, hematologic indices, and iron markers. They found that in the severely anemic patients, blood HB concentration was positively correlated with serum total cholesterol and TG concentrations. Serum total cholesterol and TG in severely anemic patients were significantly lower than in healthy controls. They also found that serum total cholesterol and TG in patients with severe anemia were significantly elevated after iron supplementation. This finding was consistent with the results obtained by Fessler et al.  who studied the relationship between serum cholesterol and red blood cells, HB, and platelet indices in adults and found that serum non-HDL-cholesterol (LDL and VLDL) was positively correlated with mean erythrocyte number, hematocrit, HB concentration and platelet count independently of age, sex, race, smoking, BMI, serum folate, and C-reactive protein.
In our study, treatment of iron deficiency in the form of oral iron for 3 months corrected dyslipidemia by significant reduction in serum cholesterol, TG, LDL, and VLDL especially in the form of significant negative correlation between serum cholesterol level and HB in both male and female patients after iron therapy. This was in agreement with the results of a study done by Al-Saedi et al.  on 200 patients with chronic kidney disease with renal anemia who were given iron and erythropoietin treatment. In patients who responded to iron and EPO therapy, the results showed increase in HB and HDL with decrease in total cholesterol and TG levels. This finding was in contrast to the results obtained by Ozdemir et al.  in premenopausal women who found significant increase in the levels of cholesterol and HB after iron therapy when compared with their pretreatment levels.
The study done by Neelam et al.  on a different type of anemia (Fanconi anemia) and dyslipidemia showed that Fanconi anemia may be accompanied by some metabolic abnormalities such as hyperglycemia and/or glucose intolerance, diabetes mellitus, and insulin resistance as well as dyslipidemia in the form of elevated LDL, low HDL, and elevated TGs.
| Conclusion and recommendations|| |
IDA may be associated with increased serum levels of cholesterol with or without TGs. When a course of iron therapy is taken for 3 months, significant beneficial changes in lipid profile may occur. These changes are in the form of significant decrease in cholesterol (especially VLDL and LDL), but the exact mechanism is still unclear, as well as serum lipid profile is affected by many factors, hence the variations of lipid concentration in IDA may not be related to iron deficiency by itself.
So we advocate routine testing of lipid profile in patients with anemia as well as performing further studies to detect the exact mechanism and means of how dyslipidemia was improved by iron therapy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Nelson DL, Cox MM. Lehninger principles of biochemistry
3rd ed. New York, NY: Worth Publishing; 2000.
Prospective Studies Collaboration, Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey R et al.
Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. Lancet
Vodnala D, Rubenfire M, Brook RD. Secondary causes of dyslipidemia. Am J Cardiol
Brady PG. Iron deficiency anemia: a call for. South Med J
Fleming RE, Bacon BR. Orchestration of iron homeostasis. N Engl J Med
Miri-Aliabad G, Dashipour A, Khajeh A, Shahmoradzade M. Correlation between serum lipid profile and iron deficiency anemia in children in Southeast of Iran. Iran J Blood Cancer
Shah T, Purohit G, Harsoda JM. Prevalence of coronary heart disease in different socioeconomic status: is dyslipidemia a future threat? Int J Biomed Adv Res
Ahmed U, Latham PS, Oates PS. Interactions between hepatic iron and lipid metabolism with possible relevance to steatohepatitis. World J Gastroenterol
Graham RM, Chua AC, Carter KW, Delima RD, Johnstone D, Herbison CE et al.
Hepatic iron loading in mice increases cholesterol biosynthesis. Hepatology
Verma U, Shankar N, Madhu SV, Tandon OP, Madan N, Verma N. Relationship between iron deficiency anaemia and serum lipid levels in Indian adults. J Indian Med Assoc
Nandyala V, Gandiah P, Karthik RS, Sivarajappa P, Indira G, Krishna Prasad T. A study of lipid profile in iron deficiency anemia. Int J Emerg Trends Sci
Antappanavar VB, Biradar SG, Patil V, Biradar PM, Mithare S, Sharma AK. A study of correlation between iron deficiency anaemia and serum lipid profile in Indian adults in BRIMS, Bidar. Int J Adv Med
Sandeep N, Rao VD, Hanumaiah A, Rampure D. Lipid profile changes in anemia. Transw Med J
Yang S, Chen XY, Xu XP. The relationship between lipoprotein-associated phospholipase A(2), cholesteryl ester transfer protein and lipid profile and risk of atherosclerosis in women with iron deficiency anaemia. Clin Lab
Chopra S, Lal AK, Huria A, Dhar M. Relationship between body iron status and cardiovascular risk factors in patients with coronary artery disease. J Cardiovasc Dis Res
Ozdemir H, O’Brien T, Nguyen TT, Kosoglou T, Stauber KL, Waters D, Havel RJ. Lipid metabolism in premenopausal women. Arch Intern Med
Narra M, Hanson J, Lederle FA, Bloomfield HE, Williams PT. The quantitative lipid sub fractions changes in anemic patients. Ann Intern Med
Jong K, Park S, Ono J, Kim S, Chang H, Yun T. Iron depletion and iron supplementation on serum lipid concentrations
. Cheongju, South Korea: Chungbuk National University; 2000.
Fessler MB, Rose K, Zhang Y, Jaramillo R, Zeldin DC. Relationship between serum cholesterol and indices of erythrocytes and platelets in the US population. J Lipid Res
Al-Saedi AJH, Alwachi SN, Karim AHA. Effect of erythropoietin therapy on the lipid profile in patients with chronic kidney disease. J Nephrol Ther
Giri N, Batista DL, Alter BP, Stratakis CA. Different types of anemia and dyslipidemia
. Bethesda, MD: National Cancer Institute Development, National Institutes of Health 2007. 20892.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]