Abstract

Background:

Stroke is a non-traumatic, focal vascular injury of the nervous system and typically results in permanent damage in the form of cerebral infarction or intracerebral hemorrhage and/ or subarachnoid hemorrhage.  This study was aimed to measure the ferritin Level   among Sudanese patients with the ischemic stroke.

 Material and method:

This was a case control hospital based study conducted at Ribat University Hospital at Khartoum state during the period of December 2022 to April 2023, It included all patients attending Ribat University Hospital and diagnosed with ischemic stroke during the aforementioned period as case group and compared to apparently healthy individuals with no history of thrombi or stroke as control group. Roche kits on the Hitachi 912 clinical analyzer were used for serum ferritin measurement.

Results:

Serum ferritin levels mean in the case group was (232.3± 36.3), in the control group was (114.1±11.7). Comparison between case and control in ferritin levels showed highly significant increase in the case group (p. v= 0.004) .Insignificant differences in ferritin levels between cases and controls in gender, past medical history and risk factors (p. v > 0.05) were shown. A negative correlation of ferritin levels was detected with age (p. v >0.05).

Conclusion: This study demonstrates the significant rise in serum ferritin in ischemic stroke Sudanese patients when compared with control, and the ferritin level had insignificant correlation with gender, age, past medical history and risk factors.

Introduction

Acute ischemic stroke (IS) is defined as a sudden loss of brain function resulting from severe interference in the flow of blood and oxygen in cerebral arteries. IS has a heterogeneous etiology caused by modifiable and non- modifiable risk factors. Genetic factors, age and gender are the non-modifiable risk factors while Hypertension, diabetes mellitus (T2DM), dyslipidemia, and smoking are modifiable risk factors. ^[1] Reports have demonstrated the increased burden of IS worldwide in the last 25 years, especially in developing countries.After acute myocardial infarction and malignancy, ischemic stroke is the third leading cause of death and disability. ^{[1, 2]}

Ferritin, a major iron storage protein, is essential to iron homeostasis and is involved in a wide range of physiologic and pathologic processes. Utilized as a serum marker of total body iron stores. In cases of iron deficiency and iron overload, serum ferritin serves a critical role in both diagnosis and management. Elevated serum and tissue ferritin are linked to coronary artery disease, malignancy, sideroblastic anemias, neurodegenerative disorders, and hemophagocytic syndrome and poor outcomes following stem cell transplantation. Additionally, recent research describes novel functions of ferritin independent of iron storage.^[3]

Serum ferritin has been used widely in clinical medicine chiefly as an indicator of body iron stores. It is an acute-phase reactant involved in cellular defense against oxidative stress and inflammation along with transferrin. Iron also plays a role in ischemic stroke by activating platelets via a protein kinase-C mechanism. Another proposed mechanism of ferritin in ischemic vascular disease, is through reperfusion injury. After the event of ischemic stroke, reperfusion causes marked increase in oxygen-radical production as well as a release of iron ions, causing further tissue damage and cellular death ^[4]

Recent animal experiments have suggested that iron overload contributes to the vascular diseases development by promoting thrombosis after arterial injury.^[5] High serum ferritin on admission of acute stroke patients (within 24 to 48 hours after stroke onset) had poor prognosis implicating that increase in body iron stores before stroke onset can aggravate the brain ischemia cytotoxicity. It also acts as a risk factor for ischemic episodes by enhancing atherogenesis.^[6]

Material and methods

This was a case-control hospital based study conducted at Ribat university hospital at Khartoum state during the period of December 2022 to April 2023, and aimed to measure ferritin level in the Sudanese patients with ischemic stroke. All patients attended to Ribat university hospital aged ≥18 years, presented within 48 hours of onset of symptoms of acute ischemic stroke, diagnosed on the basis of clinical examination and neuro-imaging (computed tomography/magnetic resonance imaging brain) were included in the study. In addition to that apparently healthy people with no history of thrombi or stroke were selected as control group.

Figure 1.

Patients presented after 48 hours of onset of symptoms of acute ischemic stroke, patients with recent infection, malignancy, anemia, or liver failure, patients received blood/blood component transfusion in the previous 7 days; and patients under anticoagulant therapy were excluded from the study. The data was collected using pre-designed structural questionnaire. The study was approved by the ethical committee of National University, faculty of medical laboratory, and the participants was fully informed about the advantages and disadvantages before participation in the research (verbal informed consent). From each participant 2.8 ml of blood samples was collected in trisodium citrate anticoagulant. Roche kits on the Hitachi 912 clinical analyzer was used for serum ferritin measurement.

Figure 2.

Results

In the present study total of sixty participants were included, thirty as a case group and thirty as control group, their mean of age was (48.9±5.5). In the case group 53% were female and 47% were male, their mean of ages was (64.9±11. 9), for the past medical history: 20% had history of thrombi, 20% had high lipid level, 13.3% had one of heart illnesses, 63.3% were hypertensive (HT) and 36.7% were diabetic (D.M). Regarding the risk factors: 40% were overweight, 13.3 % practicing exercise and only 3.3% were smoker. (table1) (figure1, 2)

Hematological Result:

In the present study the results revealed that; the mean of ferritin levels in the case group was (232.3± 36.3), in the control group was (114.1±11.7) (Figure3). Comparison between case and control in ferritin levels showed highly significant increase in the case group (p. v= 0.004) (Table 2). However, there were insignificant differences in ferritin levels between cases and controls in gender, past medical history and risk factors (p. v > 0.05). Furthermore, a negative correlation of ferritin levels was detected with age (p. v >0.05). (Table 3, 4, 5).

Discussion

Stroke is a non-traumatic, focal vascular injury of the nervous system and typically results in permanent damage in the form of cerebral infarction or intracerebral hemorrhage and/ or subarachnoid hemorrhage. An ischemic stroke occurs due to cessation of blood flow due to extra cranial or intracranial thrombosis, embolism, and hypo perfusion. ^[7] This was a case control hospital based study conducted at Ribat University Hospital at Khartoum state during the period of December 2022 to April 2023, and aimed to measure the Ferritin level among Sudanese patients with the ischemic stroke, the results revealed that; In the case group 53% were male and 47% were female, their mean of ages was (64.9±11. 9), 20% history of thrombi, 20% had high lipid level, 13.3% had heart condition, 63.3% were hypertensive and 36.7% were diabetic. Regarding the risk factors: 40% were overweight, 13.3 % practicing exercise and only 3.3% were smoker. These findings are consisting with the Dania Mohyeldin et al finding who reported; in the ischemic stroke Sudanese patients the most affected age group was between (56-60), the frequency of males is greater than the females, 94% with hypertension, 20 % of case are diabetic, 19% smoker and 16 % of case group with familial history of thrombi. ^[8] Yousufuddin et al reported; Aging is the most robust non-modifiable risk factor for ischemic stroke, which doubles every 10 years after age 55 years. Approximately three-quarters of all strokes occur in persons aged ≥65 years. ^[9] Moreover Gibson et al mentioned; men have been found to experience more ischemic stroke whereas women tend to have more infarctions involving the anterior circulation and experience more subarachnoid hemorrhages. On the other hand in terms of stroke onset, women tend to be, on average, approximately 4 years older than men at the age of ischemic stroke onset. ^[10]In addition Fahimfar et al said: the risk factors for ischemic stroke include aging, hypertension, diabetes, smoking, history of cardiovascular diseases (CVD), atrial fibrillation, and left ventricular hypertrophy. ^[11]In the present study when compared the ferritin mean between the case and control group there was highly significant increase with (p. v= 0.004). While the ferritin level had insignificant differences with gender, past medical history and risk factors. Also has negative correlation with the age. These results agreed with Garg et al results who revealed : Serum ferritin has a significant positive correlation with the severity of acute ischemic stroke (P < 0.001), and the levels correlate with the outcome of the disease (P < 0.001) , patients with higher serum ferritin at admission tend to deteriorate more as compared to those with lower levels. Thus, serum ferritin can be used as a prognostic marker in acute ischemic stroke. ^[12] It also consists with Hrishikesh et al study which concluded to that serum Ferritin level had a positive correlation with the severity of ischemic stroke indicating that serum Ferritin levels can also be used as an adjuvant tool for assessing the severity of stroke along with other tools and facilitate adequate and timely management of the patients. ^[13]A study by Van der DL et al.  in postmenopausal women between 49 and 70 years of age observed that higher serum ferritin concentrations in those postmenopausal women were associated with an increased risk of ischemic stroke. ^[14] Egovindarajulu et al. in their study also noted that there was no significant difference in the serum ferritin levels between the two age groups (≤50 years and >50 years) taken in their study (P = 0.918). ^[15]

In one study there was no significant correlation between serum ferritin and age, sex, smoking, cholesterol level, but there was significant correlation between serum ferritin and diabetes, hypertension and cardiovascular risk factors. ^[16] Finally, Previous studies had suggested that iron overload contributes to the development of vascular disease by promoting thrombosis after arterial injury. High serum ferritin at admission was reported to predict a poor prognosis in acute stroke patients (within 24–48 h after stroke onset), implicating that increase in the body iron stores before stroke onset can aggravate the cytotoxicity of brain ischemia. Thus, it has been suggested that high serum ferritin influences the prognosis of ischemic stroke and also acts as a risk factor for ischemic episodes by enhancing atherogenesis. ^[17]

Conclusion

This study demonstrates the significant rise in serum ferritin in ischemic stroke Sudanese patients, and the ferritin level had insignificant corelation with gender, age, past medical history and risk factors.

References

1. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics-2019 update: a report from the american heart association. Circulation. 2019;139 (10):e56-528.
2. Feigin VL, Mensah GA, Norrving B, Murray CJL, Roth GA. Atlas of the global burden of stroke (1990- 2013): The GBD 2013 study. Neuroepidemiol. 2015; 45(3):230-6.
3. Andrews NC, Schmidt PJ. Iron homeostasis. Annu Rev Physiol. 2007;69(69–85):69–85. [PubMed] [Google Scholar]
4. Millerot E, Prigent-Tessier AS, Bertrand NM, Faure PJC, Mossiat CM, Giroud ME, et al. Serum ferritin in stroke: A marker of increased body iron stores or stroke severity?. J Cereb Blood Flow Metab. 2005;25(10):1386-93
5. Van Der ADL, Grobbee DE, Roest M, Marx JJM, Voorbij HA, Van Der Schouw YT. Serum ferritin is a risk factor for stroke in postmenopausal women. Stroke. 2005;36(8):1637-41
6. Ortiz GAL, Sacco R. National institutes of health stroke scale NIHSS. Available at: https://onlinelibrary.wiley.com/doi/epdf/10.1002/978 1118445112.stat06823. Accessed on 20 August 2020.
7. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993 Jan;24(1):35-41. doi: 10.1161/01.str.24.1.35. PMID: 7678184.
8. Dania Mohyeldin Bashir Mohamed1, Nihad Elsadig Babiker. Estimation of Fibrinogen Level among Ischemic Stroke Patients in Khartoum State-2021. Journal of Drug Delivery & Therapeutics. 2021; 11(6-S):132-139.
9. Yousufuddin M, Young N. Aging and ischemic stroke. Aging (Albany NY). 2019 May 1;11(9):2542-2544. doi: 10.18632/aging.101931. PMID: 31043575; PMCID: PMC6535078.
10. Gibson CL. Cerebral ischemic stroke: is gender important? J Cereb Blood Flow Metab. 2013 Sep;33(9):1355-61. doi: 10.1038/jcbfm.2013.102. Epub 2013 Jun 12. PMID: 23756694; PMCID: PMC3764377.
11. Fahimfar, N., Khalili, D., Mohebi, R. et al. Risk factors for ischemic stroke; results from 9 years of follow-up in a population based cohort of Iran. BMC Neurol 12, 117 (2012). https://doi.org/10.1186/1471-2377-12-117
12. Garg R, Aravind S, Kaur S, Singh Chawla SP, Aggarwal S, Goyal G. Role of serum ferritin as a prognostic marker in acute ischemic stroke: A preliminary observation. Ann Afr Med. 2020 Apr-Jun;19(2):95-102. doi: 10.4103/aam.aam_35_19. PMID: 32499465; PMCID: PMC7453951.
13. Hrishikesh Shivakumar1 , Anugraha Durairaj2 , Madhu G2,*, Nirmala A C. A cross sectional study of correlation of serum ferritin levels with NIHSS scoring scale in patients of acute ischemic stroke. / Panacea Journal of Medical Sciences 2022;12(1):123–127
14. Van der DL, Grobbee DE, Roest M, Marx JJ, Voorbij HA, van der Schouw YT. Serum ferritin is a risk factor for stroke in postmenopausal women. Stroke. 2005;36:1637–41. [PubMed] [Google Scholar]
15. Egovindarajulu K, Maaran AT, Prathiba P, Saiprashanth PR. A study on prognostic significance of serum ferritin in patients with acute ischemic stroke. IOSR J Dent Med Sci. 2016;15:31–9. [Google Scholar]
16. Maaran, A T . A Study on Prognostic significance of Serum Ferritin in patients with Acute Ischemic Stroke. Masters thesis, Kilpauk Medical College, Chennai 2014.
17. Millán M, Sobrino T, Arenillas JF, Rodríguez-Yáñez M, García M, Nombela F, et al. Biological signatures of brain damage associated with high serum ferritin levels in patients with acute ischemic stroke and thrombolytic treatment. Dis Markers. 2008;25:181–8. [PMC free article] [PubMed] [Google Scholar]