Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 
Home Print this page Email this page
Users Online:: 605

 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 22  |  Issue : 2  |  Page : 82-85

Prevalence of hyperhomocysteinemia and hypovitaminosis B12 among acute ischemic stroke patients


1 Department of Chemical Pathology, Ahmadu Bello University/Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
2 Department of Radiology, Ahmadu Bello University/Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
3 Department of Medicine, Ahmadu Bello University/Ahmadu Bello University Teaching Hospital, Zaria, Nigeria

Date of Submission25-Oct-2018
Date of Acceptance04-Apr-2018
Date of Web Publication20-Jun-2019

Correspondence Address:
Dr. Hafsatu Maiwada Suleiman
Department of Chemical Pathology, Ahmadu Bello University Teaching Hospital, Zaria
Nigeria
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/smj.smj_70_17

Rights and Permissions
  Abstract 


Background: Deficiency of Vitamin B12 can lead to hyperhomocysteinemia. Hyperhomocysteinemia constitutes an abnormally high level of homocysteine in the serum, above the upper limit of normal for an environment. The two conditions are significant risk factors for the development of stroke. There is a paucity of data on the prevalence of these biochemical risk factors in stroke patients in our environment which brought about this study. Objective: The objective of the study was to determine how prevalent hyperhomocysteinemia and hypovitaminosis B12 are in acute ischemic stroke patients in Zaria. Materials and Mthods: This is a cross-sectional prospective study conducted from February 2014 to March 2015 in ABUTH Zaria. One hundred patients with clinical diagnosis of first-ever ischemic stroke confirmed by brain computed tomography scan, and another apparently healthy age- and sex-matched one hundred controls were recruited. Their fasting serum homocysteine and Vitamin B12 were determined using the enzyme-linked immunosorbent assay technique. Prevalence of high homocysteine and low Vitamin B12 was determined. Results: Thirty-four percent (34%) of patients had high and 66% patients had normal serum homocysteine, whereas 81% of patients had low and 19% of patients had normal serum Vitamin B12, and the difference was found to be statistically significant (P < 0.05). There was significant negative correlation between serum homocysteine and Vitamin B12 among cases with P = 0.04 and r = −0.198. Conclusion: The Prevalence rates of hyperhomocysteinemia and hypovitaminosis B12 among ischemic stroke pateints were 34% and 81%, respectively.

Keywords: Acute ischemic stroke, homocysteine, hyperhomocysteinemia, hypovitaminosis B12, Vitamin B12


How to cite this article:
Suleiman HM, Sambo IA, Abubakar SA, Jibril EM, Zaria MI, Yusuf R, Adamu R, Manu M, Jamoh BY. Prevalence of hyperhomocysteinemia and hypovitaminosis B12 among acute ischemic stroke patients. Sahel Med J 2019;22:82-5

How to cite this URL:
Suleiman HM, Sambo IA, Abubakar SA, Jibril EM, Zaria MI, Yusuf R, Adamu R, Manu M, Jamoh BY. Prevalence of hyperhomocysteinemia and hypovitaminosis B12 among acute ischemic stroke patients. Sahel Med J [serial online] 2019 [cited 2024 Mar 28];22:82-5. Available from: https://www.smjonline.org/text.asp?2019/22/2/82/260842




  Introduction Top


Homocysteine is a small, sulfur-containing amino acid derived primarily from the breakdown of dietary methionine in the activated methylation cycle.[1] The accumulation of homocysteine and its metabolites is caused by disruption of any of the three interrelated pathways of methionine metabolism deficiency in the cystathionine B-synthase (CBS) enzyme, defective methylcobalamin synthesis, or abnormality in methylenetetrahydrofolate reductase (MTHFR).[2],[3] Vitamin B12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system and for the formation of erythrocytes. It is one of the B vitamins.[4] Deficiencies of Vitamin B12 (cobalamin) can lead to high homocysteine levels.

Hyperhomocysteinemia is a significant risk factor for the development of a wide range of cerebrovascular diseases including stroke.[5] It may cause endothelial dysfunction through oxidative stress, resulting in local thrombosis and subsequent ischemia. Another possible mechanism is the direct toxicity of homocysteine to blood vessels, but there is no definite evidence to support either of this mechanisms.[6],[7]

Stroke is defined as a clinical syndrome of sudden onset of rapidly developing symptoms or signs of focal and at times global loss of cerebral function, with symptoms lasting more than 24 h or leading to death, with no apparent cause other than that of vascular origin.[8]

High plasma concentrations of homocysteine and low Vitamin B12 constitute an enhanced risk for stroke; it is necessary to determine the prevalence of these abnormalities in ischemic stroke patients which necessitated our study.


  Materials and Methods Top


Subjects

This was a cross-sectional prospective study, and the study population was made of 100 ischemic stroke patients newly admitted to medical ward in Ahmadu Bello University Teaching Hospital, Zaria and 100 apparently healthy age- and sex-matched controls from the same community. Diagnosis of acute ischemic stroke was made clinically and that were confirmed by CT scan. Informed consent for the study was obtained from all participants or their caregivers where the patients were unconscious or were not in a state to decide for themselves. All patients who were on any medication that is known to affect homocysteine and Vitamin B12 levels such as methotrexate, tamoxifen, L-DOPA, phenytoin, bile acid sequestrants, Vitamin B12, folic acid, use of oral contraceptive pills, anticonvulsants or lipid-lowering drugs or with renal insufficiency, liver disease, thyroid disease, leukemia, or psoriasis and patients with ischemic stroke, or patients' caregiver who refused to give informed consent for the study were excluded from the study. Ethical approval (protocol number ABUTH/HREC/K60/2013) was obtained on 21st May 2014 from Ethical and Scientific committee of ABUTH, Zaria, before embarking on the study. Informed written consent was obtained from all participants. All procedures complied with the guidelines of 2013 Helsinki Declaration.

Methods

Fasting Serum homocysteine and Vitamin B12 were measured in both patients and controls. Blood specimen was collected within the first 72 h of developing stroke. Patients and controls were asked to fast for 8–12 h and the blood samples were obtained from the antecubital fossa of each participant after cleaning it with methylated spirit and allowed to dry. A tourniquet was applied 10 cm above cubital fossa 5 ml syringe and a 21 g needle was used to draw 2 ml of blood from anterior cubital vein. The blood was transferred into a plain bottle and allowed to stand for about 30 min for it to clot and retract. This was then centrifuged for 20 min at 4000 rpm using Hettich Universal 32 centrifuge (Germany) manufactured by DJB Labcare Ltd, 20 Howard Way, Interchange Business Park, Newport Pagnell, Buckinghamshire MK16 9QS, England. The serum was separated from the cells and transferred into plain (sample) bottles and then frozen at −20°C until the time for analysis. Serum homocysteine and Vitamin B12 concentrations were measured using commercially prepared enzyme-linked immunosorbent assay kits. The chemicals and kits used for measurements of serum homocysteine and vitamin B12 were procured from Wkea medical supplies corporation, Changchum China and diagonostic automation/ cortez diagonostics USA respectively.

Data obtained were analyzed using statistical program for social sciences (SPSS 20.0) for windows SPSS inc. Chicago 20). Serum levels of homocysteine and Vitamin B12 categorical data were summarized as frequencies and percentages, while continuous data were summarized as the mean and standard deviation (SD). Students' t-test was used to analyze continuous normally distributed variables. P < 0.05 was considered statistically significant.

Quality control

Quality control material was obtained from pooled sera in the Department of Chemical Pathology for homocysteine and Vitamin B12. All assays were done in duplicates. Coefficient of variation was calculated from mean and SDs obtained.


  Results Top


The mean ± SD of the patients' and controls' age was 59 ± 14.08 years and 59 ± 14.09 years, respectively (P = 0.9999). There was a predominance of males (62%) over female (38%), with a male-to-female ratio of 1.6: 1 in both patients (cases) and control groups. The majority of the participants were Hausa/Fulani which accounted for 74% and 54% for cases and controls, respectively, as shown in [Table 1]. The reference interval of serum homocysteine and Vitamin B12 in the apparently healthy control population was determined using the mean value ± 2 SD of the controls and was found to be 0.9–1.70 μmol/L and 199.72–685.48 pg/ml for homocysteine and Vitamin B12, respectively, as shown in [Table 2]. [Table 3] shows 34 acute ischemic stroke patients (34%) had high serum levels of homocysteine and 66 patients (66%) had normal serum homocysteine. All the controls had normal serum homocysteine. [Table 4] showed 81 patients (81%) had low and 19 patients (19%) had normal serum Vitamin B12, whereas all the controls had normal Vitamin B12. [Table 5] shows that there was a negative correlation between serum homocysteine and Vitamin B12 among cases with P = 0.04 and r = −0.198.
Table 1: Demographic characteristics of study population

Click here to view
Table 2: Reference intervals of serum homocysteine and vitamin B12 using healthy controls

Click here to view
Table 3: Prevalence of elevated homocysteine among patients with ischaemic stroke and apparently healthy controls

Click here to view
Table 4: Prevalence of low vitamin B12 among patients with ischaemic stroke and apparently healthy controls

Click here to view
Table 5: Correlation between serum homocysteine and vitamin B12 among acute ischaemic stroke patients

Click here to view



  Discussion Top


There has been an exponential increase in the studies pertaining to homocysteine and its various implications, most prominent among them being its effect on vessel walls. The reference interval was established for this environment and this has allowed us to classify the particpant into high and normal.

Majority of stroke patients were Hausa–Fulani; this probably because north-western Nigeria is occupied largely by Hausa–Fulani tribe as a mixture. The prevalence of hyperhomocysteinemia in stroke was high which is similar to what Glew et al. got in Jos Plateau and he found a high prevalence of hyperhomocysteinemia among Fulanis.

The high prevalence of hyperhomocysteinemia we observed in many of the acute ischemic stroke patients who were involved in this study has confirmed the previous findings in northern Nigeria by Alkali et al.[9] This is probably as a result of inadequate Vitamin B12 nutrition, since the prevalence of hypovitaminosis B12 was also high in many of the acute ischemic stroke patients. In addition to nutritional factors, genetic variability may be another important determinant of plasma homocysteine levels; the accumulation of homocysteine and its metabolites is caused by disruption of any of the three interrelated pathways of methionine metabolism deficiency in the CBS enzyme, defective methylcobalamin synthesis, or abnormality in MTHFR. This hypovitaminosis B12 we found in our stroke cases was probably the cause of significant hyperhomocysteinemia in them because Vitamin B12 is an essential cofactor in the metabolism of homocysteine[10] also variability in the prevalence of genetic mutations of the enzyme MTHFR and varied practices between countries regarding fortification of dietary flour with folic acid could explain the hyperhomocysteinemia. This is in contrast to what Omrani et al. found in Iran in which no significant difference statistically between Vitamin B12 of cases and controls.[6] Most likely because of better nutritional status of the population in the study by Omarani et al as compared to the present study population. Therefore, it has been suggested that the patients with a homocysteine level greater than the population mean should be targeted and treated for hyperhomocysteinemia. Hence, also patients with low Vitamin B12 should be treated.

We also found a significant negative correlation between serum homocysteine and serum Vitamin B12 in this study (P = 0.04, r = −0.198) which is similar to the findings of Glew et al., who found an inverse association was observed between plasma homocysteine concentrations and serum levels of Vitamin B12, especially in acute stroke patients.[11] The explanation being that low Vitamin B12 causes hyperhomocysteinemia. Other studies have found a direct relation between even mild or moderately elevated serum homocysteine levels and the risk of both coronary artery and cerebrovascular thrombosis.[10] Cobalamin deficiency, which elevates plasma homocysteine, might, thus, be a cause of otherwise unexplained ischemic stroke or cranial artery dissection.[12],[13] Total homocysteine levels are inversely related to the levels of cobalamin consumed in the diet.[14] Furthermore, Selhub et al. reported in most cases that high homocysteine concentrations were associated with low serum vitamin concentrations.[15] Thus, cobalamin deficiency might increase the risk of cerebral infarction by increasing serum homocysteine levels.


  Conclusion Top


There was a high prevalence of hyperhomocysteinemia and hypovitaminosis B12 in acute ischemic stroke patients. Hence, in all patients with vascular occlusive disease, hyperhomocysteinemia and hypovitaminosis B12 should be elucidated and treated. In addition, long-term follow-up is required to ascertain whether the reduction in homocysteine decreases the thrombotic events and whether homocysteine levels can actually be of prognostic or predictive value in acute ischemic stroke patients.

Limitations of the present investigation include none assessment of several factors that might be associated with elevated homocysteine, such as creatinine, folate, and Vitamin B6 concentrations. Because this study was cross sectional, it was not possible to evaluate the data in terms of cause-and-effect relations.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Bhargava S, Parakh R, Manocha A, Ali A, Srivastava LM. Prevalence of hyperhomocysteinemia in vascular disease: Comparative study of thrombotic venous disease vis-à-vis occlusive arterial disease. Vascular 2007;15:149-53.  Back to cited text no. 1
    
2.
Obeid R, Herrmann W, Blom H, Czeizel AE, Djuric D, Ürgen Geisel J, et al. Advances and controversies in B-Vitamins and choline. Clin Chem Lab Med 2012;50:A1-69.  Back to cited text no. 2
    
3.
Brattström L, Wilcken DE, Ohrvik J, Brudin L. Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: The result of a meta-analysis. Circulation 1998;98:2520-6.  Back to cited text no. 3
    
4.
Schifferle RE. Periodontal disease and nutrition: Separating the evidence from current fads. Periodontol 2000 2009;50:78-89.  Back to cited text no. 4
    
5.
Selhub J, Jacques PF, Bostom AG, D'Agostino RB, Wilson PW, Belanger AJ, et al. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N Engl J Med 1995;332:286-91.  Back to cited text no. 5
    
6.
Omrani HQ, Shandiz EE, Qabai M, Chaman R, Fard HA, Qaffarpoor M, et al. Hyperhomocysteinemia, folateo and B12 Vitamin in Iranian patients with acute ischemic stroke. ARYA Atheroscler 2011;7:97-101.  Back to cited text no. 6
    
7.
Ashjazadeh N, Fathi M, Shariat A. Evaluation of homocysteine level as a risk factor among patients with ischemic stroke and its subtypes. Iran J Med Sci 2013;38:233-9.  Back to cited text no. 7
    
8.
Sacco RL, Kasner SE, Broderick JP, Caplan LR, Connors JJ, Culebras A, et al. An updated definition of stroke for the 21st century: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:2064-89.  Back to cited text no. 8
    
9.
Alkali NH, Watt H, Bwala SA, Gadzama A. Association of plasma homocysteine and ischaemic stroke in a Nigerian population. Pak J Med Sci 2006;22:405-8.  Back to cited text no. 9
    
10.
Yoo JH, Chung CS, Kang SS. Relation of plasma homocyst(e)ine to cerebral infarction and cerebral atherosclerosis. Stroke 1998;29:2478-83.  Back to cited text no. 10
    
11.
Glew RH, Okolie H, Crossey M, Suberu O, Trujillo M, Pereyra M, et al. Serum lipid profiles and homocysteine levels in adults with stroke or myocardial infarction in the town of Gombe in Northern Nigeria. J Health Popul Nutr 2004;22:341-7.  Back to cited text no. 11
    
12.
Penix LP. Ischemic strokes secondary to Vitamin B12 deficiency-induced hyperhomocystinemia. Neurology 1998;51:622-4.  Back to cited text no. 12
    
13.
O'Brien W, Crimmins D, Donaldson W, Risti R, Clarke TA, Whyte S, et al. FASTER (Face, arm, speech, time, emergency response): Experience of central coast stroke services implementation of a pre-hospital notification system for expedient management of acute stroke. J Clin Neurosci 2012;19:241-5.  Back to cited text no. 13
    
14.
Siri PW, Verhoef P, Kok FJ. Vitamins B6, B12, and folate: Association with plasma total homocysteine and risk of coronary atherosclerosis. J Am Coll Nutr 1998;17:435-41.  Back to cited text no. 14
    
15.
Selhub J, Jacques PF, Rosenberg IH, Rogers G, Bowman BA, Gunter EW, et al. Serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey (1991-1994): Population reference ranges and contribution of vitamin status to high serum concentrations. Ann Intern Med 1999;131:331-9.  Back to cited text no. 15
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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
   Materials and Me...
  Results
  Discussion
  Conclusion
   References
   Article Tables

 Article Access Statistics
    Viewed3467    
    Printed245    
    Emailed0    
    PDF Downloaded228    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]